supplements – methods - surveys · web viewrecord linkage until 3ist of march 2015, using...

Metabolite association with incident dementia, Supplements

SUPPLEMENT

Association of branched chain amino acids and other circulating metabolites

with risk of incident dementia and Alzheimer’s disease: a prospective study in

eight cohorts

Juho Tynkkynen*(1), Vincent Chouraki*(2–4), Sven J. van der Lee(5), Jussi Hernesniemi(1),

Qiong Yang(3,6), Shuo Li(3,6), Alexa Beiser(2,3,6), Martin G Larson(3,6), Katri Sääksjärvi(7),

Martin J Shipley(8), Archana Singh-Manoux(8,9), Robert E Gerszten(10–12), Thomas J. Wang(13),

Aki S. Havulinna(7), Peter Wȕrtz(14,15), Krista Fischer(16), Ayse Demirkan(5), M. Arfan

Ikram(5,17,18), Najaf Amin(5), Terho Lehtimäki(19,20), Mika Kähönen(21,22), Markus

Perola(7,15,16), Andres Metspalu(16), Antti J. Kangas(14), Pasi Soininen(14,23,24), Mika Ala-

Korpela(23–28), Ramachandran S. Vasan(3,29), Mika Kivimäki(8,30), Cornelia M. van

Duijn(5,31), Sudha Seshadri†(2,3,32), Veikko Salomaa†(7).

*Equal contribution as first authors; †Equal contribution as senior authors

Address of Correspondence: Veikko Salomaa, email: [email protected] Seshadri, email: [email protected]

1. Department of Cardiology, Tays Heart Hospital, Tampere University Hospital and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.

2. Department of Neurology, Boston University School of Medicine, Boston, MA, USA.

3. The Framingham Heart Study, Framingham, MA, USA.

4. Lille University, Inserm, Lille University Hospital, Institut Pasteur de Lille, U1167 - RID-AGE - Risk factors and molecular determinants of aging-related diseases; Labex Distalz, F-59000 Lille, France.

5. Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.

6. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.

7. Department of Health, National Institute for Health and Welfare, Helsinki, Finland.

8. Department of Epidemiology and Public Health, University College London, London, UK.

9. INSERM, U1018, Centre for Research in Epidemiology and Population Health, France


10. Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

11. Broad Institute of MIT and Harvard, Cambridge, MA, USA.

12. Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

13. Vanderbilt Heart and Vascular Institute, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.

14. Nightingale Health Ltd, Helsinki, Finland.

15. Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.

16. Estonian Genome Center, University of Tartu, Tartu, Estonia.

17. Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, 3015 CE, The Netherlands.

18. Department of Neurology, Erasmus MC, Rotterdam, 3015 CE, The Netherlands.

19. Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland.

20. Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere 33014, Finland.

21. Department of Clinical Physiology, Tampere University Hospital, Tampere 33521, Finland.

22. Department of Clinical Physiology, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere 33014, Finland.

23. Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.

24. NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.

25. Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK.

26. Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.

27. Systems Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.

28. Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia.

29. Department of Medicine (Sections of Preventive Medicine and Cardiology), Boston University School of Medicine, Boston, MA, USA.

30. Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

31. Leiden Academic Center for Drug Reseach (LACDR), Leiden University, Leiden, Netherlands.

32. Director, Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX.


Supplements – Methods - Surveys

FINRISK 1997 and DILGOM

The FINRISK Studies 1997 and 2007 are population-based health examination surveys which were

carried out in 6 areas in Finland. [1] DILGOM (Dietary, Lifestyle and Genetic determinants of

Obesity and Metabolic Syndrome) was an extension of the FINRISK 2007 survey, focused on

obesity. The original random samples were stratified by area, sex, and 10-year age group according

to the World Health Organization (WHO) MONICA (MONItoring trends and determinants of

CArdiovascular disease) protocol [2]. The samples comprised of men and women aged 25 to 74.

Participation rates were 72% and 60.9% in years 1997 and 2007, respectively. [1] In the FINRISK

1997 sample we excluded 11 persons with prevalent dementia or AD at baseline, 8 persons with

prevalent MS, 121 with prevalent epilepsy, 105 with prevalent stroke and 76 women who were

pregnant. In the DILGOM sample we excluded 6 persons with prevalent dementia or AD, 11

persons with prevalent MS, 81 persons with prevalent epilepsy, 85 with prevalent stroke and 24

women with pregnancy. In addition, all participants aged less than 40 years at baseline examination

were excluded from the analyses. The final analyzed sample size was 4,581 in FINRISK 1997 and

3,399 in DILGOM. These surveys were conducted in accordance with the Declaration of Helsinki.

For the FINRISK 1997 study, ethics approval was obtained from the Ethics Committee of the

National Public Health Institute and for DILGOM from the Coordinating Ethics Committee of the

Helsinki and Uusimaa Hospital District. The participants gave a written, informed consent.

FINRISK 1997 participants were advised to fast for four hours before the scheduled examination

and avoid heavy meals earlier during the day. The length of fasting and the time of blood drawing

were recorded. DILGOM participants were examined in the morning after an overnight fast. A self-

administered questionnaire included questions on medical history and socioeconomic factors. [1] In

the health examination, specially trained research nurses measured participants’ height and weight

following the standardized WHO MONICA protocol. [2] BMI was calculated as

weight(kg)/height(m2). Blood pressure was measured in each survey from the right arm after 5

minutes of sitting using a mercury sphygmomanometer. After blood pressure measurement, a

venous blood specimen was taken. In both surveys blood samples were analyzed for traditional

cardiovascular risk factors in the same central laboratory (National Public Health Institute, Helsinki,

Finland), standardized with the Center for Disease Control (CDC), Atlanta, Georgia. Blood


sampling, sample handling, laboratory methods, accuracy and precision for total- and HDL

cholesterol (HDL-C) measurements have been described previously. [3,4] The samples were

genotyped on a number of different genome-wide genotyping arrays and subsequently imputed

using ShapeIt2 and IMPUTE2 standard protocols. The apo E genotype was obtained from the

imputed GWAS data as described in more detail elsewhere. (Tynkkynen, et al. in Press DOI:

10.1007/s11357-016-9950-x). Description of covariates (prevalent diseases and antihypertensive

medication) in FINRISK 1997 and DILGOM studies covariate has been presented previously. [5,6]

Education was graded into tertiles by years of education adjusted for the birth year. Similar methods

were used in the Health 2000 cohort except for antihypertensive medication data were obtained

from the National Social Insurance Institution’s Drug Reimbursement Register. Identification of

dementia cases was carried out by annual record linkage of the FINRISK and DILGOM data on the

basis of personal ID code to the Finnish Hospital Discharge Register (HDR), Causes of Death

Register (CDR) and national Social Insurance Institution’s Drug Reimbursement Register. These

registers cover all deaths and hospitalizations in Finland, purchases of all drugs prescribed by a

doctor and all drug reimbursements. With these country-wide electronic registers the coverage of

the follow-up is 100% as long as the participant continues to live in Finland. Incident dementia was

identified if a participant was hospitalized or died with the ICD-10 codes of F00, F01, F02, F03 or

G30 or he/she made drug purchases of acetylcholinesterase inhibitors (AChRis) or NMDA-receptor

antagonist, memantine, more than three times during the follow-up. A participant entitled to

reimbursements for these therapeutic agents with the indication of dementia, was considered as

having incident dementia. To be granted the right to such reimbursements, a person must present a

written statement by a neurologist or a geriatrician documenting the findings which have led to the

diagnosis of dementia. Incident AD was identified only if the drug reimbursement was granted with

the ICD-10 code of G30. For these analyses the follow-up was available until Dec. 31st, 2013.

Health 2000

The Health 2000 Survey (BRIF8901) was a population-based health examination survey carried out

in 80 areas throughout Finland in 2000-2001. [7,8] The sample collection was performed in two

stages with stratified cluster sampling. The study population consisted of 8,028 participants (85% of

the sample) and was representative of the Finnish population aged ≥30 years. The Health 2000

Survey included interviews, self-administered questionnaires and a comprehensive health

examination. In-depth cardiovascular examinations were performed in the cardiovascular disease

and diabetes subcohort (SVT-D, sample size 1,867 and participation rate 82%), the participants of


which were aged 45 to 74 years and living in the area of Helsinki, Kuopio, Oulu, Tampere, Turku or

Joensuu. Data on education, smoking, and previous diseases (e.g. type 2 diabetes and cardiovascular

diseases), and antihypertensive medication were self-reported in a health interview or a self-

administered questionnaire at baseline. Height, weight and waist circumference were measured at a

health examination, and body mass index (BMI) was calculated. Blood pressure was measured

three times from the right arm after 10 minutes of sitting with automatic OMRON M4 device.

Fasting blood samples were taken and stored at − 70°C. More detailed description of the study

protocol is given elsewhere. [7] The linkage to the Finnish national registers is done in the same

way as described for FINRISK 1997. APOE genotyping was performed using the MassARRAY

System (Sequenom, San Diego, CA, USA) with a modified protocol, which has been described

elsewhere. [9]

Rotterdam - RS

This study included participants from the Rotterdam Study (RS), which is a prospective population-

based cohort study. In 1990, all residents aged 55 and older residing in Ommoord, a district of

Rotterdam, the Netherlands, were invited to participate in the study. Of the 10,215 invited

inhabitants, 7,983 agreed to participate in the baseline examinations. In 2000, 3,011 participants

(out of 4,472 invitees) who had become 55 years of age or moved into the study district since the

start of the study were added to the cohort. Follow-up examinations take place every 3 to 4 years.

[10] The Rotterdam Study has been approved by the Medical Ethics Committee of the Erasmus MC

and by the Ministry of Health, Welfare and Sport of the Netherlands, implementing the Population

Studies Act: Rotterdam Study (Erasmus Rotterdam Gezondheid Onderzoek). All participants

provided written informed consent to participate in the study and to obtain information from their

treating physicians. Measurements of the co-variates are described in detail elsewhere. [11]

Participants were screened for dementia at baseline and at follow-up examinations using a three-

step protocol. [12] Screening was done using the Mini-Mental State Examination (MMSE) and the

Geriatric Mental Schedule (GMS) organic level. Screen-positives (MMSE <26 or GMS organic

level >0) subsequently underwent an examination and informant interview with the Cambridge

Examination for Mental Disorders in the Elderly. [12] Additionally, the total cohort was

continuously monitored for dementia through computerized linkage of the study database with

digitized medical records from general practitioners and the Regional Institute for Outpatient

Mental Health Care. When information on neuroimaging was required and available, it was used for

decision making on the diagnosis. Ultimately, a consensus panel, led by a neurologist, decided on


the fil diagnosis in accordance with standard criteria for dementia (DSM-III-R) and Alzheimer’s

disease (NINCDS-ADRDA). [11,12] Of the 2938 individuals with metabolite data 507 participants

developed dementia of which 13 were classified as Parkinson’s’ disease (excluded), 13 were rare

specific causes of dementia and 346 were classified as AD.

Erasmus Ruchen Famlily Study - ERF

The Erasmus Ruchen Family study (ERF) is a prospective family-based study from a genetically

isolated population in Southwest of the Netherlands. The ERF study is described in detail

previously. [13,14] The baseline demographic data and measurements of the ERF participants were

collected around 2002 to 2006. Blood samples were collected through venipuncture in the morning

after at least 8 hours fasting at baseline. From 2015 until May 2016 records of 1368 participants in

the original cohort had complete covariate data, were scanned for incident dementia in general

practitioner’s databases (9 to 14 years after baseline visit) and contributed to the analysis. Three

individuals developed Parkinson’s’ disease dementia and were excluded, 145 died without

dementia, 35 participants developed dementia and 25 were classified as AD.

Whitehall II

The Whitehall II study is a prospective cohort study of 10 308 participants (70% men), aged 35–55

years and recruited between 1985 and 1989 from 20 London-based Civil service departments

(https://www.ucl.ac.uk/whitehallII). Clinical examinations have been performed in 1991-1994,

1997-1999, 2002-2004, 2007-2009, 2012-2013, 2015-2016 with the data from circulating

metabolomic traits and cognitive testing for the present study obtained from the 1997-1999 clinic

phase. The participants have been linked to electronic medical records. The study was approved by

the UCL Research Ethics Committee. All participants gave written informed consent to each aspect

of the study.

We used comprehensive tracing of electronic health records for dementia ascertainment using three

databases: the national hospital episode statistics (HES) database, the Mental Health Services Data

Set (MHSDS) and the mortality register. Record linkage until 3Ist of March 2015, using

International Classification of Diseases Tenth Edition (ICD-10) codes F00, F01, F02, F03, F05.1,

G30, G31.0, G31.1 and G31.8 identified cases of dementia, following the national Health Service

(NHS) guidelines. In the UK (England, Scotland, Wales), the NHS provides most of the health care,


including out- and in-patient care. Private medical insurance, held by around 12% of the UK

population (1997 figures), is mainly used for elective surgery rather than chronic conditions such as

dementia. MHSDS is a national database which contains information for persons in contact with

mental health services in hospitals, outpatient clinics, and the community.

Framingham Heart Study - FHS

The Framingham Heart Study (FHS) is an ongoing community-based prospective cohort study

initiated in 1948 with the enrollment of 5209 women and men aged 28 to 74 years (Original

Cohort). [15] In 1971, offspring of the Original Cohort and the spouses of these offspring

(n=5124; age, 5–70 years; 3548 biological offspring and 1576 offspring spouses) were enrolled in

the Framingham Offspring Cohort. [16] They have been examined every 4 to 8 years since, 9 times

to date, for a core examination. [17] In addition, the Offspring cohort has been under ongoing

surveillance for cognitive decline and dementia since the fifth examination (1991-1995, n=3799). A

total of 2526 participants among those who attended this fifth examination had their plasma

metabolome measured. In FHS cohort education was graded to three levels: college graduate, high

school degree and no high school degree. We screened participants at each examination for possible

cognitive decline through a number of mechanisms, including an administration of the Folstein

Mini-Mental Status Examination (MMSE). [18] Persons “flagged” as having possible cognitive

decline or otherwise being at risk for developing dementia underwent a more detailed

neuropsychological and neurological evaluation and when required a structured family interview

was administered to one or more family members and caregivers over the telephone. All persons

were assigned a Clinical Dementia Rating [19] scale score. We then determined whether each

person fulfilled criteria for a diagnosis of dementia, the probable date of onset, and type of dementia

at a consensus review conducted by a panel comprising at least one behavioral neurologist and one

neuropsychologist. Participants with dementia met criteria outlined in the fourth edition of the

Diagnostic and Statistical Manual of Mental Disorders criteria. [20] Participants with AD met

national Institute of Neurological and Communicative Diseases and Stroke/Alzheimer’s Disease

and Related Disorders Association criteria for definite, probable, or possible AD. [21] For the

present analyses, data for incident dementia obtained till December 2013 were used.

Estonia Biobank (Estonian Genome Center, University of Tartu, EGCUT)


Estonian Biobank (Estonian Genome Center, University of Tartu) is a population-based biobank

that recruited a cohort of 51,830 participants, including adults from all counties in Estonia and

accounting for approximately 5% of the Estonian adult population during the recruitment period

(2002-2011). At baseline, an extensive phenotype questionnaire was conducted together with a

measurement panel. In ECCUT cohort education was graded to four levels: university, secondary,

basic and primary or less. Follow-up data is available from linkage with national health-related

registries and the Estonian Health Insurance database. The NMR-biomarkers are available for a

random subset of 11000 individuals from the cohort. [22]


Supplements – Methods – Metabolite analysis

Briefly, the metabolome was assessed in FHS Offspring on plasma samples collected following an

overnight fast and stored at -80°C. Plasma metabolites were analyzed using liquid chromatography-

tandem mass spectrometry (LC-MS). LC-MS data were acquired using either an AB SCIEX 4000

QTRAP triple quadrupole mass spectrometer (positively charged polar compounds and lipids) or an

AB SCIEX 5500 QTRAP triple quadrupole mass spectrometer (negatively charged polar

compounds). Polar, positively charged metabolites were separated using hydrophobic interaction

liquid chromatography (HILIC) and analyzed using multiple reaction monitoring (MRM) in the

positive ion mode. Polar, negatively charged compounds, including central and polar

phosphorylated metabolites, were separated using a Luna NH2 column (150 × 2 mm, Luna NH2,

Phenomenex) and analyzed using MRM in the negative ion mode. Lipids were separated on a

Prosphere C4 HPLC column and underwent full scan MS analysis in the positive ion mode.

MultiQuant software (Version 1.2, AB SCIEX) was used for automated peak integration and

manual review of data quality prior to statistical analysis.


References – Supplement – Methods – Surveys, Metabolite analysis, Covariates

[1] Vartiainen E, Laatikainen T, Peltonen M, Juolevi A, Mannisto S, Sundvall J, Jousilahti P, Salomaa V, Valsta L, Puska P (2010) Thirty-five-year trends in cardiovascular risk factors in Finland. Int J Epidemiol 39, 504-518.

[2] Pajak A, Kuulasmaa K, Tuomilehto J, Ruokokoski E. (1988) Geographical variation in the major risk factors of coronary heart disease in men and women aged 35-64 years. The WHO MONICA Project. World Health Stat Q 41, 115-140.

[3] Sundvall J, Leiviska J, Alfthan G, Vartiainen E (2007) Serum cholesterol during 27 years: assessment of systematic error and affecting factors and their role in interpreting population trends. Clin Chim Acta 378, 93-98.

[4] Leiviska J, Sundvall J, Alfthan G, Tahtela R, Salomaa V, Jauhiainen M, Vartiainen E (2013) What have we learnt about high-density lipoprotein cholesterol measurements during 32 years? Experiences in Finland 1980-2012. Clin Chim Acta 415, 118-123.

[5] Kastarinen M, Antikainen R, Peltonen M, Laatikainen T, Barengo NC, Jula A, Salomaa V, Jousilahti P, Nissinen A, Vartiainen E, Tuomilehto J (2009) Prevalence, awareness and treatment of hypertension in Finland during 1982-2007. J Hypertens 27, 1552-1559.

[6] Blankenberg S, Zeller T, Saarela O, Havulinna AS, Kee F, Tunstall-Pedoe H, Kuulasmaa K, Yarnell J, Schnabel RB, Wild PS, Munzel TF, Lackner KJ, Tiret L, Evans A, Salomaa V, MORGAM Project (2010) Contribution of 30 biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: the MONICA, risk, genetics, archiving, and monograph (MORGAM) biomarker project. Circulation 121, 2388-2397.

[7] Heistaro S http://www.terveys2000.fi/doc/methodologyrep.pdf.

[8] Heistaro S (2005) Menetelmäraportti. Terveys 2000 -tutkimuksen toteutus, aineisto ja menetelmät. Helsinki: National Public Health Institute.

[9] Janis MT, Siggins S, Tahvanainen E, Vikstedt R, Silander K, Metso J, Aromaa A, Taskinen MR, Olkkonen VM, Jauhiainen M, Ehnholm C (2004) Active and low-active forms of serum phospholipid transfer protein in a normal Finnish population sample. J Lipid Res 45, 2303-2309.

[10] Hofman A, Brusselle GG, Darwish Murad S, van Duijn CM, Franco OH, Goedegebure A, Ikram MA, Klaver CC, Nijsten TE, Peeters RP, Stricker BH, Tiemeier HW, Uitterlinden AG, Vernooij MW (2015) The Rotterdam Study: 2016 objectives and design update. Eur J Epidemiol 30, 661-708.

[11] de Bruijn RF, Bos MJ, Portegies ML, Hofman A, Franco OH, Koudstaal PJ, Ikram MA (2015) The potential for prevention of dementia across two decades: the prospective, population-based Rotterdam Study. BMC Med 13, 132-015-0377-5.

http://www.terveys2000.fi/doc/methodologyrep.pdf


[12] Schrijvers EM, Verhaaren BF, Koudstaal PJ, Hofman A, Ikram MA, Breteler MM (2012) Is dementia incidence declining?: Trends in dementia incidence since 1990 in the Rotterdam Study. Neurology 78, 1456-1463.

[13] Sayed-Tabatabaei FA, van Rijn MJ, Schut AF, Aulchenko YS, Croes EA, Zillikens MC, Pols HA, Witteman JC, Oostra BA, van Duijn CM (2005) Heritability of the function and structure of the arterial wall: findings of the Erasmus Rucphen Family (ERF) study. Stroke 36, 2351-2356.

[14] Aulchenko YS, Heutink P, Mackay I, Bertoli-Avella AM, Pullen J, Vaessen N, Rademaker TA, Sandkuijl LA, Cardon L, Oostra B, van Duijn CM (2004) Linkage disequilibrium in young genetically isolated Dutch population. Eur J Hum Genet 12, 527-534.

[15] DAWBER TR, MEADORS GF, MOORE FE,Jr (1951) Epidemiological approaches to heart disease: the Framingham Study. Am J Public Health Nations Health 41, 279-281.

[16] Feinleib M, Kannel WB, Garrison RJ, McNamara PM, Castelli WP (1975) The Framingham Offspring Study. Design and preliminary data. Prev Med 4, 518-525.

[17] Au R, Seshadri S, Wolf PA, Elias M, Elias P, Sullivan L, Beiser A, D'Agostino RB (2004) New norms for a new generation: cognitive performance in the framingham offspring cohort. Exp Aging Res 30, 333-358.

[18] Folstein MF, Folstein SE, McHugh PR (1975) "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12, 189-198.

[19] Berg L (1988) Clinical Dementia Rating (CDR). Psychopharmacol Bull 24, 637-639.

[20] American Psychiatric Association and American Psychiatric Association. Task Force on DSM-IV. Diagnostic and statistical manual of mental disorders: DSM-IV. 1994.

[21] McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 34, 939-944.

[22] Leitsalu L, Haller T, Esko T, Tammesoo ML, Alavere H, Snieder H, Perola M, Ng PC, Magi R, Milani L, Fischer K, Metspalu A (2015) Cohort Profile: Estonian Biobank of the Estonian Genome Center, University of Tartu. Int J Epidemiol 44, 1137-1147.

STable 1

Supplement – Tables

STable 1. Descriptive statistics of discovery cohorts at baseline investigation1

FINRISK 1997 DILGOM Whitehall II EGCUT

Participants/Incident dementia/Incident AD/Death

4580/105/78 /471

3399/69/65/176 4612/114/35/379 2570/41/NA/409

Follow-up time, y Max/Median (IQR)/mean

10.0/10.0 (0.0)/9.6

7.9/7.9 (0.1)/7.7

17.9/17.0 (0.7)/16.7 12.8/7.5 (1.2)/7.03

Time from baseline to detection, y Mean/Median (IQR)

Dementia 6.4, 6.5 (3.8) 5.1, 5.3 (2.6) 14.0, 14.5 (3.7) 3.2, 3.3 (2.4)Alzheimer’s

Disease6.4, 6.5 (3.4) 5.02, 5.3 (2.7) 13.8, 14.2 (3.5) NA

Age,y Mean (SD) 55.1(9.19) 57.54(9.49) 55.9 (6.0) 59.6 (12.4)Sex, M % 50.4 47.0 73.5 41.1SBP,(mmHg) Mean (SD) 140.4 (20.2) 140.2 (20.5) 121.0 (15.9) 133.7 (17.2)

BP medication % 18.1 26.8 10.7 42.2

Cholesterol medication % 4.9 18.6 2.9 7.32Education %high/intermediate/low

32.0/34.0/34.0 29.9/35.4/34.7 34.9/28.1/37.0 22.1/60.5/16.8(4.2 very low)

Current Smoking, yes % 21.7 15.9 8.7 23.6

Body Mass Index (kg/m2), mean (SD) 27.4 (4.5) 27.6 (4.7) 25.87 (3.81) 28.0 (5.49)

Prevalent diseases

Diabetes% 7.1 10.7 3.3 6.6

Atrial fibrillation% 2.3 3.1 0.3 4.2

CHD% 3.5 3.6 5.1 11.4

Heart failure% 2.8 2.8 NA 9.5PAD% 0.9 0.9 NA 3.1

APOE ε4 (none/1/2) % 66.1/30.4/3.5 64.4/31.6/4.0 72.1/25.5/2.4 76.1/22.5/1.4

NA-not recorded separately

STable 1

1Stored blood samples drawn at baseline investigation were used for metabolomics determinations. 2See education description Supplement – Methods – Covariates

STable 2

STable 2 Descriptive statistics of replication cohorts at baseline investigation1

RS ERF Health 2000 FHS

Participants/Incident dementia/Incident AD/Death

2759/481/325/620 1366/35/25/126 1166/44/38/111 2171/106/78/548

Follow-up time, y Max/Median (IQR)/mean

11.7/9.4(4.3)/7.63 14.1/11.6(0.7)/11.31 10.0/10.0(0)/9.5 22.6/17.9(6.8)/

15.6

Time from baseline to detection, y Mean/Median (IQR)

Dementia 4.4, 4.7 (6.1) 8.2, 8.7 (3.6) 5.9, 6.9 (4.1) 11.1/11.4 (6.9)Alzheimer’s Disease 6.0, 7.0 (4.1) 10.6/10.6 (7.2)

Age,y Mean (SD) 75(6.6) 49.2(14.1) 56.7(8.0) 56.7 (9.0)

Sex, M % 42.4 42.5 42.9 47.4

SBP,(mmHg) Mean (SD) 152.1(21.3) 139.4(20.2) 138.5(21.7) 126.7 (18.7)

BP medication % 49.8 34.3 27.3 20.0

Cholesterol lowering medication % 22.5 13.7 9.8 8.12Education %high/intermediate/low

14.3/42.7/30.8(11.6 very low)

34.5/43.9/18.2(very low 3.5) 38.8/30.4/30.8 6.0/59.5/34.5

Current Smoking, yes % 40.3 42.3 18.1 18.0

Body Mass Index (kg/m2), mean (SD) 27.4(4.1) 27.1(4.6) 27.2 (4.6) 27.5 (4.9)

Prevalent diseases

Diabetes% 16.6 7.8 4.8 6.8

Atrial fibrillation % 11.8 NA 2.8 2.1

Coronary heart disease% NA NA 3.6 9.1 (CVD)

Heart failure% NA NA 3.6 NA

Peripheral artery disease % NA NA 1.3 NA

APOE ε4 (none/1/2) % 72.6/25.4/2 64.4/31.3/4.2 66.0/30.2/3.8 77.2/21.2/1.7

NA-not recorded separately, CVD-cardiovascular disease1Stored blood samples drawn at baseline investigation were used for metabolomics determinations.2See education description Supplement – Methods – Covariates

STable 3

STable 3. Methods of dementia and Alzheimer’s disease detection in different cohorts.Cohort Primary method for dementia

and AD detection Identification of dementia Identification of AD

FINRISK 1997

Using three electronic national health care registers:

Finnish Hospital Discharge Register (HDR)

Causes of Death Register (CDR)

National Social Insurance Institution’s Drug Reimbursement Register

ICD-10 codes F00, F01, F02, F03 or G30 detected in any register.

OR

Drug purchases of acetylcholinesterase inhibitors (AChRis) or NMDA-receptor antagonist, memantine, more than three times during the follow-up.

Only if the drug reimbursement was granted with the ICD-10 code of G30

DILGOM See FINRISK 1997 See FINRISK 1997 See FINRISK 1997

Whitehall II

Using three databases:

The national hospital episode statistics (HES) database

The Mental Health Services Data Set (MHSDS)

The mortality register.

ICD-10 codes F00, F01, F02, F03, F05.1, G30, G31.0, G31.1 or G31.8 detected in any register.

ICD-10 codes F00, G30 detected in any register.

EGCUT

Using two registers:

National health-related registries

The Estonian Health Insurance database

ICD-10 codes F00, F01, F02, F03 or G30 detected in any register

NA

STable 3

Rotterdam

Follow-up examinations every 3 to 4 years

and

Registers of general practitioners and the Regional Institute for Outpatient Mental Health Care

Screening was done using the Mini-Mental State Examination (MMSE) and the Geriatric Mental Schedule (GMS) organic level. Screen-positives (MMSE <26 or GMS organic level >0) subsequently underwent an examination and informant interview with the Cambridge Examination for Mental Disorders in the Elderly.

and

Monitored for dementia through computerized linkage from registers

A consensus panel, led by a neurologist, decided on the fil diagnosis in accordance with standard criteria for dementia (DSM-III-R) and Alzheimer’s disease (NINCDS-ADRDA)

ERFUsing health care registers. Participants in the original cohort with

complete covariate data were scanned for incident dementia in general practitioner’s databases (9 to 14 years after baseline visit).

Confirmed diagnosis of AD in letters from medical specialists.

Health 2000 See FINRISK 1997 See FINRISK 1997 See FINRISK 1997

FHS

Screening every 4 to 8 years. Screening cognitive tests were administered once in 2-4 years and this is supplemented by ongoing surevillance, annual health status updates, medical record review and detailed neuropsychological batteries and brain MRI administered once in ~6 years since 1999. Persons suspected to have cognitive decline have annual neuropsychological and neurological assessments. Family interviews are conducted after the participant's death where indicated to retrospectively ascertain cognitive status at death.

Participants with AD met national Institute of Neurological and Communicative Diseases and Stroke/Alzheimer’s Disease and Related Disorders Association criteria for definite, probable, or possible AD.

NA-not recorded separately

STable 4

STable 4. List of all metabolites quantified by NMR in the present study.

Metabolite, lipid, or lipoprotein lipid Short nameSD(Finrisk 1997) Unit Class

Alanine Ala 0.07 mmol/l Amino AcidsGlutamine Gln 0.07 mmol/l Amino AcidsGlycine Gly 0.06 mmol/l Amino AcidsHistidine His 0.01 mmol/l Amino AcidsIsoleucine Ile 0.02 mmol/l Amino AcidsLeucine Leu 0.02 mmol/l Amino AcidsPhenylalanine Phe 0.01 mmol/l Amino AcidsTyrosine Tyr 0.01 mmol/l Amino AcidsValine Val 0.04 mmol/l Amino Acids

Docosahexaenoic acid DHA 0.08 mmol/lFatty Acids & Saturation

Ratio of docosahexaenoic acid to total fatty acids DHA/FA 0.49 %Fatty Acids & Saturation

Omega-3 fatty acids FAw3 0.21 mmol/lFatty Acids & Saturation

Ratio of omega-3 fatty acids to total fatty acids FAw3/FA 1.39 %Fatty Acids & Saturation

Omega-6 fatty acids FAw6 0.78 mmol/lFatty Acids & Saturation

Ratio of omega-6 fatty acids to total fatty acids FAw6/FA 3.4 %Fatty Acids & Saturation

Linoleic acid LA 0.65 mmol/lFatty Acids & Saturation

Ratio of linoleic acid to total fatty acids LA/FA 3.35 %Fatty Acids & Saturation

Monounsaturated fatty acids; 16:1, 18:1 MUFA 1.08 mmol/lFatty Acids & Saturation

Ratio of monounsaturated fatty acids to total fatty acids MUFA/FA 2.91 %

Fatty Acids & Saturation

Polyunsaturated fatty acids PUFA 0.89 mmol/lFatty Acids & Saturation

Ratio of polyunsaturated fatty acids to total fatty acids PUFA/FA 3.86 %


Saturated fatty acids SAFA 1.24 mmol/lFatty Acids & Saturation

Ratio of saturated fatty acids to total fatty acids SAFA/FA 2.14 %Fatty Acids & Saturation

Total fatty acids TotFA 2.97 mmol/lFatty Acids & Saturation

Fatty acids degree of unsaturation UnSat 0.07Fatty Acids & Saturation

Albumin Alb 0.01 signal area Fluid BalanceCreatinine Crea 0.01 mmol/l Fluid Balance

Citrate Cit 0.02 mmol/l

Glycolysis Related Metabolites

Glucose Glc 1.16 mmol/l


Glycerol Glol 0.08 mmol/l


Lactate Lac 0.34 mmol/l


STable 4

Pyruvate Pyr 0.03 mmol/l


Acetoacetate AcAce 0.06 mmol/l Ketone BodiesAcetate Ace 0.05 mmol/l Ketone Bodies3-hydroxybutyrate bOHBut 0.15 mmol/l Ketone BodiesGlycoprotein acetyls, mainly a1-acid glycoprotein Gp 0.25 mmol/l Inflammation

Triglycerides in HDL HDL-TG 0.06 mmol/lGlycerides & Phospholipids

Triglycerides in LDL LDL-TG 0.13 mmol/lGlycerides & Phospholipids

Phosphatidylcholine and other cholines PC 0.39 mmol/lGlycerides & Phospholipids

Serum total triglycerides Serum-TG 0.69 mmol/lGlycerides & Phospholipids

Sphingomyelins SM 0.09 mmol/lGlycerides & Phospholipids

Ratio of triglycerides to phosphoglycerides TG/PG 0.22Glycerides & Phospholipids

Total cholines TotCho 0.43 mmol/lGlycerides & Phospholipids

Total phosphoglycerides TotPG 0.45 mmol/lGlycerides & Phospholipids

Triglycerides in VLDL VLDL-TG 0.47 mmol/lGlycerides & Phospholipids

Apolipoprotein A-I ApoA1 0.23 g/l ApolipoproteinsApolipoprotein B ApoB 0.24 g/l ApolipoproteinsRatio of apolipoprotein B to apolipoprotein A-I ApoB/ApoA1 0.18 ApolipoproteinsEsterified cholesterol EstC 0.77 mmol/l CholesterolFree cholesterol FreeC 0.31 mmol/l CholesterolTotal cholesterol in HDL2 HDL2-C 0.38 mmol/l CholesterolTotal cholesterol in HDL3 HDL3-C 0.05 mmol/l CholesterolTotal cholesterol in HDL HDL-C 0.39 mmol/l CholesterolTotal cholesterol in LDL LDL-C 0.58 mmol/l CholesterolRemnant cholesterol (non-HDL, non-LDL -cholesterol) Remnant-C 0.53 mmol/l CholesterolSerum total cholesterol Serum-C 1.07 mmol/l CholesterolTotal cholesterol in VLDL VLDL-C 0.36 mmol/l Cholesterol

Mean diameter for HDL particles HDL-D 0.29 nmLipoprotein Particle Sizes

Mean diameter for LDL particles LDL-D 0.16 nmLipoprotein Particle Sizes

Mean diameter for VLDL particles VLDL-D 1.05 nmLipoprotein Particle Sizes

Total cholesterol in IDL IDL-C 0.23 mmol/lLipoprotein Subclasses

Total cholesterol to total lipids ratio in IDL IDL-C-% 3.71 %Lipoprotein Subclasses

Cholesterol esters in IDL IDL-CE 0.17 mmol/lLipoprotein Subclasses

Cholesterol esters to total lipids ratio in IDL IDL-CE-% 3 %Lipoprotein Subclasses

Free cholesterol in IDL IDL-FC 0.07 mmol/lLipoprotein Subclasses

Free cholesterol to total lipids ratio in IDL IDL-FC-% 1.03 %Lipoprotein Subclasses

Total lipids in IDL IDL-L 0.36 mmol/lLipoprotein Subclasses

STable 4

Concentration of IDL particles IDL-P 0.04 umol/lLipoprotein Subclasses

Phospholipids in IDL IDL-PL 0.09 mmol/lLipoprotein Subclasses

Phospholipids to total lipds ratio in IDL IDL-PL-% 0.64 %Lipoprotein Subclasses

Triglycerides in IDL IDL-TG 0.07 mmol/lLipoprotein Subclasses

Triglycerides to total lipids ratio in IDL IDL-TG-% 3.82 %Lipoprotein Subclasses

Total cholesterol in large HDL L-HDL-C 0.21 mmol/lLipoprotein Subclasses

Total cholesterol to total lipids ratio in large HDL L-HDL-C-% 4.44 %Lipoprotein Subclasses

Cholesterol esters in large HDL L-HDL-CE 0.16 mmol/lLipoprotein Subclasses

Cholesterol esters to total lipids ratio in large HDL L-HDL-CE-% 3.26 %Lipoprotein Subclasses

Free cholesterol in large HDL L-HDL-FC 0.05 mmol/lLipoprotein Subclasses

Free cholesterol to total lipids ratio in large HDL L-HDL-FC-% 1.82 %Lipoprotein Subclasses

Total lipids in large HDL L-HDL-L 0.38 mmol/lLipoprotein Subclasses

Concentration of large HDL particles L-HDL-P 0.59 umol/lLipoprotein Subclasses

Phospholipids in large HDL L-HDL-PL 0.17 mmol/lLipoprotein Subclasses

Phospholipids to total lipds ratio in large HDL L-HDL-PL-% 3.7 %Lipoprotein Subclasses

Triglycerides in large HDL L-HDL-TG 0.02 mmol/lLipoprotein Subclasses

Triglycerides to total lipids ratio in large HDL L-HDL-TG-% 3.08 %Lipoprotein Subclasses

Total cholesterol in medium HDL M-HDL-C 0.13 mmol/lLipoprotein Subclasses

Total cholesterol to total lipids ratio in medium HDL M-HDL-C-% 7.91 %

Lipoprotein Subclasses

Cholesterol esters in medium HDL M-HDL-CE 0.11 mmol/lLipoprotein Subclasses

Cholesterol esters to total lipids ratio in medium HDL M-HDL-CE-% 7.28 %


Free cholesterol in medium HDL M-HDL-FC 0.03 mmol/lLipoprotein Subclasses

Free cholesterol to total lipids ratio in medium HDL M-HDL-FC-% 1 %


Total lipids in medium HDL M-HDL-L 0.23 mmol/lLipoprotein Subclasses

Concentration of medium HDL particles M-HDL-P 0.53 umol/lLipoprotein Subclasses

Phospholipids in medium HDL M-HDL-PL 0.1 mmol/lLipoprotein Subclasses

Phospholipids to total lipds ratio in medium HDL M-HDL-PL-% 4.29 %Lipoprotein Subclasses

Triglycerides in medium HDL M-HDL-TG 0.02 mmol/lLipoprotein Subclasses

Triglycerides to total lipids ratio in medium HDL M-HDL-TG-% 4.36 %Lipoprotein Subclasses

Total cholesterol in small HDL S-HDL-C 0.08 mmol/l Lipoprotein

STable 4

Subclasses

Total cholesterol to total lipids ratio in small HDL S-HDL-C-% 4.77 %Lipoprotein Subclasses

Cholesterol esters in small HDL S-HDL-CE 0.07 mmol/lLipoprotein Subclasses

Cholesterol esters to total lipids ratio in small HDL S-HDL-CE-% 5.48 %Lipoprotein Subclasses

Free cholesterol in small HDL S-HDL-FC 0.02 mmol/lLipoprotein Subclasses

Free cholesterol to total lipids ratio in small HDL S-HDL-FC-% 1.03 %Lipoprotein Subclasses

Total lipids in small HDL S-HDL-L 0.16 mmol/lLipoprotein Subclasses

Concentration of small HDL particles S-HDL-P 0.71 umol/lLipoprotein Subclasses

Phospholipids in small HDL S-HDL-PL 0.11 mmol/lLipoprotein Subclasses

Phospholipids to total lipds ratio in small HDL S-HDL-PL-% 4.7 %Lipoprotein Subclasses

Triglycerides in small HDL S-HDL-TG 0.03 mmol/lLipoprotein Subclasses

Triglycerides to total lipids ratio in small HDL S-HDL-TG-% 2.95 %Lipoprotein Subclasses

Total cholesterol in very large HDL XL-HDL-C 0.13 mmol/lLipoprotein Subclasses

Total cholesterol to total lipids ratio in very large HDL XL-HDL-C-% 5.37 %


Cholesterol esters in very large HDL XL-HDL-CE 0.1 mmol/lLipoprotein Subclasses

Cholesterol esters to total lipids ratio in very large HDL XL-HDL-CE-% 5.13 %


Free cholesterol in very large HDL XL-HDL-FC 0.04 mmol/lLipoprotein Subclasses

Free cholesterol to total lipids ratio in very large HDL XL-HDL-FC-% 1.41 %


Total lipids in very large HDL XL-HDL-L 0.26 mmol/lLipoprotein Subclasses

Concentration of very large HDL particles XL-HDL-P 0.26 umol/lLipoprotein Subclasses

Phospholipids in very large HDL XL-HDL-PL 0.14 mmol/lLipoprotein Subclasses

Phospholipids to total lipds ratio in very large HDL XL-HDL-PL-% 6.43 %Lipoprotein Subclasses

Triglycerides in very large HDL XL-HDL-TG 0.01 mmol/lLipoprotein Subclasses

Triglycerides to total lipids ratio in very large HDL XL-HDL-TG-% 1.75 %Lipoprotein Subclasses

Total cholesterol in large LDL L-LDL-C 0.3 mmol/lLipoprotein Subclasses

Total cholesterol to total lipids ratio in large LDL L-LDL-C-% 3.22 %Lipoprotein Subclasses

Cholesterol esters in large LDL L-LDL-CE 0.22 mmol/lLipoprotein Subclasses

Cholesterol esters to total lipids ratio in large LDL L-LDL-CE-% 2.93 %Lipoprotein Subclasses

Free cholesterol in large LDL L-LDL-FC 0.07 mmol/lLipoprotein Subclasses

Free cholesterol to total lipids ratio in large LDL L-LDL-FC-% 1.07 %Lipoprotein Subclasses

STable 4

Total lipids in large LDL L-LDL-L 0.41 mmol/lLipoprotein Subclasses

Concentration of large LDL particles L-LDL-P 0.06 umol/lLipoprotein Subclasses

Phospholipids in large LDL L-LDL-PL 0.08 mmol/lLipoprotein Subclasses

Phospholipids to total lipds ratio in large LDL L-LDL-PL-% 1.5 %Lipoprotein Subclasses

Triglycerides in large LDL L-LDL-TG 0.07 mmol/lLipoprotein Subclasses

Triglycerides to total lipids ratio in large LDL L-LDL-TG-% 3.38 %Lipoprotein Subclasses

Total cholesterol in medium LDL M-LDL-C 0.18 mmol/lLipoprotein Subclasses

Total cholesterol to total lipids ratio in medium LDL M-LDL-C-% 4.77 %


Cholesterol esters in medium LDL M-LDL-CE 0.15 mmol/lLipoprotein Subclasses

Cholesterol esters to total lipids ratio in medium LDL M-LDL-CE-% 5.93 %


Free cholesterol in medium LDL M-LDL-FC 0.03 mmol/lLipoprotein Subclasses

Free cholesterol to total lipids ratio in medium LDL M-LDL-FC-% 2.03 %


Total lipids in medium LDL M-LDL-L 0.25 mmol/lLipoprotein Subclasses

Concentration of medium LDL particles M-LDL-P 0.05 umol/lLipoprotein Subclasses

Phospholipids in medium LDL M-LDL-PL 0.05 mmol/lLipoprotein Subclasses

Phospholipids to total lipds ratio in medium LDL M-LDL-PL-% 2.97 %Lipoprotein Subclasses

Triglycerides in medium LDL M-LDL-TG 0.04 mmol/lLipoprotein Subclasses

Triglycerides to total lipids ratio in medium LDL M-LDL-TG-% 3.52 %Lipoprotein Subclasses

Total cholesterol in small LDL S-LDL-C 0.11 mmol/lLipoprotein Subclasses

Total cholesterol to total lipids ratio in small LDL S-LDL-C-% 5.07 %Lipoprotein Subclasses

Cholesterol esters in small LDL S-LDL-CE 0.09 mmol/lLipoprotein Subclasses

Cholesterol esters to total lipids ratio in small LDL S-LDL-CE-% 6.23 %Lipoprotein Subclasses

Free cholesterol in small LDL S-LDL-FC 0.02 mmol/lLipoprotein Subclasses

Free cholesterol to total lipids ratio in small LDL S-LDL-FC-% 1.76 %Lipoprotein Subclasses

Total lipids in small LDL S-LDL-L 0.15 mmol/lLipoprotein Subclasses

Concentration of small LDL particles S-LDL-P 0.05 umol/lLipoprotein Subclasses

Phospholipids in small LDL S-LDL-PL 0.03 mmol/lLipoprotein Subclasses

Phospholipids to total lipds ratio in small LDL S-LDL-PL-% 3.64 %Lipoprotein Subclasses

Triglycerides in small LDL S-LDL-TG 0.02 mmol/lLipoprotein Subclasses

Triglycerides to total lipids ratio in small LDL S-LDL-TG-% 3.44 % Lipoprotein

STable 4

Subclasses

Total cholesterol in large VLDL L-VLDL-C 0.06 mmol/lLipoprotein Subclasses

Total cholesterol to total lipids ratio in large VLDL L-VLDL-C-% 6.89 %Lipoprotein Subclasses

Cholesterol esters in large VLDL L-VLDL-CE 0.03 mmol/lLipoprotein Subclasses

Cholesterol esters to total lipids ratio in large VLDL L-VLDL-CE-% 6.89 %


Free cholesterol in large VLDL L-VLDL-FC 0.03 mmol/lLipoprotein Subclasses

Free cholesterol to total lipids ratio in large VLDL L-VLDL-FC-% 2.68 %Lipoprotein Subclasses

Total lipids in large VLDL L-VLDL-L 0.19 mmol/lLipoprotein Subclasses

Concentration of large VLDL particles L-VLDL-P 0 umol/lLipoprotein Subclasses

Phospholipids in large VLDL L-VLDL-PL 0.04 mmol/lLipoprotein Subclasses

Phospholipids to total lipds ratio in large VLDL L-VLDL-PL-% 2.56 %Lipoprotein Subclasses

Triglycerides in large VLDL L-VLDL-TG 0.1 mmol/lLipoprotein Subclasses

Triglycerides to total lipids ratio in large VLDL L-VLDL-TG-% 8.04 %Lipoprotein Subclasses

Total cholesterol in medium VLDL M-VLDL-C 0.1 mmol/lLipoprotein Subclasses

Total cholesterol to total lipids ratio in medium VLDL M-VLDL-C-% 6.01 %


Cholesterol esters in medium VLDL M-VLDL-CE 0.06 mmol/lLipoprotein Subclasses

Cholesterol esters to total lipids ratio in medium VLDL M-VLDL-CE-% 6.21 %


Free cholesterol in medium VLDL M-VLDL-FC 0.04 mmol/lLipoprotein Subclasses

Free cholesterol to total lipids ratio in medium VLDL M-VLDL-FC-% 1.51 %


Total lipids in medium VLDL M-VLDL-L 0.29 mmol/lLipoprotein Subclasses

Concentration of medium VLDL particles M-VLDL-P 0.01 umol/lLipoprotein Subclasses

Phospholipids in medium VLDL M-VLDL-PL 0.06 mmol/lLipoprotein Subclasses

Phospholipids to total lipds ratio in medium VLDL M-VLDL-PL-% 1.08 %Lipoprotein Subclasses

Triglycerides in medium VLDL M-VLDL-TG 0.15 mmol/lLipoprotein Subclasses

Triglycerides to total lipids ratio in medium VLDL M-VLDL-TG-% 6.67 %Lipoprotein Subclasses

Total cholesterol in small VLDL S-VLDL-C 0.11 mmol/lLipoprotein Subclasses

Total cholesterol to total lipids ratio in small VLDL S-VLDL-C-% 5.16 %Lipoprotein Subclasses

Cholesterol esters in small VLDL S-VLDL-CE 0.07 mmol/lLipoprotein Subclasses

Cholesterol esters to total lipids ratio in small VLDL S-VLDL-CE-% 5.01 %


Free cholesterol in small VLDL S-VLDL-FC 0.04 mmol/lLipoprotein Subclasses

STable 4

Free cholesterol to total lipids ratio in small VLDL S-VLDL-FC-% 0.67 %Lipoprotein Subclasses

Total lipids in small VLDL S-VLDL-L 0.28 mmol/lLipoprotein Subclasses

Concentration of small VLDL particles S-VLDL-P 0.01 umol/lLipoprotein Subclasses

Phospholipids in small VLDL S-VLDL-PL 0.06 mmol/lLipoprotein Subclasses

Phospholipids to total lipds ratio in small VLDL S-VLDL-PL-% 1.26 %Lipoprotein Subclasses

Triglycerides in small VLDL S-VLDL-TG 0.12 mmol/lLipoprotein Subclasses

Triglycerides to total lipids ratio in small VLDL S-VLDL-TG-% 5.24 %Lipoprotein Subclasses

Total cholesterol in very large VLDL XL-VLDL-C 0.02 mmol/lLipoprotein Subclasses

Total cholesterol to total lipids ratio in very large VLDL XL-VLDL-C-% 9.76 %


Cholesterol esters in very large VLDL XL-VLDL-CE 0.01 mmol/lLipoprotein Subclasses

Cholesterol esters to total lipids ratio in very large VLDL XL-VLDL-CE-% 5.6 %


Free cholesterol in very large VLDL XL-VLDL-FC 0.01 mmol/lLipoprotein Subclasses

Free cholesterol to total lipids ratio in very large VLDL XL-VLDL-FC-% 5.76 %


Total lipids in very large VLDL XL-VLDL-L 0.07 mmol/lLipoprotein Subclasses

Concentration of very large VLDL particles XL-VLDL-P 0 umol/lLipoprotein Subclasses

Phospholipids in very large VLDL XL-VLDL-PL 0.01 mmol/lLipoprotein Subclasses

Phospholipids to total lipds ratio in very large VLDL XL-VLDL-PL-% 3.81 %


Triglycerides in very large VLDL XL-VLDL-TG 0.04 mmol/lLipoprotein Subclasses

Triglycerides to total lipids ratio in very large VLDL XL-VLDL-TG-% 11.69 %


Total cholesterol in very small VLDL XS-VLDL-C 0.1 mmol/lLipoprotein Subclasses

Total cholesterol to total lipids ratio in very small VLDL XS-VLDL-C-% 3.61 %


Cholesterol esters in very small VLDL XS-VLDL-CE 0.07 mmol/lLipoprotein Subclasses

Cholesterol esters to total lipids ratio in very small VLDL XS-VLDL-CE-% 3.26 %


Free cholesterol in very small VLDL XS-VLDL-FC 0.03 mmol/lLipoprotein Subclasses

Free cholesterol to total lipids ratio in very small VLDL XS-VLDL-FC-% 1.02 %


Total lipids in very small VLDL XS-VLDL-L 0.2 mmol/lLipoprotein Subclasses

Concentration of very small VLDL particles XS-VLDL-P 0.02 umol/lLipoprotein Subclasses

Phospholipids in very small VLDL XS-VLDL-PL 0.06 mmol/lLipoprotein Subclasses

Phospholipids to total lipds ratio in very small VLDL XS-VLDL-PL-% 1.81 %


Triglycerides in very small VLDL XS-VLDL-TG 0.06 mmol/l Lipoprotein

STable 4

SubclassesTriglycerides to total lipids ratio in very small VLDL XS-VLDL-TG-% 4.5 %


Total cholesterol in chylomicrons and extremely large VLDL XXL-VLDL-C 0.01 mmol/l


Total cholesterol to total lipids ratio in chylomicrons and extremely large VLDL XXL-VLDL-C-% 3.61 %


Cholesterol esters in chylomicrons and extremely large VLDL XXL-VLDL-CE 0 mmol/l


Cholesterol esters to total lipids ratio in chylomicrons and extremely large VLDL XXL-VLDL-CE-% 3.5 %


Free cholesterol in chylomicrons and extremely large VLDL XXL-VLDL-FC 0 mmol/l


Free cholesterol to total lipids ratio in chylomicrons and extremely large VLDL XXL-VLDL-FC-% 1.31 %


Total lipids in chylomicrons and extremely large VLDL XXL-VLDL-L 0.03 mmol/l


Concentration of chylomicrons and extremely large VLDL particles XXL-VLDL-P 0 umol/l


Phospholipids in chylomicrons and extremely large VLDL XXL-VLDL-PL 0 mmol/l


Phospholipids to total lipds ratio in chylomicrons and extremely large VLDL XXL-VLDL-PL-% 1.57 %


Triglycerides in chylomicrons and extremely large VLDL XXL-VLDL-TG 0.02 mmol/l


Triglycerides to total lipids ratio in chylomicrons and extremely large VLDL XXL-VLDL-TG-% 3.96 %


STable 5STable 5. Associations of covariates with incident dementia. HR and 95%CI is presented

FINRISK 97HR(95%CI)

DILGOMHR(95%CI)

WHITEHALLHR(95%CI)

EGCUTHR(95%CI)

HEALTH 2000HR(95%CI)

ROTTERDAMHR(95%CI)

ERFHR(95%CI)

FSHHR(95%CI)

FIXED EFFECTHR(95%CI)

RANDOM EFFECTHR(95%CI) I2 p.fixed

p.random

Age, years 1.21(1.17;1.24)

1.25 (1.19;1.31)

1.23 (1.18;1.28)

1.11(1.08;1.14)

1.24(1.17;1.32)

1.12 (1.1;1.14)

1.19 (1.12;1.25)

1.08 (1.07;1.1)

1.12(1.11;1.13)

1.17(1.13;1.22) 0.929 <0.001 <0.001

Sex, HR for women

1.6(1.07;2.38)

1.01(0.63;1.63)

0.66(0.44;0.99)

0.90(0.47;1.71)

0.71(0.38;1.33)

1.15(0.91;1.45)

0.58(0.25;1.34)

0.98(0.82;1.17)

1.01(0.9;1.13)

0.98(0.81;1.19) 0.485 0.898 0.824

Education level, in three levels compared to the lowest

0.96(0.76;1.21)

0.6(0.44;0.82)

1.02(0.81;1.29)

0.59(0.41;0.83)

0.59(0.37;0.93)

0.87(0.77;0.99)

0.66 (0.32;1.4)

0.79 (0.58;1.07) college*

0.84(0.77;0.92)

0.79(0.66;0.93) 0.611 <0.001 0.006

apo E (number of ε4 alleles)

2.84(2.14;3.77)

2.78(1.96;3.95)

2.83(2.11;3.78)

1.32(0.73;2.37)

3.77(2.31;6.15)

2.41(2.01;2.9)

2.45(1.35;4.44)

1.58(1.33;1.89)

2.22(2.02;2.45)

2.39(1.91;2.99) 0.766 <0.001 <0.001

Systolic blood pressure, mmHg

1.00 (0.99;1.01)

0.99 (0.98;1.01)

1.00 (0.99;1.01)

1.01(0.99;1.02)

1.00 (0.99;1.02)

1.00 (1;1.01)

1 .00 (0.98;1.01)

1.00(1;1.01)

1.00(1;1)

1.00(1;1) 0 0.675 0.675

Antihypertensive medication

1.4 (0.91;2.15)

0.88 (0.53;1.46)

0.69 (0.38;1.25)

0.58(0.31;1.08)

1.01 (0.52;1.95)

0.9(0.72;1.12) NA

1.14 (0.95;1.37)

1.01(0.89;1.14)

0.97(0.81;1.17) 0.388 0.879 0.772

Current smoking

1.12 (0.62;2.01)

0.57 (0.21;1.59)

0.77 (0.34;1.78)

1.92(0.74;4.98)

1.26 (0.5;3.18)

1.01 (0.9;1.13)

0.49(0.17;1.36)

0.92 (0.67;1.27)

1(0.9;1.1)

1(0.9;1.1) 0 0.930 0.930

Prevalent

Diabetes 0.97 (0.52;1.81)

1.64 (0.82;3.28)

1.96(0.94;4.05)

0.97(0.37;2.54)

0.74(0.17;3.24)

1.13 0.86;1.49)

2.61(1.04;6.56)

1.1(0.84;1.43)

1.18(1;1.4)

1.18(1;1.4) 0 0.049 0.049

Atrial fibrillation

1.34(0.55;3.24)

0.86(0.33;2.26) NA

1.70(0.60;4.85)

2.35(0.58;9.59) NA NA

1.11(0.66;1.86)

1.23(0.85;1.76)

1.23(0.85;1.76) 0 0.273 0.273

Coronary heart disease

0.88(0.42;1.86)

0.69(0.26;1.85) NA

1.47(0.70;3.06)

2.61(0.99;6.9)

1.15(0.81;1.63) NA NA

1.17(0.9;1.54)

1.18(0.86;1.62) 0.14 0.243 0.300

Heart failure 1.01(0.46;2.2)

2.4(1.06;5.43) NA

1.60(0.77;3.32)

1.13(0.3;4.22) NA NA NA

1.5(0.98;2.29)

1.5(0.98;2.29) 0 0.060 0.060

Peripheral artery disease

0.83(0.24;2.93)

1.43(0.33;6.17) NA NA NA NA NA NA

1.05(0.4;2.73)

1.05(0.4;2.73) 0 0.921 0.921

Cardiovascular disease NA NA

1.24(0.64;2.42) NA NA NA NA

1.05(0.83;1.34)

1.07(0.86;1.34)

1.07(0.86;1.34) 0 0.545 0.545

* HR and 95%CI for a college education. Not included in the meta-analysis result. NA - not detected separately.

STable 6

STable 6. HRs and 95% CIs of metabolites, lipids and lipoprotein lipids for incident dementia. Adjusted for Model 1.* Metabolite which did not fulfill the proportional hazard assumption (see Methods)

Metabolite, lipid,

lipoprotein lipid

FINRISK 97HR(95%CI)

DILGOMHR(95%CI)

WHITEHALLHR(95%CI)

EGCUTHR(95%CI)

FIXEDEFFECTHR(95%CI)

RANDOMEFFECT,HR(95%CI) I2 p.fixed p.random

Amino Acids

ALA1.1(0.85;1.4)

0.84(0.63;1.12)

0.77(0.63;0.93)

1.19(0.87;1.62)

0.91(0.8;1.03)

0.94(0.76;1.16) 0.636 0.1322 0.5767

GLN1.04(0.81;1.33)

0.77(0.57;1.05)

1(0.82;1.23)

1(0.72;1.4)

0.97(0.85;1.1)

0.97(0.85;1.1) 0 0.6060 0.6060

GLY1.05(0.81;1.36)

0.9(0.69;1.17)

1.02(0.84;1.23)

NA(NA;NA)

1(0.87;1.13)

1(0.87;1.13) 0 0.9366 0.9366

HIS0.96(0.8;1.16)

0.74(0.56;1)

0.83(0.7;0.98)

1.02(0.66;1.57)

0.87(0.78;0.98)

0.87(0.78;0.98) 0.048 0.0172 0.0216

ILE0.92(0.71;1.18)

0.84(0.63;1.13)

0.71(0.58;0.88)

0.64(0.43;0.97)

0.78(0.69;0.9)

0.78(0.68;0.91) 0.119 0.0004 0.0010

LEU0.89(0.68;1.16)

0.75(0.55;1.04)

0.73(0.59;0.89)

0.54(0.34;0.84)

0.75(0.65;0.86)

0.75(0.64;0.88) 0.178 0.0000 0.0003

PHE0.95(0.72;1.24)

0.69(0.49;0.97)

0.85(0.7;1.04)

1.04(0.76;1.42)

0.88(0.77;1)

0.88(0.76;1.01) 0.142 0.0470 0.0720

TYR0.89(0.73;1.1)

0.71(0.55;0.91)

0.84(0.7;1.02)

1.03(0.78;1.36)

0.86(0.77;0.96)

0.86(0.75;0.98) 0.263 0.0074 0.0236

VAL0.83(0.64;1.07)

0.7(0.51;0.96)

0.86(0.72;1.04)

0.59(0.41;0.86)

0.79(0.7;0.9)

0.78(0.67;0.91) 0.22 0.0003 0.0012


DHA0.89(0.72;1.12)

1.14(0.91;1.43)

0.77(0.63;0.94)

0.72(0.5;1.04)

0.89(0.79;1)

0.88(0.72;1.07) 0.62 0.0464 0.2135

DHA-FA0.84(0.68;1.04)

1.2(0.94;1.54)

0.93(0.76;1.14)

0.67(0.45;0.99)

0.93(0.82;1.05)

0.91(0.75;1.12) 0.612 0.2174 0.3845

FAW30.9(0.73;1.12)

1.14(0.89;1.47)

0.77(0.63;0.94)

0.65(0.44;0.96)

0.87(0.78;0.98)

0.87(0.7;1.07) 0.649 0.0256 0.1800

FAW3-FA0.86(0.72;1.04)

1.24(0.97;1.6)

0.95(0.78;1.16)

0.59(0.39;0.89)

0.93(0.83;1.05)

0.91(0.73;1.15) 0.713 0.2374 0.4299

FAW60.97(0.79;1.19)

0.82(0.62;1.08)

0.74(0.61;0.89)

0.95(0.69;1.3)

0.85(0.75;0.95)

0.85(0.74;0.98) 0.297 0.0051 0.0275

FAW6-FA0.86(0.7;1.05)

0.88(0.66;1.18)

1.11(0.9;1.36)

0.92(0.69;1.24)

0.95(0.84;1.07)

0.95(0.83;1.08) 0.146 0.3903 0.4165

STable 6

LA0.96(0.79;1.17)

0.76(0.59;0.99)

0.77(0.64;0.94)

0.97(0.71;1.33)

0.86(0.76;0.96)

0.86(0.75;0.98) 0.217 0.0071 0.0193

LA-FA0.85(0.68;1.06)

0.78(0.6;1.03)

1.12(0.92;1.37)

0.96(0.72;1.29)

0.94(0.84;1.06)

0.93(0.79;1.1) 0.469 0.3496 0.4049

MUFA1.16(0.93;1.45)

0.9(0.68;1.2)

0.68(0.56;0.84)

0.96(0.69;1.34)

0.89(0.79;1.01)

0.91(0.7;1.17) 0.756 0.0710 0.4604

MUFA-FA1.19(0.98;1.45)

0.95(0.71;1.27)

0.78(0.64;0.95)

0.91(0.67;1.25)

0.96(0.85;1.07)

0.95(0.77;1.17) 0.664 0.4534 0.6266

PUFA0.95(0.76;1.17)

0.88(0.67;1.17)

0.73(0.6;0.88)

0.87(0.64;1.19)

0.84(0.74;0.94)

0.84(0.74;0.95) 0.159 0.0025 0.0076

PUFA-FA0.83(0.68;1.01)

0.99(0.75;1.31)

1.09(0.89;1.34)

0.79(0.58;1.09)

0.93(0.83;1.05)

0.93(0.8;1.08) 0.379 0.2535 0.3499

SFA1.13(0.9;1.43)

0.94(0.69;1.28)

0.76(0.62;0.92)

1.13(0.82;1.54)

0.94(0.83;1.06)

0.96(0.78;1.19) 0.639 0.3070 0.7348

SFA-FA1.14(0.92;1.42)

1.12(0.84;1.49)

1.25(1.03;1.52)

1.62(1.18;2.21)

1.24(1.1;1.4)

1.24(1.09;1.43) 0.204 0.0004 0.0017

TOTFA1.1(0.87;1.38)

0.91(0.68;1.22)

0.7(0.58;0.85)

0.98(0.72;1.34)

0.88(0.78;0.99)

0.9(0.72;1.12) 0.674 0.0350 0.3554

UNSAT0.82(0.68;1.01)

1.17(0.92;1.49)

1.01(0.83;1.23)

0.66(0.47;0.92)

0.93(0.83;1.04)

0.91(0.74;1.13) 0.69 0.2067 0.3902

Fluid Balance

ALB0.99(0.78;1.25)

1.45(1.03;2.04)

0.82(0.69;0.96)

0.77(0.55;1.08)

0.91(0.81;1.02)

0.96(0.75;1.21) 0.707 0.1165 0.7139

CREA0.92(0.75;1.13)

0.81(0.6;1.09)

0.64(0.5;0.81)

0.86(0.59;1.25)

0.8(0.7;0.91)

0.8(0.66;0.96) 0.453 0.0008 0.0148


*CIT0.93(0.77;1.13)

1.04(0.78;1.39)

1.02(0.84;1.23)

0.98(0.72;1.34)

0.99(0.88;1.1)

0.99(0.88;1.1) 0 0.7942 0.7942

GLC0.95(0.76;1.18)

0.99(0.77;1.25)

1.22(1.01;1.48)

1.13(0.91;1.4)

1.08(0.97;1.2)

1.08(0.96;1.21) 0.177 0.1597 0.2189

*GLOL0.93(0.71;1.21)

0.84(0.6;1.19)

0.89(0.73;1.08)

NA(NA;NA)

0.89(0.77;1.03)

0.89(0.77;1.03) 0 0.1090 0.1090

LAC1.02(0.85;1.23)

1.04(0.77;1.41)

0.89(0.74;1.08)

0.83(0.58;1.18)

0.96(0.85;1.07)

0.96(0.85;1.07) 0 0.4319 0.4319

PYR1.13(0.92;1.39)

1.01(0.76;1.35)

1(0.83;1.2)

NA(NA;NA)

1.04(0.92;1.18)

1.04(0.92;1.18) 0 0.4925 0.4925

Ketone Bodies

STable 6

*ACACE0.92(0.74;1.15)

1.35(1.01;1.81)

1.04(0.87;1.25)

1.04(0.76;1.42)

1.05(0.93;1.18)

1.06(0.92;1.22) 0.299 0.4187 0.4504

ACE1.09(0.88;1.35)

1(0.77;1.3)

0.98(0.81;1.19)

0.81(0.29;2.25)

1.02(0.9;1.15)

1.02(0.9;1.15) 0 0.7511 0.7511

*BOHBUT0.85(0.64;1.13)

1.27(0.95;1.69)

0.98(0.82;1.17)

1.01(0.72;1.41)

1(0.89;1.14)

1.01(0.87;1.17) 0.261 0.9446 0.9161

Inflammation

GP1.09(0.87;1.37)

0.82(0.62;1.07)

0.71(0.58;0.86)

0.83(0.56;1.22)

0.84(0.74;0.95)

0.85(0.68;1.05) 0.641 0.0061 0.1388

Glycerides & Phospholipids

HDL-TG1.12(0.9;1.38)

1.02(0.72;1.44)

0.75(0.63;0.9)

1.08(0.78;1.51)

0.93(0.82;1.04)

0.97(0.77;1.21) 0.677 0.2146 0.7619

LDL-TG1.12(0.88;1.41)

0.94(0.66;1.33)

0.71(0.58;0.87)

1.04(0.75;1.45)

0.9(0.79;1.03)

0.93(0.73;1.17) 0.667 0.1176 0.5320

PC1.03(0.81;1.3)

1.02(0.76;1.38)

0.82(0.67;1)

1.09(0.78;1.53)

0.95(0.83;1.07)

0.95(0.83;1.09) 0.129 0.3820 0.4720

SERUM-TG1.12(0.9;1.38)

0.83(0.62;1.12)

0.68(0.56;0.84)

0.84(0.57;1.25)

0.86(0.76;0.97)

0.86(0.67;1.1) 0.722 0.0144 0.2232

SM0.92(0.71;1.19)

0.95(0.7;1.29)

0.91(0.76;1.11)

1.11(0.81;1.51)

0.95(0.84;1.08)

0.95(0.84;1.08) 0 0.4159 0.4159

TG-PG1.2(0.96;1.5)

0.84(0.65;1.09)

0.71(0.57;0.87)

0.76(0.51;1.15)

0.87(0.77;0.99)

0.87(0.66;1.13) 0.76 0.0341 0.2882

TOTCHO0.99(0.77;1.28)

1(0.72;1.38)

0.85(0.7;1.03)

1.11(0.79;1.54)

0.94(0.83;1.07)

0.94(0.83;1.07) 0 0.3774 0.3774

TOTPG1.05(0.84;1.32)

1.02(0.75;1.38)

0.82(0.67;0.99)

1.12(0.8;1.56)

0.95(0.84;1.08)

0.96(0.83;1.12) 0.273 0.4482 0.6390

VLDL-TG1.1(0.89;1.36)

0.81(0.61;1.07)

0.72(0.59;0.87)

0.82(0.54;1.24)

0.85(0.76;0.96)

0.85(0.69;1.06) 0.652 0.0106 0.1561

Apolipoproteins

APOA10.95(0.78;1.14)

1.14(0.88;1.48)

0.93(0.76;1.13)

1.19(0.85;1.65)

1(0.89;1.12)

1(0.89;1.12) 0 0.9869 0.9869

APOB1.02(0.82;1.27)

0.89(0.67;1.17)

0.76(0.63;0.92)

0.86(0.62;1.2)

0.87(0.77;0.98)

0.87(0.76;1) 0.245 0.0195 0.0549

APOB-APOA11.06(0.86;1.31)

0.82(0.61;1.1)

0.81(0.66;0.98)

0.77(0.54;1.1)

0.88(0.78;1)

0.88(0.75;1.02) 0.344 0.0418 0.0936

Cholesterol

STable 6

ESTC0.92(0.74;1.16)

0.97(0.73;1.27)

0.81(0.67;0.98)

0.95(0.69;1.3)

0.89(0.79;1)

0.89(0.79;1) 0 0.0506 0.0506

FREEC0.94(0.76;1.18)

0.97(0.74;1.28)

0.84(0.69;1.02)

1.08(0.81;1.45)

0.93(0.83;1.04)

0.93(0.83;1.04) 0 0.2175 0.2175

HDL2-C0.93(0.77;1.12)

1.19(0.9;1.57)

1.05(0.86;1.28)

1.27(0.89;1.81)

1.04(0.93;1.17)

1.05(0.92;1.2) 0.15 0.4541 0.4360

HDL3-C0.92(0.73;1.16)

1.03(0.72;1.46)

1.05(0.87;1.27)

1.22(0.91;1.64)

1.04(0.92;1.17)

1.04(0.92;1.17) 0 0.5606 0.5606

HDL-C0.91(0.75;1.11)

1.17(0.89;1.53)

1.05(0.86;1.28)

1.28(0.92;1.79)

1.04(0.93;1.17)

1.06(0.92;1.21) 0.268 0.4662 0.4468

LDL-C0.94(0.76;1.16)

0.9(0.69;1.17)

0.84(0.7;1.01)

0.96(0.7;1.32)

0.89(0.8;1)

0.89(0.8;1) 0 0.0560 0.0560

REMNANT-C1.01(0.79;1.29)

0.91(0.67;1.24)

0.76(0.63;0.92)

0.84(0.6;1.18)

0.86(0.76;0.97)

0.86(0.76;0.98) 0.077 0.0168 0.0258

SERUM-C0.94(0.75;1.18)

0.97(0.74;1.28)

0.81(0.67;0.98)

0.99(0.72;1.36)

0.9(0.8;1.01)

0.9(0.8;1.01) 0 0.0759 0.0759

VLDL-C1.04(0.81;1.35)

0.89(0.65;1.22)

0.72(0.6;0.87)

0.79(0.55;1.15)

0.83(0.73;0.94)

0.85(0.7;1.02) 0.452 0.0047 0.0755

Lipoprotein Particle Sizes

HDL-D0.86(0.69;1.08)

1.27(0.96;1.68)

1.22(1;1.48)

1.58(1.14;2.21)

1.15(1.02;1.3)

1.19(0.94;1.5) 0.717 0.0230 0.1590

LDL-D1.16(0.93;1.45)

1.4(0.99;2)

1.18(0.97;1.44)

0.91(0.64;1.3)

1.16(1.02;1.32)

1.16(1.02;1.32) 0 0.0219 0.0219

VLDL-D1.06(0.83;1.34)

0.81(0.63;1.05)

0.77(0.63;0.94)

0.9(0.65;1.26)

0.87(0.77;0.98)

0.87(0.75;1.02) 0.304 0.0258 0.0766


IDL-C0.95(0.76;1.18)

0.95(0.71;1.26)

0.87(0.72;1.05)

0.94(0.69;1.29)

0.91(0.81;1.03)

0.91(0.81;1.03) 0 0.1380 0.1380

IDL-C-%0.89(0.74;1.06)

1(0.74;1.34)

1.16(0.92;1.46)

1(0.72;1.4)

0.98(0.87;1.11)

0.99(0.87;1.12) 0.065 0.7810 0.8213

IDL-CE0.94(0.76;1.18)

0.95(0.71;1.27)

0.87(0.72;1.05)

0.93(0.68;1.28)

0.91(0.81;1.03)

0.91(0.81;1.03) 0 0.1389 0.1389

*IDL-CE-%0.89(0.74;1.07)

1.05(0.79;1.4)

1.15(0.92;1.45)

0.88(0.64;1.2)

0.98(0.87;1.1)

0.98(0.86;1.13) 0.228 0.7373 0.8173

IDL-FC0.97(0.78;1.2)

0.93(0.7;1.24)

0.86(0.71;1.04)

0.99(0.72;1.36)

0.92(0.82;1.04)

0.92(0.82;1.04) 0 0.1679 0.1679

STable 6

IDL-FC-%0.88(0.71;1.11)

1.07(0.85;1.36)

1.07(0.86;1.32)

1.4(0.88;2.25)

1.03(0.91;1.17)

1.03(0.9;1.19) 0.177 0.6692 0.6571

IDL-L1(0.79;1.25)

0.93(0.7;1.25)

0.83(0.69;1.01)

0.94(0.69;1.29)

0.91(0.81;1.03)

0.91(0.81;1.03) 0 0.1223 0.1223

IDL-P1.01(0.8;1.27)

0.93(0.69;1.24)

0.82(0.68;1)

0.94(0.69;1.29)

0.91(0.8;1.02)

0.91(0.8;1.02) 0 0.1123 0.1123

IDL-PL1(0.8;1.24)

0.94(0.71;1.24)

0.84(0.7;1.01)

0.97(0.71;1.33)

0.92(0.82;1.03)

0.92(0.82;1.03) 0 0.1565 0.1565

IDL-PL-%1(0.75;1.32)

1(0.71;1.4)

1.15(0.94;1.39)

1.32(0.95;1.85)

1.11(0.98;1.27)

1.11(0.98;1.27) 0 0.1127 0.1127

IDL-TG1.13(0.9;1.42)

0.92(0.65;1.3)

0.69(0.57;0.85)

0.91(0.64;1.3)

0.88(0.77;1)

0.89(0.7;1.14) 0.691 0.0472 0.3759

*IDL-TG-%1.13(0.94;1.37)

1.02(0.77;1.34)

0.79(0.64;0.98)

0.91(0.64;1.3)

0.97(0.86;1.09)

0.96(0.8;1.15) 0.524 0.5831 0.6640

L-HDL-C0.93(0.75;1.14)

1.22(0.93;1.6)

1.17(0.95;1.43)

1.46(1.05;2.04)

1.12(1;1.27)

1.15(0.96;1.37) 0.508 0.0574 0.1265

L-HDL-C-%1.02(0.83;1.26)

1.28(0.95;1.73)

1.38(1.12;1.71)

1.3(0.89;1.88)

1.21(1.07;1.38)

1.22(1.04;1.43) 0.319 0.0025 0.0129

L-HDL-CE0.93(0.76;1.15)

1.22(0.93;1.6)

1.17(0.96;1.43)

1.48(1.06;2.06)

1.13(1;1.27)

1.15(0.96;1.37) 0.517 0.0497 0.1180

L-HDL-CE-%1.05(0.85;1.29)

1.29(0.95;1.76)

1.43(1.15;1.78)

1.35(0.93;1.96)

1.24(1.1;1.41)

1.25(1.07;1.47) 0.346 0.0007 0.0063

L-HDL-FC0.92(0.75;1.13)

1.21(0.92;1.6)

1.16(0.94;1.42)

1.42(1.02;1.98)

1.11(0.98;1.25)

1.13(0.95;1.34) 0.484 0.0916 0.1575

L-HDL-FC-%0.95(0.79;1.15)

1.26(0.92;1.73)

1.23(0.99;1.52)

1.15(0.82;1.6)

1.1(0.98;1.24)

1.11(0.96;1.29) 0.262 0.1209 0.1512

L-HDL-L0.91(0.74;1.13)

1.21(0.92;1.59)

1.13(0.92;1.39)

1.49(1.05;2.12)

1.1(0.98;1.24)

1.13(0.94;1.36) 0.537 0.1119 0.1846

L-HDL-P0.91(0.74;1.13)

1.21(0.93;1.59)

1.13(0.92;1.38)

1.49(1.05;2.12)

1.1(0.98;1.24)

1.13(0.94;1.36) 0.536 0.1116 0.1857

L-HDL-PL0.9(0.74;1.11)

1.2(0.92;1.58)

1.1(0.9;1.35)

1.45(1;2.1)

1.08(0.96;1.22)

1.11(0.93;1.32) 0.489 0.2256 0.2666

*L-HDL-PL-%0.94(0.75;1.17)

0.81(0.58;1.13)

0.76(0.62;0.93)

0.66(0.44;0.97)

0.81(0.71;0.92)

0.81(0.71;0.93) 0.067 0.0015 0.0023

L-HDL-TG0.99(0.81;1.21)

1.14(0.84;1.54)

1(0.81;1.23)

1.62(1.16;2.25)

1.09(0.96;1.23)

1.13(0.93;1.36) 0.567 0.1804 0.2293

*L-HDL-TG-%1.07(0.88;1.3)

0.89(0.65;1.21)

0.87(0.71;1.06)

1.12(0.83;1.5)

0.97(0.87;1.1)

0.98(0.86;1.11) 0.11 0.6641 0.6917

M-HDL-C1.02(0.82;1.27)

1.07(0.77;1.47)

0.92(0.76;1.12)

0.88(0.62;1.25)

0.97(0.86;1.09)

0.97(0.86;1.09) 0 0.6030 0.6030

STable 6

M-HDL-C-%0.94(0.74;1.19)

0.99(0.69;1.42)

1.16(0.95;1.42)

0.96(0.72;1.29)

1.03(0.91;1.17)

1.03(0.91;1.17) 0 0.6029 0.6029

M-HDL-CE1.02(0.82;1.27)

1.07(0.77;1.47)

0.94(0.77;1.14)

0.87(0.61;1.24)

0.97(0.86;1.1)

0.97(0.86;1.1) 0 0.6351 0.6351

*M-HDL-CE-%0.91(0.71;1.17)

0.96(0.66;1.41)

1.22(1;1.49)

0.96(0.72;1.29)

1.05(0.92;1.19)

1.03(0.89;1.21) 0.238 0.4960 0.6597

M-HDL-FC1.03(0.84;1.26)

1.06(0.79;1.42)

0.87(0.72;1.05)

0.88(0.62;1.25)

0.95(0.84;1.07)

0.95(0.84;1.07) 0 0.3899 0.3899

M-HDL-FC-%1.03(0.86;1.23)

1.09(0.83;1.45)

0.94(0.77;1.14)

0.98(0.7;1.37)

1(0.9;1.12)

1(0.9;1.12) 0 0.9566 0.9566

M-HDL-L1.02(0.83;1.26)

1.07(0.79;1.45)

0.87(0.72;1.06)

0.86(0.6;1.23)

0.95(0.84;1.07)

0.95(0.84;1.07) 0 0.4001 0.4001

M-HDL-P1.02(0.83;1.26)

1.07(0.79;1.45)

0.87(0.71;1.05)

0.86(0.6;1.23)

0.95(0.84;1.07)

0.95(0.84;1.07) 0 0.3705 0.3705

M-HDL-PL1(0.82;1.22)

1.09(0.81;1.45)

0.87(0.71;1.05)

0.89(0.62;1.26)

0.95(0.84;1.07)

0.95(0.84;1.07) 0 0.3818 0.3818

*M-HDL-PL-%0.98(0.76;1.25)

1.22(0.83;1.79)

0.98(0.8;1.19)

1.25(0.99;1.58)

1.07(0.94;1.2)

1.07(0.94;1.22) 0.12 0.3067 0.3219

M-HDL-TG1.07(0.89;1.28)

0.87(0.62;1.22)

0.74(0.62;0.87)

0.78(0.55;1.11)

0.86(0.77;0.96)

0.86(0.7;1.06) 0.677 0.0084 0.1638

M-HDL-TG-%1.08(0.88;1.32)

0.82(0.58;1.15)

0.8(0.68;0.95)

0.87(0.61;1.24)

0.89(0.8;1)

0.9(0.76;1.05) 0.424 0.0585 0.1858

S-HDL-C0.97(0.79;1.2)

0.84(0.64;1.12)

0.86(0.71;1.04)

0.84(0.6;1.18)

0.89(0.79;1)

0.89(0.79;1) 0 0.0499 0.0499

S-HDL-C-%0.87(0.73;1.04)

0.87(0.65;1.17)

1.08(0.89;1.31)

1.11(0.79;1.54)

0.96(0.86;1.08)

0.96(0.85;1.09) 0.151 0.5040 0.5680

S-HDL-CE0.92(0.75;1.14)

0.83(0.62;1.1)

0.92(0.76;1.11)

0.86(0.63;1.18)

0.9(0.8;1.01)

0.9(0.8;1.01) 0 0.0671 0.0671

S-HDL-CE-%0.87(0.73;1.04)

0.85(0.63;1.15)

1.11(0.91;1.36)

1.07(0.77;1.5)

0.96(0.86;1.08)

0.97(0.84;1.11) 0.286 0.5086 0.6200

S-HDL-FC1.1(0.93;1.31)

1(0.75;1.34)

0.77(0.64;0.93)

0.85(0.6;1.21)

0.94(0.84;1.05)

0.93(0.76;1.13) 0.627 0.2438 0.4454

S-HDL-FC-%1.1(0.92;1.31)

1.24(0.9;1.71)

0.8(0.66;0.97)

1.17(0.84;1.64)

1.01(0.9;1.13)

1.04(0.84;1.28) 0.668 0.9321 0.7233

S-HDL-L1.07(0.88;1.31)

0.91(0.68;1.21)

0.78(0.65;0.95)

0.76(0.57;1.02)

0.89(0.79;1)

0.88(0.74;1.05) 0.52 0.0411 0.1485

S-HDL-P1.08(0.89;1.31)

0.91(0.68;1.21)

0.78(0.64;0.94)

0.76(0.57;1.02)

0.89(0.79;1)

0.88(0.74;1.05) 0.544 0.0409 0.1554

S-HDL-PL1.11(0.91;1.34)

1(0.74;1.35)

0.8(0.66;0.97)

0.76(0.55;1.03)

0.92(0.82;1.03)

0.91(0.76;1.1) 0.586 0.1701 0.3458

STable 6

S-HDL-PL-%1.1(0.91;1.32)

1.21(0.89;1.66)

1(0.82;1.2)

0.9(0.65;1.26)

1.05(0.94;1.18)

1.05(0.94;1.18) 0 0.3985 0.3985

S-HDL-TG1.12(0.92;1.36)

0.83(0.58;1.19)

0.74(0.62;0.89)

0.9(0.64;1.29)

0.89(0.79;1)

0.89(0.72;1.11) 0.663 0.0510 0.3097

S-HDL-TG-%1.09(0.89;1.34)

0.88(0.61;1.26)

0.8(0.67;0.96)

0.99(0.71;1.38)

0.92(0.82;1.04)

0.93(0.79;1.1) 0.397 0.1820 0.3840

XL-HDL-C0.77(0.58;1.02)

1.31(0.94;1.82)

1.21(0.98;1.51)

1.57(1.15;2.15)

1.16(1.01;1.33)

1.17(0.88;1.56) 0.757 0.0369 0.2826

XL-HDL-C-%1.04(0.79;1.37)

1.07(0.79;1.45)

1.01(0.79;1.29)

1.06(0.75;1.51)

1.04(0.9;1.2)

1.04(0.9;1.2) 0 0.5943 0.5943

XL-HDL-CE0.77(0.58;1.02)

1.29(0.92;1.82)

1.24(0.99;1.54)

1.57(1.15;2.15)

1.16(1.01;1.34)

1.17(0.88;1.57) 0.76 0.0330 0.2847

XL-HDL-CE-%1.04(0.8;1.35)

0.99(0.75;1.31)

1.09(0.84;1.4)

1.07(0.75;1.53)

1.05(0.91;1.2)

1.05(0.91;1.2) 0 0.5284 0.5284

XL-HDL-FC0.8(0.61;1.05)

1.32(0.96;1.8)

1.16(0.93;1.44)

1.55(1.13;2.13)

1.14(1;1.3)

1.16(0.89;1.52) 0.734 0.0560 0.2658

XL-HDL-FC-%1.01(0.79;1.28)

1.38(0.95;2.01)

0.86(0.7;1.05)

0.99(0.72;1.36)

0.97(0.86;1.11)

1(0.84;1.19) 0.409 0.6984 0.9969

XL-HDL-L0.78(0.59;1.02)

1.28(0.95;1.73)

1.21(0.98;1.5)

1.55(1.13;2.13)

1.15(1.01;1.31)

1.16(0.88;1.53) 0.757 0.0383 0.2826

XL-HDL-P0.78(0.59;1.02)

1.28(0.95;1.72)

1.21(0.98;1.5)

1.55(1.13;2.13)

1.15(1.01;1.31)

1.16(0.89;1.53) 0.755 0.0374 0.2796

XL-HDL-PL0.81(0.64;1.03)

1.23(0.93;1.64)

1.23(0.99;1.53)

1.48(1.08;2.02)

1.13(0.99;1.28)

1.15(0.9;1.48) 0.728 0.0631 0.2674

XL-HDL-PL-%0.91(0.69;1.21)

0.97(0.74;1.28)

1.16(0.92;1.48)

1.03(0.71;1.49)

1.03(0.89;1.18)

1.03(0.89;1.18) 0 0.7114 0.7114

XL-HDL-TG1.01(0.8;1.28)

1.1(0.82;1.49)

0.84(0.7;1.02)

1.42(1.06;1.9)

1.01(0.89;1.14)

1.05(0.85;1.31) 0.671 0.9112 0.6346

XL-HDL-TG-%1.26(1;1.58)

0.86(0.66;1.13)

0.75(0.64;0.89)

0.86(0.56;1.32)

0.89(0.79;1)

0.92(0.71;1.19) 0.754 0.0575 0.5095

L-LDL-C0.96(0.77;1.18)

0.92(0.7;1.2)

0.84(0.7;1.01)

0.95(0.69;1.3)

0.9(0.8;1.01)

0.9(0.8;1.01) 0 0.0831 0.0831

L-LDL-C-%0.87(0.72;1.06)

0.88(0.68;1.15)

0.99(0.79;1.25)

1.01(0.74;1.38)

0.92(0.82;1.04)

0.92(0.82;1.04) 0 0.1973 0.1973

L-LDL-CE0.96(0.78;1.18)

0.91(0.7;1.19)

0.84(0.69;1.01)

0.94(0.69;1.29)

0.9(0.8;1.01)

0.9(0.8;1.01) 0 0.0698 0.0698

L-LDL-CE-%0.89(0.73;1.1)

0.88(0.69;1.12)

0.88(0.69;1.11)

0.92(0.7;1.21)

0.89(0.79;1)

0.89(0.79;1) 0 0.0586 0.0586

L-LDL-FC0.95(0.77;1.18)

0.93(0.71;1.22)

0.86(0.72;1.04)

1(0.73;1.37)

0.92(0.82;1.03)

0.92(0.82;1.03) 0 0.1487 0.1487

STable 6

L-LDL-FC-%0.9(0.72;1.12)

1.19(0.91;1.55)

1.48(1.18;1.84)

1.4(0.89;2.21)

1.18(1.04;1.34)

1.2(0.93;1.55) 0.711 0.0122 0.1525

L-LDL-L0.98(0.79;1.22)

0.91(0.7;1.2)

0.82(0.68;0.99)

0.96(0.7;1.32)

0.9(0.8;1.01)

0.9(0.8;1.01) 0 0.0832 0.0832

L-LDL-P0.99(0.8;1.23)

0.91(0.69;1.2)

0.82(0.68;0.98)

0.96(0.7;1.32)

0.9(0.8;1.01)

0.9(0.8;1.01) 0 0.0797 0.0797

L-LDL-PL0.96(0.78;1.19)

0.93(0.71;1.21)

0.82(0.68;0.99)

0.94(0.69;1.29)

0.9(0.8;1.01)

0.9(0.8;1.01) 0 0.0662 0.0662

L-LDL-PL-%0.99(0.79;1.24)

1.16(0.85;1.57)

1.19(0.99;1.43)

0.83(0.57;1.2)

1.08(0.96;1.22)

1.07(0.93;1.23) 0.218 0.2233 0.3627

L-LDL-TG1.13(0.89;1.44)

0.96(0.68;1.36)

0.72(0.59;0.89)

1.04(0.75;1.45)

0.91(0.8;1.04)

0.94(0.74;1.18) 0.651 0.1514 0.5864

*L-LDL-TG-%1.15(0.93;1.42)

1.15(0.85;1.56)

0.87(0.71;1.08)

1.08(0.79;1.48)

1.04(0.92;1.17)

1.04(0.9;1.2) 0.243 0.5812 0.5893

M-LDL-C0.93(0.76;1.14)

0.89(0.68;1.15)

0.83(0.7;1)

0.96(0.7;1.32)

0.89(0.8;0.99)

0.89(0.8;0.99) 0 0.0394 0.0394

*M-LDL-C-%0.84(0.69;1.04)

0.84(0.65;1.09)

0.97(0.79;1.19)

1.06(0.75;1.51)

0.91(0.8;1.02)

0.91(0.8;1.02) 0 0.1149 0.1149

M-LDL-CE0.92(0.76;1.13)

0.88(0.68;1.14)

0.83(0.69;1)

0.95(0.69;1.3)

0.88(0.79;0.99)

0.88(0.79;0.99) 0 0.0303 0.0303

M-LDL-CE-%0.85(0.69;1.05)

0.84(0.66;1.07)

0.88(0.7;1.11)

1.02(0.73;1.42)

0.88(0.78;0.99)

0.88(0.78;0.99) 0 0.0365 0.0365

M-LDL-FC0.97(0.78;1.21)

0.91(0.69;1.2)

0.83(0.69;1)

1(0.73;1.37)

0.9(0.8;1.02)

0.9(0.8;1.02) 0 0.0959 0.0959

M-LDL-FC-%1.03(0.85;1.24)

1.19(0.92;1.54)

1.29(1.08;1.54)

1.07(0.82;1.41)

1.15(1.03;1.28)

1.15(1.03;1.29) 0.061 0.0096 0.0130

M-LDL-L0.97(0.78;1.19)

0.89(0.68;1.16)

0.81(0.67;0.97)

0.96(0.7;1.32)

0.89(0.79;1)

0.89(0.79;1) 0 0.0414 0.0414

M-LDL-P0.97(0.79;1.2)

0.89(0.68;1.16)

0.8(0.67;0.96)

0.96(0.7;1.32)

0.89(0.79;1)

0.89(0.79;1) 0 0.0404 0.0404

M-LDL-PL1(0.8;1.24)

0.92(0.7;1.2)

0.78(0.64;0.94)

0.92(0.67;1.26)

0.88(0.79;0.99)

0.88(0.78;1) 0.056 0.0372 0.0465

M-LDL-PL-%1.08(0.89;1.3)

1.18(0.91;1.53)

1.08(0.9;1.31)

0.8(0.52;1.23)

1.08(0.96;1.21)

1.08(0.96;1.21) 0 0.2104 0.2104

M-LDL-TG1.11(0.88;1.39)

0.93(0.65;1.34)

0.73(0.6;0.9)

1.08(0.79;1.48)

0.92(0.81;1.05)

0.94(0.76;1.18) 0.634 0.2011 0.5972

*M-LDL-TG-%1.14(0.93;1.4)

1.22(0.86;1.71)

0.92(0.75;1.13)

1.13(0.86;1.48)

1.07(0.94;1.2)

1.07(0.94;1.2) 0.015 0.3008 0.3025

S-LDL-C0.91(0.74;1.11)

0.88(0.68;1.15)

0.83(0.69;1)

0.97(0.71;1.33)

0.88(0.79;0.99)

0.88(0.79;0.99) 0 0.0277 0.0277

STable 6

S-LDL-C-%0.84(0.69;1.01)

0.84(0.65;1.09)

0.96(0.79;1.18)

1.07(0.74;1.56)

0.9(0.8;1.01)

0.9(0.8;1.01) 0 0.0693 0.0693

S-LDL-CE0.9(0.74;1.1)

0.88(0.67;1.14)

0.84(0.7;1.01)

0.95(0.69;1.3)

0.88(0.79;0.98)

0.88(0.79;0.98) 0 0.0235 0.0235

S-LDL-CE-%0.83(0.69;1.01)

0.84(0.65;1.08)

0.92(0.73;1.15)

1.02(0.72;1.45)

0.88(0.78;0.99)

0.88(0.78;0.99) 0 0.0296 0.0296

S-LDL-FC0.96(0.77;1.2)

0.9(0.68;1.19)

0.81(0.67;0.98)

1.02(0.75;1.4)

0.89(0.8;1.01)

0.89(0.8;1.01) 0 0.0650 0.0650

S-LDL-FC-%1.08(0.89;1.32)

1.17(0.9;1.53)

1.21(1.01;1.45)

1.15(0.87;1.51)

1.15(1.03;1.29)

1.15(1.03;1.29) 0 0.0110 0.0110

S-LDL-L0.94(0.77;1.16)

0.89(0.68;1.16)

0.8(0.67;0.97)

0.96(0.7;1.32)

0.88(0.78;0.99)

0.88(0.78;0.99) 0 0.0277 0.0277

S-LDL-P0.95(0.77;1.17)

0.89(0.68;1.16)

0.8(0.66;0.96)

0.96(0.7;1.32)

0.88(0.78;0.99)

0.88(0.78;0.99) 0 0.0269 0.0269

S-LDL-PL0.99(0.81;1.22)

0.94(0.72;1.22)

0.79(0.66;0.96)

0.97(0.71;1.33)

0.9(0.8;1.01)

0.9(0.8;1.01) 0 0.0724 0.0724

S-LDL-PL-%1.1(0.92;1.33)

1.23(0.94;1.62)

1.16(0.96;1.4)

0.93(0.64;1.35)

1.13(1.01;1.26)

1.13(1.01;1.26) 0 0.0381 0.0381

S-LDL-TG1.09(0.88;1.36)

0.87(0.61;1.25)

0.67(0.55;0.82)

0.97(0.7;1.35)

0.87(0.76;0.98)

0.88(0.69;1.14) 0.725 0.0255 0.3395

*S-LDL-TG-%1.14(0.94;1.4)

1.06(0.75;1.51)

0.78(0.63;0.97)

0.95(0.67;1.35)

0.97(0.85;1.1)

0.97(0.79;1.19) 0.564 0.6205 0.7659

L-VLDL-C1.06(0.85;1.32)

0.82(0.61;1.1)

0.74(0.62;0.89)

0.87(0.58;1.31)

0.85(0.75;0.96)

0.86(0.71;1.04) 0.516 0.0079 0.1112

L-VLDL-C-%0.81(0.59;1.11)

0.92(0.59;1.44)

1.09(0.89;1.33)

1.08(0.79;1.48)

1.01(0.88;1.16)

1.01(0.88;1.16) 0 0.9067 0.9067

L-VLDL-CE1.04(0.84;1.3)

0.81(0.6;1.11)

0.75(0.63;0.89)

0.88(0.59;1.3)

0.85(0.75;0.96)

0.86(0.72;1.02) 0.451 0.0067 0.0868

L-VLDL-CE-%0.78(0.57;1.07)

1.04(0.68;1.61)

1.2(1;1.45)

1.07(0.78;1.47)

1.07(0.93;1.23)

1.04(0.85;1.26) 0.434 0.3260 0.7224

L-VLDL-FC1.09(0.87;1.35)

0.81(0.61;1.08)

0.76(0.64;0.9)

0.87(0.58;1.31)

0.86(0.76;0.97)

0.87(0.72;1.05) 0.542 0.0119 0.1481

L-VLDL-FC-%1.05(0.83;1.32)

0.77(0.51;1.17)

0.85(0.73;0.99)

1.01(0.72;1.41)

0.9(0.81;1.01)

0.91(0.8;1.03) 0.097 0.0798 0.1313

L-VLDL-L1.08(0.86;1.35)

0.81(0.62;1.06)

0.74(0.61;0.89)

0.85(0.56;1.29)

0.85(0.76;0.96)

0.86(0.71;1.04) 0.541 0.0096 0.1177

L-VLDL-P1.08(0.86;1.35)

0.81(0.62;1.06)

0.74(0.61;0.89)

0.85(0.56;1.29)

0.85(0.76;0.96)

0.86(0.71;1.04) 0.543 0.0103 0.1219

L-VLDL-PL1.09(0.87;1.36)

0.81(0.62;1.06)

0.73(0.6;0.88)

0.84(0.56;1.27)

0.85(0.75;0.96)

0.86(0.7;1.05) 0.584 0.0094 0.1318

STable 6

L-VLDL-PL-%1.06(0.84;1.34)

1.08(0.83;1.41)

1.04(0.87;1.24)

0.91(0.62;1.35)

1.04(0.92;1.17)

1.04(0.92;1.17) 0 0.5266 0.5266

L-VLDL-TG1.09(0.87;1.37)

0.81(0.62;1.05)

0.76(0.63;0.91)

0.84(0.56;1.27)

0.86(0.76;0.97)

0.87(0.72;1.04) 0.535 0.0114 0.1299

L-VLDL-TG-%1.16(0.85;1.59)

1.03(0.66;1.6)

0.89(0.72;1.1)

0.96(0.69;1.34)

0.97(0.84;1.12)

0.97(0.84;1.12) 0 0.7001 0.7001

M-VLDL-C1.07(0.85;1.34)

0.83(0.63;1.11)

0.72(0.59;0.87)

0.85(0.58;1.26)

0.84(0.75;0.96)

0.86(0.7;1.04) 0.57 0.0074 0.1241

M-VLDL-C-%0.93(0.7;1.23)

1.05(0.73;1.51)

1.14(0.94;1.38)

1.14(0.83;1.56)

1.08(0.95;1.23)

1.08(0.95;1.23) 0 0.2633 0.2633

M-VLDL-CE1.05(0.83;1.32)

0.86(0.64;1.15)

0.72(0.6;0.87)

0.87(0.6;1.26)

0.84(0.74;0.96)

0.86(0.71;1.03) 0.489 0.0075 0.1003

M-VLDL-CE-%0.88(0.67;1.16)

1.14(0.82;1.6)

1.22(1;1.48)

1.16(0.85;1.59)

1.11(0.98;1.27)

1.11(0.95;1.28) 0.192 0.1083 0.1853

M-VLDL-FC1.1(0.89;1.36)

0.81(0.61;1.07)

0.72(0.6;0.87)

0.84(0.57;1.25)

0.85(0.76;0.96)

0.86(0.69;1.06) 0.644 0.0089 0.1598

M-VLDL-FC-%1.19(0.96;1.47)

0.79(0.57;1.11)

0.73(0.62;0.85)

0.86(0.64;1.15)

0.86(0.77;0.96)

0.88(0.68;1.13) 0.78 0.0061 0.3198

M-VLDL-L1.08(0.87;1.34)

0.82(0.62;1.07)

0.73(0.6;0.89)

0.84(0.56;1.24)

0.85(0.76;0.96)

0.86(0.71;1.04) 0.572 0.0101 0.1208

M-VLDL-P1.07(0.86;1.34)

0.82(0.62;1.07)

0.73(0.61;0.89)

0.83(0.56;1.22)

0.85(0.76;0.96)

0.86(0.71;1.04) 0.56 0.0101 0.1138

M-VLDL-PL1.08(0.87;1.34)

0.81(0.61;1.06)

0.72(0.6;0.88)

0.83(0.56;1.22)

0.85(0.75;0.96)

0.85(0.7;1.05) 0.607 0.0087 0.1258

M-VLDL-PL-%1(0.78;1.28)

1.06(0.84;1.34)

1.12(0.93;1.35)

1.04(0.76;1.42)

1.07(0.95;1.2)

1.07(0.95;1.2) 0 0.2843 0.2843

M-VLDL-TG1.08(0.87;1.33)

0.81(0.61;1.07)

0.75(0.62;0.91)

0.83(0.55;1.25)

0.86(0.77;0.97)

0.86(0.72;1.04) 0.543 0.0168 0.1291

M-VLDL-TG-%1.06(0.8;1.39)

0.94(0.66;1.33)

0.87(0.71;1.07)

0.89(0.65;1.21)

0.93(0.81;1.06)

0.93(0.81;1.06) 0 0.2669 0.2669

S-VLDL-C1.02(0.79;1.32)

0.84(0.6;1.17)

0.72(0.6;0.86)

0.77(0.54;1.1)

0.81(0.71;0.92)

0.82(0.69;0.98) 0.391 0.0011 0.0268

S-VLDL-C-%0.8(0.61;1.04)

1.14(0.83;1.56)

1.23(1.01;1.5)

1.22(0.89;1.67)

1.09(0.96;1.24)

1.08(0.88;1.34) 0.593 0.1773 0.4707

S-VLDL-CE0.99(0.76;1.29)

0.87(0.62;1.22)

0.75(0.63;0.9)

0.79(0.56;1.13)

0.82(0.72;0.94)

0.82(0.72;0.94) 0 0.0032 0.0032

S-VLDL-CE-%0.79(0.6;1.02)

1.14(0.83;1.55)

1.28(1.04;1.57)

1.25(0.91;1.71)

1.11(0.97;1.26)

1.09(0.87;1.38) 0.662 0.1327 0.4532

S-VLDL-FC1.08(0.86;1.36)

0.81(0.59;1.11)

0.68(0.56;0.82)

0.76(0.52;1.1)

0.81(0.71;0.91)

0.82(0.65;1.04) 0.687 0.0008 0.0980

STable 6

S-VLDL-FC-%1.07(0.84;1.37)

1.05(0.83;1.32)

0.77(0.63;0.94)

0.87(0.61;1.24)

0.92(0.81;1.04)

0.93(0.78;1.11) 0.495 0.1725 0.4055

S-VLDL-L1.08(0.86;1.36)

0.81(0.59;1.1)

0.7(0.58;0.84)

0.76(0.52;1.1)

0.82(0.72;0.93)

0.83(0.66;1.03) 0.648 0.0016 0.0929

S-VLDL-P1.09(0.87;1.36)

0.81(0.6;1.09)

0.7(0.58;0.84)

0.76(0.53;1.11)

0.82(0.73;0.93)

0.83(0.66;1.04) 0.656 0.0020 0.1013

S-VLDL-PL1.1(0.88;1.38)

0.8(0.59;1.1)

0.68(0.57;0.83)

0.72(0.5;1.04)

0.82(0.72;0.92)

0.82(0.64;1.05) 0.72 0.0012 0.1116

S-VLDL-PL-%1.18(0.93;1.5)

1.16(0.89;1.51)

1.03(0.84;1.26)

0.75(0.52;1.09)

1.06(0.94;1.2)

1.05(0.89;1.23) 0.361 0.3617 0.5476

S-VLDL-TG1.11(0.9;1.36)

0.8(0.6;1.07)

0.71(0.59;0.86)

0.79(0.54;1.18)

0.85(0.75;0.96)

0.85(0.67;1.07) 0.706 0.0075 0.1632

S-VLDL-TG-%1.2(0.93;1.54)

0.85(0.62;1.16)

0.81(0.68;0.98)

0.87(0.62;1.21)

0.91(0.8;1.03)

0.92(0.76;1.11) 0.519 0.1182 0.3770

XL-VLDL-C1.05(0.83;1.33)

0.84(0.6;1.17)

0.71(0.6;0.84)

0.93(0.63;1.38)

0.83(0.73;0.93)

0.86(0.7;1.06) 0.611 0.0018 0.1648

XL-VLDL-C-%0.92(0.67;1.26)

1.07(0.73;1.57)

1.29(1.08;1.53)

1.34(1.06;1.69)

1.21(1.08;1.37)

1.19(1.02;1.39) 0.316 0.0017 0.0279

XL-VLDL-CE1.05(0.83;1.32)

0.82(0.59;1.14)

0.79(0.69;0.91)

0.94(0.64;1.39)

0.86(0.77;0.95)

0.88(0.76;1.02) 0.328 0.0039 0.0786

XL-VLDL-CE-%0.89(0.66;1.19)

1.01(0.7;1.46)

1.16(0.95;1.43)

1.32(1.11;1.58)

1.16(1.03;1.3)

1.12(0.95;1.33) 0.492 0.0109 0.1850

XL-VLDL-FC1.06(0.84;1.34)

0.86(0.62;1.2)

0.69(0.58;0.83)

0.92(0.62;1.37)

0.83(0.73;0.94)

0.86(0.69;1.08) 0.639 0.0025 0.1902

XL-VLDL-FC-%0.98(0.71;1.35)

1.17(0.79;1.73)

1.26(1.07;1.49)

1.09(0.82;1.47)

1.17(1.04;1.33)

1.17(1.04;1.33) 0 0.0116 0.0116

XL-VLDL-L1.06(0.85;1.33)

0.83(0.63;1.09)

0.72(0.6;0.85)

0.89(0.59;1.34)

0.83(0.74;0.94)

0.86(0.7;1.04) 0.589 0.0026 0.1224

XL-VLDL-P1.06(0.85;1.33)

0.83(0.63;1.08)

0.72(0.61;0.85)

0.89(0.59;1.34)

0.83(0.74;0.94)

0.86(0.7;1.04) 0.588 0.0024 0.1212

XL-VLDL-PL1.06(0.84;1.33)

0.85(0.64;1.13)

0.71(0.6;0.83)

0.9(0.59;1.35)

0.82(0.73;0.92)

0.86(0.69;1.06) 0.637 0.0009 0.1503

XL-VLDL-PL-%1.06(0.8;1.39)

1.18(0.86;1.61)

1.06(0.84;1.33)

0.87(0.61;1.24)

1.05(0.91;1.21)

1.05(0.91;1.21) 0 0.5089 0.5089

XL-VLDL-TG1.07(0.85;1.34)

0.83(0.64;1.07)

0.79(0.68;0.9)

0.88(0.58;1.33)

0.85(0.77;0.95)

0.87(0.75;1.02) 0.428 0.0028 0.0850

XL-VLDL-TG-%1.06(0.77;1.46)

0.89(0.6;1.32)

0.79(0.68;0.91)

0.83(0.63;1.09)

0.83(0.74;0.94)

0.83(0.74;0.94) 0 0.0021 0.0021

XS-VLDL-C1.02(0.78;1.34)

0.96(0.67;1.37)

0.8(0.66;0.97)

0.8(0.58;1.12)

0.87(0.76;0.99)

0.87(0.76;0.99) 0 0.0352 0.0352

STable 6

XS-VLDL-C-%0.82(0.64;1.05)

1.33(0.92;1.92)

1.41(1.11;1.8)

1.12(0.78;1.59)

1.12(0.97;1.29)

1.14(0.86;1.5) 0.717 0.1208 0.3664

XS-VLDL-CE1(0.75;1.31)

1.02(0.7;1.48)

0.83(0.69;1.01)

0.81(0.58;1.13)

0.89(0.78;1.01)

0.89(0.78;1.01) 0 0.0754 0.0754

XS-VLDL-CE-%0.8(0.62;1.04)

1.41(0.97;2.04)

1.45(1.15;1.83)

1.09(0.78;1.53)

1.15(1;1.33)

1.15(0.86;1.55) 0.753 0.0526 0.3496

XS-VLDL-FC1.06(0.83;1.34)

0.86(0.62;1.19)

0.75(0.62;0.9)

0.8(0.58;1.12)

0.85(0.75;0.96)

0.86(0.72;1.01) 0.399 0.0091 0.0698

XS-VLDL-FC-%1.02(0.82;1.28)

0.96(0.75;1.21)

0.94(0.77;1.15)

1.08(0.75;1.57)

0.98(0.87;1.11)

0.98(0.87;1.11) 0 0.7695 0.7695

XS-VLDL-L1.07(0.83;1.38)

0.89(0.64;1.24)

0.74(0.61;0.9)

0.78(0.55;1.11)

0.85(0.74;0.96)

0.86(0.71;1.03) 0.448 0.0109 0.0995

XS-VLDL-P1.08(0.84;1.38)

0.88(0.63;1.23)

0.73(0.61;0.89)

0.78(0.55;1.11)

0.84(0.74;0.96)

0.86(0.71;1.04) 0.498 0.0091 0.1104

XS-VLDL-PL1.06(0.85;1.32)

0.88(0.65;1.19)

0.76(0.63;0.92)

0.82(0.59;1.14)

0.87(0.77;0.98)

0.87(0.75;1.03) 0.379 0.0239 0.0993

XS-VLDL-PL-%1(0.75;1.32)

0.88(0.62;1.25)

1.09(0.89;1.34)

1.2(0.83;1.74)

1.05(0.91;1.2)

1.05(0.91;1.2) 0 0.5151 0.5151

XS-VLDL-TG1.12(0.91;1.39)

0.8(0.58;1.12)

0.68(0.56;0.83)

0.79(0.55;1.15)

0.84(0.75;0.95)

0.84(0.65;1.09) 0.75 0.0068 0.1956

XS-VLDL-TG-%1.15(0.94;1.41)

0.87(0.67;1.14)

0.73(0.6;0.89)

0.84(0.59;1.2)

0.9(0.8;1.01)

0.89(0.71;1.12) 0.703 0.0740 0.3216

XXL-VLDL-C1.02(0.79;1.32)

0.9(0.66;1.24)

0.73(0.61;0.88)

0.94(0.64;1.39)

0.84(0.74;0.96)

0.87(0.73;1.03) 0.369 0.0095 0.1010

XXL-VLDL-C-%0.96(0.73;1.26)

0.87(0.64;1.19)

0.78(0.66;0.93)

1.23(0.92;1.66)

0.89(0.79;1.01)

0.93(0.76;1.13) 0.588 0.0596 0.4723

XXL-VLDL-CE1(0.77;1.29)

0.9(0.64;1.26)

0.74(0.61;0.89)

0.96(0.65;1.42)

0.84(0.74;0.96)

0.86(0.73;1.01) 0.286 0.0086 0.0677

XXL-VLDL-CE-%

0.91(0.71;1.18)

0.94(0.7;1.26)

0.96(0.78;1.2)

1.14(0.83;1.56)

0.98(0.86;1.11)

0.98(0.86;1.11) 0 0.7043 0.7043

XXL-VLDL-FC1.06(0.83;1.36)

0.89(0.67;1.19)

0.73(0.61;0.88)

0.92(0.61;1.39)

0.85(0.75;0.96)

0.88(0.73;1.06) 0.492 0.0094 0.1658

XXL-VLDL-FC-%

1.18(0.91;1.54)

0.91(0.72;1.14)

0.79(0.67;0.93)

1.22(0.95;1.58)

0.94(0.85;1.05)

0.99(0.8;1.23) 0.733 0.3040 0.9542

XXL-VLDL-L1.03(0.8;1.33)

0.89(0.67;1.19)

0.75(0.62;0.91)

0.9(0.6;1.37)

0.86(0.76;0.97)

0.87(0.74;1.02) 0.282 0.0169 0.0789

XXL-VLDL-P1.03(0.8;1.33)

0.89(0.67;1.19)

0.75(0.62;0.91)

0.9(0.6;1.37)

0.86(0.76;0.97)

0.87(0.75;1.01) 0.267 0.0177 0.0754

XXL-VLDL-PL1.05(0.82;1.34)

0.89(0.67;1.18)

0.73(0.61;0.88)

0.89(0.59;1.34)

0.85(0.75;0.96)

0.87(0.73;1.04) 0.445 0.0113 0.1203

STable 6

XXL-VLDL-PL-%

1.15(0.89;1.49)

0.92(0.74;1.15)

0.81(0.67;0.98)

0.79(0.59;1.06)

0.89(0.8;1.01)

0.9(0.77;1.06) 0.447 0.0598 0.2062

XXL-VLDL-TG1.03(0.8;1.32)

0.89(0.67;1.18)

0.76(0.63;0.92)

0.9(0.59;1.35)

0.86(0.76;0.98)

0.87(0.75;1.01) 0.226 0.0203 0.0667

XXL-VLDL-TG-%

0.99(0.76;1.29)

1.18(0.88;1.59)

1.31(1.11;1.55)

0.88(0.65;1.18)

1.14(1.02;1.29)

1.1(0.91;1.33) 0.557 0.0249 0.3186

STable 7

STable 7. HRs and 95% CIs of metabolites, lipids and lipoprotein lipids for incident dementia. Adjusted for Model 2.

Metabolite, lipid,

lipoprotein lipid

FINRISK 97HR(95%CI)

DILGOMHR(95%CI)

WHITEHALLHR(95%CI)

EGCUTHR(95%CI)

FIXED EFFECT(HR(95%CI

RANDOM EFFECT(HR(95%CI I2 p.fixed p.random

Amino Acids

ALA1.08(0.84;1.39)

0.82(0.61;1.09)

0.78(0.64;0.94)

1.16(0.85;1.59)

0.9(0.8;1.02)

0.93(0.76;1.13) 0.581 0.1102 0.4653

GLN1.07(0.83;1.37)

0.79(0.58;1.07)

1(0.82;1.22)

0.98(0.7;1.37)

0.97(0.85;1.11)

0.97(0.85;1.11) 0 0.6534 0.6534

GLY1.03(0.79;1.35)

0.9(0.69;1.18)

1.04(0.86;1.26)

NA(NA;NA)

1(0.88;1.15)

1(0.88;1.15) 0 0.9507 0.9507

HIS0.97(0.8;1.16)

0.74(0.55;1)

0.8(0.67;0.96)

1.05(0.72;1.53)

0.87(0.78;0.98)

0.87(0.76;1) 0.25 0.0171 0.0491

ILE0.9(0.7;1.16)

0.8(0.59;1.08)

0.72(0.58;0.9)

0.64(0.42;0.96)

0.78(0.68;0.89)

0.78(0.68;0.89) 0 0.0003 0.0003

LEU0.86(0.66;1.13)

0.72(0.52;1)

0.75(0.6;0.92)

0.54(0.34;0.84)

0.75(0.65;0.86)

0.74(0.64;0.86) 0.047 0.0000 0.0001

PHE0.93(0.71;1.22)

0.65(0.46;0.92)

0.88(0.72;1.07)

1.02(0.72;1.45)

0.87(0.76;1)

0.87(0.74;1.01) 0.185 0.0416 0.0690

TYR0.85(0.69;1.06)

0.69(0.53;0.89)

0.85(0.7;1.03)

1.05(0.8;1.38)

0.85(0.76;0.95)

0.85(0.73;0.98) 0.375 0.0046 0.0281

VAL0.81(0.62;1.06)

0.64(0.46;0.89)

0.87(0.72;1.06)

0.59(0.4;0.88)

0.78(0.69;0.89)

0.76(0.64;0.9) 0.354 0.0002 0.0018


DHA0.9(0.72;1.12)

1.14(0.91;1.43)

0.77(0.63;0.94)

0.73(0.51;1.06)

0.89(0.79;1)

0.89(0.73;1.07) 0.6 0.0503 0.2166

DHA-FA0.85(0.68;1.05)

1.17(0.91;1.5)

0.91(0.74;1.12)

0.7(0.48;1.04)

0.92(0.81;1.04)

0.92(0.77;1.09) 0.477 0.1835 0.3215

FAW30.92(0.74;1.13)

1.15(0.89;1.47)

0.76(0.62;0.94)

0.66(0.44;0.97)

0.88(0.78;0.99)

0.87(0.71;1.07) 0.645 0.0326 0.1947

FAW3-FA0.88(0.72;1.06)

1.21(0.93;1.56)

0.94(0.76;1.14)

0.62(0.41;0.93)

0.93(0.83;1.04)

0.92(0.75;1.12) 0.625 0.2212 0.3995

FAW60.98(0.8;1.21)

0.87(0.65;1.17)

0.72(0.59;0.88)

0.93(0.68;1.28)

0.85(0.76;0.96)

0.86(0.74;1.01) 0.384 0.0084 0.0588

FAW6-FA0.88(0.72;1.08)

0.9(0.67;1.22)

1.06(0.85;1.31)

0.96(0.7;1.32)

0.95(0.84;1.08)

0.95(0.84;1.08) 0 0.4318 0.4318

LA 0.97 0.8 0.75 0.95 0.86 0.86 0.291 0.0092 0.0321

STable 7

(0.8;1.18) (0.61;1.05) (0.61;0.91) (0.69;1.3) (0.76;0.96) (0.75;0.99)

LA-FA0.87(0.70;1.10)

0.8(0.6;1.06)

1.06(0.86;1.31)

0.99(0.72;1.36)

0.94(0.83;1.06)

0.94(0.83;1.07) 0.052 0.3232 0.3299

MUFA1.14(0.91;1.41)

0.94(0.71;1.26)

0.69(0.56;0.85)

0.9(0.65;1.26)

0.89(0.79;1.01)

0.9(0.71;1.15) 0.712 0.0795 0.3974

MUFA-FA1.15(0.94;1.4)

0.93(0.69;1.25)

0.79(0.64;0.98)

0.87(0.62;1.21)

0.95(0.84;1.07)

0.94(0.78;1.13) 0.547 0.3629 0.4805

PUFA0.96(0.78;1.19)

0.94(0.7;1.25)

0.72(0.59;0.87)

0.86(0.62;1.2)

0.84(0.75;0.95)

0.85(0.73;0.99) 0.37 0.0045 0.0406

PUFA-FA0.86(0.7;1.05)

1(0.75;1.33)

1.04(0.84;1.28)

0.84(0.61;1.14)

0.93(0.83;1.05)

0.93(0.83;1.05) 0 0.2569 0.2569

SFA1.12(0.88;1.41)

1(0.73;1.37)

0.77(0.63;0.94)

1.09(0.78;1.53)

0.95(0.83;1.07)

0.97(0.79;1.18) 0.549 0.3889 0.7449

SFA-FA1.13(0.9;1.4)

1.13(0.84;1.52)

1.31(1.07;1.6)

1.6(1.17;2.19)

1.26(1.11;1.42)

1.26(1.09;1.45) 0.227 0.0002 0.0013

TOTFA1.08(0.86;1.36)

0.96(0.72;1.3)

0.71(0.58;0.86)

0.94(0.68;1.31)

0.88(0.78;1)

0.9(0.73;1.12) 0.641 0.0502 0.3586

UNSAT0.85(0.69;1.04)

1.13(0.88;1.45)

0.99(0.81;1.21)

0.69(0.49;0.98)

0.93(0.83;1.05)

0.92(0.77;1.1) 0.525 0.2282 0.3611

Fluid Balance

ALB0.98(0.77;1.25)

1.54(1.08;2.19)

0.82(0.69;0.96)

0.76(0.53;1.08)

0.91(0.81;1.03)

0.97(0.74;1.26) 0.743 0.1363 0.7971

CREA0.92(0.75;1.12)

0.78(0.58;1.05)

0.64(0.5;0.82)

0.85(0.59;1.24)

0.8(0.7;0.91)

0.79(0.67;0.94) 0.383 0.0007 0.0077


CIT0.94(0.78;1.13)

0.99(0.73;1.33)

1(0.83;1.21)

0.96(0.7;1.32)

0.97(0.87;1.09)

0.97(0.87;1.09) 0 0.6168 0.6168

GLC0.92(0.74;1.15)

0.96(0.74;1.25)

1.2(0.96;1.49)

1.17(0.93;1.48)

1.06(0.94;1.19)

1.06(0.93;1.21) 0.257 0.3194 0.4008

GLOL0.88(0.67;1.16)

0.85(0.59;1.2)

0.88(0.72;1.08)

NA(NA;NA)

0.87(0.75;1.01)

0.87(0.75;1.01) 0 0.0718 0.0718

LAC0.98(0.81;1.19)

1.04(0.76;1.43)

0.91(0.75;1.11)

0.82(0.58;1.17)

0.94(0.84;1.06)

0.94(0.84;1.06) 0 0.3326 0.3326

PYR1.1(0.88;1.36)

1.02(0.76;1.38)

1.02(0.85;1.23)

NA(NA;NA)

1.05(0.92;1.19)

1.05(0.92;1.19) 0 0.4846 0.4846

Ketone BodiesACACE 0.92 1.41 1.01 1.03 1.04 1.05 0.426 0.5182 0.5204

STable 7

(0.74;1.15) (1.04;1.9) (0.84;1.21) (0.8;1.33) (0.93;1.17) (0.9;1.23)

ACE1.11(0.89;1.38)

1.01(0.78;1.3)

1(0.82;1.21)

0.8(0.31;2.1)

1.03(0.91;1.17)

1.03(0.91;1.17) 0 0.6213 0.6213

BOHBUT0.85(0.64;1.14)

1.34(0.99;1.8)

0.94(0.78;1.13)

1.03(0.74;1.44)

1(0.88;1.14)

1.01(0.85;1.21) 0.43 0.9892 0.8875

Inflammation

GP1.06(0.84;1.34)

0.82(0.62;1.08)

0.71(0.57;0.87)

0.79(0.53;1.2)

0.83(0.73;0.95)

0.84(0.69;1.02) 0.539 0.0059 0.0820


HDL-TG1.09(0.89;1.35)

1.02(0.72;1.43)

0.76(0.63;0.92)

1.05(0.74;1.5)

0.92(0.82;1.04)

0.95(0.78;1.17) 0.598 0.2017 0.6441

LDL-TG1.08(0.86;1.37)

0.97(0.69;1.37)

0.71(0.58;0.88)

0.98(0.7;1.37)

0.89(0.78;1.02)

0.91(0.74;1.13) 0.596 0.0939 0.4164

PC1.03(0.81;1.32)

1.1(0.81;1.5)

0.82(0.67;1)

1.09(0.78;1.53)

0.96(0.85;1.09)

0.97(0.84;1.13) 0.259 0.5435 0.7309

SERUM-TG1.09(0.88;1.34)

0.83(0.62;1.12)

0.69(0.56;0.85)

0.8(0.53;1.21)

0.85(0.75;0.96)

0.84(0.67;1.07) 0.665 0.0118 0.1543

SM0.94(0.72;1.23)

1.01(0.74;1.4)

0.9(0.75;1.09)

1.11(0.81;1.51)

0.96(0.84;1.09)

0.96(0.84;1.09) 0 0.5098 0.5098

TG-PG1.15(0.92;1.45)

0.81(0.62;1.05)

0.72(0.59;0.9)

0.7(0.46;1.08)

0.86(0.76;0.98)

0.84(0.66;1.08) 0.697 0.0202 0.1753

TOTCHO1.01(0.78;1.3)

1.08(0.77;1.51)

0.85(0.7;1.04)

1.11(0.79;1.54)

0.96(0.84;1.1)

0.96(0.84;1.1) 0 0.5476 0.5476

TOTPG1.06(0.84;1.33)

1.09(0.81;1.49)

0.82(0.67;1)

1.09(0.78;1.53)

0.97(0.85;1.1)

0.98(0.84;1.14) 0.298 0.5934 0.7981

VLDL-TG1.07(0.86;1.32)

0.81(0.61;1.07)

0.72(0.59;0.88)

0.79(0.51;1.21)

0.85(0.75;0.96)

0.84(0.69;1.03) 0.574 0.0093 0.1002

Apolipoproteins

APOA10.97(0.8;1.18)

1.19(0.92;1.55)

0.93(0.76;1.13)

1.23(0.87;1.76)

1.02(0.91;1.15)

1.03(0.91;1.17) 0.157 0.6908 0.6489

APOB1.02(0.82;1.27)

0.95(0.71;1.27)

0.75(0.61;0.91)

0.84(0.59;1.19)

0.87(0.77;0.98)

0.87(0.75;1.03) 0.36 0.0243 0.0999

APOB-APOA11.04(0.84;1.29)

0.85(0.63;1.15)

0.8(0.65;0.97)

0.74(0.52;1.05)

0.87(0.77;0.99)

0.87(0.75;1.01) 0.292 0.0275 0.0626

Cholesterol

ESTC0.94(0.75;1.19)

1.06(0.79;1.43)

0.79(0.66;0.96)

0.95(0.68;1.33)

0.9(0.8;1.02)

0.9(0.79;1.02) 0.057 0.0854 0.1054

FREEC 0.96 1.05 0.81 1.07 0.93 0.93 0.181 0.2181 0.3272

STable 7

(0.77;1.21) (0.79;1.4) (0.66;0.98) (0.78;1.47) (0.82;1.05) (0.82;1.07)

HDL2-C0.96(0.79;1.17)

1.23(0.93;1.61)

1.04(0.85;1.28)

1.35(0.95;1.92)

1.07(0.95;1.21)

1.08(0.94;1.24) 0.225 0.2486 0.2533

HDL3-C0.92(0.72;1.16)

1.05(0.75;1.48)

1.05(0.87;1.28)

1.23(0.94;1.62)

1.05(0.93;1.18)

1.05(0.93;1.18) 0 0.4579 0.4579

HDL-C0.94(0.76;1.15)

1.2(0.92;1.57)

1.05(0.86;1.28)

1.35(0.95;1.92)

1.07(0.95;1.2)

1.08(0.94;1.24) 0.27 0.2949 0.3018

LDL-C0.95(0.77;1.17)

0.98(0.73;1.3)

0.82(0.68;0.98)

0.95(0.69;1.3)

0.9(0.8;1.01)

0.9(0.8;1.01) 0 0.0735 0.0735

REMNANT-C1.01(0.79;1.29)

0.99(0.71;1.36)

0.75(0.62;0.91)

0.83(0.58;1.18)

0.86(0.76;0.98)

0.87(0.75;1.02) 0.27 0.0208 0.0789

SERUM-C0.96(0.76;1.2)

1.06(0.79;1.42)

0.8(0.66;0.96)

0.99(0.72;1.36)

0.91(0.8;1.03)

0.91(0.8;1.04) 0.147 0.1184 0.1871

VLDL-C1.03(0.79;1.33)

0.93(0.68;1.28)

0.72(0.59;0.87)

0.76(0.52;1.13)

0.83(0.73;0.95)

0.85(0.7;1.02) 0.436 0.0055 0.0750


HDL-D0.9(0.71;1.13)

1.28(0.97;1.7)

1.19(0.97;1.45)

1.62(1.16;2.25)

1.16(1.03;1.32)

1.19(0.96;1.49) 0.668 0.0177 0.1162

LDL-D1.16(0.93;1.45)

1.36(0.95;1.93)

1.16(0.95;1.42)

0.9(0.64;1.29)

1.15(1.01;1.3)

1.15(1.01;1.3) 0 0.0385 0.0385

VLDL-D1.03(0.81;1.3)

0.8(0.61;1.04)

0.79(0.63;0.97)

0.89(0.62;1.26)

0.87(0.76;0.98)

0.87(0.76;0.99) 0.073 0.0249 0.0323


IDL-C0.96(0.77;1.21)

1.04(0.77;1.42)

0.84(0.69;1.02)

0.94(0.68;1.31)

0.92(0.81;1.04)

0.92(0.81;1.04) 0 0.1760 0.1760

IDL-C-%0.91(0.76;1.1)

1.13(0.82;1.57)

1.1(0.87;1.4)

1.07(0.75;1.53)

1.01(0.89;1.15)

1.01(0.89;1.15) 0 0.8501 0.8501

IDL-CE0.96(0.77;1.21)

1.05(0.77;1.43)

0.84(0.69;1.02)

0.92(0.66;1.29)

0.92(0.81;1.04)

0.92(0.81;1.04) 0 0.1731 0.1731

IDL-CE-%0.92(0.76;1.11)

1.19(0.87;1.61)

1.11(0.88;1.39)

0.92(0.66;1.29)

1.01(0.89;1.14)

1.01(0.89;1.14) 0.002 0.8909 0.8903

IDL-FC0.98(0.79;1.22)

1.02(0.75;1.39)

0.83(0.69;1.01)

0.98(0.72;1.34)

0.92(0.82;1.04)

0.92(0.82;1.04) 0 0.1907 0.1907

IDL-FC-%0.92(0.73;1.15)

1.12(0.88;1.44)

1.03(0.83;1.28)

1.48(0.89;2.46)

1.04(0.91;1.19)

1.04(0.91;1.2) 0.105 0.5418 0.5395

IDL-L1(0.8;1.26)

1.02(0.74;1.39)

0.81(0.67;0.98)

0.93(0.68;1.28)

0.91(0.81;1.03)

0.91(0.81;1.03) 0 0.1360 0.1360

STable 7

IDL-P1.01(0.8;1.27)

1.01(0.74;1.38)

0.8(0.66;0.97)

0.92(0.67;1.26)

0.91(0.8;1.03)

0.91(0.8;1.03) 0 0.1178 0.1178

IDL-PL1.01(0.81;1.25)

1.02(0.75;1.39)

0.82(0.67;0.99)

0.96(0.7;1.32)

0.92(0.82;1.04)

0.92(0.82;1.04) 0 0.1790 0.1790

IDL-PL-%0.99(0.75;1.32)

0.99(0.71;1.37)

1.16(0.95;1.41)

1.32(0.97;1.81)

1.12(0.98;1.27)

1.12(0.98;1.27) 0 0.0965 0.0965

IDL-TG1.1(0.87;1.38)

0.92(0.65;1.3)

0.7(0.56;0.86)

0.86(0.6;1.23)

0.87(0.76;0.99)

0.88(0.7;1.1) 0.634 0.0319 0.2614

IDL-TG-%1.1(0.9;1.34)

0.92(0.68;1.24)

0.82(0.66;1.02)

0.84(0.58;1.22)

0.94(0.83;1.06)

0.93(0.8;1.09) 0.289 0.3311 0.3685

L-HDL-C0.96(0.78;1.19)

1.21(0.92;1.58)

1.15(0.94;1.42)

1.52(1.09;2.12)

1.14(1.01;1.29)

1.16(0.98;1.38) 0.46 0.0343 0.0835

L-HDL-C-%1.05(0.85;1.29)

1.26(0.93;1.7)

1.36(1.1;1.7)

1.34(0.92;1.94)

1.22(1.07;1.38)

1.22(1.07;1.39) 0.089 0.0026 0.0041

L-HDL-CE0.96(0.78;1.19)

1.21(0.93;1.59)

1.16(0.94;1.42)

1.54(1.1;2.14)

1.14(1.01;1.29)

1.17(0.98;1.38) 0.471 0.0297 0.0789

L-HDL-CE-%1.06(0.87;1.3)

1.25(0.91;1.71)

1.4(1.13;1.75)

1.39(0.96;2.02)

1.23(1.09;1.4)

1.24(1.07;1.44) 0.211 0.0011 0.0037

L-HDL-FC0.95(0.77;1.18)

1.21(0.92;1.6)

1.14(0.93;1.41)

1.46(1.05;2.04)

1.13(1;1.27)

1.14(0.97;1.34) 0.4 0.0569 0.1028

L-HDL-FC-%0.98(0.81;1.19)

1.26(0.92;1.73)

1.21(0.97;1.51)

1.17(0.82;1.67)

1.11(0.98;1.26)

1.11(0.98;1.26) 0 0.0901 0.0901

L-HDL-L0.94(0.76;1.17)

1.21(0.93;1.58)

1.12(0.91;1.38)

1.55(1.09;2.21)

1.12(0.99;1.27)

1.15(0.96;1.37) 0.501 0.0669 0.1301

L-HDL-P0.94(0.76;1.17)

1.21(0.93;1.58)

1.12(0.91;1.37)

1.57(1.08;2.28)

1.12(0.99;1.26)

1.14(0.96;1.37) 0.495 0.0787 0.1403

L-HDL-PL0.94(0.76;1.16)

1.21(0.93;1.58)

1.09(0.89;1.34)

1.54(1.06;2.23)

1.1(0.97;1.24)

1.13(0.95;1.35) 0.483 0.1241 0.1799

L-HDL-PL-%0.94(0.75;1.17)

0.85(0.6;1.19)

0.78(0.63;0.96)

0.65(0.43;0.98)

0.83(0.73;0.94)

0.83(0.73;0.94) 0 0.0046 0.0046

L-HDL-TG1.00(0.81;1.22)

1.12(0.83;1.5)

0.99(0.8;1.22)

1.63(1.15;2.32)

1.08(0.95;1.22)

1.11(0.92;1.34) 0.541 0.2336 0.2609

L-HDL-TG-%1.04(0.85;1.27)

0.86(0.62;1.18)

0.86(0.71;1.05)

1.06(0.79;1.42)

0.95(0.85;1.07)

0.95(0.85;1.07) 0 0.4241 0.4241

M-HDL-C1.05(0.84;1.31)

1.11(0.8;1.54)

0.94(0.77;1.14)

0.9(0.62;1.31)

1(0.88;1.13)

1(0.88;1.13) 0 0.9347 0.9347

M-HDL-C-%0.97(0.76;1.23)

1(0.69;1.45)

1.15(0.94;1.41)

1.01(0.74;1.38)

1.05(0.93;1.2)

1.05(0.93;1.2) 0 0.4217 0.4217

M-HDL-CE1.05(0.84;1.31)

1.11(0.8;1.54)

0.96(0.79;1.16)

0.9(0.62;1.31)

1(0.88;1.13)

1(0.88;1.13) 0 0.9839 0.9839

STable 7

M-HDL-CE-%0.95(0.74;1.21)

0.97(0.66;1.42)

1.21(0.99;1.49)

1(0.73;1.37)

1.06(0.93;1.21)

1.06(0.93;1.21) 0 0.3799 0.3799

M-HDL-FC1.06(0.86;1.3)

1.1(0.81;1.48)

0.88(0.73;1.07)

0.9(0.62;1.31)

0.98(0.86;1.1)

0.98(0.86;1.1) 0 0.6855 0.6855

M-HDL-FC-%1.06(0.89;1.28)

1.13(0.85;1.49)

0.95(0.78;1.16)

1.02(0.72;1.45)

1.03(0.92;1.15)

1.03(0.92;1.15) 0 0.6144 0.6144

M-HDL-L1.05(0.85;1.3)

1.11(0.81;1.52)

0.89(0.73;1.09)

0.88(0.61;1.27)

0.98(0.86;1.1)

0.98(0.86;1.1) 0 0.6928 0.6928

M-HDL-P1.04(0.85;1.29)

1.11(0.82;1.52)

0.89(0.73;1.08)

0.88(0.61;1.27)

0.97(0.86;1.1)

0.97(0.86;1.1) 0 0.6455 0.6455

M-HDL-PL1.02(0.83;1.25)

1.13(0.84;1.51)

0.89(0.73;1.08)

0.91(0.63;1.33)

0.97(0.86;1.1)

0.97(0.86;1.1) 0 0.6697 0.6697

M-HDL-PL-%0.94(0.73;1.21)

1.22(0.82;1.79)

0.99(0.81;1.2)

1.21(0.94;1.56)

1.05(0.92;1.18)

1.05(0.92;1.18) 0 0.4831 0.4831

M-HDL-TG1.05(0.88;1.25)

0.89(0.63;1.24)

0.74(0.63;0.88)

0.75(0.52;1.09)

0.87(0.78;0.97)

0.86(0.7;1.05) 0.626 0.0116 0.1344

M-HDL-TG-%1.05(0.86;1.29)

0.81(0.57;1.13)

0.81(0.68;0.96)

0.82(0.56;1.19)

0.88(0.78;0.99)

0.88(0.76;1.02) 0.289 0.0357 0.0916

S-HDL-C0.98(0.79;1.2)

0.88(0.66;1.18)

0.88(0.73;1.06)

0.86(0.62;1.2)

0.91(0.81;1.02)

0.91(0.81;1.02) 0 0.1077 0.1077

S-HDL-C-%0.89(0.74;1.06)

0.9(0.66;1.23)

1.05(0.86;1.28)

1.13(0.81;1.57)

0.97(0.86;1.09)

0.97(0.86;1.09) 0 0.5794 0.5794

S-HDL-CE0.93(0.75;1.15)

0.87(0.65;1.17)

0.93(0.77;1.12)

0.88(0.63;1.23)

0.91(0.81;1.03)

0.91(0.81;1.03) 0 0.1353 0.1353

S-HDL-CE-%0.89(0.74;1.06)

0.88(0.64;1.22)

1.08(0.88;1.32)

1.08(0.78;1.51)

0.97(0.86;1.09)

0.97(0.86;1.09) 0 0.5738 0.5738

S-HDL-FC1.09(0.91;1.29)

1.01(0.75;1.36)

0.79(0.65;0.97)

0.86(0.59;1.25)

0.95(0.85;1.06)

0.94(0.79;1.11) 0.492 0.3610 0.4665

S-HDL-FC-%1.09(0.91;1.29)

1.18(0.84;1.65)

0.83(0.68;1)

1.16(0.83;1.62)

1.01(0.9;1.13)

1.03(0.86;1.22) 0.521 0.9005 0.7815

S-HDL-L1.07(0.87;1.3)

0.94(0.7;1.26)

0.81(0.67;0.99)

0.76(0.56;1.04)

0.9(0.8;1.02)

0.9(0.77;1.05) 0.391 0.0946 0.1783

S-HDL-P1.07(0.87;1.3)

0.94(0.7;1.26)

0.81(0.66;0.98)

0.76(0.56;1.04)

0.9(0.8;1.02)

0.9(0.77;1.05) 0.414 0.0924 0.1807

S-HDL-PL1.10(0.9;1.33)

1.02(0.75;1.4)

0.83(0.68;1.02)

0.76(0.55;1.07)

0.94(0.84;1.06)

0.93(0.79;1.11) 0.47 0.3204 0.4204

S-HDL-PL-%1.10(0.91;1.32)

1.19(0.86;1.65)

1.02(0.84;1.23)

0.9(0.66;1.24)

1.05(0.94;1.18)

1.05(0.94;1.18) 0 0.3910 0.3910

S-HDL-TG1.08(0.88;1.32)

0.81(0.56;1.16)

0.76(0.63;0.92)

0.86(0.59;1.25)

0.88(0.78;1)

0.88(0.72;1.07) 0.547 0.0412 0.1864

STable 7

S-HDL-TG-%1.06(0.86;1.31)

0.84(0.58;1.21)

0.81(0.68;0.98)

0.93(0.66;1.33)

0.91(0.8;1.03)

0.91(0.79;1.04) 0.161 0.1183 0.1731

XL-HDL-C0.79(0.59;1.05)

1.38(0.98;1.93)

1.18(0.95;1.48)

1.62(1.18;2.21)

1.17(1.02;1.35)

1.19(0.89;1.59) 0.756 0.0254 0.2334

XL-HDL-C-%1.01(0.76;1.33)

1.13(0.83;1.54)

1.03(0.8;1.32)

1.08(0.75;1.57)

1.05(0.91;1.22)

1.05(0.91;1.22) 0 0.4899 0.4899

XL-HDL-CE0.78(0.59;1.04)

1.37(0.97;1.93)

1.21(0.96;1.51)

1.62(1.18;2.21)

1.18(1.02;1.36)

1.19(0.89;1.6) 0.759 0.0228 0.2357

XL-HDL-CE-%1.00(0.76;1.31)

1.04(0.78;1.38)

1.1(0.85;1.43)

1.09(0.75;1.59)

1.06(0.91;1.22)

1.06(0.91;1.22) 0 0.4634 0.4634

XL-HDL-FC0.83(0.63;1.09)

1.37(1;1.87)

1.13(0.9;1.41)

1.58(1.16;2.17)

1.16(1.01;1.33)

1.18(0.91;1.54) 0.72 0.0376 0.2149

XL-HDL-FC-%1.01(0.8;1.29)

1.46(1;2.14)

0.87(0.71;1.07)

1(0.72;1.4)

0.99(0.87;1.13)

1.02(0.85;1.24) 0.468 0.8955 0.8200

XL-HDL-L0.80(0.61;1.06)

1.32(0.98;1.78)

1.18(0.95;1.47)

1.58(1.16;2.17)

1.16(1.02;1.33)

1.18(0.9;1.54) 0.735 0.0282 0.2301

XL-HDL-P0.80(0.61;1.06)

1.31(0.97;1.77)

1.18(0.95;1.47)

1.58(1.16;2.17)

1.16(1.02;1.33)

1.18(0.9;1.53) 0.732 0.0280 0.2284

XL-HDL-PL0.84(0.66;1.08)

1.25(0.94;1.66)

1.2(0.96;1.5)

1.52(1.09;2.12)

1.14(1;1.3)

1.16(0.92;1.47) 0.678 0.0559 0.2131

XL-HDL-PL-%0.95(0.72;1.27)

0.93(0.7;1.22)

1.14(0.89;1.45)

1.02(0.7;1.48)

1.02(0.88;1.17)

1.02(0.88;1.17) 0 0.8275 0.8275

XL-HDL-TG1.00(0.79;1.26)

1.12(0.83;1.51)

0.84(0.69;1.01)

1.39(1.02;1.9)

1(0.88;1.12)

1.04(0.85;1.29) 0.638 0.9437 0.6938

XL-HDL-TG-%1.22(0.97;1.54)

0.86(0.66;1.13)

0.76(0.63;0.9)

0.84(0.53;1.31)

0.89(0.79;1)

0.91(0.71;1.15) 0.71 0.0504 0.4281

L-LDL-C0.97(0.78;1.2)

1(0.75;1.33)

0.82(0.68;0.99)

0.95(0.69;1.3)

0.91(0.81;1.02)

0.91(0.81;1.02) 0 0.1114 0.1114

L-LDL-C-%0.90(0.74;1.09)

0.96(0.72;1.27)

0.95(0.76;1.19)

1.06(0.76;1.48)

0.95(0.84;1.07)

0.95(0.84;1.07) 0 0.3645 0.3645

L-LDL-CE0.97(0.79;1.2)

0.99(0.74;1.32)

0.81(0.68;0.98)

0.93(0.68;1.28)

0.9(0.8;1.02)

0.9(0.8;1.02) 0 0.0902 0.0902

L-LDL-CE-%0.92(0.75;1.13)

0.95(0.73;1.23)

0.85(0.68;1.07)

0.93(0.69;1.25)

0.91(0.8;1.03)

0.91(0.8;1.03) 0 0.1184 0.1184

L-LDL-FC0.96(0.77;1.2)

1.01(0.75;1.36)

0.84(0.69;1.01)

0.99(0.72;1.36)

0.92(0.82;1.04)

0.92(0.82;1.04) 0 0.1802 0.1802

L-LDL-FC-%0.93(0.74;1.15)

1.16(0.89;1.51)

1.46(1.16;1.84)

1.46(0.93;2.3)

1.18(1.04;1.34)

1.21(0.95;1.53) 0.662 0.0130 0.1194

L-LDL-L0.99(0.79;1.23)

1(0.74;1.34)

0.8(0.67;0.97)

0.95(0.69;1.3)

0.9(0.8;1.02)

0.9(0.8;1.02) 0 0.1003 0.1003

STable 7

L-LDL-P0.99(0.8;1.24)

0.99(0.73;1.33)

0.8(0.66;0.96)

0.94(0.69;1.29)

0.9(0.8;1.02)

0.9(0.8;1.02) 0 0.0892 0.0892

L-LDL-PL0.97(0.78;1.2)

1.01(0.76;1.35)

0.8(0.66;0.97)

0.93(0.67;1.3)

0.9(0.8;1.02)

0.9(0.8;1.02) 0 0.0927 0.0927

L-LDL-PL-%1.00(0.8;1.25)

1.1(0.8;1.51)

1.22(1.02;1.46)

0.84(0.58;1.22)

1.09(0.96;1.23)

1.08(0.93;1.24) 0.215 0.1708 0.3127

L-LDL-TG1.10(0.86;1.4)

0.99(0.7;1.39)

0.72(0.58;0.89)

0.99(0.71;1.38)

0.9(0.79;1.03)

0.92(0.75;1.15) 0.587 0.1269 0.4760

L-LDL-TG-%1.11(0.89;1.38)

1.05(0.76;1.45)

0.91(0.73;1.12)

1.03(0.74;1.44)

1.01(0.89;1.15)

1.01(0.89;1.15) 0 0.8384 0.8384

M-LDL-C0.94(0.77;1.16)

0.96(0.72;1.27)

0.82(0.68;0.98)

0.95(0.69;1.3)

0.89(0.8;1)

0.89(0.8;1) 0 0.0532 0.0532

M-LDL-C-%0.87(0.7;1.07)

0.9(0.68;1.18)

0.94(0.77;1.15)

1.11(0.76;1.6)

0.92(0.82;1.04)

0.92(0.82;1.04) 0 0.1993 0.1993

M-LDL-CE0.94(0.77;1.14)

0.95(0.71;1.25)

0.81(0.68;0.98)

0.94(0.69;1.29)

0.89(0.79;1)

0.89(0.79;1) 0 0.0420 0.0420

M-LDL-CE-%0.87(0.7;1.08)

0.88(0.68;1.15)

0.86(0.69;1.07)

1.04(0.75;1.45)

0.89(0.79;1.01)

0.89(0.79;1.01) 0 0.0723 0.0723

M-LDL-FC0.97(0.78;1.22)

1(0.74;1.34)

0.81(0.67;0.98)

0.99(0.72;1.36)

0.91(0.81;1.03)

0.91(0.81;1.03) 0 0.1241 0.1241

M-LDL-FC-%1.03(0.85;1.25)

1.13(0.87;1.48)

1.31(1.09;1.56)

1.08(0.82;1.42)

1.15(1.03;1.28)

1.15(1.02;1.29) 0.123 0.0117 0.0214

M-LDL-L0.97(0.79;1.19)

0.96(0.72;1.28)

0.79(0.66;0.95)

0.95(0.69;1.3)

0.89(0.79;1)

0.89(0.79;1) 0 0.0534 0.0534

M-LDL-P0.97(0.79;1.2)

0.96(0.72;1.28)

0.79(0.65;0.95)

0.94(0.69;1.29)

0.89(0.79;1)

0.89(0.79;1) 0 0.0486 0.0486

M-LDL-PL1.00(0.8;1.25)

1(0.75;1.34)

0.76(0.63;0.92)

0.91(0.66;1.28)

0.89(0.79;1)

0.9(0.77;1.04) 0.291 0.0561 0.1514

M-LDL-PL-%1.07(0.88;1.29)

1.13(0.85;1.49)

1.12(0.92;1.35)

0.79(0.52;1.22)

1.07(0.96;1.21)

1.07(0.96;1.21) 0 0.2291 0.2291

M-LDL-TG1.08(0.86;1.35)

0.97(0.68;1.39)

0.74(0.6;0.91)

1.03(0.74;1.44)

0.91(0.8;1.04)

0.93(0.76;1.14) 0.546 0.1598 0.4794

M-LDL-TG-%1.11(0.89;1.37)

1.11(0.78;1.59)

0.95(0.77;1.17)

1.07(0.8;1.44)

1.04(0.92;1.18)

1.04(0.92;1.18) 0 0.5080 0.5080

S-LDL-C0.92(0.75;1.13)

0.95(0.72;1.26)

0.81(0.68;0.98)

0.96(0.7;1.32)

0.89(0.79;0.99)

0.89(0.79;0.99) 0 0.0390 0.0390

S-LDL-C-%0.86(0.71;1.03)

0.89(0.67;1.18)

0.93(0.76;1.14)

1.11(0.75;1.64)

0.91(0.81;1.02)

0.91(0.81;1.02) 0 0.1117 0.1117

S-LDL-CE0.91(0.75;1.12)

0.94(0.71;1.25)

0.82(0.68;0.99)

0.95(0.69;1.3)

0.89(0.79;0.99)

0.89(0.79;0.99) 0 0.0356 0.0356

STable 7

S-LDL-CE-%0.85(0.7;1.03)

0.88(0.67;1.15)

0.89(0.72;1.11)

1.04(0.73;1.48)

0.89(0.79;1)

0.89(0.79;1) 0 0.0560 0.0560

S-LDL-FC0.96(0.77;1.21)

0.98(0.73;1.32)

0.8(0.66;0.96)

1.02(0.75;1.4)

0.9(0.8;1.02)

0.9(0.8;1.02) 0 0.0937 0.0937

S-LDL-FC-%1.08(0.89;1.31)

1.12(0.85;1.47)

1.23(1.02;1.48)

1.17(0.89;1.54)

1.15(1.03;1.29)

1.15(1.03;1.29) 0 0.0126 0.0126

S-LDL-L0.95(0.77;1.17)

0.96(0.72;1.28)

0.79(0.65;0.95)

0.96(0.7;1.32)

0.89(0.79;1)

0.89(0.79;1) 0 0.0405 0.0405

S-LDL-P0.95(0.77;1.18)

0.96(0.72;1.28)

0.78(0.65;0.94)

0.95(0.69;1.3)

0.88(0.79;0.99)

0.88(0.79;0.99) 0 0.0369 0.0369

S-LDL-PL1.00(0.81;1.23)

1.03(0.78;1.36)

0.78(0.65;0.95)

0.96(0.69;1.34)

0.91(0.81;1.02)

0.92(0.8;1.05) 0.247 0.1127 0.2212

S-LDL-PL-%1.10(0.91;1.32)

1.18(0.88;1.59)

1.19(0.99;1.43)

0.93(0.64;1.35)

1.13(1.01;1.26)

1.13(1.01;1.26) 0 0.0407 0.0407

S-LDL-TG1.07(0.86;1.32)

0.91(0.64;1.3)

0.68(0.55;0.83)

0.91(0.64;1.3)

0.86(0.76;0.98)

0.87(0.69;1.11) 0.672 0.0224 0.2646

S-LDL-TG-%1.11(0.91;1.36)

0.96(0.66;1.4)

0.81(0.65;1.01)

0.89(0.6;1.31)

0.95(0.83;1.08)

0.94(0.8;1.12) 0.343 0.4484 0.5121

L-VLDL-C1.03(0.83;1.29)

0.82(0.61;1.11)

0.75(0.62;0.91)

0.84(0.56;1.27)

0.85(0.75;0.96)

0.86(0.73;1.01) 0.366 0.0099 0.0607

L-VLDL-C-%0.81(0.59;1.12)

0.94(0.59;1.49)

1.09(0.89;1.34)

1.07(0.77;1.5)

1.01(0.87;1.17)

1.01(0.87;1.17) 0 0.8919 0.8919

L-VLDL-CE1.02(0.82;1.27)

0.82(0.59;1.12)

0.76(0.64;0.91)

0.84(0.56;1.27)

0.85(0.75;0.96)

0.85(0.74;0.99) 0.273 0.0086 0.0406

L-VLDL-CE-%0.79(0.58;1.09)

1.05(0.67;1.65)

1.19(0.99;1.45)

1.08(0.79;1.48)

1.07(0.93;1.23)

1.04(0.87;1.26) 0.36 0.3365 0.6490

L-VLDL-FC1.06(0.85;1.32)

0.82(0.61;1.09)

0.77(0.64;0.92)

0.84(0.54;1.29)

0.86(0.76;0.97)

0.87(0.73;1.02) 0.412 0.0148 0.0922

L-VLDL-FC-%1.04(0.82;1.31)

0.78(0.52;1.16)

0.86(0.74;1)

0.97(0.7;1.35)

0.91(0.81;1.02)

0.91(0.81;1.02) 0 0.0914 0.0914

L-VLDL-L1.05(0.84;1.31)

0.81(0.62;1.06)

0.75(0.62;0.91)

0.82(0.53;1.26)

0.85(0.75;0.96)

0.85(0.72;1.01) 0.423 0.0105 0.0698

L-VLDL-P1.05(0.84;1.32)

0.81(0.62;1.06)

0.75(0.62;0.91)

0.82(0.53;1.26)

0.85(0.75;0.96)

0.85(0.72;1.02) 0.429 0.0112 0.0734

L-VLDL-PL1.06(0.85;1.32)

0.81(0.62;1.07)

0.74(0.6;0.9)

0.82(0.53;1.26)

0.85(0.75;0.96)

0.85(0.71;1.02) 0.488 0.0108 0.0889

L-VLDL-PL-%1.08(0.85;1.37)

1.12(0.85;1.47)

1.01(0.84;1.22)

0.9(0.6;1.37)

1.04(0.92;1.18)

1.04(0.92;1.18) 0 0.5251 0.5251

L-VLDL-TG1.07(0.85;1.34)

0.81(0.62;1.05)

0.76(0.63;0.92)

0.82(0.53;1.26)

0.86(0.76;0.97)

0.86(0.73;1.02) 0.426 0.0129 0.0826

STable 7

L-VLDL-TG-%1.15(0.83;1.58)

1(0.64;1.57)

0.89(0.72;1.11)

0.97(0.68;1.38)

0.97(0.83;1.13)

0.97(0.83;1.13) 0 0.6858 0.6858

M-VLDL-C1.05(0.84;1.32)

0.85(0.64;1.13)

0.72(0.59;0.88)

0.82(0.55;1.21)

0.84(0.74;0.96)

0.85(0.71;1.02) 0.503 0.0078 0.0883

M-VLDL-C-%0.96(0.72;1.27)

1.12(0.76;1.63)

1.12(0.92;1.36)

1.14(0.83;1.56)

1.08(0.95;1.24)

1.08(0.95;1.24) 0 0.2481 0.2481

M-VLDL-CE1.03(0.81;1.3)

0.89(0.66;1.19)

0.72(0.59;0.88)

0.84(0.56;1.24)

0.84(0.74;0.96)

0.86(0.72;1.02) 0.441 0.0089 0.0854

M-VLDL-CE-%0.91(0.69;1.21)

1.25(0.88;1.8)

1.19(0.98;1.46)

1.17(0.86;1.61)

1.13(0.98;1.29)

1.13(0.98;1.29) 0 0.0835 0.0835

M-VLDL-FC1.07(0.86;1.33)

0.81(0.61;1.07)

0.73(0.6;0.88)

0.81(0.54;1.22)

0.85(0.75;0.96)

0.85(0.7;1.03) 0.567 0.0080 0.1041

M-VLDL-FC-%1.16(0.94;1.43)

0.77(0.55;1.07)

0.73(0.63;0.86)

0.84(0.62;1.12)

0.85(0.76;0.95)

0.86(0.68;1.09) 0.747 0.0046 0.2237

M-VLDL-L1.05(0.84;1.31)

0.82(0.62;1.08)

0.74(0.6;0.9)

0.8(0.53;1.21)

0.85(0.75;0.96)

0.85(0.71;1.02) 0.478 0.0095 0.0757

M-VLDL-P1.05(0.84;1.3)

0.82(0.62;1.08)

0.74(0.61;0.9)

0.8(0.53;1.21)

0.85(0.75;0.96)

0.85(0.71;1.02) 0.466 0.0102 0.0739

M-VLDL-PL1.06(0.85;1.31)

0.81(0.62;1.07)

0.73(0.6;0.89)

0.79(0.53;1.2)

0.85(0.75;0.96)

0.85(0.7;1.02) 0.529 0.0085 0.0837

M-VLDL-PL-%1.01(0.78;1.29)

1.07(0.85;1.35)

1.11(0.92;1.35)

1.04(0.75;1.45)

1.07(0.95;1.2)

1.07(0.95;1.2) 0 0.2870 0.2870

M-VLDL-TG1.05(0.85;1.3)

0.81(0.61;1.07)

0.76(0.62;0.92)

0.8(0.53;1.21)

0.86(0.76;0.97)

0.86(0.72;1.02) 0.437 0.0151 0.0774

M-VLDL-TG-%1.02(0.77;1.35)

0.89(0.62;1.27)

0.89(0.72;1.1)

0.89(0.65;1.21)

0.92(0.8;1.06)

0.92(0.8;1.06) 0 0.2331 0.2331

S-VLDL-C1.01(0.78;1.3)

0.87(0.62;1.23)

0.72(0.59;0.87)

0.76(0.53;1.08)

0.81(0.71;0.92)

0.82(0.69;0.97) 0.355 0.0013 0.0230

S-VLDL-C-%0.83(0.63;1.08)

1.26(0.9;1.78)

1.19(0.97;1.47)

1.26(0.9;1.76)

1.11(0.97;1.27)

1.11(0.91;1.36) 0.51 0.1353 0.3096

S-VLDL-CE0.98(0.75;1.28)

0.92(0.65;1.31)

0.75(0.62;0.9)

0.79(0.55;1.12)

0.83(0.72;0.94)

0.83(0.72;0.94) 0.023 0.0039 0.0049

S-VLDL-CE-%0.82(0.62;1.07)

1.27(0.91;1.76)

1.23(1;1.53)

1.3(0.95;1.78)

1.13(0.99;1.29)

1.13(0.91;1.4) 0.594 0.0772 0.2732

S-VLDL-FC1.05(0.84;1.33)

0.81(0.59;1.11)

0.68(0.56;0.83)

0.73(0.5;1.05)

0.8(0.71;0.91)

0.81(0.65;1.01) 0.645 0.0007 0.0656

S-VLDL-FC-%1.09(0.85;1.39)

1.04(0.83;1.3)

0.78(0.64;0.95)

0.85(0.6;1.21)

0.92(0.82;1.04)

0.93(0.78;1.1) 0.467 0.2025 0.4078

S-VLDL-L1.06(0.84;1.33)

0.81(0.6;1.11)

0.7(0.58;0.85)

0.73(0.49;1.07)

0.82(0.72;0.93)

0.82(0.66;1.01) 0.594 0.0016 0.0651

STable 7

S-VLDL-P1.06(0.84;1.33)

0.81(0.6;1.1)

0.7(0.58;0.85)

0.73(0.49;1.07)

0.82(0.72;0.93)

0.82(0.66;1.01) 0.603 0.0019 0.0677

S-VLDL-PL1.08(0.86;1.34)

0.81(0.59;1.11)

0.69(0.57;0.84)

0.69(0.47;1.02)

0.81(0.72;0.92)

0.81(0.64;1.03) 0.684 0.0014 0.0860

S-VLDL-PL-%1.19(0.93;1.52)

1.14(0.87;1.49)

1.06(0.87;1.29)

0.75(0.52;1.09)

1.07(0.94;1.21)

1.06(0.9;1.24) 0.334 0.3099 0.4899

S-VLDL-TG1.08(0.87;1.33)

0.79(0.58;1.06)

0.72(0.59;0.87)

0.75(0.5;1.13)

0.84(0.74;0.95)

0.83(0.67;1.04) 0.652 0.0054 0.1004

S-VLDL-TG-%1.15(0.89;1.49)

0.77(0.56;1.06)

0.83(0.69;1)

0.84(0.6;1.18)

0.89(0.78;1.01)

0.89(0.75;1.06) 0.422 0.0728 0.2056

XL-VLDL-C1.03(0.82;1.3)

0.85(0.61;1.19)

0.72(0.6;0.86)

0.9(0.6;1.37)

0.83(0.73;0.94)

0.85(0.71;1.04) 0.508 0.0028 0.1090

XL-VLDL-C-%0.94(0.68;1.29)

1.06(0.72;1.56)

1.28(1.07;1.53)

1.35(1.07;1.71)

1.22(1.08;1.38)

1.2(1.03;1.4) 0.259 0.0017 0.0171

XL-VLDL-CE1.02(0.81;1.29)

0.83(0.6;1.16)

0.81(0.71;0.93)

0.91(0.61;1.38)

0.86(0.78;0.96)

0.86(0.78;0.96) 0 0.0085 0.0085

XL-VLDL-CE-%0.89(0.66;1.2)

1.01(0.7;1.45)

1.17(0.96;1.44)

1.34(1.12;1.59)

1.17(1.04;1.32)

1.13(0.95;1.35) 0.507 0.0070 0.1699

XL-VLDL-FC1.03(0.82;1.31)

0.88(0.63;1.23)

0.7(0.58;0.84)

0.9(0.59;1.35)

0.83(0.73;0.94)

0.86(0.69;1.06) 0.575 0.0032 0.1462

XL-VLDL-FC-%1.01(0.73;1.4)

1.16(0.79;1.72)

1.24(1.05;1.48)

1.11(0.81;1.51)

1.17(1.03;1.33)

1.17(1.03;1.33) 0 0.0161 0.0161

XL-VLDL-L1.03(0.82;1.3)

0.84(0.64;1.11)

0.72(0.6;0.87)

0.86(0.56;1.32)

0.84(0.74;0.94)

0.85(0.71;1.02) 0.486 0.0037 0.0772

XL-VLDL-P1.04(0.83;1.3)

0.84(0.64;1.1)

0.73(0.61;0.87)

0.85(0.55;1.31)

0.83(0.74;0.94)

0.85(0.71;1.02) 0.484 0.0032 0.0724

XL-VLDL-PL1.04(0.83;1.3)

0.86(0.64;1.15)

0.71(0.6;0.84)

0.87(0.56;1.34)

0.82(0.73;0.93)

0.85(0.7;1.04) 0.583 0.0013 0.1132

XL-VLDL-PL-%1.09(0.83;1.44)

1.23(0.9;1.69)

1.02(0.82;1.28)

0.87(0.6;1.26)

1.06(0.91;1.22)

1.06(0.91;1.22) 0 0.4601 0.4601

XL-VLDL-TG1.04(0.83;1.31)

0.83(0.64;1.08)

0.8(0.69;0.92)

0.84(0.55;1.3)

0.86(0.77;0.95)

0.87(0.76;0.99) 0.234 0.0043 0.0314

XL-VLDL-TG-%1.03(0.75;1.42)

0.88(0.59;1.32)

0.78(0.67;0.91)

0.81(0.62;1.07)

0.82(0.73;0.93)

0.82(0.73;0.93) 0 0.0013 0.0013

XS-VLDL-C1.02(0.78;1.34)

1.05(0.72;1.53)

0.79(0.65;0.95)

0.8(0.58;1.12)

0.87(0.76;0.99)

0.88(0.76;1.02) 0.146 0.0402 0.0817

XS-VLDL-C-%0.85(0.66;1.1)

1.52(1.03;2.25)

1.37(1.07;1.76)

1.2(0.84;1.7)

1.16(1;1.34)

1.19(0.91;1.56) 0.68 0.0513 0.2043

XS-VLDL-CE1.00(0.76;1.32)

1.14(0.77;1.7)

0.81(0.67;0.99)

0.82(0.59;1.14)

0.89(0.78;1.02)

0.89(0.77;1.03) 0.061 0.0866 0.1123

STable 7

XS-VLDL-CE-%0.84(0.64;1.1)

1.61(1.09;2.37)

1.41(1.11;1.8)

1.16(0.82;1.65)

1.19(1.02;1.38)

1.21(0.9;1.61) 0.724 0.0233 0.2077

XS-VLDL-FC1.05(0.82;1.34)

0.9(0.65;1.26)

0.74(0.61;0.9)

0.79(0.57;1.11)

0.85(0.75;0.96)

0.86(0.72;1.02) 0.423 0.0103 0.0857

XS-VLDL-FC-%1.05(0.84;1.31)

0.96(0.75;1.21)

0.93(0.76;1.14)

1.12(0.75;1.65)

0.99(0.88;1.12)

0.99(0.88;1.12) 0 0.8455 0.8455

XS-VLDL-L1.06(0.82;1.36)

0.94(0.66;1.33)

0.74(0.61;0.89)

0.76(0.54;1.09)

0.84(0.74;0.96)

0.86(0.71;1.04) 0.463 0.0111 0.1107

XS-VLDL-P1.06(0.83;1.36)

0.93(0.66;1.31)

0.73(0.6;0.89)

0.76(0.53;1.08)

0.84(0.74;0.96)

0.85(0.7;1.04) 0.504 0.0089 0.1126

XS-VLDL-PL1.05(0.84;1.32)

0.94(0.68;1.29)

0.75(0.62;0.91)

0.8(0.58;1.12)

0.87(0.77;0.98)

0.88(0.74;1.04) 0.447 0.0257 0.1343

XS-VLDL-PL-%1.03(0.78;1.38)

0.94(0.65;1.38)

1.06(0.86;1.3)

1.21(0.83;1.75)

1.06(0.92;1.22)

1.06(0.92;1.22) 0 0.4444 0.4444

XS-VLDL-TG1.09(0.88;1.35)

0.79(0.57;1.1)

0.69(0.56;0.84)

0.74(0.51;1.07)

0.83(0.73;0.94)

0.82(0.64;1.05) 0.71 0.0040 0.1196

XS-VLDL-TG-%1.11(0.9;1.37)

0.79(0.59;1.05)

0.75(0.61;0.92)

0.78(0.54;1.13)

0.87(0.77;0.99)

0.86(0.69;1.06) 0.633 0.0316 0.1588

XXL-VLDL-C1.00(0.77;1.29)

0.94(0.68;1.29)

0.74(0.61;0.89)

0.91(0.61;1.38)

0.85(0.74;0.97)

0.86(0.74;1.01) 0.245 0.0136 0.0648

XXL-VLDL-C-%0.97(0.74;1.28)

0.86(0.63;1.17)

0.79(0.66;0.94)

1.23(0.92;1.66)

0.9(0.8;1.02)

0.93(0.77;1.13) 0.566 0.0849 0.4817

XXL-VLDL-CE0.98(0.75;1.27)

0.94(0.67;1.32)

0.74(0.62;0.9)

0.93(0.63;1.38)

0.85(0.74;0.97)

0.86(0.74;0.99) 0.159 0.0130 0.0405

XXL-VLDL-CE-%0.93(0.72;1.21)

0.94(0.71;1.26)

0.96(0.77;1.19)

1.16(0.85;1.59)

0.98(0.86;1.12)

0.98(0.86;1.12) 0 0.7737 0.7737

XXL-VLDL-FC1.03(0.8;1.33)

0.92(0.68;1.23)

0.74(0.62;0.89)

0.9(0.59;1.35)

0.85(0.75;0.97)

0.87(0.73;1.03) 0.383 0.0128 0.1125

XXL-VLDL-FC-%1.14(0.87;1.49)

0.88(0.7;1.11)

0.8(0.67;0.95)

1.17(0.91;1.51)

0.94(0.84;1.04)

0.97(0.8;1.18) 0.654 0.2365 0.7555

XXL-VLDL-L1.01(0.79;1.3)

0.93(0.69;1.24)

0.76(0.62;0.92)

0.88(0.57;1.35)

0.86(0.76;0.98)

0.87(0.75;1) 0.147 0.0249 0.0539

XXL-VLDL-P1.01(0.79;1.3)

0.93(0.69;1.24)

0.76(0.62;0.92)

0.88(0.57;1.35)

0.86(0.76;0.98)

0.87(0.75;1) 0.133 0.0264 0.0530

XXL-VLDL-PL1.03(0.81;1.31)

0.92(0.69;1.23)

0.73(0.6;0.89)

0.85(0.55;1.31)

0.86(0.75;0.97)

0.87(0.73;1.03) 0.379 0.0173 0.1048

XXL-VLDL-PL-%1.15(0.89;1.49)

0.92(0.74;1.15)

0.81(0.66;0.98)

0.77(0.57;1.03)

0.89(0.8;1.01)

0.9(0.76;1.06) 0.473 0.0646 0.2117

XXL-VLDL-TG1.01(0.79;1.29)

0.93(0.7;1.23)

0.76(0.63;0.93)

0.87(0.56;1.34)

0.87(0.76;0.99)

0.87(0.76;1) 0.081 0.0299 0.0450

STable 7

XXL-VLDL-TG-%0.98(0.75;1.27)

1.2(0.9;1.59)

1.3(1.09;1.54)

0.89(0.66;1.19)

1.14(1.01;1.28)

1.1(0.92;1.32) 0.525 0.0362 0.3077

STable 8

STable 8. HRs and 95% CIs of metabolites, lipid and lipoprotein lipids for incident AD. Adjusted for Model 1

Metabolite, lipid,

lipoprotein lipid

FINRISK 97HR(95%CI)

DILGOMHR(95%CI)

WHITEHALLHR(95%CI)

FIXED EFFECT95%CI

RANDOM EFFECT95%CI I2 p.fixed p.random

Amino Acids

ALA1.02(0.76;1.36)

0.82(0.61;1.1)

0.86(0.62;1.19)

0.9(0.75;1.07)

0.9(0.75;1.07) 0 0.2208 0.2208

GLN1.17(0.88;1.55)

0.76(0.56;1.04)

0.78(0.57;1.07)

0.9(0.76;1.07)

0.89(0.68;1.18) 0.595 0.2482 0.4200

GLY1.06(0.78;1.44)

0.92(0.71;1.2)

1.1(0.79;1.53)

1.01(0.85;1.2)

1.01(0.85;1.2) 0 0.9141 0.9141

HIS1.03(0.83;1.27)

0.77(0.57;1.05)

0.76(0.59;0.98)

0.87(0.76;1.01)

0.86(0.7;1.05) 0.489 0.0634 0.1454

ILE1.04(0.78;1.4)

0.83(0.61;1.12)

0.67(0.46;0.98)

0.87(0.72;1.04)

0.85(0.67;1.09) 0.41 0.1206 0.1975

LEU1(0.73;1.35)

0.75(0.54;1.05)

0.74(0.52;1.05)

0.83(0.69;1.01)

0.83(0.69;1.01) 0.062 0.0610 0.0683

PHE0.89(0.65;1.22)

0.7(0.5;0.99)

0.94(0.66;1.33)

0.84(0.69;1.02)

0.84(0.69;1.02) 0 0.0770 0.0770

TYR0.99(0.78;1.26)

0.71(0.54;0.92)

0.71(0.5;0.99)

0.82(0.7;0.96)

0.8(0.63;1.02) 0.549 0.0113 0.0702

VAL0.93(0.69;1.26)

0.7(0.5;0.97)

0.8(0.59;1.1)

0.81(0.68;0.98)

0.81(0.68;0.98) 0 0.0260 0.0260


DHA0.85(0.66;1.09)

1.17(0.93;1.48)

0.89(0.64;1.26)

0.99(0.85;1.15)

0.98(0.79;1.21) 0.474 0.8627 0.8186

DHA_FA0.79(0.61;1.01)

1.25(0.97;1.61)

0.97(0.68;1.38)

0.98(0.84;1.15)

0.98(0.73;1.32) 0.694 0.8345 0.9174

FAW30.85(0.67;1.08)

1.18(0.92;1.53)

0.88(0.62;1.24)

0.97(0.83;1.13)

0.97(0.78;1.2) 0.47 0.6907 0.7541

FAW3_FA0.81(0.65;1.01)

1.3(1;1.7)

0.96(0.68;1.36)

0.98(0.84;1.14)

1(0.74;1.36) 0.729 0.8163 0.9859

FAW60.98(0.77;1.25)

0.83(0.62;1.1)

1.02(0.72;1.45)

0.94(0.8;1.1)

0.94(0.8;1.1) 0 0.4308 0.4308

FAW6_FA0.89(0.71;1.12)

0.92(0.69;1.25)

1.38(0.95;2)

0.98(0.83;1.16)

1.01(0.79;1.29) 0.5 0.8256 0.9357

LA 0.97 0.78 1.11 0.92 0.93 0.311 0.3105 0.4305

STable 8

(0.78;1.22) (0.6;1.01) (0.78;1.58) (0.79;1.08) (0.77;1.12)

LA_FA0.88(0.68;1.14)

0.83(0.62;1.1)

1.42(1;2.03)

0.96(0.81;1.14)

0.99(0.73;1.34) 0.671 0.6467 0.9641

MUFA1.16(0.9;1.5)

0.87(0.65;1.17)

0.74(0.52;1.05)

0.96(0.81;1.13)

0.93(0.71;1.21) 0.574 0.5888 0.5798

MUFA_FA1.2(0.96;1.51)

0.89(0.66;1.21)

0.68(0.47;0.97)

0.98(0.83;1.15)

0.92(0.66;1.28) 0.73 0.8211 0.6198

PUFA0.94(0.74;1.21)

0.9(0.67;1.19)

1(0.7;1.4)

0.94(0.8;1.11)

0.94(0.8;1.11) 0 0.4583 0.4583

PUFA_FA0.85(0.68;1.07)

1.05(0.78;1.41)

1.35(0.93;1.95)

0.99(0.84;1.17)

1.03(0.8;1.33) 0.549 0.9245 0.8162

SFA1.11(0.85;1.45)

0.91(0.66;1.25)

0.86(0.61;1.22)

0.98(0.82;1.17)

0.98(0.82;1.17) 0 0.7950 0.7950

SFA_FA1.06(0.83;1.37)

1.09(0.81;1.47)

1.02(0.73;1.41)

1.06(0.9;1.25)

1.06(0.9;1.25) 0 0.4933 0.4933

TOTFA1.09(0.84;1.42)

0.89(0.66;1.21)

0.85(0.6;1.2)

0.96(0.81;1.14)

0.96(0.81;1.14) 0 0.6503 0.6503

UNSAT0.79(0.63;1)

1.21(0.94;1.56)

1.09(0.78;1.53)

0.99(0.85;1.15)

1.01(0.76;1.33) 0.683 0.8960 0.9570

Fluid Balance

ALB1.11(0.84;1.46)

1.4(0.99;1.99)

0.87(0.64;1.17)

1.08(0.91;1.29)

1.09(0.84;1.41) 0.528 0.3788 0.5005

CREA0.9(0.71;1.15)

0.85(0.62;1.15)

0.64(0.41;1)

0.84(0.71;1)

0.84(0.71;1) 0 0.0490 0.0490


CIT0.92(0.73;1.14)

1.06(0.79;1.42)

0.89(0.64;1.24)

0.95(0.81;1.11)

0.95(0.81;1.11) 0 0.4936 0.4936

GLC0.9(0.7;1.16)

0.97(0.76;1.25)

1.21(0.86;1.7)

0.99(0.85;1.16)

0.99(0.85;1.16) 0 0.9084 0.9084

GLOL0.99(0.73;1.35)

0.78(0.55;1.11)

0.66(0.5;0.88)

0.79(0.66;0.94)

0.8(0.63;1.01) 0.434 0.0095 0.0600

LAC0.96(0.77;1.2)

0.91(0.66;1.25)

0.81(0.57;1.15)

0.92(0.78;1.07)

0.92(0.78;1.07) 0 0.2800 0.2800

PYR0.96(0.75;1.22)

0.95(0.7;1.28)

1.02(0.74;1.4)

0.97(0.82;1.14)

0.97(0.82;1.14) 0 0.7136 0.7136

Ketone BodiesACACE 1.06 1.31 0.75 1.04 1.03 0.651 0.6152 0.8672

STable 8

(0.82;1.37) (0.97;1.77) (0.53;1.06) (0.88;1.24) (0.76;1.38)

ACE1.09(0.85;1.39)

0.96(0.73;1.26)

1.01(0.72;1.42)

1.02(0.87;1.2)

1.02(0.87;1.2) 0 0.7778 0.7778

BOHBUT0.88(0.63;1.24)

1.29(0.96;1.72)

0.75(0.53;1.07)

0.99(0.82;1.19)

0.96(0.69;1.33) 0.666 0.8824 0.8108

Inflammation

GP1(0.77;1.3)

0.78(0.59;1.03)

0.72(0.51;1.03)

0.85(0.72;1.01)

0.84(0.69;1.03) 0.264 0.0581 0.0931


HDL_TG1.04(0.82;1.33)

1(0.7;1.43)

0.85(0.61;1.2)

0.98(0.82;1.16)

0.98(0.82;1.16) 0 0.8178 0.8178

LDL_TG1.14(0.87;1.49)

0.97(0.67;1.4)

0.86(0.6;1.24)

1.02(0.84;1.22)

1.02(0.84;1.22) 0 0.8641 0.8641

PC1(0.75;1.31)

1(0.73;1.35)

0.98(0.69;1.4)

0.99(0.83;1.19)

0.99(0.83;1.19) 0 0.9314 0.9314

SERUM_TG1.13(0.88;1.44)

0.81(0.6;1.11)

0.69(0.48;1.01)

0.92(0.78;1.09)

0.88(0.66;1.18) 0.637 0.3490 0.3949

SM0.88(0.65;1.19)

0.96(0.7;1.32)

1.06(0.74;1.51)

0.96(0.79;1.15)

0.96(0.79;1.15) 0 0.6253 0.6253

TG_PG1.2(0.93;1.55)

0.82(0.63;1.08)

0.69(0.48;1.01)

0.93(0.79;1.1)

0.9(0.65;1.24) 0.712 0.4229 0.5146

TOTCHO0.95(0.71;1.29)

0.97(0.7;1.36)

1.06(0.74;1.52)

0.99(0.82;1.19)

0.99(0.82;1.19) 0 0.9110 0.9110

TOTPG1.03(0.79;1.34)

0.99(0.73;1.34)

1.03(0.72;1.46)

1.02(0.85;1.21)

1.02(0.85;1.21) 0 0.8685 0.8685

VLDL_TG1.11(0.87;1.42)

0.79(0.59;1.05)

0.69(0.48;0.99)

0.9(0.76;1.06)

0.86(0.65;1.15) 0.657 0.1909 0.3148

APOA10.92(0.74;1.15)

1.09(0.83;1.42)

1.11(0.77;1.58)

1.01(0.86;1.18)

1.01(0.86;1.18) 0 0.9200 0.9200

APOB1.02(0.79;1.32)

0.9(0.68;1.21)

0.87(0.61;1.24)

0.94(0.8;1.12)

0.94(0.8;1.12) 0 0.5103 0.5103

APOB_APOA11.08(0.85;1.38)

0.86(0.63;1.16)

0.82(0.56;1.19)

0.95(0.8;1.13)

0.95(0.8;1.13) 0.058 0.5570 0.5513

Cholesterol

ESTC0.88(0.68;1.14)

0.98(0.74;1.3)

0.97(0.68;1.37)

0.93(0.79;1.11)

0.93(0.79;1.11) 0 0.4296 0.4296

FREEC 0.95 1 1.09 1 1 0 0.9496 0.9496

STable 8

(0.73;1.23) (0.75;1.32) (0.76;1.57) (0.84;1.18) (0.84;1.18)

HDL2_C0.92(0.74;1.15)

1.13(0.85;1.51)

1.25(0.86;1.81)

1.04(0.88;1.21)

1.04(0.88;1.25) 0.171 0.6645 0.6242

HDL3_C0.83(0.64;1.09)

0.99(0.69;1.43)

1.16(0.83;1.64)

0.96(0.8;1.15)

0.96(0.79;1.17) 0.138 0.6298 0.6956

HDL_C0.89(0.71;1.12)

1.11(0.84;1.47)

1.23(0.86;1.77)

1.02(0.87;1.19)

1.03(0.85;1.25) 0.282 0.8225 0.7447

LDL_C0.93(0.73;1.18)

0.94(0.72;1.24)

0.98(0.68;1.41)

0.94(0.8;1.11)

0.94(0.8;1.11) 0 0.4839 0.4839

REMNANT_C0.97(0.73;1.29)

0.93(0.68;1.28)

0.88(0.61;1.25)

0.93(0.78;1.12)

0.93(0.78;1.12) 0 0.4583 0.4583

SERUM_C0.91(0.7;1.18)

0.99(0.75;1.31)

1(0.7;1.42)

0.96(0.81;1.13)

0.96(0.81;1.13) 0 0.6073 0.6073

VLDL_C1.02(0.76;1.37)

0.9(0.65;1.24)

0.77(0.54;1.1)

0.9(0.75;1.09)

0.9(0.75;1.09) 0 0.2917 0.2917


HDL_D0.84(0.64;1.09)

1.23(0.92;1.64)

1.58(1.12;2.23)

1.11(0.94;1.32)

1.16(0.81;1.67) 0.774 0.2173 0.4227

LDL_D1.06(0.81;1.37)

1.34(0.93;1.93)

1.27(0.89;1.83)

1.18(0.98;1.41)

1.18(0.98;1.41) 0 0.0814 0.0814

VLDL_D1.05(0.8;1.38)

0.77(0.59;1.01)

0.68(0.46;0.99)

0.85(0.71;1.01)

0.83(0.65;1.07) 0.515 0.0567 0.1574


IDL_C0.91(0.7;1.17)

0.98(0.73;1.31)

1.03(0.72;1.47)

0.96(0.81;1.13)

0.96(0.81;1.13) 0 0.6001 0.6001

IDL_C_PC0.87(0.71;1.07)

0.98(0.72;1.33)

1.14(0.76;1.7)

0.93(0.8;1.09)

0.93(0.8;1.09) 0 0.3981 0.3981

IDL_CE0.9(0.69;1.16)

0.97(0.73;1.31)

1.02(0.71;1.46)

0.95(0.8;1.13)

0.95(0.8;1.13) 0 0.5509 0.5509

IDL_CE_PC0.86(0.7;1.06)

0.99(0.73;1.33)

1.07(0.73;1.56)

0.93(0.79;1.09)

0.93(0.79;1.09) 0 0.3520 0.3520

IDL_FC0.94(0.73;1.2)

0.98(0.73;1.32)

1.05(0.73;1.51)

0.97(0.82;1.15)

0.97(0.82;1.15) 0 0.7439 0.7439

IDL_FC_PC0.87(0.67;1.14)

1.11(0.87;1.42)

1.28(0.82;1.98)

1.03(0.87;1.22)

1.04(0.85;1.27) 0.289 0.7327 0.7283

IDL_L0.96(0.74;1.25)

0.97(0.72;1.31)

1.01(0.7;1.45)

0.98(0.82;1.16)

0.98(0.82;1.16) 0 0.7792 0.7792

STable 8

IDL_P0.98(0.75;1.28)

0.96(0.71;1.3)

1(0.69;1.43)

0.98(0.82;1.17)

0.98(0.82;1.17) 0 0.8110 0.8110

IDL_PL0.97(0.75;1.25)

0.98(0.73;1.3)

1.01(0.71;1.45)

0.98(0.83;1.16)

0.98(0.83;1.16) 0 0.8065 0.8065

IDL_PL_PC0.96(0.7;1.33)

1.05(0.74;1.49)

1.04(0.71;1.52)

1.02(0.83;1.24)

1.02(0.83;1.24) 0 0.8869 0.8869

IDL_TG1.15(0.88;1.5)

0.97(0.67;1.39)

0.83(0.58;1.2)

1.01(0.84;1.22)

1.01(0.84;1.22) 0.028 0.8835 0.8961

IDL_TG_PC1.16(0.93;1.45)

1.03(0.77;1.37)

0.81(0.56;1.17)

1.05(0.89;1.23)

1.03(0.85;1.25) 0.259 0.5727 0.7465

L_HDL_C0.9(0.71;1.14)

1.16(0.88;1.54)

1.46(0.99;2.14)

1.07(0.91;1.27)

1.12(0.85;1.46) 0.588 0.4000 0.4222

L_HDL_C_PC1.09(0.86;1.39)

1.24(0.91;1.7)

1.62(1.08;2.43)

1.22(1.02;1.45)

1.24(1.01;1.53) 0.274 0.0254 0.0451

L_HDL_CE0.9(0.71;1.15)

1.16(0.88;1.54)

1.45(0.99;2.13)

1.08(0.91;1.27)

1.12(0.86;1.45) 0.578 0.3846 0.4162

L_HDL_CE_PC1.13(0.89;1.44)

1.23(0.9;1.7)

1.53(1.03;2.25)

1.23(1.04;1.46)

1.23(1.04;1.46) 0 0.0183 0.0183

L_HDL_FC0.89(0.7;1.13)

1.16(0.87;1.55)

1.48(1;2.18)

1.07(0.9;1.26)

1.12(0.85;1.47) 0.612 0.4418 0.4354

L_HDL_FC_PC0.98(0.79;1.22)

1.24(0.89;1.72)

1.65(1.06;2.57)

1.12(0.95;1.33)

1.2(0.9;1.6) 0.58 0.1753 0.2109

L_HDL_L0.87(0.69;1.11)

1.15(0.87;1.53)

1.41(0.96;2.08)

1.05(0.89;1.24)

1.09(0.84;1.43) 0.598 0.5344 0.5142

L_HDL_P0.87(0.68;1.11)

1.16(0.88;1.53)

1.41(0.96;2.07)

1.05(0.89;1.24)

1.09(0.83;1.43) 0.606 0.5452 0.5235

L_HDL_PL0.87(0.68;1.1)

1.15(0.87;1.52)

1.36(0.92;1.99)

1.04(0.88;1.22)

1.07(0.83;1.39) 0.561 0.6652 0.5913

L_HDL_PL_PC0.96(0.74;1.24)

0.84(0.59;1.2)

0.61(0.41;0.89)

0.84(0.7;1.01)

0.81(0.63;1.05) 0.471 0.0560 0.1182

L_HDL_TG0.86(0.69;1.09)

1.11(0.81;1.51)

1.4(0.92;2.14)

1.01(0.85;1.19)

1.05(0.81;1.38) 0.54 0.9554 0.6962

L_HDL_TG_PC0.97(0.78;1.21)

0.92(0.66;1.27)

1.02(0.69;1.5)

0.97(0.82;1.14)

0.97(0.82;1.14) 0 0.6842 0.6842

M_HDL_C1.03(0.8;1.32)

0.98(0.7;1.36)

0.97(0.68;1.37)

1(0.84;1.19)

1(0.84;1.19) 0 0.9787 0.9787

M_HDL_C_PC0.99(0.75;1.3)

0.93(0.64;1.36)

1.23(0.86;1.77)

1.03(0.86;1.25)

1.03(0.86;1.25) 0 0.7205 0.7205

M_HDL_CE1.02(0.79;1.32)

0.97(0.69;1.36)

0.98(0.69;1.39)

1(0.84;1.19)

1(0.84;1.19) 0 0.9683 0.9683

STable 8

M_HDL_CE_PC0.97(0.74;1.29)

0.91(0.62;1.36)

1.25(0.87;1.8)

1.03(0.85;1.25)

1.03(0.85;1.25) 0 0.7627 0.7627

M_HDL_FC1.03(0.81;1.3)

0.99(0.73;1.33)

0.93(0.67;1.31)

0.99(0.84;1.17)

0.99(0.84;1.17) 0 0.9274 0.9274

M_HDL_FC_PC1.04(0.85;1.28)

1.07(0.8;1.43)

0.99(0.69;1.41)

1.04(0.89;1.21)

1.04(0.89;1.21) 0 0.6259 0.6259

M_HDL_L1.02(0.8;1.3)

0.98(0.72;1.35)

0.91(0.64;1.29)

0.99(0.83;1.16)

0.99(0.83;1.16) 0 0.8566 0.8566

M_HDL_P1.02(0.8;1.3)

0.98(0.72;1.35)

0.9(0.64;1.28)

0.98(0.83;1.16)

0.98(0.83;1.16) 0 0.8205 0.8205

M_HDL_PL0.99(0.79;1.25)

1.01(0.74;1.36)

0.9(0.63;1.27)

0.98(0.83;1.15)

0.98(0.83;1.15) 0 0.7621 0.7621

M_HDL_PL_PC0.91(0.69;1.2)

1.31(0.87;1.95)

0.92(0.65;1.31)

0.99(0.82;1.2)

1(0.81;1.23) 0.148 0.9389 0.9844

M_HDL_TG1(0.82;1.23)

0.84(0.6;1.19)

0.72(0.53;0.98)

0.89(0.77;1.04)

0.87(0.71;1.07) 0.36 0.1490 0.1879

M_HDL_TG_PC1.02(0.81;1.28)

0.84(0.59;1.19)

0.77(0.56;1.06)

0.9(0.77;1.07)

0.9(0.76;1.07) 0.072 0.2278 0.2330

S_HDL_C0.95(0.75;1.21)

0.87(0.65;1.16)

0.78(0.55;1.1)

0.88(0.75;1.04)

0.88(0.75;1.04) 0 0.1362 0.1362

S_HDL_C_PC0.85(0.69;1.04)

0.94(0.7;1.28)

1.13(0.79;1.62)

0.92(0.79;1.07)

0.92(0.79;1.07) 0 0.2842 0.2842

S_HDL_CE0.91(0.71;1.17)

0.87(0.65;1.16)

0.84(0.6;1.19)

0.88(0.75;1.04)

0.88(0.75;1.04) 0 0.1364 0.1364

S_HDL_CE_PC0.86(0.7;1.06)

0.92(0.68;1.26)

1.15(0.8;1.67)

0.92(0.79;1.08)

0.92(0.79;1.08) 0 0.3179 0.3179

S_HDL_FC1.07(0.88;1.31)

0.94(0.7;1.26)

0.7(0.5;0.97)

0.95(0.82;1.1)

0.91(0.72;1.16) 0.573 0.5025 0.4595

S_HDL_FC_PC1.03(0.84;1.26)

1.13(0.81;1.59)

0.81(0.58;1.14)

1(0.86;1.17)

1(0.85;1.17) 0.033 0.9834 0.9917

S_HDL_L1.06(0.85;1.34)

0.88(0.65;1.18)

0.68(0.48;0.95)

0.91(0.78;1.07)

0.88(0.68;1.13) 0.575 0.2471 0.3195

S_HDL_P1.07(0.85;1.34)

0.87(0.65;1.17)

0.67(0.48;0.94)

0.91(0.77;1.07)

0.88(0.67;1.14) 0.602 0.2447 0.3225

S_HDL_PL1.12(0.89;1.39)

0.92(0.67;1.25)

0.69(0.49;0.98)

0.96(0.82;1.12)

0.91(0.7;1.2) 0.62 0.5858 0.5193

S_HDL_PL_PC1.13(0.91;1.4)

1.09(0.79;1.51)

0.95(0.67;1.34)

1.08(0.92;1.26)

1.08(0.92;1.26) 0 0.3460 0.3460

S_HDL_TG1.11(0.88;1.39)

0.83(0.57;1.19)

0.69(0.49;0.95)

0.92(0.78;1.09)

0.87(0.64;1.18) 0.667 0.3314 0.3832

STable 8

S_HDL_TG_PC1.09(0.86;1.39)

0.9(0.62;1.3)

0.77(0.56;1.08)

0.95(0.8;1.13)

0.94(0.76;1.16) 0.301 0.5928 0.5609

XL_HDL_C0.72(0.52;1.01)

1.25(0.89;1.78)

1.51(0.99;2.3)

1.05(0.86;1.3)

1.1(0.71;1.7) 0.772 0.6198 0.6814

XL_HDL_C_PC1.2(0.88;1.64)

1.05(0.76;1.45)

0.81(0.52;1.27)

1.06(0.87;1.29)

1.06(0.86;1.29) 0.013 0.5943 0.6000

XL_HDL_CE0.73(0.52;1.02)

1.24(0.87;1.76)

1.51(0.99;2.31)

1.05(0.85;1.29)

1.09(0.71;1.68) 0.758 0.6517 0.6875

XL_HDL_CE_PC1.18(0.87;1.6)

0.98(0.73;1.32)

0.83(0.52;1.33)

1.03(0.85;1.25)

1.03(0.85;1.25) 0 0.7756 0.7756

XL_HDL_FC0.74(0.54;1.01)

1.27(0.92;1.76)

1.52(0.99;2.34)

1.06(0.87;1.3)

1.11(0.72;1.71) 0.776 0.5624 0.6348

XL_HDL_FC_PC1.01(0.76;1.34)

1.34(0.91;1.97)

0.9(0.62;1.31)

1.05(0.87;1.28)

1.05(0.86;1.29) 0.089 0.6106 0.6199

XL_HDL_L0.71(0.52;0.98)

1.24(0.91;1.69)

1.56(1.04;2.34)

1.06(0.88;1.29)

1.1(0.7;1.73) 0.805 0.5338 0.6728

XL_HDL_P0.71(0.52;0.98)

1.24(0.91;1.68)

1.56(1.04;2.34)

1.07(0.88;1.29)

1.1(0.7;1.72) 0.806 0.5260 0.6720

XL_HDL_PL0.75(0.57;1)

1.2(0.89;1.61)

1.62(1.07;2.47)

1.04(0.87;1.25)

1.11(0.73;1.71) 0.808 0.6617 0.6203

XL_HDL_PL_PC0.8(0.59;1.1)

0.98(0.74;1.31)

1.41(0.88;2.28)

0.97(0.8;1.17)

0.99(0.75;1.31) 0.476 0.7354 0.9522

XL_HDL_TG0.93(0.71;1.22)

1.07(0.78;1.46)

1.18(0.77;1.79)

1.02(0.85;1.23)

1.02(0.85;1.23) 0 0.8108 0.8108

XL_HDL_TG_PC1.21(0.92;1.57)

0.88(0.66;1.16)

0.85(0.6;1.2)

0.99(0.83;1.17)

0.98(0.78;1.23) 0.442 0.8905 0.8486

L_LDL_C0.94(0.74;1.2)

0.96(0.73;1.26)

1(0.69;1.43)

0.96(0.81;1.13)

0.96(0.81;1.13) 0 0.6058 0.6058

L_LDL_C_PC0.88(0.71;1.1)

0.92(0.7;1.2)

1.1(0.7;1.73)

0.92(0.78;1.08)

0.92(0.78;1.08) 0 0.3004 0.3004

L_LDL_CE0.95(0.74;1.21)

0.95(0.72;1.25)

0.99(0.68;1.43)

0.96(0.81;1.13)

0.96(0.81;1.13) 0 0.5877 0.5877

L_LDL_CE_PC0.92(0.73;1.16)

0.91(0.71;1.17)

1.01(0.62;1.63)

0.93(0.79;1.09)

0.93(0.79;1.09) 0 0.3470 0.3470

L_LDL_FC0.92(0.72;1.18)

0.97(0.73;1.29)

1.03(0.72;1.47)

0.96(0.81;1.13)

0.96(0.81;1.13) 0 0.6252 0.6252

L_LDL_FC_PC0.84(0.66;1.09)

1.22(0.93;1.59)

1.38(0.92;2.07)

1.06(0.89;1.25)

1.09(0.81;1.47) 0.649 0.5237 0.5493

L_LDL_L0.97(0.75;1.24)

0.96(0.72;1.27)

0.98(0.69;1.41)

0.97(0.82;1.14)

0.97(0.82;1.14) 0 0.6832 0.6832

STable 8

L_LDL_P0.98(0.76;1.27)

0.95(0.71;1.27)

0.98(0.68;1.4)

0.97(0.82;1.15)

0.97(0.82;1.15) 0 0.7174 0.7174

L_LDL_PL0.93(0.73;1.19)

0.96(0.73;1.26)

0.96(0.68;1.37)

0.95(0.81;1.12)

0.95(0.81;1.12) 0 0.5213 0.5213

L_LDL_PL_PC0.93(0.71;1.21)

1.08(0.78;1.48)

0.92(0.61;1.38)

0.97(0.81;1.17)

0.97(0.81;1.17) 0 0.7590 0.7590

L_LDL_TG1.15(0.87;1.52)

1(0.7;1.44)

0.89(0.62;1.28)

1.03(0.86;1.25)

1.03(0.86;1.25) 0 0.7353 0.7353

L_LDL_TG_PC1.16(0.91;1.48)

1.14(0.83;1.57)

0.89(0.62;1.29)

1.09(0.92;1.29)

1.09(0.92;1.29) 0 0.3277 0.3277

M_LDL_C0.92(0.73;1.17)

0.94(0.72;1.22)

0.96(0.67;1.38)

0.94(0.8;1.1)

0.94(0.8;1.1) 0 0.4118 0.4118

M_LDL_C_PC0.85(0.67;1.08)

0.89(0.69;1.16)

1.08(0.7;1.67)

0.9(0.76;1.06)

0.9(0.76;1.06) 0 0.1961 0.1961

M_LDL_CE0.92(0.73;1.16)

0.93(0.71;1.21)

0.96(0.66;1.4)

0.93(0.79;1.09)

0.93(0.79;1.09) 0 0.3627 0.3627

M_LDL_CE_PC0.86(0.67;1.1)

0.89(0.69;1.14)

1.02(0.6;1.71)

0.89(0.75;1.05)

0.89(0.75;1.05) 0 0.1628 0.1628

M_LDL_FC0.96(0.74;1.23)

0.95(0.72;1.26)

0.95(0.67;1.35)

0.95(0.81;1.13)

0.95(0.81;1.13) 0 0.5803 0.5803

M_LDL_FC_PC0.98(0.79;1.23)

1.12(0.86;1.46)

1.1(0.76;1.6)

1.05(0.9;1.23)

1.05(0.9;1.23) 0 0.5451 0.5451

M_LDL_L0.97(0.76;1.23)

0.93(0.71;1.23)

0.94(0.66;1.34)

0.95(0.81;1.12)

0.95(0.81;1.12) 0 0.5390 0.5390

M_LDL_P0.98(0.77;1.25)

0.93(0.71;1.23)

0.94(0.66;1.34)

0.95(0.81;1.12)

0.95(0.81;1.12) 0 0.5751 0.5751

M_LDL_PL1(0.78;1.29)

0.94(0.71;1.25)

0.88(0.62;1.25)

0.95(0.81;1.13)

0.95(0.81;1.13) 0 0.5726 0.5726

M_LDL_PL_PC1.07(0.86;1.33)

1.1(0.84;1.43)

0.88(0.59;1.33)

1.05(0.89;1.23)

1.05(0.89;1.23) 0 0.5659 0.5659

M_LDL_TG1.13(0.87;1.47)

0.97(0.67;1.41)

0.89(0.62;1.28)

1.03(0.85;1.23)

1.03(0.85;1.23) 0 0.7933 0.7933

M_LDL_TG_PC1.14(0.9;1.45)

1.18(0.83;1.68)

0.94(0.65;1.35)

1.1(0.93;1.31)

1.1(0.93;1.31) 0 0.2755 0.2755

S_LDL_C0.9(0.71;1.14)

0.93(0.71;1.22)

0.96(0.67;1.38)

0.92(0.79;1.08)

0.92(0.79;1.08) 0 0.3310 0.3310

S_LDL_C_PC0.84(0.67;1.04)

0.9(0.69;1.18)

1.08(0.7;1.67)

0.89(0.76;1.04)

0.89(0.76;1.04) 0 0.1314 0.1314

S_LDL_CE0.89(0.71;1.13)

0.93(0.71;1.21)

0.97(0.66;1.41)

0.92(0.78;1.08)

0.92(0.78;1.08) 0 0.2917 0.2917

STable 8

S_LDL_CE_PC0.84(0.67;1.04)

0.89(0.69;1.16)

1.05(0.63;1.74)

0.88(0.75;1.03)

0.88(0.75;1.03) 0 0.1059 0.1059

S_LDL_FC0.96(0.74;1.25)

0.93(0.7;1.24)

0.93(0.66;1.31)

0.94(0.8;1.12)

0.94(0.8;1.12) 0 0.5019 0.5019

S_LDL_FC_PC1.05(0.84;1.31)

1.1(0.84;1.44)

1.01(0.68;1.49)

1.06(0.9;1.24)

1.06(0.9;1.24) 0 0.4823 0.4823

S_LDL_L0.95(0.75;1.21)

0.93(0.71;1.22)

0.94(0.66;1.33)

0.94(0.8;1.11)

0.94(0.8;1.11) 0 0.4548 0.4548

S_LDL_P0.96(0.75;1.23)

0.93(0.71;1.22)

0.93(0.65;1.33)

0.94(0.8;1.11)

0.94(0.8;1.11) 0 0.4801 0.4801

S_LDL_PL1.02(0.8;1.3)

0.95(0.73;1.25)

0.91(0.65;1.28)

0.97(0.83;1.14)

0.97(0.83;1.14) 0 0.7171 0.7171

S_LDL_PL_PC1.11(0.9;1.38)

1.14(0.85;1.51)

0.99(0.67;1.44)

1.1(0.94;1.28)

1.1(0.94;1.28) 0 0.2362 0.2362

S_LDL_TG1.12(0.87;1.44)

0.88(0.61;1.27)

0.76(0.54;1.09)

0.96(0.8;1.15)

0.94(0.74;1.19) 0.396 0.6695 0.6005

S_LDL_TG_PC1.14(0.91;1.44)

1.02(0.71;1.47)

0.76(0.52;1.12)

1.03(0.86;1.22)

1(0.79;1.26) 0.378 0.7672 0.9897

L_VLDL_C1.04(0.81;1.34)

0.79(0.58;1.08)

0.71(0.51;0.99)

0.87(0.73;1.03)

0.85(0.68;1.07) 0.447 0.0996 0.1744

L_VLDL_C_PC0.72(0.5;1.05)

0.98(0.61;1.57)

1.36(0.99;1.88)

1.03(0.83;1.28)

1(0.67;1.49) 0.687 0.7867 0.9979

L_VLDL_CE1.02(0.79;1.32)

0.79(0.57;1.1)

0.72(0.53;0.99)

0.86(0.73;1.02)

0.85(0.68;1.06) 0.392 0.0876 0.1493

L_VLDL_CE_PC0.73(0.5;1.06)

1.15(0.73;1.81)

1.35(0.97;1.87)

1.06(0.85;1.31)

1.04(0.71;1.53) 0.671 0.6151 0.8242

L_VLDL_FC1.07(0.83;1.38)

0.78(0.58;1.04)

0.75(0.55;1.04)

0.88(0.75;1.04)

0.87(0.69;1.09) 0.479 0.1328 0.2298

L_VLDL_FC_PC0.96(0.74;1.25)

0.75(0.49;1.15)

0.98(0.69;1.4)

0.92(0.76;1.11)

0.92(0.76;1.11) 0 0.3871 0.3871

L_VLDL_L1.07(0.83;1.39)

0.78(0.59;1.03)

0.68(0.49;0.96)

0.86(0.73;1.02)

0.84(0.65;1.1) 0.6 0.0809 0.2110

L_VLDL_P1.08(0.83;1.4)

0.78(0.59;1.03)

0.68(0.48;0.96)

0.86(0.73;1.02)

0.84(0.64;1.11) 0.615 0.0798 0.2177

L_VLDL_PL1.08(0.84;1.4)

0.78(0.59;1.03)

0.68(0.48;0.97)

0.87(0.73;1.03)

0.85(0.64;1.11) 0.613 0.0979 0.2321

L_VLDL_PL_PC1(0.76;1.31)

1.14(0.86;1.5)

1.2(0.92;1.56)

1.11(0.95;1.3)

1.11(0.95;1.3) 0 0.1949 0.1949

L_VLDL_TG1.1(0.85;1.44)

0.78(0.59;1.02)

0.69(0.5;0.96)

0.86(0.73;1.02)

0.85(0.64;1.12) 0.654 0.0782 0.2491

STable 8

L_VLDL_TG_PC1.28(0.88;1.86)

0.95(0.6;1.5)

0.74(0.55;1.01)

0.93(0.75;1.14)

0.95(0.68;1.34) 0.587 0.4712 0.7767

M_VLDL_C1.04(0.8;1.36)

0.83(0.62;1.11)

0.74(0.51;1.06)

0.89(0.75;1.06)

0.88(0.72;1.08) 0.263 0.1790 0.2209

M_VLDL_C_PC0.86(0.62;1.19)

1.1(0.76;1.6)

1.35(0.97;1.88)

1.08(0.89;1.32)

1.09(0.83;1.42) 0.465 0.4203 0.5543

M_VLDL_CE1.01(0.76;1.32)

0.86(0.64;1.16)

0.75(0.52;1.08)

0.89(0.74;1.06)

0.89(0.74;1.06) 0 0.1937 0.1937

M_VLDL_CE_PC0.82(0.6;1.13)

1.21(0.85;1.71)

1.38(0.98;1.96)

1.09(0.9;1.33)

1.1(0.81;1.51) 0.613 0.3805 0.5402

M_VLDL_FC1.09(0.85;1.4)

0.79(0.59;1.05)

0.73(0.51;1.04)

0.89(0.76;1.06)

0.87(0.68;1.13) 0.558 0.1879 0.2948

M_VLDL_FC_PC1.16(0.91;1.48)

0.78(0.55;1.1)

0.84(0.59;1.18)

0.97(0.82;1.15)

0.94(0.72;1.22) 0.553 0.7438 0.6215

M_VLDL_L1.07(0.83;1.38)

0.8(0.6;1.05)

0.71(0.5;1.02)

0.89(0.75;1.04)

0.87(0.68;1.11) 0.513 0.1495 0.2475

M_VLDL_P1.07(0.83;1.38)

0.8(0.6;1.06)

0.71(0.5;1.02)

0.89(0.75;1.04)

0.87(0.68;1.11) 0.519 0.1495 0.2492

M_VLDL_PL1.08(0.84;1.39)

0.79(0.59;1.05)

0.72(0.5;1.03)

0.89(0.75;1.05)

0.87(0.67;1.12) 0.541 0.1660 0.2667

M_VLDL_PL_PC1.01(0.76;1.34)

1.09(0.86;1.38)

1.3(0.94;1.78)

1.11(0.95;1.3)

1.11(0.95;1.3) 0 0.1974 0.1974

M_VLDL_TG1.09(0.85;1.39)

0.79(0.59;1.05)

0.71(0.5;1.01)

0.89(0.76;1.05)

0.87(0.66;1.13) 0.59 0.1686 0.2794

M_VLDL_TG_PC1.12(0.81;1.55)

0.89(0.63;1.28)

0.75(0.54;1.03)

0.91(0.75;1.1)

0.91(0.72;1.15) 0.319 0.3244 0.4186

S_VLDL_C0.98(0.73;1.32)

0.86(0.61;1.21)

0.76(0.54;1.07)

0.87(0.72;1.05)

0.87(0.72;1.05) 0 0.1583 0.1583

S_VLDL_C_PC0.73(0.54;1)

1.2(0.86;1.66)

1.38(0.96;1.98)

1.03(0.85;1.25)

1.06(0.72;1.55) 0.746 0.7323 0.7755

S_VLDL_CE0.93(0.68;1.27)

0.9(0.64;1.28)

0.8(0.57;1.13)

0.88(0.73;1.07)

0.88(0.73;1.07) 0 0.1929 0.1929

S_VLDL_CE_PC0.72(0.53;0.99)

1.2(0.87;1.64)

1.41(0.96;2.06)

1.03(0.85;1.25)

1.06(0.71;1.57) 0.763 0.7682 0.7801

S_VLDL_FC1.07(0.82;1.4)

0.81(0.59;1.12)

0.7(0.49;0.98)

0.88(0.74;1.05)

0.86(0.67;1.11) 0.508 0.1580 0.2543

S_VLDL_FC_PC1.06(0.79;1.4)

1.06(0.83;1.34)

0.89(0.64;1.25)

1.02(0.87;1.19)

1.02(0.87;1.19) 0 0.8428 0.8428

S_VLDL_L1.08(0.83;1.41)

0.81(0.59;1.11)

0.7(0.5;1)

0.89(0.74;1.06)

0.87(0.67;1.12) 0.52 0.1795 0.2782

STable 8

S_VLDL_P1.09(0.84;1.42)

0.81(0.59;1.11)

0.7(0.49;0.99)

0.89(0.75;1.06)

0.87(0.67;1.13) 0.551 0.1863 0.2902

S_VLDL_PL1.11(0.85;1.43)

0.81(0.58;1.11)

0.68(0.48;0.96)

0.89(0.75;1.06)

0.86(0.64;1.15) 0.635 0.1944 0.3154

S_VLDL_PL_PC1.22(0.93;1.61)

1.13(0.86;1.49)

0.87(0.58;1.3)

1.11(0.93;1.32)

1.11(0.93;1.32) 0 0.2405 0.2405

S_VLDL_TG1.13(0.89;1.43)

0.79(0.59;1.07)

0.69(0.49;0.98)

0.91(0.77;1.07)

0.87(0.64;1.17) 0.681 0.2467 0.3515

S_VLDL_TG_PC1.27(0.95;1.71)

0.81(0.59;1.11)

0.76(0.55;1.05)

0.94(0.78;1.12)

0.92(0.67;1.28) 0.696 0.4828 0.6416

XL_VLDL_C1.02(0.78;1.33)

0.81(0.57;1.15)

0.8(0.59;1.08)

0.89(0.75;1.06)

0.89(0.75;1.06) 0 0.1777 0.1777

XL_VLDL_C_PC0.94(0.65;1.37)

1.12(0.76;1.65)

1.36(1;1.83)

1.16(0.95;1.42)

1.15(0.93;1.43) 0.123 0.1507 0.1927

XL_VLDL_CE1.01(0.78;1.32)

0.8(0.56;1.12)

0.87(0.67;1.14)

0.91(0.77;1.07)

0.91(0.77;1.07) 0 0.2366 0.2366

XL_VLDL_CE_PC

0.88(0.63;1.24)

1.05(0.72;1.53)

1.35(0.93;1.94)

1.07(0.87;1.31)

1.07(0.84;1.36) 0.282 0.5477 0.5945

XL_VLDL_FC1.02(0.78;1.34)

0.83(0.59;1.17)

0.78(0.58;1.06)

0.89(0.75;1.06)

0.89(0.75;1.06) 0 0.1870 0.1870

XL_VLDL_FC_PC1(0.68;1.46)

1.2(0.81;1.8)

1.25(0.94;1.68)

1.16(0.95;1.42)

1.16(0.95;1.42) 0 0.1368 0.1368

XL_VLDL_L1.04(0.79;1.35)

0.8(0.61;1.07)

0.74(0.54;1.03)

0.87(0.74;1.03)

0.87(0.71;1.06) 0.299 0.1013 0.1540

XL_VLDL_P1.04(0.8;1.36)

0.8(0.61;1.06)

0.75(0.54;1.02)

0.87(0.74;1.02)

0.86(0.71;1.06) 0.326 0.0948 0.1550

XL_VLDL_PL1.03(0.79;1.35)

0.82(0.61;1.1)

0.77(0.56;1.05)

0.88(0.75;1.04)

0.88(0.73;1.05) 0.142 0.1413 0.1650

XL_VLDL_PL_PC1.03(0.75;1.42)

1.21(0.88;1.66)

1.16(0.79;1.71)

1.13(0.93;1.37)

1.13(0.93;1.37) 0 0.2255 0.2255

XL_VLDL_TG1.05(0.81;1.37)

0.8(0.62;1.05)

0.82(0.64;1.05)

0.88(0.76;1.02)

0.88(0.74;1.05) 0.228 0.0985 0.1493

XL_VLDL_TG_PC

1.05(0.73;1.51)

0.85(0.56;1.28)

0.76(0.59;1)

0.85(0.7;1.03)

0.85(0.7;1.03) 0 0.0931 0.0931

XS_VLDL_C0.97(0.71;1.33)

1(0.69;1.44)

0.92(0.65;1.32)

0.96(0.79;1.17)

0.96(0.79;1.17) 0 0.7004 0.7004

XS_VLDL_C_PC0.76(0.57;1.01)

1.31(0.9;1.92)

1.33(0.87;2.03)

1(0.82;1.22)

1.07(0.72;1.6) 0.725 0.9930 0.7280

XS_VLDL_CE0.94(0.68;1.3)

1.05(0.71;1.54)

0.94(0.66;1.35)

0.97(0.79;1.19)

0.97(0.79;1.19) 0 0.7684 0.7684

STable 8

XS_VLDL_CE_PC0.74(0.54;1)

1.36(0.93;1.99)

1.3(0.87;1.95)

1.02(0.83;1.25)

1.07(0.71;1.63) 0.744 0.8481 0.7330

XS_VLDL_FC1.03(0.79;1.36)

0.91(0.66;1.28)

0.89(0.63;1.26)

0.96(0.8;1.15)

0.96(0.8;1.15) 0 0.6381 0.6381

XS_VLDL_FC_PC1.01(0.78;1.31)

0.97(0.76;1.23)

1.1(0.75;1.62)

1.01(0.86;1.18)

1.01(0.86;1.18) 0 0.9455 0.9455

XS_VLDL_L1.06(0.79;1.41)

0.93(0.66;1.31)

0.86(0.6;1.23)

0.96(0.8;1.16)

0.96(0.8;1.16) 0 0.6796 0.6796

XS_VLDL_P1.07(0.8;1.42)

0.92(0.65;1.3)

0.84(0.59;1.21)

0.96(0.8;1.16)

0.96(0.8;1.16) 0 0.6654 0.6654

XS_VLDL_PL1.06(0.82;1.36)

0.94(0.69;1.28)

0.92(0.64;1.32)

0.99(0.83;1.17)

0.99(0.83;1.17) 0 0.8641 0.8641

XS_VLDL_PL_PC1.04(0.75;1.45)

0.96(0.66;1.38)

1.32(0.9;1.93)

1.09(0.88;1.34)

1.09(0.88;1.34) 0 0.4275 0.4275

XS_VLDL_TG1.14(0.9;1.45)

0.82(0.58;1.16)

0.72(0.51;1.03)

0.94(0.79;1.12)

0.9(0.68;1.2) 0.612 0.5110 0.4775

XS_VLDL_TG_PC

1.19(0.95;1.51)

0.86(0.65;1.13)

0.69(0.48;1)

0.96(0.82;1.13)

0.91(0.67;1.25) 0.72 0.6381 0.5641

XXL_VLDL_C1(0.74;1.34)

0.88(0.64;1.23)

0.8(0.56;1.12)

0.9(0.74;1.08)

0.9(0.74;1.08) 0 0.2552 0.2552

XXL_VLDL_C_PC

0.83(0.6;1.13)

0.9(0.66;1.23)

1.06(0.71;1.58)

0.9(0.75;1.1)

0.9(0.75;1.1) 0 0.3124 0.3124

XXL_VLDL_CE0.96(0.71;1.31)

0.9(0.63;1.27)

0.8(0.56;1.13)

0.89(0.73;1.08)

0.89(0.73;1.08) 0 0.2293 0.2293

XXL_VLDL_CE_PC

0.81(0.6;1.09)

0.98(0.73;1.32)

1.23(0.84;1.81)

0.96(0.8;1.15)

0.97(0.77;1.21) 0.319 0.6571 0.7772

XXL_VLDL_FC1.05(0.79;1.41)

0.87(0.64;1.17)

0.81(0.58;1.13)

0.91(0.76;1.09)

0.91(0.76;1.09) 0 0.3161 0.3161

XXL_VLDL_FC_PC

1.14(0.84;1.54)

0.89(0.7;1.13)

0.9(0.63;1.29)

0.96(0.81;1.13)

0.96(0.81;1.13) 0 0.6241 0.6241

XXL_VLDL_L1.03(0.77;1.38)

0.87(0.64;1.17)

0.77(0.54;1.1)

0.9(0.75;1.07)

0.9(0.75;1.07) 0 0.2410 0.2410

XXL_VLDL_P1.03(0.77;1.38)

0.87(0.64;1.17)

0.77(0.54;1.1)

0.9(0.75;1.07)

0.9(0.75;1.07) 0 0.2381 0.2381

XXL_VLDL_PL1.05(0.8;1.4)

0.86(0.65;1.15)

0.8(0.56;1.13)

0.91(0.77;1.09)

0.91(0.77;1.09) 0 0.3046 0.3046

XXL_VLDL_PL_PC

1.2(0.89;1.63)

0.9(0.71;1.13)

0.92(0.61;1.38)

0.99(0.83;1.16)

0.99(0.82;1.19) 0.171 0.8595 0.9144

XXL_VLDL_TG1.04(0.78;1.38)

0.87(0.65;1.16)

0.77(0.54;1.09)

0.9(0.75;1.07)

0.9(0.75;1.07) 0 0.2394 0.2394

STable 8

XXL_VLDL_TG_PC

1.13(0.83;1.53)

1.17(0.87;1.58)

1.04(0.73;1.47)

1.12(0.93;1.34)

1.12(0.93;1.34) 0 0.2315 0.2315

STable 9

STable 9. HRs and 95% CIs of metabolites, lipid and lipoprotein lipids for incident AD. Adjusted for Model 2.

Metabolite, lipid,

lipoprotein lipid

FINRISK 97HR(95%CI)

DILGOMHR(95%CI)

WHITEHALLHR(95%CI)

FIXED EFFECTHR95%CI

RANDOM EFFECTHR95%CI I2 p.fixed p.random

Amino Acids

ALA1.01(0.75;1.36)

0.79(0.59;1.07)

0.89(0.63;1.26)

0.89(0.74;1.07)

0.89(0.74;1.07) 0 0.2118 0.2118

GLN1.15(0.85;1.54)

0.78(0.57;1.07)

0.73(0.53;1.01)

0.88(0.73;1.05)

0.87(0.66;1.16) 0.595 0.1623 0.3417

GLY1.06(0.77;1.44)

0.92(0.7;1.21)

1.13(0.79;1.61)

1.01(0.85;1.21)

1.01(0.85;1.21) 0 0.8863 0.8863

HIS1.01(0.81;1.26)

0.77(0.57;1.04)

0.78(0.61;0.99)

0.87(0.75;1.01)

0.86(0.71;1.04) 0.403 0.0580 0.1177

ILE1.03(0.77;1.39)

0.79(0.58;1.08)

0.72(0.48;1.08)

0.86(0.71;1.04)

0.86(0.69;1.07) 0.2 0.1319 0.1651

LEU0.99(0.72;1.36)

0.72(0.51;1.01)

0.81(0.55;1.19)

0.84(0.69;1.02)

0.84(0.69;1.02) 0 0.0837 0.0837

PHE0.89(0.65;1.23)

0.67(0.47;0.95)

1(0.69;1.44)

0.84(0.69;1.03)

0.84(0.67;1.06) 0.228 0.0902 0.1361

TYR0.95(0.74;1.22)

0.68(0.52;0.89)

0.73(0.51;1.04)

0.8(0.68;0.94)

0.79(0.64;0.98) 0.426 0.0062 0.0336

VAL0.93(0.68;1.27)

0.64(0.46;0.9)

0.87(0.62;1.23)

0.81(0.67;0.98)

0.81(0.65;1.02) 0.297 0.0315 0.0680


DHA0.85(0.66;1.1)

1.17(0.92;1.48)

0.85(0.61;1.2)

0.97(0.83;1.14)

0.96(0.77;1.2) 0.484 0.7328 0.7223

DHA-FA0.78(0.61;1.01)

1.22(0.94;1.58)

0.91(0.64;1.31)

0.96(0.82;1.13)

0.96(0.72;1.27) 0.65 0.6051 0.7596

FAW30.85(0.67;1.09)

1.18(0.91;1.53)

0.83(0.59;1.18)

0.96(0.82;1.12)

0.95(0.76;1.2) 0.502 0.5921 0.6754

FAW3-FA0.81(0.65;1.01)

1.26(0.97;1.65)

0.9(0.63;1.29)

0.96(0.82;1.12)

0.97(0.73;1.3) 0.69 0.6031 0.8541

FAW60.99(0.78;1.27)

0.87(0.64;1.18)

0.98(0.68;1.4)

0.95(0.8;1.12)

0.95(0.8;1.12) 0 0.5507 0.5507

FAW6-FA0.9(0.71;1.15)

0.94(0.69;1.28)

1.38(0.91;2.08)

0.98(0.83;1.17)

1.01(0.81;1.25) 0.35 0.8584 0.9633

LA 0.98 0.8 1.06 0.93 0.93 0 0.4066 0.4066

STable 9

(0.78;1.23) (0.61;1.07) (0.73;1.53) (0.8;1.1) (0.8;1.1)

LA-FA0.9(0.69;1.17)

0.84(0.62;1.13)

1.42(0.96;2.1)

0.96(0.81;1.15)

0.99(0.75;1.31) 0.588 0.6577 0.9568

MUFA1.15(0.89;1.48)

0.91(0.67;1.22)

0.72(0.5;1.06)

0.96(0.81;1.15)

0.94(0.73;1.21) 0.523 0.6840 0.6195

MUFA-FA1.18(0.93;1.49)

0.88(0.65;1.2)

0.67(0.45;0.99)

0.97(0.82;1.15)

0.91(0.66;1.26) 0.694 0.7596 0.5774

PUFA0.95(0.75;1.22)

0.94(0.7;1.27)

0.95(0.67;1.34)

0.95(0.8;1.12)

0.95(0.8;1.12) 0 0.5278 0.5278

PUFA-FA0.86(0.68;1.09)

1.05(0.78;1.41)

1.28(0.86;1.91)

0.99(0.83;1.16)

1.01(0.81;1.25) 0.359 0.8598 0.9465

SFA1.11(0.84;1.46)

0.96(0.7;1.33)

0.87(0.61;1.25)

1(0.83;1.2)

1(0.83;1.2) 0 0.9857 0.9857

SFA-FA1.07(0.83;1.38)

1.1(0.81;1.49)

1.11(0.78;1.58)

1.09(0.92;1.29)

1.09(0.92;1.29) 0 0.3301 0.3301

TOTFA1.09(0.84;1.42)

0.94(0.69;1.28)

0.84(0.59;1.2)

0.98(0.82;1.16)

0.98(0.82;1.16) 0 0.7804 0.7804

UNSAT0.8(0.63;1.02)

1.18(0.91;1.52)

1.02(0.72;1.45)

0.97(0.83;1.13)

0.98(0.76;1.26) 0.58 0.6957 0.8727

Fluid Balance

ALB1.11(0.83;1.47)

1.5(1.05;2.15)

0.86(0.63;1.18)

1.1(0.92;1.32)

1.11(0.83;1.5) 0.612 0.3026 0.4736

CREA0.9(0.7;1.14)

0.82(0.6;1.12)

0.66(0.41;1.05)

0.83(0.7;0.99)

0.83(0.7;0.99) 0 0.0428 0.0428


CIT0.91(0.73;1.14)

1(0.74;1.35)

0.85(0.61;1.18)

0.92(0.79;1.08)

0.92(0.79;1.08) 0 0.2989 0.2989

GLC0.89(0.68;1.16)

0.95(0.73;1.25)

1.44(0.9;2.31)

0.98(0.82;1.17)

1(0.8;1.26) 0.363 0.8149 0.9912

GLOL0.96(0.69;1.32)

0.79(0.55;1.13)

0.63(0.48;0.84)

0.77(0.64;0.92)

0.77(0.61;0.99) 0.436 0.0042 0.0404

LAC0.93(0.75;1.17)

0.91(0.65;1.26)

0.83(0.56;1.2)

0.9(0.77;1.07)

0.9(0.77;1.07) 0 0.2403 0.2403

PYR0.94(0.73;1.22)

0.96(0.7;1.3)

1.06(0.75;1.49)

0.98(0.82;1.16)

0.98(0.82;1.16) 0 0.7706 0.7706

Ketone BodiesACACE 1.05 1.37 0.69 1.04 1.01 0.74 0.6611 0.9424

STable 9

(0.81;1.36) (1.01;1.88) (0.48;1) (0.87;1.24) (0.71;1.44)

ACE1.09(0.85;1.41)

0.96(0.74;1.26)

1.05(0.75;1.48)

1.03(0.88;1.22)

1.03(0.88;1.22) 0 0.6835 0.6835

BOHBUT0.88(0.62;1.24)

1.37(1.01;1.86)

0.67(0.47;0.97)

0.98(0.81;1.19)

0.94(0.62;1.43) 0.783 0.8163 0.7812

Inflammation

GP1(0.76;1.31)

0.79(0.59;1.05)

0.7(0.47;1.03)

0.85(0.71;1.01)

0.84(0.69;1.03) 0.217 0.0678 0.0968


HDL-TG1.03(0.81;1.31)

0.99(0.69;1.41)

0.84(0.58;1.2)

0.97(0.82;1.16)

0.97(0.82;1.16) 0 0.7388 0.7388

LDL-TG1.13(0.86;1.47)

1(0.7;1.43)

0.84(0.57;1.22)

1.01(0.84;1.22)

1.01(0.84;1.22) 0 0.8945 0.8945

PC1.01(0.76;1.34)

1.06(0.77;1.45)

0.94(0.66;1.35)

1.01(0.84;1.21)

1.01(0.84;1.21) 0 0.9369 0.9369

SERUM-TG1.11(0.87;1.42)

0.82(0.6;1.11)

0.69(0.47;1.02)

0.92(0.77;1.09)

0.88(0.67;1.16) 0.586 0.3331 0.3731

SM0.9(0.66;1.23)

1.02(0.73;1.42)

0.96(0.68;1.36)

0.96(0.79;1.16)

0.96(0.79;1.16) 0 0.6511 0.6511

TG-PG1.17(0.9;1.53)

0.8(0.6;1.05)

0.73(0.49;1.08)

0.92(0.78;1.1)

0.9(0.67;1.21) 0.651 0.3607 0.4750

TOTCHO0.97(0.72;1.32)

1.04(0.74;1.47)

1.02(0.71;1.46)

1.01(0.83;1.22)

1.01(0.83;1.22) 0 0.9563 0.9563

TOTPG1.04(0.79;1.36)

1.05(0.77;1.44)

1(0.7;1.44)

1.03(0.86;1.24)

1.03(0.86;1.24) 0 0.7178 0.7178

VLDL-TG1.1(0.86;1.4)

0.79(0.59;1.05)

0.7(0.48;1.02)

0.89(0.76;1.06)

0.87(0.66;1.14) 0.599 0.1944 0.2973

Apolipoproteins

APOA10.94(0.75;1.18)

1.13(0.86;1.48)

1.06(0.74;1.53)

1.02(0.87;1.2)

1.02(0.87;1.2) 0 0.7702 0.7702

APOB1.02(0.79;1.33)

0.96(0.71;1.3)

0.81(0.56;1.17)

0.95(0.8;1.13)

0.95(0.8;1.13) 0 0.5655 0.5655

APOB-APOA11.07(0.83;1.37)

0.89(0.65;1.21)

0.79(0.54;1.15)

0.95(0.8;1.13)

0.95(0.8;1.13) 0.005 0.5385 0.5381

Cholesterol

ESTC0.89(0.68;1.17)

1.07(0.79;1.45)

0.9(0.64;1.28)

0.95(0.8;1.13)

0.95(0.8;1.13) 0 0.5583 0.5583

FREEC 0.96 1.07 0.96 1 1 0 0.9702 0.9702

STable 9

(0.74;1.25) (0.79;1.44) (0.67;1.38) (0.84;1.19) (0.84;1.19)

HDL2-C0.94(0.75;1.18)

1.16(0.87;1.54)

1.2(0.82;1.74)

1.05(0.89;1.23)

1.05(0.89;1.23) 0 0.5561 0.5561

HDL3-C0.83(0.64;1.08)

1.02(0.72;1.44)

1.13(0.8;1.62)

0.95(0.79;1.14)

0.95(0.79;1.15) 0.043 0.5980 0.6197

HDL-C0.9(0.71;1.14)

1.14(0.87;1.5)

1.18(0.82;1.71)

1.03(0.88;1.21)

1.03(0.87;1.23) 0.11 0.7218 0.7043

LDL-C0.94(0.73;1.2)

1.02(0.76;1.37)

0.9(0.63;1.28)

0.96(0.81;1.13)

0.96(0.81;1.13) 0 0.5918 0.5918

REMNANT-C0.97(0.73;1.3)

1(0.71;1.39)

0.82(0.57;1.17)

0.94(0.78;1.13)

0.94(0.78;1.13) 0 0.4880 0.4880

SERUM-C0.92(0.7;1.21)

1.07(0.79;1.45)

0.92(0.65;1.3)

0.97(0.81;1.15)

0.97(0.81;1.15) 0 0.7057 0.7057

VLDL-C1.01(0.75;1.36)

0.93(0.67;1.3)

0.75(0.52;1.07)

0.91(0.75;1.1)

0.91(0.75;1.1) 0 0.3075 0.3075


HDL-D0.85(0.65;1.12)

1.23(0.92;1.64)

1.46(1.02;2.09)

1.1(0.93;1.31)

1.13(0.83;1.56) 0.689 0.2768 0.4348

LDL-D1.05(0.81;1.36)

1.3(0.9;1.88)

1.25(0.85;1.81)

1.16(0.96;1.39)

1.16(0.96;1.39) 0 0.1257 0.1257

VLDL-D1.03(0.78;1.36)

0.76(0.58;1)

0.71(0.48;1.06)

0.85(0.71;1.01)

0.84(0.67;1.06) 0.384 0.0647 0.1367


IDL-C0.91(0.7;1.19)

1.07(0.77;1.47)

0.93(0.65;1.33)

0.96(0.81;1.15)

0.96(0.81;1.15) 0 0.6696 0.6696

IDL-C-%0.88(0.71;1.09)

1.1(0.78;1.53)

1.02(0.68;1.54)

0.95(0.81;1.12)

0.95(0.81;1.12) 0 0.5575 0.5575

IDL-CE0.91(0.69;1.18)

1.07(0.77;1.47)

0.92(0.64;1.32)

0.96(0.8;1.14)

0.96(0.8;1.14) 0 0.6224 0.6224

IDL-CE-%0.88(0.7;1.09)

1.09(0.79;1.51)

0.98(0.67;1.45)

0.95(0.8;1.12)

0.95(0.8;1.12) 0 0.5122 0.5122

IDL-FC0.94(0.73;1.22)

1.06(0.77;1.47)

0.95(0.66;1.35)

0.98(0.82;1.16)

0.98(0.82;1.16) 0 0.7935 0.7935

IDL-FC-%0.89(0.68;1.17)

1.15(0.89;1.49)

1.16(0.75;1.79)

1.04(0.88;1.23)

1.04(0.87;1.25) 0.075 0.6466 0.6576

IDL-L0.97(0.74;1.27)

1.05(0.76;1.45)

0.92(0.64;1.31)

0.98(0.82;1.17)

0.98(0.82;1.17) 0 0.8227 0.8227

STable 9

IDL-P0.99(0.75;1.29)

1.04(0.75;1.44)

0.91(0.63;1.3)

0.98(0.82;1.18)

0.98(0.82;1.18) 0 0.8450 0.8450

IDL-PL0.97(0.75;1.26)

1.06(0.77;1.45)

0.92(0.65;1.32)

0.99(0.83;1.17)

0.99(0.83;1.17) 0 0.8692 0.8692

IDL-PL-%0.98(0.7;1.35)

1.04(0.74;1.47)

1.09(0.75;1.61)

1.03(0.84;1.26)

1.03(0.84;1.26) 0 0.7728 0.7728

IDL-TG1.13(0.87;1.48)

0.97(0.68;1.38)

0.82(0.56;1.2)

1.01(0.83;1.21)

1.01(0.83;1.21) 0 0.9607 0.9607

IDL-TG-%1.14(0.91;1.43)

0.94(0.69;1.28)

0.87(0.58;1.28)

1.03(0.87;1.21)

1.03(0.87;1.21) 0 0.7660 0.7660

L-HDL-C0.91(0.71;1.17)

1.15(0.87;1.52)

1.38(0.94;2.03)

1.07(0.91;1.27)

1.09(0.87;1.37) 0.428 0.4219 0.4415

L-HDL-C-%1.11(0.87;1.42)

1.21(0.89;1.66)

1.53(1.01;2.32)

1.21(1.02;1.44)

1.21(1.02;1.44) 0 0.0331 0.0331

L-HDL-CE0.91(0.71;1.17)

1.15(0.87;1.52)

1.37(0.94;2.02)

1.07(0.91;1.27)

1.09(0.87;1.37) 0.415 0.4103 0.4333

L-HDL-CE-%1.15(0.9;1.47)

1.2(0.87;1.65)

1.45(0.97;2.16)

1.22(1.02;1.45)

1.22(1.02;1.45) 0 0.0280 0.0280

L-HDL-FC0.9(0.71;1.16)

1.16(0.87;1.54)

1.39(0.94;2.06)

1.07(0.9;1.26)

1.09(0.86;1.39) 0.473 0.4610 0.4615

L-HDL-FC-%1(0.8;1.25)

1.23(0.89;1.72)

1.53(0.98;2.4)

1.13(0.95;1.34)

1.17(0.92;1.47) 0.369 0.1705 0.1927

L-HDL-L0.88(0.69;1.13)

1.15(0.87;1.51)

1.34(0.91;1.98)

1.05(0.89;1.24)

1.08(0.85;1.36) 0.476 0.5512 0.5445

L-HDL-P0.88(0.68;1.13)

1.15(0.87;1.52)

1.34(0.91;1.97)

1.05(0.89;1.24)

1.07(0.85;1.37) 0.489 0.5648 0.5552

L-HDL-PL0.88(0.68;1.12)

1.15(0.87;1.52)

1.3(0.88;1.91)

1.04(0.88;1.23)

1.06(0.84;1.34) 0.449 0.6386 0.6066

L-HDL-PL-%0.96(0.74;1.24)

0.89(0.62;1.26)

0.66(0.44;0.98)

0.86(0.72;1.04)

0.86(0.7;1.05) 0.161 0.1162 0.1360

L-HDL-TG0.86(0.68;1.08)

1.07(0.79;1.45)

1.31(0.86;2.02)

0.98(0.83;1.17)

1.01(0.8;1.28) 0.403 0.8491 0.9053

L-HDL-TG-%0.95(0.76;1.19)

0.89(0.64;1.24)

0.99(0.66;1.49)

0.94(0.79;1.12)

0.94(0.79;1.12) 0 0.4844 0.4844

M-HDL-C1.05(0.81;1.36)

1.01(0.72;1.42)

1(0.7;1.42)

1.03(0.86;1.23)

1.03(0.86;1.23) 0 0.7803 0.7803

M-HDL-C-%1.02(0.78;1.35)

0.94(0.64;1.38)

1.24(0.85;1.8)

1.05(0.87;1.28)

1.05(0.87;1.28) 0 0.5837 0.5837

M-HDL-CE1.04(0.8;1.36)

1.01(0.71;1.42)

1.01(0.71;1.44)

1.03(0.86;1.23)

1.03(0.86;1.23) 0 0.7859 0.7859

STable 9

M-HDL-CE-%1.01(0.76;1.33)

0.91(0.61;1.36)

1.27(0.87;1.85)

1.05(0.86;1.27)

1.05(0.86;1.27) 0 0.6479 0.6479

M-HDL-FC1.05(0.82;1.34)

1.02(0.75;1.39)

0.95(0.67;1.35)

1.02(0.86;1.2)

1.02(0.86;1.2) 0 0.8500 0.8500

M-HDL-FC-%1.07(0.86;1.32)

1.1(0.82;1.47)

0.97(0.68;1.39)

1.06(0.9;1.23)

1.06(0.9;1.23) 0 0.4837 0.4837

M-HDL-L1.04(0.81;1.34)

1.02(0.74;1.4)

0.94(0.66;1.34)

1.01(0.85;1.2)

1.01(0.85;1.2) 0 0.8969 0.8969

M-HDL-P1.04(0.81;1.33)

1.02(0.74;1.4)

0.93(0.65;1.33)

1.01(0.85;1.2)

1.01(0.85;1.2) 0 0.9327 0.9327

M-HDL-PL1.01(0.79;1.28)

1.04(0.76;1.41)

0.93(0.65;1.33)

1(0.85;1.18)

1(0.85;1.18) 0 0.9923 0.9923

M-HDL-PL-%0.88(0.66;1.16)

1.32(0.87;1.98)

0.92(0.64;1.33)

0.98(0.8;1.19)

0.99(0.79;1.24) 0.258 0.8180 0.9210

M-HDL-TG0.98(0.8;1.21)

0.85(0.6;1.21)

0.72(0.52;1)

0.89(0.76;1.04)

0.88(0.73;1.05) 0.188 0.1448 0.1618

M-HDL-TG-%0.99(0.78;1.24)

0.83(0.58;1.18)

0.77(0.55;1.06)

0.89(0.75;1.05)

0.89(0.75;1.05) 0 0.1660 0.1660

S-HDL-C0.96(0.75;1.23)

0.91(0.67;1.22)

0.8(0.56;1.13)

0.9(0.76;1.07)

0.9(0.76;1.07) 0 0.2286 0.2286

S-HDL-C-%0.85(0.69;1.06)

0.98(0.71;1.36)

1.06(0.73;1.53)

0.92(0.78;1.08)

0.92(0.78;1.08) 0 0.3070 0.3070

S-HDL-CE0.92(0.72;1.18)

0.91(0.67;1.24)

0.84(0.59;1.2)

0.9(0.76;1.07)

0.9(0.76;1.07) 0 0.2187 0.2187

S-HDL-CE-%0.87(0.7;1.07)

0.96(0.69;1.35)

1.08(0.74;1.57)

0.92(0.79;1.09)

0.92(0.79;1.09) 0 0.3429 0.3429

S-HDL-FC1.06(0.87;1.3)

0.94(0.69;1.28)

0.73(0.52;1.04)

0.96(0.83;1.12)

0.94(0.76;1.15) 0.389 0.6244 0.5389

S-HDL-FC-%1.03(0.84;1.26)

1.08(0.76;1.53)

0.85(0.6;1.21)

1(0.85;1.17)

1(0.85;1.17) 0 0.9806 0.9806

S-HDL-L1.06(0.84;1.34)

0.9(0.67;1.23)

0.71(0.5;1.02)

0.93(0.79;1.1)

0.91(0.73;1.13) 0.404 0.3952 0.4020

S-HDL-P1.07(0.85;1.34)

0.9(0.66;1.22)

0.71(0.49;1.01)

0.93(0.79;1.1)

0.91(0.72;1.14) 0.445 0.3967 0.4017

S-HDL-PL1.11(0.89;1.4)

0.93(0.68;1.29)

0.74(0.52;1.07)

0.98(0.83;1.15)

0.95(0.75;1.2) 0.441 0.8005 0.6614

S-HDL-PL-%1.13(0.91;1.4)

1.06(0.76;1.5)

1.01(0.71;1.44)

1.09(0.93;1.28)

1.09(0.93;1.28) 0 0.3003 0.3003

S-HDL-TG1.08(0.86;1.37)

0.81(0.56;1.17)

0.7(0.49;0.99)

0.92(0.77;1.09)

0.87(0.66;1.15) 0.582 0.3172 0.3417

STable 9

S-HDL-TG-%1.07(0.84;1.37)

0.86(0.59;1.25)

0.79(0.56;1.11)

0.94(0.79;1.12)

0.93(0.77;1.14) 0.161 0.5068 0.4908

XL-HDL-C0.73(0.52;1.02)

1.31(0.92;1.85)

1.36(0.88;2.09)

1.05(0.85;1.29)

1.08(0.71;1.63) 0.733 0.6714 0.7293

XL-HDL-C-%1.19(0.87;1.63)

1.12(0.81;1.55)

0.81(0.51;1.3)

1.08(0.88;1.32)

1.08(0.88;1.32) 0 0.4565 0.4565

XL-HDL-CE0.73(0.52;1.02)

1.29(0.91;1.85)

1.35(0.88;2.09)

1.04(0.84;1.29)

1.07(0.71;1.61) 0.717 0.7061 0.7361

XL-HDL-CE-%1.17(0.85;1.59)

1.03(0.77;1.39)

0.84(0.52;1.37)

1.05(0.86;1.28)

1.05(0.86;1.28) 0 0.6383 0.6383

XL-HDL-FC0.75(0.54;1.03)

1.31(0.94;1.81)

1.37(0.88;2.13)

1.05(0.86;1.29)

1.09(0.73;1.62) 0.733 0.6111 0.6865

XL-HDL-FC-%1.02(0.77;1.35)

1.4(0.95;2.08)

0.88(0.59;1.31)

1.07(0.88;1.3)

1.07(0.84;1.37) 0.3 0.5146 0.5692

XL-HDL-L0.72(0.52;1)

1.26(0.92;1.73)

1.41(0.93;2.14)

1.05(0.86;1.29)

1.07(0.71;1.62) 0.76 0.6094 0.7324

XL-HDL-P0.72(0.52;1)

1.26(0.92;1.72)

1.41(0.93;2.14)

1.05(0.86;1.28)

1.07(0.71;1.62) 0.76 0.6066 0.7333

XL-HDL-PL0.76(0.57;1.01)

1.21(0.9;1.62)

1.47(0.96;2.25)

1.03(0.86;1.24)

1.08(0.74;1.59) 0.751 0.7265 0.6842

XL-HDL-PL-%0.81(0.59;1.12)

0.93(0.7;1.25)

1.38(0.84;2.25)

0.94(0.77;1.15)

0.96(0.74;1.24) 0.362 0.5643 0.7625

XL-HDL-TG0.92(0.71;1.21)

1.08(0.79;1.47)

1.12(0.73;1.73)

1.01(0.84;1.22)

1.01(0.84;1.22) 0 0.9024 0.9024

XL-HDL-TG-%1.19(0.91;1.56)

0.88(0.66;1.16)

0.86(0.59;1.26)

0.99(0.83;1.18)

0.98(0.79;1.22) 0.336 0.8945 0.8633

L-LDL-C0.95(0.74;1.23)

1.04(0.77;1.4)

0.91(0.64;1.3)

0.97(0.82;1.15)

0.97(0.82;1.15) 0 0.7209 0.7209

L-LDL-C-%0.9(0.72;1.13)

0.99(0.73;1.33)

0.99(0.64;1.53)

0.94(0.8;1.11)

0.94(0.8;1.11) 0 0.4574 0.4574

L-LDL-CE0.96(0.75;1.23)

1.03(0.76;1.39)

0.91(0.63;1.3)

0.97(0.82;1.15)

0.97(0.82;1.15) 0 0.7101 0.7101

L-LDL-CE-%0.94(0.74;1.19)

0.98(0.75;1.28)

0.92(0.58;1.45)

0.95(0.8;1.12)

0.95(0.8;1.12) 0 0.5484 0.5484

L-LDL-FC0.93(0.72;1.2)

1.06(0.78;1.44)

0.93(0.65;1.33)

0.97(0.81;1.15)

0.97(0.81;1.15) 0 0.7109 0.7109

L-LDL-FC-%0.86(0.66;1.11)

1.19(0.91;1.56)

1.35(0.87;2.09)

1.05(0.88;1.25)

1.08(0.82;1.41) 0.555 0.5872 0.5863

L-LDL-L0.98(0.75;1.26)

1.03(0.76;1.41)

0.9(0.63;1.29)

0.98(0.82;1.16)

0.98(0.82;1.16) 0 0.7737 0.7737

STable 9

L-LDL-P0.99(0.76;1.28)

1.03(0.75;1.4)

0.9(0.63;1.28)

0.98(0.82;1.16)

0.98(0.82;1.16) 0 0.7991 0.7991

L-LDL-PL0.94(0.73;1.21)

1.04(0.78;1.41)

0.89(0.62;1.26)

0.96(0.81;1.14)

0.96(0.81;1.14) 0 0.6331 0.6331

L-LDL-PL-%0.93(0.72;1.22)

1.03(0.74;1.43)

1(0.68;1.49)

0.98(0.81;1.17)

0.98(0.81;1.17) 0 0.8014 0.8014

L-LDL-TG1.13(0.86;1.5)

1.02(0.72;1.46)

0.86(0.59;1.26)

1.03(0.85;1.24)

1.03(0.85;1.24) 0 0.7807 0.7807

L-LDL-TG-%1.14(0.89;1.45)

1.05(0.75;1.47)

0.95(0.65;1.39)

1.07(0.9;1.28)

1.07(0.9;1.28) 0 0.4493 0.4493

M-LDL-C0.93(0.74;1.19)

1.01(0.75;1.34)

0.89(0.63;1.26)

0.95(0.8;1.11)

0.95(0.8;1.11) 0 0.5117 0.5117

M-LDL-C-%0.86(0.68;1.11)

0.95(0.71;1.26)

0.99(0.66;1.49)

0.91(0.77;1.08)

0.91(0.77;1.08) 0 0.2989 0.2989

M-LDL-CE0.93(0.73;1.17)

1(0.75;1.33)

0.89(0.62;1.28)

0.94(0.8;1.11)

0.94(0.8;1.11) 0 0.4614 0.4614

M-LDL-CE-%0.87(0.68;1.13)

0.93(0.71;1.22)

0.94(0.59;1.51)

0.91(0.76;1.08)

0.91(0.76;1.08) 0 0.2635 0.2635

M-LDL-FC0.97(0.74;1.25)

1.04(0.76;1.41)

0.88(0.62;1.24)

0.96(0.81;1.15)

0.96(0.81;1.15) 0 0.6801 0.6801

M-LDL-FC-%0.99(0.79;1.23)

1.07(0.81;1.41)

1.14(0.79;1.65)

1.04(0.89;1.22)

1.04(0.89;1.22) 0 0.6383 0.6383

M-LDL-L0.98(0.76;1.25)

1.01(0.75;1.35)

0.87(0.61;1.24)

0.96(0.81;1.14)

0.96(0.81;1.14) 0 0.6374 0.6374

M-LDL-P0.99(0.77;1.26)

1(0.74;1.36)

0.87(0.61;1.24)

0.96(0.82;1.14)

0.96(0.82;1.14) 0 0.6708 0.6708

M-LDL-PL1.01(0.78;1.31)

1.02(0.76;1.38)

0.82(0.58;1.17)

0.97(0.82;1.15)

0.97(0.82;1.15) 0 0.7079 0.7079

M-LDL-PL-%1.06(0.85;1.33)

1.05(0.79;1.4)

0.96(0.65;1.43)

1.04(0.89;1.23)

1.04(0.89;1.23) 0 0.6093 0.6093

M-LDL-TG1.12(0.86;1.46)

1(0.69;1.45)

0.86(0.59;1.26)

1.02(0.85;1.23)

1.02(0.85;1.23) 0 0.8381 0.8381

M-LDL-TG-%1.12(0.88;1.43)

1.09(0.75;1.58)

1(0.68;1.45)

1.08(0.9;1.3)

1.08(0.9;1.3) 0 0.3832 0.3832

S-LDL-C0.91(0.72;1.16)

1(0.75;1.34)

0.89(0.63;1.26)

0.93(0.79;1.1)

0.93(0.79;1.1) 0 0.4161 0.4161

S-LDL-C-%0.84(0.68;1.05)

0.95(0.7;1.27)

0.99(0.66;1.47)

0.9(0.76;1.05)

0.9(0.76;1.05) 0 0.1875 0.1875

S-LDL-CE0.9(0.72;1.14)

0.99(0.74;1.33)

0.89(0.62;1.28)

0.93(0.79;1.09)

0.93(0.79;1.09) 0 0.3737 0.3737

STable 9

S-LDL-CE-%0.84(0.67;1.06)

0.94(0.71;1.24)

0.96(0.62;1.51)

0.89(0.76;1.05)

0.89(0.76;1.05) 0 0.1615 0.1615

S-LDL-FC0.97(0.75;1.27)

1.01(0.74;1.38)

0.86(0.61;1.21)

0.95(0.8;1.13)

0.95(0.8;1.13) 0 0.5918 0.5918

S-LDL-FC-%1.05(0.84;1.31)

1.05(0.79;1.4)

1.05(0.72;1.55)

1.05(0.89;1.23)

1.05(0.89;1.23) 0 0.5593 0.5593

S-LDL-L0.96(0.75;1.23)

1(0.74;1.34)

0.87(0.61;1.23)

0.95(0.8;1.12)

0.95(0.8;1.12) 0 0.5521 0.5521

S-LDL-P0.97(0.76;1.24)

1(0.74;1.34)

0.87(0.61;1.23)

0.95(0.81;1.13)

0.95(0.81;1.13) 0 0.5746 0.5746

S-LDL-PL1.03(0.81;1.32)

1.04(0.77;1.39)

0.85(0.6;1.2)

0.99(0.84;1.17)

0.99(0.84;1.17) 0 0.8971 0.8971

S-LDL-PL-%1.12(0.9;1.39)

1.09(0.8;1.49)

1.07(0.74;1.54)

1.1(0.94;1.29)

1.1(0.94;1.29) 0 0.2390 0.2390

S-LDL-TG1.11(0.86;1.42)

0.91(0.63;1.32)

0.74(0.51;1.08)

0.96(0.8;1.15)

0.94(0.74;1.19) 0.354 0.6787 0.6075

S-LDL-TG-%1.12(0.89;1.42)

0.93(0.63;1.37)

0.8(0.53;1.2)

1.01(0.84;1.21)

1(0.83;1.22) 0.102 0.9055 0.9828

L-VLDL-C1.03(0.79;1.32)

0.79(0.58;1.08)

0.73(0.52;1.03)

0.87(0.73;1.03)

0.86(0.7;1.06) 0.328 0.1147 0.1622

L-VLDL-C-%0.71(0.48;1.04)

1.01(0.62;1.64)

1.32(0.95;1.83)

1.02(0.81;1.27)

0.99(0.67;1.46) 0.652 0.8930 0.9576

L-VLDL-CE1.01(0.78;1.3)

0.79(0.57;1.1)

0.73(0.53;1.02)

0.87(0.73;1.03)

0.86(0.7;1.05) 0.26 0.1006 0.1349

L-VLDL-CE-%0.73(0.5;1.06)

1.17(0.73;1.86)

1.31(0.93;1.83)

1.04(0.83;1.3)

1.03(0.71;1.5) 0.632 0.7166 0.8586

L-VLDL-FC1.06(0.82;1.36)

0.78(0.58;1.05)

0.77(0.55;1.07)

0.89(0.75;1.05)

0.88(0.71;1.09) 0.378 0.1583 0.2249

L-VLDL-FC-%0.94(0.71;1.22)

0.76(0.5;1.16)

1(0.69;1.46)

0.91(0.75;1.11)

0.91(0.75;1.11) 0 0.3452 0.3452

L-VLDL-L1.06(0.82;1.38)

0.78(0.59;1.03)

0.7(0.49;1)

0.87(0.73;1.03)

0.85(0.66;1.09) 0.525 0.0955 0.2011

L-VLDL-P1.07(0.82;1.39)

0.78(0.59;1.03)

0.7(0.49;1)

0.87(0.73;1.03)

0.85(0.66;1.09) 0.538 0.0946 0.2073

L-VLDL-PL1.07(0.82;1.39)

0.79(0.59;1.04)

0.69(0.48;1)

0.87(0.74;1.03)

0.85(0.66;1.1) 0.547 0.1138 0.2243

L-VLDL-PL-%1.02(0.77;1.34)

1.17(0.89;1.55)

1.15(0.86;1.53)

1.11(0.94;1.3)

1.11(0.94;1.3) 0 0.2094 0.2094

L-VLDL-TG1.09(0.84;1.43)

0.78(0.59;1.02)

0.71(0.5;1)

0.87(0.74;1.02)

0.85(0.66;1.11) 0.589 0.0948 0.2413

STable 9

L-VLDL-TG-%1.29(0.88;1.89)

0.92(0.57;1.47)

0.78(0.57;1.08)

0.95(0.76;1.18)

0.96(0.71;1.32) 0.483 0.6392 0.8209

M-VLDL-C1.03(0.79;1.35)

0.84(0.63;1.13)

0.73(0.5;1.07)

0.89(0.75;1.06)

0.89(0.73;1.07) 0.171 0.1956 0.2198

M-VLDL-C-%0.87(0.62;1.22)

1.17(0.79;1.74)

1.27(0.91;1.79)

1.08(0.88;1.33)

1.08(0.86;1.37) 0.246 0.4530 0.5060

M-VLDL-CE1(0.76;1.31)

0.89(0.65;1.2)

0.74(0.51;1.08)

0.89(0.75;1.07)

0.89(0.75;1.07) 0 0.2209 0.2209

M-VLDL-CE-%0.83(0.6;1.15)

1.33(0.91;1.92)

1.3(0.91;1.87)

1.1(0.9;1.35)

1.12(0.82;1.52) 0.57 0.3473 0.4828

M-VLDL-FC1.08(0.84;1.39)

0.79(0.59;1.05)

0.73(0.51;1.06)

0.89(0.75;1.06)

0.87(0.69;1.11) 0.495 0.1894 0.2774

M-VLDL-FC-%1.14(0.9;1.45)

0.75(0.53;1.06)

0.84(0.58;1.21)

0.96(0.8;1.14)

0.92(0.7;1.21) 0.555 0.6172 0.5431

M-VLDL-L1.06(0.82;1.37)

0.8(0.61;1.07)

0.72(0.5;1.05)

0.89(0.75;1.05)

0.87(0.69;1.09) 0.427 0.1630 0.2370

M-VLDL-P1.06(0.82;1.37)

0.8(0.61;1.07)

0.72(0.5;1.05)

0.89(0.75;1.05)

0.87(0.69;1.1) 0.431 0.1630 0.2384

M-VLDL-PL1.07(0.83;1.37)

0.8(0.6;1.06)

0.72(0.5;1.05)

0.89(0.75;1.05)

0.87(0.69;1.11) 0.465 0.1790 0.2569

M-VLDL-PL-%1.01(0.76;1.35)

1.1(0.87;1.4)

1.24(0.9;1.72)

1.11(0.94;1.3)

1.11(0.94;1.3) 0 0.2174 0.2174

M-VLDL-TG1.07(0.84;1.38)

0.79(0.59;1.05)

0.73(0.51;1.05)

0.89(0.75;1.05)

0.87(0.69;1.11) 0.5 0.1770 0.2638

M-VLDL-TG-%1.1(0.79;1.54)

0.85(0.58;1.23)

0.8(0.57;1.12)

0.91(0.75;1.11)

0.91(0.75;1.11) 0 0.3600 0.3600

S-VLDL-C0.97(0.72;1.31)

0.89(0.63;1.27)

0.73(0.52;1.04)

0.87(0.72;1.06)

0.87(0.72;1.06) 0 0.1580 0.1580

S-VLDL-C-%0.74(0.54;1.02)

1.34(0.94;1.9)

1.28(0.88;1.86)

1.05(0.86;1.28)

1.07(0.73;1.58) 0.728 0.6548 0.7261

S-VLDL-CE0.92(0.67;1.26)

0.96(0.66;1.38)

0.77(0.55;1.09)

0.88(0.72;1.07)

0.88(0.72;1.07) 0 0.1920 0.1920

S-VLDL-CE-%0.73(0.53;1.01)

1.34(0.95;1.88)

1.3(0.88;1.93)

1.05(0.86;1.28)

1.08(0.72;1.61) 0.75 0.6530 0.7224

S-VLDL-FC1.05(0.81;1.38)

0.82(0.59;1.13)

0.69(0.48;0.98)

0.88(0.73;1.05)

0.86(0.67;1.1) 0.471 0.1495 0.2312

S-VLDL-FC-%1.06(0.79;1.41)

1.05(0.83;1.32)

0.88(0.63;1.22)

1.01(0.86;1.18)

1.01(0.86;1.18) 0 0.9165 0.9165

S-VLDL-L1.07(0.81;1.4)

0.82(0.6;1.13)

0.7(0.48;1)

0.88(0.74;1.06)

0.87(0.68;1.11) 0.468 0.1724 0.2549

STable 9

S-VLDL-P1.07(0.82;1.4)

0.81(0.59;1.11)

0.69(0.48;1)

0.89(0.74;1.06)

0.87(0.67;1.12) 0.499 0.1770 0.2648

S-VLDL-PL1.09(0.84;1.41)

0.81(0.59;1.12)

0.67(0.47;0.96)

0.89(0.74;1.06)

0.86(0.65;1.14) 0.593 0.1898 0.2941

S-VLDL-PL-%1.23(0.92;1.63)

1.12(0.85;1.47)

0.91(0.61;1.37)

1.12(0.93;1.33)

1.12(0.93;1.33) 0 0.2306 0.2306

S-VLDL-TG1.11(0.87;1.41)

0.78(0.57;1.06)

0.7(0.49;1)

0.9(0.76;1.07)

0.86(0.65;1.15) 0.639 0.2232 0.3193

S-VLDL-TG-%1.25(0.93;1.7)

0.73(0.52;1.03)

0.8(0.57;1.13)

0.93(0.77;1.12)

0.91(0.65;1.28) 0.686 0.4274 0.5846

XL-VLDL-C1.01(0.77;1.32)

0.82(0.58;1.17)

0.8(0.58;1.12)

0.89(0.75;1.07)

0.89(0.75;1.07) 0 0.2194 0.2194

XL-VLDL-C-%0.95(0.66;1.39)

1.09(0.73;1.61)

1.32(0.97;1.81)

1.14(0.93;1.4)

1.14(0.93;1.4) 0 0.2178 0.2178

XL-VLDL-CE1(0.77;1.31)

0.8(0.57;1.14)

0.9(0.68;1.18)

0.91(0.77;1.08)

0.91(0.77;1.08) 0 0.2980 0.2980

XL-VLDL-CE-%0.87(0.61;1.23)

1.03(0.71;1.49)

1.36(0.94;1.96)

1.06(0.86;1.3)

1.06(0.82;1.37) 0.321 0.5995 0.6501

XL-VLDL-FC1.02(0.78;1.33)

0.84(0.59;1.2)

0.77(0.55;1.09)

0.89(0.75;1.07)

0.89(0.75;1.07) 0 0.2278 0.2278

XL-VLDL-FC-%1.03(0.7;1.51)

1.18(0.79;1.76)

1.2(0.89;1.62)

1.14(0.93;1.4)

1.14(0.93;1.4) 0 0.2038 0.2038

XL-VLDL-L1.03(0.79;1.34)

0.81(0.61;1.08)

0.76(0.54;1.06)

0.88(0.74;1.04)

0.87(0.73;1.05) 0.135 0.1263 0.1475

XL-VLDL-P1.03(0.79;1.34)

0.81(0.61;1.07)

0.76(0.55;1.06)

0.88(0.74;1.04)

0.87(0.73;1.05) 0.165 0.1219 0.1489

XL-VLDL-PL1.02(0.78;1.34)

0.83(0.62;1.12)

0.77(0.55;1.07)

0.89(0.75;1.05)

0.89(0.75;1.05) 0.003 0.1690 0.1695

XL-VLDL-PL-%1.05(0.76;1.46)

1.26(0.91;1.74)

1.1(0.74;1.63)

1.14(0.93;1.39)

1.14(0.93;1.39) 0 0.2054 0.2054

XL-VLDL-TG1.04(0.8;1.36)

0.81(0.62;1.06)

0.84(0.65;1.09)

0.89(0.77;1.04)

0.89(0.77;1.04) 0.007 0.1413 0.1427

XL-VLDL-TG-%1.03(0.71;1.5)

0.86(0.57;1.3)

0.77(0.59;1.02)

0.86(0.7;1.04)

0.86(0.7;1.04) 0 0.1147 0.1147

XS-VLDL-C0.97(0.7;1.33)

1.08(0.73;1.61)

0.85(0.6;1.22)

0.96(0.78;1.17)

0.96(0.78;1.17) 0 0.6706 0.6706

XS-VLDL-C-%0.77(0.57;1.03)

1.49(1;2.24)

1.24(0.79;1.93)

1.02(0.83;1.26)

1.1(0.72;1.69) 0.742 0.8450 0.6622

XS-VLDL-CE0.94(0.67;1.3)

1.17(0.77;1.78)

0.87(0.6;1.24)

0.96(0.78;1.19)

0.96(0.78;1.19) 0 0.7404 0.7404

STable 9

XS-VLDL-CE-%0.75(0.54;1.02)

1.54(1.03;2.3)

1.24(0.81;1.9)

1.04(0.84;1.29)

1.11(0.7;1.74) 0.766 0.6981 0.6590

XS-VLDL-FC1.03(0.78;1.36)

0.96(0.68;1.35)

0.84(0.59;1.18)

0.95(0.79;1.14)

0.95(0.79;1.14) 0 0.5861 0.5861

XS-VLDL-FC-%1.03(0.79;1.34)

0.96(0.75;1.23)

1.03(0.71;1.5)

1(0.85;1.18)

1(0.85;1.18) 0 0.9950 0.9950

XS-VLDL-L1.05(0.78;1.41)

0.98(0.68;1.4)

0.81(0.57;1.17)

0.96(0.79;1.16)

0.96(0.79;1.16) 0 0.6535 0.6535

XS-VLDL-P1.06(0.79;1.42)

0.97(0.68;1.38)

0.8(0.56;1.15)

0.96(0.79;1.16)

0.96(0.79;1.16) 0 0.6399 0.6399

XS-VLDL-PL1.06(0.81;1.37)

0.99(0.71;1.37)

0.86(0.6;1.23)

0.99(0.83;1.18)

0.99(0.83;1.18) 0 0.8756 0.8756

XS-VLDL-PL-%1.08(0.77;1.52)

1.02(0.69;1.51)

1.25(0.84;1.86)

1.11(0.9;1.38)

1.11(0.9;1.38) 0 0.3395 0.3395

XS-VLDL-TG1.12(0.88;1.43)

0.81(0.58;1.15)

0.72(0.49;1.04)

0.93(0.78;1.11)

0.89(0.68;1.18) 0.573 0.4420 0.4299

XS-VLDL-TG-%1.18(0.92;1.5)

0.78(0.58;1.05)

0.73(0.5;1.07)

0.94(0.8;1.11)

0.89(0.65;1.23) 0.691 0.4826 0.4882

XXL-VLDL-C0.99(0.73;1.33)

0.91(0.65;1.27)

0.8(0.55;1.15)

0.91(0.75;1.1)

0.91(0.75;1.1) 0 0.3158 0.3158

XXL-VLDL-C-%0.82(0.6;1.13)

0.88(0.65;1.21)

1.03(0.69;1.56)

0.89(0.73;1.08)

0.89(0.73;1.08) 0 0.2501 0.2501

XXL-VLDL-CE0.95(0.7;1.29)

0.92(0.65;1.32)

0.79(0.55;1.15)

0.9(0.74;1.09)

0.9(0.74;1.09) 0 0.2801 0.2801

XXL-VLDL-CE-%0.81(0.59;1.09)

0.98(0.73;1.32)

1.17(0.79;1.74)

0.95(0.79;1.14)

0.95(0.78;1.16) 0.102 0.5609 0.5988

XXL-VLDL-FC1.04(0.77;1.39)

0.89(0.65;1.2)

0.81(0.57;1.17)

0.92(0.77;1.11)

0.92(0.77;1.11) 0 0.3815 0.3815

XXL-VLDL-FC-%1.11(0.82;1.52)

0.87(0.68;1.1)

0.91(0.62;1.34)

0.94(0.8;1.12)

0.94(0.8;1.12) 0 0.5096 0.5096

XXL-VLDL-L1.02(0.76;1.36)

0.89(0.66;1.21)

0.78(0.53;1.13)

0.91(0.76;1.1)

0.91(0.76;1.1) 0 0.3223 0.3223

XXL-VLDL-P1.02(0.76;1.37)

0.89(0.66;1.21)

0.78(0.53;1.13)

0.91(0.76;1.1)

0.91(0.76;1.1) 0 0.3221 0.3221

XXL-VLDL-PL1.04(0.79;1.39)

0.89(0.66;1.2)

0.8(0.54;1.16)

0.92(0.77;1.11)

0.92(0.77;1.11) 0 0.3977 0.3977

XXL-VLDL-PL-%1.2(0.89;1.62)

0.9(0.72;1.13)

0.91(0.59;1.42)

0.99(0.83;1.17)

0.99(0.82;1.19) 0.141 0.8787 0.9253

XXL-VLDL-TG1.03(0.77;1.37)

0.89(0.66;1.2)

0.77(0.53;1.13)

0.91(0.76;1.1)

0.91(0.76;1.1) 0 0.3271 0.3271

STable 9

XXL-VLDL-TG-%1.13(0.83;1.53)

1.18(0.88;1.59)

1.05(0.73;1.51)

1.13(0.94;1.36)

1.13(0.94;1.36) 0 0.1915 0.1915

STable 10

STable 10. Replication results of the ten preliminary significant metabolites associated with incident dementia in four separate cohorts. HRs and 95% CIs for incident dementia. Adjusted for Model 1. (Model 2 results are presented in Table 2)

Metabolite, lipoprotein lipid

HEALT2000HR(95%CI)

ROTTERDAMHR(95%CI)

ERFHR(95%CI)

FHSHR(95%CI)

CREA 1.19(0.88;1.63)

0.97(0.88;1.08)

0.88(0.62;1.24)

0.98(0.79;1.2)

SFA-FA 1.12 (0.82;1.54)

0.97(0.88;1.07)

1.2(0.66;2.16) NA

ILE 0.92(0.66;1.3)

0.95(0.86;1.05)

0.84(0.55;1.31)

1.09(0.88;1.35)

LEU 0.99(0.72;1.35)

0.88(0.79;0.97)

1.07(0.71;1.61)

0.98(0.78;1.23)

VAL 0.95(0.7;1.29)

0.9(0.81;0.99)

1.08(0.71;1.64)

0.9(0.79;1.22)

L-HDL-CE-% 1.01(0.73;1.39)

1.02(0.92;1.12)

0.99(0.55;1.78) NA

L-HDL-PL-% 1.06(0.78;1.44)

1.02(0.93;1.13)

1.23(0.71;2.12) NA

S-VLDL-C 0.86(0.63;1.19)

0.94(0.86;1.04)

1.09(0.6;2) NA

XL-VLDL-C-% 0.82 (0.62;1.08)

1.02(0.93;1.12)

0.57(0.24;1.34) NA

XL-VLDL-TG-% 1.15(0.86;1.54)

0.99(0.89;1.08)

0.76(0.37;1.54) NA

STable 11

STable 11. Replication results of the ten preliminary significant metabolites associated with incident dementia in four separate cohorts. HRs and 95% CIs for incident AD. Adjusted for Model 1


HEALT2000HR(95%CI)

ROTTERDAMHR(95%CI)

ERFHR(95%CI)

FHSHR(95%CI)

CREA 1.21(0.87;1.69)

0.95(0.85;1.08)

0.89(0.59;1.35)

0.99(0.77;1.25)

SFA-FA 1.07(0.76;1.5)

0.98(0.87;1.09)

1.32(0.68;2.58) NA

ILE 1.1(0.76;1.58)

0.94(0.84;1.06)

0.89(0.52;1.51)

1.07(0.83;1.36)

LEU 1.13(0.81;1.57)

0.9(0.8;1.02)

1.05(0.64;1.72)

0.95(0.73;1.24)

VAL 1.08(0.78;1.48)

0.92(0.82;1.03)

1.08(0.66;1.78)

0.93(0.72;1.2)

L-HDL-CE-% 0.96(0.68;1.37)

1.07(0.96;1.2)

0.66(0.33;1.32) NA

L-HDL-PL-% 1.12(0.8;1.56)

0.98(0.88;1.1)

1.41(0.72;2.77) NA

S-VLDL-C 0.91(0.64;1.3)

0.97(0.87;1.08)

1.04(0.51;2.13) NA

XL-VLDL-C-% 0.75(0.56;1.01)

1.05(0.94;1.18)

0.67(0.26;1.73) NA

XL-VLDL-TG-% 1.23(0.9;1.69)

0.99(0.88;1.11)

0.56(0.25;1.29) NA

STable 12

STable 12. Replication results of the ten preliminary significant metabolites associated with incident dementia in four separate cohorts. HRs and 95% CIs for incident AD. Adjusted for Model 2.


HEALT2000HR(95%CI)

ROTTERDAMHR(95%CI)

ERFHR(95%CI)

FHSHR(95%CI)

CREA 1.21(0.86;1.7)

0.94(0.81;1.08)

0.83(0.54;1.26)

0.97(0.75;1.25)

SFA-FA 1.05(0.74;1.49)

0.94(0.83;1.07)

1.3(0.62;2.76) NA

ILE 1.03(0.7;1.52)

0.87(0.76;1)

0.71(0.41;1.21)

1.04(0.8;1.34)

LEU 1.08(0.76;1.52)

0.85(0.74;0.98)

0.92(0.56;1.51)

0.93(0.71;1.22)

VAL 1.05(0.76;1.47)

0.86(0.75;0.98)

0.85(0.51;1.41)

0.93(0.72;1.2)

L-HDL-CE-% 0.94(0.66;1.35)

1.1(0.97;1.25)

0.75(0.38;1.48) NA

L-HDL-PL-% 1.15(0.82;1.62)

1.02(0.89;1.15)

1.41(0.76;2.65) NA

S-VLDL-C 0.95(0.67;1.36)

0.94(0.83;1.07)

1.08(0.54;2.16) NA

XL-VLDL-C-% 0.77(0.56;1.06)

1.08(0.95;1.23)

0.78(0.34;1.83) NA

XL-VLDL-TG-% 1.17(0.84;1.64)

0.98(0.86;1.12)

0.63(0.3;1.35) NA

STable13

STable 13. Results of the ten preliminary significant metabolites associated with incident dementia. Discovery and replication cohorts combined. HRs and 95% CIs for incident dementia. Adjusted for Model 1.


FINRISK 97HR(95%CI)

DILGOMHR(95%CI)

WHITEHALLHR(95%CI)

EGCUTHR(95%CI)

HEALT 2000HR(95%CI)

ROTTERDAMHR(95%CI)

ERFHR(95%CI)

FSHHR(95%CI)

FIXED EFFECT, HR95%CI

RANDOM EFFECT, HR95%CI

I2 p.fixed p.random

CREA 0.92(0.75;1.13)

0.81(0.6;1.09)

0.64(0.5;0.81)

0.86(0.59;1.25)

1.19(0.88;1.63)

0.97(0.88;1.08)

0.88(0.62;1.24)

0.98(0.79;1.2)

0.92(0.86;0.99)

0.9(0.8;1.01) 0.501 0.028 0.077

SFA-FA 1.14(0.92;1.42)

1.12(0.84;1.49)

1.25(1.03;1.52)

1.62(1.18;2.21)

1.12(0.82;1.54)

0.97(0.88;1.07)

1.2(0.66;2.16)

NA 1.07(1;1.15)

1.16(1.01;1.33) 0.575 0.064 0.037

ILE 0.92(0.71;1.18)

0.84(0.63;1.13)

0.71(0.58;0.88)

0.64(0.43;0.97)

0.92(0.66;1.3)

0.95(0.86;1.05)

0.84(0.55;1.31)

1.09(0.88;1.35)

0.91(0.85;0.98)

0.88(0.79;0.99) 0.412 0.010 0.031

LEU 0.89(0.68;1.16)

0.75(0.55;1.04)

0.73(0.59;0.89)

0.54(0.34;0.84)

0.99(0.72;1.35)

0.88(0.79;0.97)

1.07(0.71;1.61)

0.98(0.78;1.23)

0.86(0.8;0.93)

0.85(0.77;0.95) 0.346 <0.001 0.004

VAL 0.83(0.64;1.07)

0.7(0.51;0.96)

0.86(0.72;1.04)

0.59(0.41;0.86)

0.95(0.7;1.29)

0.9(0.81;0.99)

1.08(0.71;1.64)

0.98(0.79;1.22)

0.88(0.82;0.94)

0.87(0.8;0.95) 0.191 <0.001 0.002

L-HDL-CE-% 1.05(0.85;1.29)

1.29(0.95;1.76)

1.43(1.15;1.78)

1.35(0.93;1.96)

1.01(0.73;1.39)

1.02(0.92;1.12)

0.99(0.55;1.78)

NA 1.09(1.01;1.17)

1.14(1.01;1.29) 0.452 0.022 0.039

L-HDL-PL-% 0.94(0.75;1.17)

0.81(0.58;1.13)

0.76(0.62;0.93)

0.66(0.44;0.97)

1.06(0.78;1.44)

1.02(0.93;1.13)

1.23(0.71;2.12)

NA 0.95(0.89;1.03)

0.91(0.79;1.04) 0.524 0.208 0.164

S-VLDL-C 1.02(0.79;1.32)

0.84(0.6;1.17)

0.72(0.6;0.86)

0.77(0.54;1.1)

0.86(0.63;1.19)

0.94(0.86;1.04)

1.09(0.6;2)

NA 0.9(0.83;0.96)

0.87(0.78;0.98) 0.339 0.003 0.019

XL-VLDL-C-%

0.92(0.67;1.26)

1.07(0.73;1.57)

1.29(1.08;1.53)

1.34(1.06;1.69)

0.82(0.62;1.08)

1.02(0.93;1.12)

0.57(0.24;1.34)

NA 1.07(0.99;1.14)

1.06(0.91;1.23) 0.606 0.090 0.458

XL-VLDL-TG-%

1.06(0.77;1.46)

0.89(0.6;1.32)

0.79(0.68;0.91)

0.83(0.63;1.09)

1.15(0.86;1.54)

0.99(0.89;1.08)

0.76(0.37;1.54)

NA 0.93(0.87;1)

0.92(0.82;1.04) 0.41 0.048 0.175

STable 14

STable 14. Results of the ten preliminary significant metabolites associated with incident dementia. Discovery and replication cohorts combined. HRs and 95% CIs for incident dementia. Adjusted for Model 2.


FINRISK 97HR(95%CI)

DILGOMHR(95%CI)

WHITEHALLHR(95%CI)

EGCUTHR(95%CI)

HEALT 2000HR(95%CI)

ROTTERDAMHR(95%CI)

ERFHR(95%CI)

FSHHR(95%CI)



I2 p.fixed p.random

CREA 0.92(0.75;1.12)

0.78(0.58;1.05)

0.64(0.5;0.82)

0.85(0.59;1.24)

1.19(0.87;1.63)

0.94(0.84;1.06)

0.82(0.57;1.18)

0.97(0.78;1.2)

0.9(0.83;0.97)

0.88(0.79;0.99) 0.434 0.007 0.034

SFA-FA 1.13(0.9;1.4)

1.13(0.84;1.52)

1.31(1.07;1.6)

1.6(1.17;2.19)

1.08(0.78;1.49)

0.94(0.84;1.04)

1.15(0.61;2.2)

NA 1.07(0.99;1.15)

1.15(0.99;1.35) 0.639 0.106 0.068

ILE 0.9(0.7;1.16)

0.8(0.59;1.08)

0.72(0.58;0.9)

0.64(0.42;0.96)

0.87(0.61;1.25)

0.9(0.8;1.01)

0.66(0.42;1.03)

1.05(0.84;1.3)

0.87(0.8;0.94)

0.85(0.76;0.94) 0.293 <0.001 0.002

LEU 0.86(0.66;1.13)

0.72(0.52;1)

0.75(0.6;0.92)

0.54(0.34;0.84)

0.94(0.69;1.3)

0.84(0.74;0.94)

0.91(0.6;1.37)

0.94(0.75;1.19)

0.83(0.76;0.9)

0.83(0.76;0.9) 0.042 <0.001 <0.001

VAL 0.81(0.62;1.06)

0.64(0.46;0.89)

0.87(0.72;1.06)

0.59(0.4;0.88)

0.93(0.68;1.26)

0.86(0.76;0.96)

0.84(0.55;1.29)

0.96(0.76;1.19)

0.84(0.78;0.91)

0.84(0.77;0.92) 0.073 <0.001 <0.001

L-HDL-CE-% 1.06(0.87;1.3)

1.25(0.91;1.71)

1.4(1.13;1.75)

1.39(0.96;2.02)

0.99(0.71;1.38)

1.04(0.94;1.17)

1.08(0.61;1.91)

NA 1.11(1.03;1.21)

1.14(1.02;1.27) 0.264 0.008 0.017

L-HDL-PL-% 0.94(0.75;1.17)

0.85(0.6;1.19)

0.78(0.63;0.96)

0.65(0.43;0.98)

1.09(0.8;1.49)

1.04(0.94;1.16)

1.25(0.74;2.11)

NA 0.96(0.89;1.04)

0.93(0.81;1.06) 0.486 0.363 0.266

S-VLDL-C 1.01(0.78;1.3)

0.87(0.62;1.23)

0.72(0.59;0.87)

0.76(0.53;1.08)

0.89(0.64;1.23)

0.91(0.82;1.01)

1.08(0.59;1.97)

NA 0.87(0.81;0.94)

0.87(0.79;0.95) 0.147 <0.001 0.003

XL-VLDL-C-%

0.94(0.68;1.29)

1.06(0.72;1.56)

1.28(1.07;1.53)

1.35(1.07;1.71)

0.87(0.65;1.16)

1.07(0.95;1.19)

0.67(0.3;1.49)

NA 1.11(1.02;1.2)

1.1(0.96;1.24) 0.452 0.013 0.165

XL-VLDL-TG-%

1.03(0.75;1.42)

0.88(0.59;1.32)

0.78(0.67;0.91)

0.81(0.62;1.07)

1.06(0.78;1.44)

0.98(0.88;1.1)

0.78(0.4;1.52)

NA 0.91(0.84;0.99)

0.9(0.81;1.01) 0.274 0.019 0.064

STable15

STable 15. Results of the ten preliminary significant metabolites associated with incident dementia. Discovery and replication cohorts combined. HRs and 95%CIs for incident AD. Adjusted for Model 1. EGCUT did not record AD cases separately.


FINRISK 97HR(95%CI)

DILGOMHR(95%CI)

WHITEHALLHR(95%CI)

HEALT 2000HR(95%CI)

ROTTERDAMHR(95%CI)

ERFHR(95%CI)

FSHHR(95%CI)



I2 p.fixed p.random

CREA 0.9(0.7;1.14)

0.82(0.6;1.12)

0.66(0.41;1.05)

1.21(0.86;1.7)

0.94(0.81;1.08)

0.83(0.54;1.26)

0.97(0.75;1.25)

0.94(0.86;1.03)

0.94(0.86;1.03) 0 0.167 0.167

SFA-FA 0.9(0.71;1.15)

0.85(0.62;1.15)

0.64(0.41;1)

1.21(0.87;1.69)

0.95(0.85;1.08)

0.89(0.59;1.35)

0.99(0.77;1.25)

1.01(0.93;1.1)

1.01(0.93;1.1) 0 0.808 0.808

ILE 1.06(0.83;1.37)

1.09(0.81;1.47)

1.02(0.73;1.41)

1.07(0.76;1.5)

0.98(0.87;1.09)

1.32(0.68;2.58)

NA 0.95(0.87;1.03)

0.95(0.87;1.03) 0 0.203 0.203

LEU 1.04(0.78;1.4)

0.83(0.61;1.12)

0.67(0.46;0.98)

1.1(0.76;1.58)

0.94(0.84;1.06)

0.89(0.52;1.51)

1.07(0.83;1.36)

0.91(0.83;1)

0.91(0.83;1) 0 0.043 0.043

VAL 1(0.73;1.35)

0.75(0.54;1.05)

0.74(0.52;1.05)

1.13(0.81;1.57)

0.9(0.8;1.02)

1.05(0.64;1.72)

0.95(0.73;1.24)

0.91(0.83;0.99)

0.91(0.83;0.99) 0 0.035 0.035

L-HDL-CE-% 0.93(0.69;1.26)

0.7(0.5;0.97)

0.8(0.59;1.1)

1.08(0.78;1.48)

0.92(0.82;1.03)

1.08(0.66;1.78)

0.93(0.72;1.2)

1.1(1;1.2)

1.11(0.98;1.25) 0.186 0.048 0.096

L-HDL-PL-% 1.13(0.89;1.44)

1.23(0.9;1.7)

1.53(1.03;2.25)

0.96(0.68;1.37)

1.07(0.96;1.2)

0.66(0.33;1.32)

NA 0.96(0.87;1.05)

0.94(0.81;1.09) 0.387 0.360 0.409

S-VLDL-C 0.96(0.74;1.24)

0.84(0.59;1.2)

0.61(0.41;0.89)

1.12(0.8;1.56)

0.98(0.88;1.1)

1.41(0.72;2.77)

NA 0.94(0.86;1.03)

0.94(0.86;1.03) 0 0.212 0.212

XL-VLDL-C-%

0.98(0.73;1.32)

0.86(0.61;1.21)

0.76(0.54;1.07)

0.91(0.64;1.3)

0.97(0.87;1.08)

1.04(0.51;2.13)

NA 1.03(0.94;1.14)

1.02(0.86;1.2) 0.437 0.472 0.861

XL-VLDL-TG-%

0.94(0.65;1.37)

1.12(0.76;1.65)

1.36(1;1.83)

0.75(0.56;1.01)

1.05(0.94;1.18)

0.67(0.26;1.73)

NA 0.96(0.88;1.06)

0.95(0.82;1.1) 0.352 0.441 0.477

STable16

STable 16. Results of the ten preliminary significant metabolites associated with incident dementia. Discovery and replication cohorts combined. HRs and 95% CIs for incident AD. Adjusted for Model 2. EGCUT did not record AD cases separately.


FINRISK 97HR(95%CI)

DILGOMHR(95%CI)

WHITEHALLHR(95%CI)

HEALT 2000HR(95%CI)

ROTTERDAMHR(95%CI)

ERFHR(95%CI)

FSHHR(95%CI)



I2 p.fixed p.random

CREA 0.9(0.7;1.14)

0.82(0.6;1.12)

0.66(0.41;1.05)

1.21(0.86;1.7)

0.94(0.81;1.08)

0.83(0.54;1.26)

0.97(0.75;1.25)

0.92(0.84;1.01)

0.92(0.84;1.01) 0 0.092 0.092

SFA-FA 1.07(0.83;1.38)

1.1(0.81;1.49)

1.11(0.78;1.58)

1.05(0.74;1.49)

0.94(0.83;1.07)

1.3(0.62;2.76)

NA 1(0.91;1.1)

1(0.91;1.1) 0 0.993 0.993

ILE 1.03(0.77;1.39)

0.79(0.58;1.08)

0.72(0.48;1.08)

1.03(0.7;1.52)

0.87(0.76;1)

0.71(0.41;1.21)

1.04(0.8;1.34)

0.89(0.81;0.98)

0.89(0.81;0.98) 0 0.022 0.022

LEU 0.99(0.72;1.36)

0.72(0.51;1.01)

0.81(0.55;1.19)

1.08(0.76;1.52)

0.85(0.74;0.98)

0.92(0.56;1.51)

0.93(0.71;1.22)

0.88(0.79;0.97)

0.88(0.79;0.97) 0 0.009 0.009

VAL 0.93(0.68;1.27)

0.64(0.46;0.9)

0.87(0.62;1.23)

1.05(0.76;1.47)

0.86(0.75;0.98)

0.85(0.51;1.41)

0.93(0.72;1.2)

0.87(0.79;0.96)

0.87(0.79;0.96) 0 0.004 0.004

L-HDL-CE-% 1.15(0.9;1.47)

1.2(0.87;1.65)

1.45(0.97;2.16)

0.94(0.66;1.35)

1.1(0.97;1.25)

0.75(0.38;1.48)

NA 1.12(1.01;1.23)

1.12(1.01;1.23) 0 0.029 0.029

L-HDL-PL-% 0.96(0.74;1.24)

0.89(0.62;1.26)

0.66(0.44;0.98)

1.15(0.82;1.62)

1.02(0.89;1.15)

1.41(0.76;2.65)

NA 0.99(0.9;1.09)

0.98(0.85;1.12) 0.256 0.813 0.717

S-VLDL-C 0.97(0.72;1.31)

0.89(0.63;1.27)

0.73(0.52;1.04)

0.95(0.67;1.36)

0.94(0.83;1.07)

1.08(0.54;2.16)

NA 0.93(0.84;1.02)

0.93(0.84;1.02) 0 0.127 0.127

XL-VLDL-C-%

0.95(0.66;1.39)

1.09(0.73;1.61)

1.32(0.97;1.81)

0.77(0.56;1.06)

1.08(0.95;1.23)

0.78(0.34;1.83)

NA 1.05(0.95;1.16)

1.03(0.89;1.19) 0.254 0.361 0.658

XL-VLDL-TG-%

1.03(0.71;1.5)

0.86(0.57;1.3)

0.77(0.59;1.02)

1.17(0.84;1.64)

0.98(0.86;1.12)

0.63(0.3;1.35)

NA 0.95(0.86;1.06)

0.95(0.85;1.07) 0.086 0.364 0.373

STable17

STable17. Inter-correlation table of eight preliminary significant metabolites associated with incident dementia. All correlations were statistically significant (p<0.001, Pearson, pairwise deletion).

CREA SFA-FA ILE LEU VALL-HDL-CE-%

L-HDL-PL-%

S-VLDL-C

XL-VLDL-C-%

XL-VLDL-TG-%

CREA 1.00SFA-FA -0.05 1.00ILE 0.35 0.34 1.00LEU 0.30 0.40 0.92 1.00VAL 0.26 0.36 0.82 0.89 1.00L-HDL-CE-% -0.20 0.15 -0.17 -0.09 -0.04 1.00L-HDL-PL-% 0.13 -0.29 -0.04 -0.10 -0.15 -0.84 1.00S-VLDL-C 0.19 0.32 0.62 0.67 0.55 -0.24 -0.10 1.00XL-VLDL-C-% -0.11 0.31 0.07 0.22 0.30 0.39 -0.48 0.39 1.00XL-VLDL-TG-% 0.12 -0.31 -0.07 -0.22 -0.29 -0.35 0.44 -0.41 -0.97 1.00

STable18

STable18. Sensitivity analysis. Results of the ten preliminary significant metabolites associated with incident dementia. Discovery and replication cohorts combined. HRs and 95% CIs for incident dementia. Adjusted for Model 2, body mass index and cholesterol lowering medication.


FINRISK 97HR(95%CI)

DILGOMHR(95%CI)

WHITEHALLHR(95%CI)

EGCUTHR(95%CI)

HEALT 2000HR(95%CI)

ROTTERDAMHR(95%CI)

ERFHR(95%CI)

FSHHR(95%CI)



I2 p.fixed p.random

CREA0.96(0.78;1.18)

0.78(0.58;1.06)

0.63(0.49;0.8)

0.89(0.62;1.29)

1.24(0.91;1.71)

0.96(0.85;1.08)

0.8(0.55;1.15)

0.99(0.8;1.22)

0.91(0.85;0.99)

0.9(0.79;1.02) 0.545 0.023 0.093

SFA-FA1.19(0.95;1.49)

1.13(0.84;1.53)

1.3(1.06;1.58)

1.51(1.09;2.09)

1.07(0.77;1.47)

0.95(0.85;1.05)

1.14(0.59;2.21) NA

1.07(0.99;1.16)

1.15(1;1.33) 0.573 0.085 0.057

ILE1.01(0.77;1.31)

0.8(0.58;1.1)

0.67(0.53;0.84)

0.68(0.45;1.04)

0.92(0.64;1.34)

0.93(0.82;1.05)

0.7(0.43;1.14)

1.09(0.87;1.36)

0.89(0.82;0.97)

0.87(0.76;0.99) 0.470 0.006 0.032

LEU0.97(0.73;1.29)

0.72(0.51;1.01)

0.69(0.55;0.87)

0.57(0.36;0.89)

1.01(0.72;1.41)

0.86(0.76;0.97)

1.01(0.64;1.6)

0.96(0.76;1.22)

0.85(0.78;0.92)

0.84(0.75;0.95) 0.353 <0.001 0.004

VAL0.9(0.69;1.19)

0.63(0.45;0.89)

0.84(0.69;1.02)

0.64(0.43;0.94)

0.99(0.71;1.38)

0.88(0.78;1)

0.97(0.6;1.56)

0.99(0.78;1.24)

0.87(0.8;0.94)

0.87(0.79;0.95) 0.106 <0.001 0.002

L-HDL-CE-%1.01(0.82;1.25)

1.26(0.91;1.75)

1.5(1.19;1.89)

1.29(0.88;1.89)

0.93(0.66;1.3)

1.03(0.92;1.15)

1.18(0.63;2.2)

NA 1.1(1.01;1.19)

1.14(1;1.31) 0.472 0.021 0.058

L-HDL-PL-%0.96(0.77;1.21)

0.85(0.6;1.21)

0.72(0.58;0.9)

0.7(0.46;1.06)

1.2(0.86;1.67)

1.05(0.95;1.18)

1.16(0.64;2.09)

NA 0.97(0.9;1.06)

0.93(0.8;1.08) 0.566 0.500 0.350

S-VLDL-C1.11(0.85;1.44)

0.86(0.6;1.23)

0.68(0.56;0.82)

0.83(0.58;1.18)

0.91(0.66;1.26)

0.92(0.83;1.03)

1.06(0.57;1.98)

NA 0.88(0.82;0.96)

0.88(0.77;1.01) 0.467 0.002 0.060

XL-VLDL-C-%0.89(0.64;1.23)

1.01(0.68;1.51)

1.33(1.11;1.6)

1.3(1.02;1.65)

0.81(0.6;1.09)

1.05(0.94;1.17)

0.81(0.34;1.97)

NA 1.09(1;1.18)

1.07(0.93;1.23) 0.535 0.043 0.363

XL-VLDL-TG-%1.1(0.8;1.52)

0.94(0.62;1.43)

0.77(0.67;0.9)

0.86(0.64;1.14)

1.14(0.83;1.57)

1.01(0.9;1.13)

0.59(0.29;1.23)

NA 0.93(0.86;1.01)

0.93(0.81;1.07) 0.509 0.065 0.284

STable 19

STable19. Sensitivity analysis. Results of the ten preliminary significant metabolites associated with incident dementia. Discovery and replication cohorts combined. HRs and 95% CIs for incident AD . Adjusted for Model 2, body mass index and cholesterol lowering medication.


FINRISK 97HR(95%CI)

DILGOMHR(95%CI)

WHITEHALLHR(95%CI)

HEALT 2000HR(95%CI)

ROTTERDAMHR(95%CI)

ERFHR(95%CI)

FSHHR(95%CI)



I2 p.fixed p.random

CREA 0.95(0.74;1.21)

0.83(0.61;1.13)

0.67(0.42;1.07)

1.27(0.9;1.79)

0.95(0.83;1.1)

0.79(0.52;1.2)

1(0.78;1.29)

0.94(0.86;1.04)

0.94(0.85;1.04) 0.073 0.224 0.246

SFA-FA 1.21(0.89;1.64)

0.8(0.58;1.12)

0.73(0.48;1.11)

1.1(0.74;1.64)

0.89(0.78;1.03)

0.78(0.44;1.4)

1.09(0.83;1.41)

0.94(0.85;1.04)

0.95(0.84;1.07) 0.192 0.210 0.378

ILE 1.09(0.84;1.4)

1.19(0.85;1.68)

1.44(0.95;2.18)

0.89(0.62;1.28)

1.09(0.96;1.24)

0.79(0.38;1.62)

NA 1.09(0.99;1.21)

1.09(0.99;1.21) 0 0.083 0.083

LEU 0.98(0.75;1.29)

0.9(0.63;1.31)

0.66(0.43;1)

1.26(0.88;1.8)

1.03(0.91;1.17)

1.3(0.64;2.63)

NA 1.01(0.91;1.11)

1(0.87;1.14) 0.238 0.888 0.953

VAL 1.17(0.84;1.62)

0.73(0.51;1.04)

0.82(0.55;1.23)

1.16(0.81;1.66)

0.87(0.75;1.01)

1.06(0.62;1.82)

0.95(0.72;1.25)

0.92(0.83;1.02)

0.92(0.83;1.03) 0.053 0.100 0.143

L-HDL-CE-% 1.09(0.8;1.48)

0.89(0.62;1.29)

0.74(0.51;1.06)

0.97(0.68;1.38)

0.96(0.84;1.08)

1.02(0.49;2.11)

NA 0.95(0.86;1.05)

0.95(0.86;1.05) 0 0.300 0.300

L-HDL-PL-% 1.16(0.89;1.51)

1.11(0.82;1.5)

1.12(0.79;1.6)

1.04(0.73;1.47)

0.95(0.84;1.08)

1.25(0.59;2.65)

NA 1.02(0.92;1.12)

1.02(0.92;1.12) 0 0.764 0.764

S-VLDL-C 1.08(0.78;1.48)

0.64(0.45;0.92)

0.89(0.62;1.26)

1.14(0.8;1.61)

0.88(0.77;1.02)

0.99(0.57;1.73)

0.96(0.73;1.26)

0.91(0.82;1)

0.91(0.82;1.02) 0.109 0.060 0.113

XL-VLDL-C-% 0.88(0.59;1.29)

1.03(0.69;1.54)

1.3(0.95;1.79)

0.72(0.52;0.99)

1.06(0.93;1.21)

0.92(0.35;2.44)

NA 1.02(0.92;1.13)

0.99(0.84;1.17) 0.354 0.723 0.937

XL-VLDL-TG-% 1.13(0.77;1.66)

0.92(0.6;1.42)

0.78(0.59;1.03)

1.26(0.89;1.78)

1.01(0.89;1.15)

0.44(0.19;1.04)

NA 0.98(0.89;1.09)

0.97(0.81;1.15) 0.427 0.764 0.700

EGCUT data not available

STable20

Stable20.. Subdistribution Hazard (SDH) results of the ten preliminary significant metabolites associated with incident dementia in Cox regression model. Discovery and replication cohorts combined. SDHs and 95% CIs for incident dementia. Adjusted for Model 2 and body mass index.


FINRISK 97SDH(95%CI)

DILGOMSDH(95%CI)

WHITEHALLSDH(95%CI)

EGCUTSDH(95%CI)

HEALT 2000SDH(95%CI)

ROTTERDAMSDH(95%CI)

ERFSDH(95%CI)

FSHSDH(95%CI)

FIXED EFFECT, SDH95%CI

RANDOM EFFECT, SDH95%CI

I2 p.fixed p.random

CREA0.96(0.78;1.18)

0.81(0.59;1.1)

0.62(0.47;0.83)

0.91(0.61;1.35)

1.14(0.81;1.6)

0.94(0.83;1.05)

0.77(0.51;1.16)

0.95(0.15;6.09)

0.9(0.83;0.98)

0.88(0.78;1) 0.285 0.016 0.040

SFA-FA1.18(0.94;1.48)

1.11(0.77;1.59)

1.26(1.06;1.5)

1.44(0.98;2.14)

1.04(0.78;1.38)

0.92(0.83;1.02)

1.28(0.75;2.17)

NA 1.04(0.97;1.13)

1.12(0.97;1.3) 0.583 0.264 0.1106

ILE1(0.77;1.3)

0.82(0.56;1.19)

0.66(0.51;0.84)

0.72(0.44;1.18)

0.94(0.64;1.38)

0.92(0.82;1.04)

0.64(0.4;1.02)

1.07(0.13;8.65)

0.87(0.79;0.95)

0.84(0.74;0.96) 0.257 0.002 0.008

LEU0.95(0.71;1.28)

0.73(0.48;1.11)

0.68(0.53;0.88)

0.56(0.31;0.99)

1.02(0.75;1.38)

0.88(0.77;1)

0.98(0.63;1.54)

1.01(0.14;7.4)

0.85(0.78;0.94)

0.85(0.76;0.95) 0.125 0.001 0.004

VAL0.89(0.68;1.17)

0.65(0.46;0.92)

0.83(0.68;1.02)

0.65(0.41;1.04)

0.98(0.69;1.4)

0.91(0.8;1.03)

1.02(0.63;1.65)

1.03(0.14;7.78)

0.87(0.79;0.95)

0.87(0.79;0.95) 0 0.002 0.002

L-HDL-CE-%1.03(0.8;1.32)

1.24(0.87;1.77)

1.52(1.18;1.97)

1.05(0.73;1.49)

0.95(0.69;1.32)

1.05(0.94;1.17)

1(0.55;1.83)

NA 1.09(1;1.19)

1.11(0.99;1.25) 0.289 0.044 0.087

L-HDL-PL-%0.95(0.73;1.23)

0.88(0.59;1.29)

0.71(0.56;0.91)

0.81(0.53;1.24)

1.18(0.86;1.62)

1.06(0.95;1.18)

1.16(0.6;2.24)

NA 0.99(0.91;1.07)

0.95(0.82;1.09) 0.459 0.736 0.446

S-VLDL-C1.11(0.85;1.44)

0.86(0.59;1.27)

0.69(0.57;0.85)

1.15(0.78;1.7)

0.88(0.66;1.17)

0.95(0.85;1.05)

1.22(0.68;2.2)

NA 0.92(0.85;0.99)

0.92(0.8;1.07) 0.517 0.035 0.276

XL-VLDL-C-%

0.89(0.64;1.23)

1.02(0.66;1.57)

1.33(1.09;1.62)

1.33(0.96;1.85)

0.81(0.61;1.07)

1.04(0.93;1.17)

0.7(0.26;1.85)

NA 1.07(0.98;1.16)

1.05(0.9;1.23) 0.525 0.136 0.501

XL-VLDL-TG-%

1.1(0.79;1.52)

0.93(0.59;1.47)

0.77(0.67;0.89)

0.87(0.57;1.32)

1.17(0.88;1.54)

1.01(0.9;1.14)

0.67(0.31;1.44)

NA 0.93(0.86;1.01)

0.94(0.81;1.09) 0.551 0.073 0.440

STable21

Stable21. Subdistribution Hazard (SDH) results of the ten preliminary significant metabolites associated with incident dementia in Cox regression model. Discovery and replication cohorts combined. SDHs and 95% CIs for incident AD. Adjusted for model 2 and body mass index.


FINRISK 97HR(95%CI)

DILGOMHR(95%CI)

WHITEHALLHR(95%CI)

HEALT 2000HR(95%CI)

ROTTERDAMHR(95%CI)

ERFHR(95%CI)

FSHHR(95%CI)



I2 p.fixed p.random

CREA0.94(0.74;1.2)

0.85(0.62;1.17)

0.67(0.34;1.29)

1.17(0.8;1.72)

0.93(0.82;1.07)

0.76(0.45;1.28)

0.96(0.76;1.21)

0.93(0.85;1.02)

0.93(0.85;1.02) 0 0.135 0.135

SFA-FA1.14(0.86;1.51)

1.08(0.74;1.58)

1.12(0.79;1.57)

0.96(0.69;1.33)

0.93(0.83;1.04)

1.34(0.75;2.38) NA

0.98(0.89;1.08)

0.98(0.89;1.08) 0 0.700 0.700

ILE1.21(0.9;1.63)

0.83(0.56;1.22)

0.73(0.45;1.18)

1.16(0.79;1.71)

0.89(0.78;1.02)

0.68(0.36;1.3)

1.07(0.83;1.37)

0.95(0.86;1.05)

0.96(0.84;1.1) 0.248 0.293 0.556

LEU1.15(0.82;1.6)

0.75(0.48;1.17)

0.82(0.5;1.33)

1.21(0.87;1.68)

0.9(0.78;1.04)

1(0.54;1.86)

1(0.79;1.27)

0.95(0.86;1.06)

0.95(0.86;1.06) 0 0.367 0.367

VAL1.07(0.79;1.47)

0.67(0.47;0.96)

0.89(0.6;1.31)

1.14(0.78;1.68)

0.91(0.79;1.05)

1.05(0.56;1.99)

1.01(0.78;1.3)

0.94(0.85;1.04)

0.94(0.85;1.04) 0 0.198 0.198

L-HDL-CE-%1.13(0.82;1.57)

1.17(0.81;1.7)

1.44(0.93;2.25)

0.9(0.63;1.29)

1.11(0.97;1.26)

0.65(0.33;1.28)

NA 1.1(0.99;1.22)

1.1(0.98;1.23) 0.024 0.078 0.096

L-HDL-PL-%0.95(0.69;1.3)

0.93(0.61;1.41)

0.66(0.42;1.03)

1.25(0.88;1.77)

1.03(0.91;1.17)

1.4(0.55;3.61)

NA 1.01(0.91;1.12)

1(0.88;1.15) 0.157 0.799 0.968

S-VLDL-C1.08(0.79;1.48)

0.89(0.6;1.34)

0.74(0.52;1.04)

0.99(0.72;1.35)

0.98(0.87;1.1)

1.22(0.6;2.5)

NA 0.97(0.88;1.06)

0.97(0.88;1.06) 0 0.483 0.483

XL-VLDL-C-%

0.88(0.56;1.36)

1.03(0.66;1.61)

1.31(0.95;1.79)

0.72(0.54;0.94)

1.04(0.91;1.19)

0.85(0.28;2.64)

NA 1(0.89;1.11)

0.98(0.81;1.17) 0.445 0.948 0.788

XL-VLDL-TG-%

1.13(0.73;1.76)

0.91(0.57;1.47)

0.78(0.61;0.98)

1.29(0.97;1.73)

1.02(0.89;1.17)

0.46(0.22;1)

NA 0.99(0.89;1.09)

0.96(0.79;1.17) 0.576 0.785 0.707

EGCUT data not available

SFig 1

Supplements – Figures

SFig1. Correlation plots of BCAAs determined by NMR (Brainshake Ltd) and LC-MS (Biocrates

p180). A subset of 2638 serum samples from FINRISK 1997.

SFig 2SFig2. Forest plot of ten discovered metabolites. Black dots indicate cohort specific hazard ratios (HR) and 95% confidence intervals (95%CI) for incident dementia. Blue dots indicate meta-analysis results based on discovery cohort (FINRISK 1997, DILGOM, Whitehall II and EGCUT). Yellow dots indicate meta-analysis based on all cohorts. Fixed effect results are presented except for SFA-FA (I2>0.5). Results are adjusted for Model 2. All metabolites were not available for the FHS cohort (see Methods).

SFig 3SFig3. Forest plot of ten discovered metabolites. Black dots indicate cohort specific hazard ratios (HR) and 95% confidence intervals (95%CI) for incident Alzheimer’s disease. Yellow dots indicate meta-analysis based on all cohorts. Fixed effect results are presented. Results are adjusted for Model 2. All metabolites were not available for the FHS cohort (see Methods).

supplements – methods - surveys · web viewrecord linkage until 3ist of march 2015, using...

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