Understanding & Diagnosing Dementia

By Kimmer Collison-Ris

MSN, FNP-BC, WOCN, MS CAM

DEMENTIA DEFINED

“The term dementia is used to define a heterogeneous group of progressive and degenerative brain pathologies, clinically characterized by deterioration in memory, learning, orientation, language, comprehension, and judgment.”

Risk FactorsAbstract• Background: Late-life depression may increase the risk of incident dementia, in

particular of Alzheimer’s disease and vascular dementia.• Aims: To conduct a systematic review and meta-analysis to evaluate the risk of

incident all-cause dementia, Alzheimer’s disease and vascular dementia in individuals with late-life depression in population-based prospective studies.

• Method: A total of 23 studies were included in the meta-analysis. We used the generic inverse variance method with a random-effects model to calculate the pooled risk of dementia, Alzheimer’s disease and vascular dementia in older adults with late-life depression.

• Results: Late-life depression was associated with a significant risk of all-cause dementia (1.85, 95% CI 1.67-2.04, P<0.001), Alzheimer’s disease (1.65, 95% CI 1.42-1.92, P<0.001) and vascular dementia (2.52, 95% CI 1.77-3.59, P<0.001). Subgroup analysis, based on five studies, showed that the risk of vascular dementia was significantly higher than for Alzheimer’s disease (P = 0.03).

• Conclusions: Late-life depression is associated with an increased risk for all-cause dementia, vascular dementia and Alzheimer’s disease. The present results suggest that it will be valuable to design clinical trials to investigate the effect of late-life depression prevention on risk of dementia, in particular vascular dementia and Alzheimer’s disease.

• Breno S. Diniz, Meryl A. Butters, Steven M. Albert, Mary Amanda Dew, Charles F. Reynolds (2013). Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies. The British Journal of Psychiatry May 2013, 202 (5) 329-335; DOI: 10.1192/bjp.bp.112.118307

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Causes of Dementia• Chronic infections

• Drugs & toxin buildup

• Degenerative

• Endocrine & Metabolic disturbances

• Psychiatric

• Trauma & diffuse brain damage

• Vitamin Deficiencies

• Miscellaneous

Dementia TypesType Description

Cortical Dementia Brain damage mainly impacts the brain’s cortex (outer layer). Tends to cause problems w/language, memory, social behavior, and thinking.

Subcortical Dementia Impacts parts of the brain below the cortex. It causes changes in emotions and movements as well as problems with memory.

Progressive Dementia Dementia that worsens over time, slowly interfering with increasing cognitive impairments and abilities.

Primary Dementia Dementia from Alzheimer’s that is not caused by any other disease.

Secondary Dementia Occurs as a result of physical disease or injury.

Dementia TypesAbstract• Recent neuropathologic autopsy studies found that 15 to 25% of elderly demented patients have

Lewy bodies (LB) in their brainstem and cortex, and in hospital series this may constitute the most common pathologic subgroup after pure Alzheimer's disease (AD).The Consortium on Dementia with Lewy bodies met to establish consensus guidelines for the clinical diagnosis of dementia with Lewy bodies (DLB) and to establish a common framework for the assessment and characterization of pathologic lesions at autopsy. The importance of accurate antemortem diagnosis of DLB includes a characteristic and often rapidly progressive clinical syndrome, a need for particular caution with neuroleptic medication, and the possibility that DLB patients may be particularly responsive to cholinesterase inhibitors. We identified progressive disabling mental impairment progressing to dementia as the central feature of DLB. Attentional impairments and disproportionate problem solving and visuospatial difficulties are often early and prominent. Fluctuation in cognitive function, persistent well-formed visual hallucinations, and spontaneous motor features of parkinsonism are core features with diagnostic significance in discriminating DLB from AD and other dementias. Appropriate clinical methods for eliciting these key symptoms are described. Brainstem or cortical LB are the only features considered essential for a pathologic diagnosis of DLB, although Lewy-related neurites, Alzheimer pathology, and spongiform change may also be seen. We identified optimal staining methods for each of these and devised a protocol for the evaluation of cortical LB frequency based on a brain sampling procedure consistent with CERAD. This allows cases to be classified into brainstem predominant, limbic (transitional), and neocortical subtypes, using a simple scoring system based on the relative distribution of semiquantitative LB counts. Alzheimer pathology is also frequently present in DLB, usually as diffuse or neuritic plaques, neocortical neurofibrillary tangles being much less common. The precise nosological relationship between DLB and AD remains uncertain, as does that between DLB and patients with Parkinson's disease who subsequently develop neuropsychiatric features. Finally, we recommend procedures for the selective sampling and storage of frozen tissue for a variety of neurochemical assays, which together with developments in molecular genetics, should assist future refinements of diagnosis and classification.

Assessing for DementiaAbstract• Article abstract-The Neuropsychiatric Inventory (NPI) was developed to assess

psychopathology in dementia patients. It evaluates 12 neuropsychiatric disturbances common in dementia: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, night-time behavior disturbances, and appetite and eating abnormalities. The severity and frequency of each neuropsychiatric symptom are rated on the basis of scripted questions administered to the patient's caregiver. The NPI also assesses the amount of caregiver distress engendered by each of the neuropsychiatric disorders. A total NPI score and a total caregiver distress score are calculated, in addition to the scores for the individual symptom domains. Content validity, concurrent validity, inter-rater reliability, and test-retest reliability of the NPI are established. Different neurologic disorders have characteristic neuropsychiatric manifestations and distinctive NPI profiles. The NPI is sensitive to treatment effects and has demonstrated the amelioration of behavioral symptoms in Alzheimer's disease by cholinergic agents. The NPI is a useful instrument for characterizing the psychopathology of dementia syndromes, investigating the neurobiology of brain disorders with neuropsychiatric manifestations, distinguishing among different dementia syndromes, and assessing the efficacy of treatment.

• Jeffrey L. Cummings (1997). The Neuropsychiatric Inventory. Neurology May 1997, 48 (5 Suppl 6) 10S-16S; DOI: 10.1212/WNL.48.5_Suppl_6.10S. Retrieved from http://n.neurology.org/content/48/5_Suppl_6/10S.short.

Dementia Comparisons

Neurobiology of DementiasAbstract: • Purpose of review Neuropsychiatric disturbances in dementia are prevalent, and research is

uncovering their neurobiological correlates.• Recent findings Late-onset depression appears to be associated with Alzheimer's disease

pathology at autopsy, and lifetime depression episodes may worsen Alzheimer's disease pathology in the hippocampus. Vascular disease and elevated homocysteine increase risk for both late-onset depression and Alzheimer's disease and may partly mediate their relationship. Monoamine changes are robust finding in Alzheimer's disease and may account for many observed depression symptoms. Risk of psychosis of Alzheimer's disease appears to be increased by several genes also implicated in schizophrenia (e.g., catechol-O-methyltransferase, neuregulin-1). Psychosis in dementia with Lewy bodies appears to be related to cholinergic deficits. Alzheimer's disease is associated with changes in the circadian sleep–wake cycles, including decreased night-time melatonin. Sleep apnea may be related to apolipoprotein E genotype and impact cognition in Alzheimer's disease. Rapid eye movement sleep behavior disorder is intricately related to synucleinopathies, such as dementia with Lewy bodies, but synuclein changes may not totally explain this relationship.

• Summary Neuropsychiatric disturbances are a core feature of dementia and worsen many clinical outcomes. Among the most validated syndromes are depression, psychosis, and sleep disturbance of Alzheimer's disease. Neuropathology, neuroimaging, and genetic studies increasingly provide insight into the origins of these psychiatric symptoms in dementia.

• Meeks TW, Ropacki SA, and Jeste DV (2006). The neurobiology of neuropsychiatric syndromes in dementia. Current Opinion in Psychiatry. Nov 2006, Vol 19, Issue 6, pp 581-586. doi: 10.1097/01.yco.0000245746.45384.0e http://journals.lww.com/co-psychiatry/Abstract/2006/11000/The_neurobiology_of_neuropsychiatric_syndromes_in.7.aspx

Dementia

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Vascular DementiaAbstract• Vascular dementia is the most common cause of dementia in the elderly after

Alzheimer's disease. Many forms of vascular dementia have been described: multi-infarct dementia, lacunar dementia, Binswanger's subcortical encephalopathy, cerebral amyloid angiopathy, white matter lesions associated with dementias, single infarct dementia, dementia linked to hypoperfusion and haemorrhagicdementia. The difficulty of diagnosing vascular dementia must not be underestimated and an international consensus is needed for epidemiological studies. The NINCDS-AIREN group has recently published diagnostic criteria. The State of California Alzheimer's Disease Diagnostic and Treatment Centers also proposed some which differ from the NINCDS-AIREN criteria in considering only ischaemic vascular dementia and not other mechanisms such as haemorrhagic or hypoxic lesions. Most studies stress hypertension as the most powerful risk factor for all forms of vascular dementia. The incidence rate ranges from 7 per 1000 person-years in normal volunteers to 16 per 1000 person-years in hypertensive patients. No therapeutic attempt has influenced the course of the disease once the dementing condition is established. The only effective approach is preventive treatment. The objective of the SYST-EUR Vascular Dementia project is to confirm that the treatment of isolated systolic hypertension is able to reduce its incidence.– F. Forette , A-S. Rigaud , M. Morin, M. Gisselbrecht, P. Bert (1995). Assessing vascular

dementia.The Netherlands Journal of Medicine Volume 47, Issue 4, October 1995, Pages 185-194

Early Onset DementiaAbstract• Early-onset familial Alzheimer's disease (EOFAD) is a condition

characterized by early onset dementia (age at onset < 65 years) and a positive family history for dementia. To date, 230 mutations in presenilin(PS1, PS2) and amyloid precursor protein (APP) genes have been identified in EOFAD. The mutations within these three genes (PS1/PS2/APP) affect a common pathogenic pathway in APP synthesis and proteolysis, which lead to excessive production of amyloid β. Compared with sporadic Alzheimer's disease (AD), EOFAD has some distinctive features including early age at onset, positive familial history, a variety of non-cognitive neurological symptoms and signs, and a more aggressive course. There is marked phenotypic heterogeneity among different mutations of EOFAD. Studies in presymptomatic mutation carriers reveal biomarkers abnormalities. EOFAD diagnosis is based on clinical and family history, neurological symptoms and examination, biomarker features, as well as genotyping in some cases. New therapeutic agents targeting amyloid formation may benefit EOFAD individuals.– Wu L, Rosa-Neto P, Hsiung, G-Y R, and Sadovnick AD (2012). Early-Onset

Familial Alzheimer’s Disease (EOFAD). Canadian Journal of Neurological Sciences. Vol 39, Iss445.ue 4, July 2012, pp 436-445.

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Frontotemporal Dementias (FTD)

• Comprises 5-10% diagnosed w/Dementia

• Affects 75% younger individuals ( ages 45-65 years)

• Different forms of FTD– Behavioral: causes changes in personality, social behavior, loss of

insight, and apathy

– Primary progressive aphasia: language impairment initially, eventually other cognitive domains affected

– Motor neuron diseases with FTD component (ALS)

• There are no approved treatments– Meds are used to treat behaviors

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Assessing for Dementia

Abstract• Accurate clinical staging of dementia in older subjects has

not previously been achieved despite the use of such methods as psychometric testing, behavioural rating, and various combinations of simpler psychometric and behavioural evaluations. The Clinical Dementia Rating (CRD), a global rating device, was developed for a prospective study of mild senile dementia--Alzheimer type (SDAT). Reliability, validity, and correlational data are discussed. The CRD was found to distinguish unambiguously among older subjects with a wide range of cognitive function, from healthy to severely impaired.

“Test Your Memory” screen• The Test Your Memory [Brown et al. 2009] test was a

recently developed 10-item cognitive test designed to be self-administered under medical supervision.

• The maximum score is 50; at a score of 30 or below, the test has good specificity and sensitivity [comparable to MMSE and Addenbrookes Cognitive Assessment –Revised (ACE-R)] in distinguishing dementia from nondementia cases [Hancock and Larner, 2011].

• This form of test may be attractive for time-limited clinicians wanting to screen for dementia, especially in primary care.

Mini-Mental State Examination

• The MMSE [Folstein et al. 1975] is by some way the best known and most widely used measure of cognition in clinical practice worldwide. This scale can be easily administered by clinicians or researchers with minimal training, takes around 10 min and assesses cognitive function in the areas of orientation, memory, attention and calculation, language and visual construction. Patients score between 0 and 30 points, and cutoffs of 23/24 have typically been used to show significant cognitive impairment. It is widely translated and used. A standardized version [Molloy et al. 1991] improves its reliability, and is probably most important for research settings. The MMSE is unfortunately sometimes misunderstood as a diagnostic test, when it is in fact a screening test with relatively modest sensitivity. It has floor and ceiling effects and limited sensitivity to change. This in theory should limit its wider use in detecting change in clinical work and in research studies, though in these contexts it is still widely used, and even advocated [NICE, 2006].

Mini-Cog• The Mini-Cog [Borson et al. 2000] is a very short test

(3 min) suitable for primary care screening for dementia. It incorporates the clock-drawing test, adding a three-item delayed word recall task. It showed comparable sensitivity and specificity to the Mini-Mental State Examination (MMSE) in classifying community cases of dementia [Borson et al. 2003].

MoCa-B Assessment Tool

• The MoCA is a helpful screening test for persons who score above the cut-off on the MMSE and for a well-educated person who complains only of memory impairment. The 30-point test can be administered in approximately 10 min, and the test protocols, administration instructions, and normative data are freely available for clinicians on the MoCA website (www.mocatest.org). Cognitive functions tested include attention and working memory, short-term memory recall, visuospatial abilities, language abilities, and executive functions such as divided attention, semantic fluency, and abstraction. Considerations for the MoCAs use in special populations such as with the visually impaired [19] and individuals with low levels of education have also been developed and validated.

– https://www.sciencedirect.com/topics/neuroscience/montreal-cognitive-assessment

Clock drawing Test

• Many versions of the clock-drawing test have been created, with multiple scoring algorithms [Brodatyand Moore, 1997].

• Patients are often asked to draw a clock face with numbers and hands (indicating a dictated time).

• The design is a quick and acceptable screening test for dementia as it is fast, requiring no training and scoring methods are simple. It demonstrates good sensitivity and specificity as a screening test. However, it assesses only a very narrow part of cognitive dysfunction seen in dementia, and many other conditions (e.g. stroke) will affect it directly.

General Practitioner assessment of Cognition

• The General Practitioner assessment of Cognition (GPCOG) [Brodaty et al. 2002] was designed for use in primary care and includes nine direct patient cognitive items, and six informant questions assessing change over several years. In total, it takes about 6 min. It has strong performance on sensitivity and specificity versus MMSE in detecting dementia in a typical primary care population [Ismail et al. 2009].

Neuropsychiatric Inventory

• The Neuropsychiatric Inventory [Cummings et al. 1994] assesses a wide range of behaviours seen in dementia for both frequency and severity. These include delusions, agitation, depression, irritability and apathy. The scale takes 10 min for a clinician to administer to a carer. It has good psychometric properties and is widely used in drug trials, while being short enough (especially with patients without a wide range of behavioural issues) to consider for use in clinical practice.

6-CIT

• The 6-CIT [Brooke and Bullock, 1999] was designed for screening in a primary care setting. It takes 3–4 min to administer, and scoring is between 0 and 28, with cutoffs of 7/8 showing good screening sensitivity and specificity. It is easy to administer, though scoring is less intuitive than AMTS.

The Geriatric Depression Scale

• The Geriatric Depression Scale (GDS) [Yesavage et al. 1983] is the most commonly used assessment of depressed mood among older people, and has been shortened to numerous versions, including a popular 15-item version (GDS-15) [Sheikh and Yesavage, 1986]. GDS-15 is usually self rated though can be rated by an assessor. It is sensitive to change and is reliable in older people in institutional care. It takes about 5–10 min to administer. Its major drawback in dementia is that it has been validated for people with mild dementia, but not for those with moderate to severe dementia (among whom completion rates may be low due to difficulty comprehending questions).

Diagnosing ADAbstract• Alzheimer’s disease (AD) is a chronic neurodegenerative disorder and the most

common cause of dementia. It is one of the principal causes of disability and decreased quality of life among older adults. Progress in our clinical knowledge of AD has led to more reliable diagnostic criteria and accuracy, and research efforts are expanding to uncover the earliest manifestations and even the presymptomatic phases of the disease. The diagnosis of AD is primarily one of inclusion and usually can be made using standardized clinical criteria. There is currently no cure for AD. Current treatment focuses on establishing an early accurate clinical diagnosis, early institution of cholinesterase inhibitors and/or N-methyl-d-aspartate (NMDA) receptor–targeted therapy. Treating medical comorbidities and dementia-related complications, ensuring that appropriate services are provided, addressing the long-term well-being of caregivers, and treating behavioral and psychological symptoms with appropriate nonpharmacologic and pharmacologic interventions also are important. The initiating and propagating pathologic processes and the anatomic location of the earliest changes will become new targets of research and therapeutic development. A possible precursor of AD, mild cognitive impairment (MCI), is under investigation as a possible therapeutic starting point for disease-modifying interventions. This article provides a research update of current understanding in the diagnosis and treatment of AD and in emerging areas of interest such as MCI, detection of AD in the predementia phase, and neuroimaging in AD.– Desai AK and Grossberg GT (2005). Diagnosis and Treatment of Alzheimer’s Disease.

Neurology June 28, 2005, 64; https://doi.org/10.1212/WNL.64.12_suppl_3.S34 .

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Comparing Memory Symptoms

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Pharmacotherapy for Dementia

• Efforts to find effective drug therapy for dementia have frustrated scientists. Many drugs used for dementia are limited by side effects, short duration of action, and the need for frequent monitoring of blood levels or other laboratory values to prevent toxicity.

• https://www.emedicinehealth.com/dementia_medication_overview/article_em.htm

Pharmacotherapy…

• treatment is involves addressing symptoms of dementia, and improving co-occurring behavioral manifestations– Anxiety

– Psychosis

– Depression

– Sleep disturbances

– Mood swings

– Disordered eating behaviors

– and assessing quality of other interventions

Acetylcholinesterase inhibitors • Acetylcholinesterase (AChE) inhibitors are approved by the

United States Food and Drug Administration (FDA) for treatment of Alzheimer disease

• Function: – delay the breakdown of acetylcholine (brain chemical needed required

for nerve cells communication. – Might be useful for mild-to-moderate AD. – Once AChE inhibitors initiated must be used indefinitely.

• Cessation may cause an abrupt, possibly severe, cognitive and behavioral decline which is often unresolved by restarting AChE inhibitor.

• cause for this significant decline with cessation is unknown

– improvement is not dramatic or permanent– may also assist in similar diseases causing dementia (ie. Parkinson

disease)• Tacrine (Cognex)• Donepezil (Aricept)• Galantamine/ galanthamine (Reminyl)• Rivastigmine (Exelon)

N-methyl-D-aspartate• Drugs within the class known as NMDA blockers

– Memantine (Namenda) • FDA approved for the treatment of moderate-to-severe

Alzheimer disease• Once NMDA blockers initiated, an obvious improvement in

basic ADL’s for is observed– can be used in combination with AChE inhibitors – observed effects often modest, but improvements tend to aid

caregivers or family members in their interactions with these individtuals.

• Function: – guard against overexcitement of NMDA receptors by

brain chemical glutamate. • Overexcitement of NMDA receptors by high levels of

glutamate is believed responsible for decreased nerve cell function which invariably results in nerve cell death

Other Rx InterventionsClass Common Meds Purpose Comments

Antipsychotics Haloperidol (Haldol),

risperidone (Risperdal),

olanzapine (Zyprexa),

quetiapine (Seroquel)

Frequently prescribed to help manage psychosis

and agitation. Use is intended to decrease

psychotic symptoms (paranoia, delusions,

hallucinations), screaming, combativeness, and/or

violence.

Antidepressants Depression is often associated with dementia and

tends to worsen the degree of cognitive and

behavioral impairment. Mood enhancement may

play a role in the apparent improvement in

cognition.

Antianxiety Buspirone (Buspar) Prescribed as anxiety is common with dementia benzodiazepines like diazepam (Valium) have

been used to treat anxiety but must be

avoided as they tend to increase agitation in

dementia and cause sedation

Other Selegiline (Eldepryl):

selegiline,

Some studies have reported this med, often used

to treat Parkinsons, may improve behavior,

functional performance, and cognitive function.

Mood enhancement may play a role in the

apparent improvement in cognition.

Antioxidants Vitamin E High doses of vitamin E (1000 units twice daily)

may be beneficial in delaying functional

deterioration in vascular dementia.

Such high doses of vitamin E can cause

bleeding problems in some people. The

addition of vitamin C may enhance the

beneficial effects.

Anti-inflammatory

agents

ibuprofen (Motrin, Advil)

naproxen (Aleve).

Nonsteroidal anti-inflammatory drugs (NSAIDs)

may decrease inflammatory changes that are

common in Alzheimer disease, or they may inhibit

platelets, thereby protecting blood flow in the

brain.

Natural Cognitive Support

Statins & Memory• Abstract• Objective. To review case reports of statin-associated memory loss as well as the available

published evidence for and against such a link.• Methods. We searched the MedWatch drug surveillance system of the Food and Drug

Administration (FDA) from November 1997-February 2002 for reports of statin-associated memory loss. We also reviewed the published literature (using MEDLINE) and prescribing information for these drugs.

• Results. Of the 60 patients identified who had memory loss associated with statins, 36 received simvastatin, 23 atorvastatin, and 1 pravastatin. About 50% of the patients noted cognitive adverse effects within 2 months of therapy. Fourteen (56%) of 25 patients noted improvement when the statin was discontinued. Memory loss recurred in four patients who were rechallenged with the drug. None of the 60 reported cognitive test results. Two placebo-controlled trials found no benefits for statins on cognition or disability. One randomized controlled trial of simvastatin found no effects on cerebrospinal amyloid levels. In one small, randomized study, patients receiving statins showed a trend toward lower cognitive performance than those receiving placebo. Five observational studies found a lower risk of dementia among patients receiving statins.

• Conclusion. Current literature is conflicting with regard to the effects of statins on memory loss. Experimental studies support links between cholesterol intake and amyloid synthesis; observational studies indicate that patients receiving statins have a reduced risk of dementia. However, available prospective studies show no cognitive or antiamyloid benefits for any statin. In addition, case reports raise the possibility that statins, in rare cases, may be associated with cognitive impairment, though causality is not certain.

– Wagstaff LR, Mitton MW, McClendon Arvik B, and Doraisswamy PM (2003). Statin-Associated Memory Loss: Analysis of 60 Case Reports and Review of the Literature. Volume 23, Issue 7, July 2003, Pages 871–880 Pharmacotherapy DOI: 10.1592/phco.23.7.871.32720. Retrieved from http://onlinelibrary.wiley.com/doi/10.1592/phco.23.7.871.32720/full

Statin Case Study #1Abstract• Background: There have been a number of published reports of central nervous

system (CNS) adverse effects with statins.• Case summary: A 79-year-old woman developed paranoia, anxiety, and behavioral

changes ~2.5 weeks after starting atorvastatin 10 mg/d. The patient had no other medication changes at this time. After 2 months of therapy, the patient discontinued atorvastatin, and her symptoms fully resolved after 4 days.

• Conclusions: This is the first case report, to our knowledge, describing paranoia as one of the symptoms associated with statin therapy. Our report suggests an adverse reaction due to the initiation of atorvastatin via the temporal relationship between the start of atorvastatin and symptom onset, as well as termination of therapy and subsequent symptom disappearance. Use of the Naranjo adverse drug reaction probability scale to assess causality revealed a “probable” association (score, 5) for this adverse event. This report emphasizes the possibility of paranoia as a CNS adverse effect due to statin therapy. Statins are frequently used in older populations and should therefore be considered when such CNS adverse effects occur during therapy.

– Peters JT, Garwood CL, and Lepczyk MB (2008). Behavioral changes with paranoia in an elderly woman taking atorvastatin. The American Journal of Geriatric Pharmacotherapy. Volume 6, Issue 1, March 2008, Pages 28-32. http://www.sciencedirect.com/science/article/pii/S1543594608000032

Case Study #2Abstract• Memory loss and cognitive impairment have been reported in the literature in

association with several 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), but we found no published case reports associated with rosuvastatin. To our knowledge, this is the first reported case of rosuvastatin-related short-term memory loss. A 53-year-old Caucasian man with hypercholesterolemia experienced memory loss after being treated with rosuvastatin 10 mg/day. He had no other concomitant conditions or drug therapies. After discontinuation of rosuvastatin, the neuropsychiatric adverse reaction resolved gradually, suggesting a probable drug association. During the following year, the patient remained free from neuropsychiatric disturbances. Clinicians should be aware of possible adverse cognitive reactions during statin therapy, including rosuvastatin.

• Galatti L, Polimeni G, Salvo F, Romani M, Sessa A, and Spina E (2006). Short-Term Memory Loss Associated with Rosuvastatin. Pharmacotherapy. Volume 26, Issue 8 August 2006, Pages 1190–1192. DOI: 10.1592/phco.26.8.1190. Retrieved from http://onlinelibrary.wiley.com/doi/10.1592/phco.26.8.1190/full

Considering Antipsychotics• 1.Assess patients for the type, frequency, severity, pattern, and timing of

symptoms. (1C)• 2.Assess patients for pain and other potentially modifiable contributors to

symptoms as well as for factors such as dementia subtype that may influence choices of treatment. (1C)

• 3.In patients with dementia with agitation or psychosis, assess response to treatment using a quantitative measure. (1C)

• 4.Develop a comprehensive treatment plan that includes appropriate person-centered nonpharmacologic and pharmacologic interventions, as indicated. (1C)

• 5.Only use nonemergency antipsychotic medication when agitation and psychosis symptoms are severe, are dangerous, and/or cause significant distress to the patient. (1B)

• 6.Review the clinical response to nonpharmacologic interventions prior to nonemergency use of an antipsychotic medication to treat agitation or psychosis in patients with dementia. (1C)

• 7.Before starting nonemergency treatment with an antipsychotic, assess and discuss with the patient/family/decision maker the potential risks and benefits. (1C) 8.If a risk/benefit assessment favors the use of an antipsychotic for behavioral/psychological symptoms in patients with dementia, start treatment at a low dose and titrate up to the minimum effective dose as tolerated. (1B)

Considering Antipsychotics…• 9.If a clinically significant side effect of antipsychotic treatment emerges, review the potential risks and

benefits of antipsychotic medication to determine whether tapering and discontinuance of the medication are indicated. (1C)

• 10.If there is no clinically significant response after a 4-week trial of an adequate dose of an antipsychotic drug, the medication should be tapered and withdrawn. (1B)

• 11.In a patient who has shown a positive response to an antipsychotic, decisions about possible tapering of the medication should be made with input from the patient (if feasible) or surrogate decision maker, family, or other caregiver, with the aim of eliciting their preferences and concerns and reviewing the initial goals, observed benefit, and side effects of antipsychotic treatment and potential risks of continued use, as well as past experience with antipsychotic medication trials and tapering attempts. (1C)

• 12.For a patient who has an adequate response of behavioral/psychological symptoms to antipsychotic treatment, an attempt to taper and withdraw the drug should be made within 4 months of initiation unless the patient experienced a recurrence of symptoms with prior attempts at tapering of antipsychotic medication. (1C)

• 13.For a patient whose antipsychotic medication is being tapered, assess symptoms at least monthly during the taper and for at least 4 months after medication discontinuance to identify signs of recurrence and trigger a reassessment of the benefits and risks of antipsychotic treatment. (1C)

• 14.In the absence of delirium, if nonemergency antipsychotic medication treatment is indicated, haloperidol should not be used as a first-line agent. (1B)

• 15.A long-acting injectable antipsychotic medication should not be utilized unless it is otherwise indicated for a co-occurring chronic psychotic disorder. (1B)

• https://www.medscape.com/viewarticle/862795

Dementia & Communication• Ten Tips

– Set a positive mood for interaction

– Get the person’s attention

– State your message clearly

– Ask simple, answerable questions

– Listen with your eyes, ears, and heart

– Break down activities into a series of steps

– When the going gets tough, distract & redirect

– Respond with affection and reassurance

– Remember the good old days

– Maintain your sense of humor

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Handling troubling Behavior• Challenges of caring for dementia are personality and

behavior changes

• meet these by using creativity, flexibility, patience & compassion.

• helps to not take things personally

• Remember:– cannot change the person

– Check with the health provider: behavioral problems have an underlying medical reason

– Behavior has a purpose

– Behavior is triggered.

– What works today, may not tomorrow

– Get support from others

Early Onset Dementia (EOD)Abstract

• Dementia is characterized by a decline in cognitive faculties and occurrence of behavioral abnormalities which interfere with an individual's activities of daily living. Dementing disorders usually affect elderly individuals but may occur in individuals younger than 65 years (early-onset dementia or EOD). EOD is often misdiagnosed or its diagnosis is delayed due to the fact that it has a more varied differential diagnosis than late-onset dementia. EOD affects individuals at the height of their career and productivity and produces devastating consequences and financial loss for the patient's family as well as society. EOD is not uncommon and is diagnosed in up to a third of patients presenting with dementia. Most importantly, some of the causes of EOD are curable which makes the need for a specific and timely diagnosis crucial. The present chapter presents a systematic approach to the differential diagnosis of EOD and provides readers with the clinical and neuroimaging features of these disorders as well as important considerations for their diagnostic evaluation. Specifically, the nuances of assessing the history and examination are discussed with careful attention to the various methods of cognitive and behavioral evaluation. A step-wise approach to diagnostic testing is followed by a discussion of anatomical localization, which often aids in identifying specific etiologies. Finally, in order to organize the subject for the reader, the various etiologies are grouped under the general categories of vascular, infectious, toxic-metabolic, immune-mediated, neoplastic/metastatic, and neurodegenerative. International Review of Neurobiology– Fadil, H and Minagar, A, et al (2009). Early Onset Dementia. International Review of Neurobiology.

Volume 84, 2009, Pahttps://doi.org/10.1016/S0074-7742(09)00413-9ges 245-262

Early Onset DementiaAbstract• Dementia is is stereotypically associated with older people.

However, in a significant minority it can affect people in their 40s and 50s, or even younger. Currently there is a lack of awareness, even among healthcare professionals, and there is a dearth of appropriate services for such patients. Despite the attention given to this condition by National Institute for Health and Clinical Excellence guidelines, provision of specialist early-onset dementia services in the UK remains patchy. Carers and patients often find themselves being passed ‘from pillar to post’ between psychiatry and neurology, and also between adult, old age and liaison psychiatry. The responsibility for identifying available and appropriate help is often left with carers. This leads to unnecessary delays, causes undue distress to patients and places an added burden on carers.

• Jefferies K and Agrawal N (2009). Early-onset dementia. Advances in Psychiatric Treatment Aug 2009, 15 (5) 380-388; DOI: 10.1192/apt.bp.107.004572

EOD• Abstract• BACKGROUND: It is estimated that 1,200 people under the age of 65 have

been diagnosed with dementia in Norway. This article provides an overview of the types of dementia frequently seen in younger patients. MATERIAL AND METHODS: The article is based on a non-systematic search in PubMed, as well as the authors' own clinical and research experience. RESULTS: Alzheimer's disease, frontotemporal dementia, vascular dementia and dementia with Lewy bodies, are the most common types of dementia occurring more often in younger than in older patients. The cognitive symptoms are more variable in younger patients than in older. Only a small percentage of early onset dementia is caused by genetic factors. There are few diagnostic tools available for this age group and it takes considerable time to reach a correct diagnosis. Early diagnosis allows the patient and carer to plan for the future. INTERPRETATION: Physicians should be aware that dementia can occur in younger people, and more diagnostic assessments should be developed for this patient group. Better coordination from the public health authority and municipalities is needed to provide respite care for early onset dementia patients and their carers. – Rosness TA, Haugen PK, and Engeal K (2011). Early Onset Dementia. Europe

PMC. DOI: 10.4045/tidsskr.09.0845. http://europepmc.org/abstract/med/21694746

Hypotheses of EOD

• Global cerebral blood flow, oxidative brain metabolism, and the cerebral arteriovenous differences of amino acids and ammonia were studied in 20 clinically diagnosed patients with early-onset dementia of Alzheimer type (DAT). Eleven healthy age-matched subjects and 15 healthy young volunteers served as controls. The most prominent abnormality in patients with early-onset DAT was a 44% reduction in the cerebral metabolic rate of glucose and a fourfold increase of lactate production, whereas cerebral blood flow and the cerebral metabolic rate of oxygen were found not to be altered. The cerebral amino-N balance substantially changed in patients with early-onset DAT, showing a massive loss of amino acids and ammonia from the brain, which was indicative of excess protein catabolism due to cell degeneration in the acutely diseased brain. The abnormality found in glucose metabolism may suggest a perturbed control of glycolytic breakdown of glucose and its first oxidation step at the pyruvate dehydrogenase complex level, this thus being of pivotal significance in early-onset DAT.

• Hoyer S, Oesterreich K and Wagner O (1987). Glucose metabolism as the site of the primary abnormality in early-onset dementia of Alzheimer https://link.springer.com/article/10.1007%2FBF00314304?LI=truetype? Journal of Neurology January 1988, Volume 235, Issue 3, pp 143–148 .

Accurate Dx of EOD• Abstract• Early-onset dementia (EOD, <65 years at onset) is a relatively common and

frequently misdiagnosed condition. One reason for misdiagnosis is that EOD has a more varied differential diagnosis than late-onset dementia (LOD). For example, Alzheimer's disease (AD), the preponderant LOD, makes up only about one-third of EODs; the rest are due to vascular dementias, frontotemporal lobar degenerations, traumatic head injury, alcohol-related dementia, and a great many other conditions. Another reason for misdiagnosis is that early-onset AD may have predominant cognitive deficits other than memory loss and a potential familial inheritance with spastic paraparesis, seizures, or myoclonus. A third reason is that EOD often presents with neuropsychiatric features out-of-proportion to any cognitive deficits. Despite these obstacles, it is important to accurately diagnose EODs, particularly because they differ in management and course. Clinicians can successfully diagnose most EODs with careful cognitive and family histories, mental status and neurological examinations, and neuroimaging.– Mendez MF (2006). The Accurate Diagnosis of Early-Onset Dementia. The

International Journal of Psychiatry in Medicine, Vol 36, Issue 4, 2006. http://journals.sagepub.com/doi/pdf/10.2190/Q6J4-R143-P630-KW41

Early vs Late Onset DementiaAbstract• Background: Research on the epidemiology of dementia has focused on the elderly. Few

investigations have studied differences in etiologic frequencies between early-onset dementia (EOD), with onset at an age of less than 65 years old, and the more common late-onset disorder. Objectives: To determine relative frequencies and characteristics of EOD versus late-onset dementia (LOD; age of onset ≧65 years) diagnosed in a large memory disorders program over a 4-year period. Methods: We reviewed medical records, including an extensive neurobehavioral and neurological evaluation, of all patients seen at a large Veteran’s Affairs Medical Center Memory Disorders clinic between 2001 and 2004 and assessed demographic variables, final diagnoses, presence of dementia, and differential diagnosis of dementing illnesses. Results: Among 1,683 patients presenting for evaluation of an acquired decline in memory or cognition, 948 (56%) met established clinical criteria for a dementing illness. About 30% (n = 278) of these had an age of onset of <65 years, compared to 670 with LOD. Patients were predominantly male (98%). Compared to the late-onset group, the EOD patients were less severely impaired on presentation, but they did not differ in gender distribution or educational background. The EOD group had significantly more dementia attributed to traumatic brain injury, alcohol, human immunodeficiency virus (HIV), and frontotemporal lobar degeneration compared to the LOD patients. In contrast, the LOD group had significantly more Alzheimer’s disease compared to the EOD group. Conclusions: This study, conducted at a Veterans Affairs Hospital, is the largest series to date on EOD, and found a previously unexpectedly large number of patients below the age of 65 with cognitive deficits and impaired functioning consequent to head trauma, alcohol abuse, and HIV. These findings highlight the differential distribution and importance of preventable causes of dementia in the young.

– McMurtray A. · Clark D.G. · Christine D. · Mendez M.F. (2006). Early-Onset Dementia: Frequency and Causes Compared to Late-Onset Dementia. Dementia and Geriatric Cognitive Disorders. 2006;21:59–64 https://doi.org/10.1159/000089546 .

4 Genes Implicated in EODSummary• Clinical differential diagnosis of early-onset dementia (EOD) includes familial Alzheimer disease

(FAD) and hereditary prion disease. In both disease entities, postmortem brain histopathological examination is essential for unambiguous diagnosis. Mutations in the genes encoding the presenilins (PS1 and PS2) and amyloid precursor protein (APP) are associated with FAD, whereas mutations in the prion protein (PrP) gene are associated with prion disease. To investigate the proportion of EOD attributable to known genes, we prospectively (i.e., antemortem) screened these four genes for mutations by sequencing genomic PCR products from patients with EOD before age 60 years. Family history for dementia was positive (PFH) in 16 patients, negative (NFH) in 17 patients, and unknown (UFH) in 3 patients. In 12 patients, we found five novel mutations (in PS1, F105L; in PS2, T122P and M239I; and in PrP, Q160X and T188K) and five previously reported mutations (in APP, in three patients who were most likely unrelated, V717I; in PS1, A79V and M139V; and in PrP, P102L and T183A) that are all considered to be disease causing. Of these 12 patients, 9 had PFH. This indicates a detection rate of 56% (9/16) in patients with PFH. We found two mutations (APP V717I) in two of the three UFH patients, and only one mutation (PrP T188K) in 1 of the 17 patients with NFH. We conclude that because of the lack of specific antemortemdiagnostic markers for FAD and hereditary prion disease, all four genes should be included in a molecular diagnostic program in patients with EOD who had PFH.

– Finckh U, Mueller-Thompson T, Mann U, Eggers C, Marksteiner J, Meins W, Binetti G, Alberici A, Hock C, Nitsch RM, and Gal A (2000). High Prevalence of Pathogenic Mutations in Patients with Early-Onset Dementia Detected by Sequence Analyses of Four Different Genes. AJHG Vol 66, Issue 1, Jan 2000, pp i-ii, 1-346. http://www.sciencedirect.com/science/article/pii/S000292970762237X

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