EDITORIAL
The Mediterranean Diet: Good for theHeart ¼ Good for the Brain?
T he prevalence of Alzheimer disease (AD) and other
dementias is expected to nearly quadruple worldwide
over the next 40 years if a prevention or cure is not
developed.1 Currently available dementia medications
have been shown to have relatively small effect sizes in
clinical trials and do not clearly modify the disease
course.2 In addition, several agents have recently failed in
phase III clinical trials.3–5 There is growing awareness
that treatment at the time patients develop AD symp-
toms may be too late, as these symptoms likely reflect
the end stage of a neurodegenerative process that has
occurred over many years or even decades. Therefore, the
field has begun to shift away from treatment and toward
prevention efforts.Dietary factors have been identified as 1 of the
more promising strategies for dementia prevention.6
Some observational studies have found that individualswho consume diets higher in folate, fish, omega-3 fattyacids, or antioxidants have a decreased risk of developingdementia.7 However, randomized controlled trials(RCTs) of specific dietary components—including folicacid with or without other B vitamins, docosahexaenoicacid, eicosapentaenoic acid,7 and vitamins C, E, or beta-carotene8,9—have yielded disappointing results to date.This has led some to suggest that the overall diet may bemore important than a single component.6
The Mediterranean diet (MeDi) is a particularlypromising dietary pattern for lowering dementia risk.MeDi is characterized by high consumption of fruits,vegetables, legumes, and complex carbohydrates; moder-ate consumption of fish; olive oil as the primary sourceof fat; and low-to-moderate alcohol consumption (<30g,approximately 3 drinks/day).10 A recent meta-analysis ofobservational studies found that individuals who adhereto MeDi experience a lower risk of overall mortality (rel-ative risk [RR], 0.92; 95% confidence interval [CI],0.90–0.94), cardiovascular disease (RR, 0.90; 95% CI,0.87–0.93), neoplastic disease (RR, 0.94; 95% CI, 0.92–0.96), and neurodegenerative disease (RR, 0.87; 95% CI,0.81–0.94).10
Much of the work in this area has been spear-headed by Scarmeas and colleagues using data from theWashington Heights/Hamilton Heights Columbia Aging
Project (WHICAP) cohort, a study of ethnically diverseolder adults in Northern Manhattan. In this cohort,MeDi adherence has been associated with a reduced riskof AD11 and mild cognitive impairment12 as well asmortality in those with13 and without14 AD. However, ithas proven more difficult to identify the mechanism(s)underlying the association between MeDi and AD, andprior analyses in WHICAP have found that the associa-tion was not attributable to vascular risk factors (stroke,diabetes mellitus, hypertension, heart disease, or lipid lev-els),15 inflammatory markers (high-sensitivity C-reactiveprotein),16 or metabolic biomarkers (fasting insulin oradiponectin).16
The study by Scarmeas and colleagues in this issueof Annals of Neurology appears to have shed some lighton the mechanism underlying Medi’s benefit.17 Theirstudy included 707 WHICAP participants who com-pleted detailed dietary assessments at baseline and hadhigh-resolution structural magnetic resonance imaging(MRI) approximately 6 years later. They found thatlower MeDi adherence was strongly associated with cere-bral infarcts, but not white matter hyperintensities(WMH), on the MRIs. Furthermore, the magnitude ofthe association was comparable to that of hypertension(36% lower odds of cerebral infarcts for those in thehighest MeDi tertile, compared with 37% lower odds forthose without hypertension). This finding is importantbecause it supports the hypothesis that MeDi exerts itseffects on the brain through a vascular mechanism, thatis, by lowering the risk of cerebral infarcts.
There are several limitations to the study, however.First, as the authors note, this study provides evidencerelated to only 1 link in the causal chain (cerebralinfarcts), and it will be important to follow these subjectsto determine whether those with low MeDi adherenceand MRI infarcts are more likely to go on to developAD. Second, it is somewhat surprising that low MeDiadherence was associated with infarcts but not WMH,which are commonly seen in patients with AD. Althoughthe precise etiology of WMH remains somewhat murky,it is believed that they reflect the chronic effects of smallvessel disease,18 whereas infarcts reflect large vessel dis-ease. It is not clear why MeDi adherence would affect 1but not the other. Finally, the vast majority of the work
226 VC 2011 American Neurological Association
examining the association between MeDi and neurodege-nerative outcomes has been performed using the WHI-CAP cohort, which raises concern regarding the general-izability of the findings. Although this study populationis ethnically diverse, it is restricted to a small geographicregion in New York, and the dietary patterns in thisregion may not reflect the full range of dietary patternsin other regions. For example, a recent study in Francefound that greater MeDi adherence was associated withslower cognitive decline but not lower dementia inci-dence.19 Moving forward, it will be critical to examinethe association between MeDi and neurodegenerativeoutcomes in other cohorts.
Ultimately, RCTs will be needed to determinewhether the association between MeDi and AD is causaland whether dietary intervention in high-risk elders canprevent or delay onset of AD. However, it is encouragingthat RCTs that have examined MeDi in other settingshave yielded promising results, particularly for improvingcardiovascular and metabolic profiles. A recent RCT inindividuals with a high cardiovascular disease risk foundthat MeDi was more effective than a low-fat diet forimproving plasma glucose, systolic blood pressure, andcholesterol levels.20 Another trial of individuals withnewly diagnosed type II diabetes found that MeDi wasassociated with greater weight loss, greater improvementsin glycemic control and coronary risk measures, and lessmedication use compared to a low-fat diet.21 MeDi alsohas been associated with greater ability to reverse meta-bolic syndrome status22 and lower diabetes incidence23,24
compared with a low-fat diet. However, several otherRCTs have found that MeDi is equivalent to otherhealthy diets. An RCT in individuals who had had theirfirst myocardial infarction found that low-fat and MeDidiets were both associated with an approximately 70%reduction in subsequent cardiovascular events or mortal-ity compared with a matched usual care control group.25
Another trial found that low-fat, MeDi, and low-carbo-hydrate diets were associated with similar improvementsin carotid atherosclerosis.26 Nonetheless, these trials dem-onstrate that dietary modifications do affect cardiovascu-lar risk and metabolic status and raise hope that, over thelong term, dietary changes could lead to lower incidenceof AD.
For a dementia prevention strategy to be feasible, itmust first do no harm. Many individuals considered tobe at high risk for AD—even those with high levels ofAD biomarkers or evidence of AD neuropathology—willnever develop dementia symptoms in their lifetimes.Therefore, it is crucial that prevention interventions tar-geting these individuals have low side effect profiles. Oneof the appealing aspects of lifestyle interventions such asMeDi is that they are exceptionally low risk with a highpotential for gain. In addition, they are relatively inex-pensive and have the potential to reduce other diseasessuch as cardiovascular disease and metabolic disorders.
Although neurologists should not be expected to play therole of dietary counselors, recommendation of MeDi tohigh-risk patients may be an option for AD preventionwhere pharmaceutical interventions have so far beenineffective.
Potential Conflicts of Interest
Nothing to report.
Deborah E. Barnes, PhD, MPH
Department of Psychiatry
University of California, San Francisco
and San Francisco Veterans Affairs Medical Center
San Francisco, CA
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DOI: 10.1002/ana.22376
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