After two decades of research on nutrition and dementia there is strong evidence for preventive effects of vitamin E, B vitamins, and n‐3 fatty acids and deleterious effects of saturated fat on ...dementia. Among specific foods with evidence of neuroprotection are green leafy vegetables, other vegetables, berries, and seafood. A number of studies have examined dietary patterns, particularly the Mediterranean diet and DASH (Dietary Approaches to Stop Hypertension), neither of which is tailored to the specific foods and nutrients that have been identified as neuroprotective. A new diet called MIND (Mediterranean–DASH Intervention for Neurodegenerative Delay) incorporates many elements of the Mediterranean diet and DASH but with modifications that reflect current evidence for brain neuroprotection. The evidence in support of the relation of various nutrients and the Mediterranean diet to dementia has been inconsistent. The inconsistencies may be explained by inattention to nutrient/food intake levels in the interpretation of study findings and trial design, including a shifting metric among studies for scoring adherence to the Mediterranean diet. Future studies should pay particular attention to levels of intake in the design and analyses of nutritional studies.
Abstract
Fish are a primary source of long-chain omega-3 fatty acids, which may help delay cognitive aging. We pooled participants from the French Three-City study and 4 US cohorts (Nurses’ Health ...Study, Women’s Health Study, Chicago Health and Aging Project, and Rush Memory and Aging Project) for whom diet and cognitive data were available (n = 23,688 white persons, aged ≥65 years, 88% female, baseline year range of 1992–1999, and median follow-up range of 3.9–9.1 years) to investigate the relationship of fish intake to cognitive decline and examine interactions with genes related to Alzheimer disease. We estimated cohort-specific associations between fish and change in composite scores of global cognition and episodic memory using linear mixed models, and we pooled results using inverse-variance weighted meta-analysis. In multivariate analyses, higher fish intake was associated with slower decline in both global cognition and memory (P for trend ≤ 0.031). Consuming ≥4 servings/week versus <1 serving/week of fish was associated with a lower rate of memory decline: 0.018 (95% confidence interval: 0.004, 0.032) standard units, an effect estimate equivalent to that found for 4 years of age. For global cognition, no comparisons of higher versus low fish intake reached statistical significance. In this meta-analysis, higher fish intake was associated with a lower rate of memory decline. We found no evidence of effect modification by genes associated with Alzheimer disease.
Age-related cognitive decline is a well-known phenomenon after age 65 but little is known about earlier changes and prior studies are based on relatively small samples. We investigated the impact of ...age on cognitive decline in the largest population sample to date including young to old adults.
Between 100,352 and 468,534 participants aged 38-73 years from UK Biobank completed at least one of seven self-administered cognitive functioning tests: prospective memory (PM), pairs matching (Pairs), fluid intelligence (FI), reaction time (RT), symbol digit substitution, trail making A and B. Up to 26,005 participants completed at least one of two follow-up assessments of PM, Pairs, FI and RT. Multivariable regression models examined the association between age (<45reference, 45-49, 50-54, 55-59, 60-64, 65+) and cognition scores at baseline. Mixed models estimated the impact of age on cognitive decline over follow-up (~5.1 years).
FI was higher between ages 50 and 64 and lower at 65+ compared to <45 at baseline. Performance on all other baseline tests was lower with older age: with increasing age category, difference in test scores ranged from 2.5 to 7.8%(P<0.0001). Compared to <45 at baseline, RT and Pairs performance declined faster across all older age cohorts (3.0 and 1.2% change, respectively, with increasing age category, P<0.0001). Cross-sectional results yielded 8 to 12-fold higher differences in RT and Pairs with age compared to longitudinal results.
Our findings suggest that declines in cognitive abilities <65 are small. The cross-sectional differences in cognition scores for middle to older adult years may be due in part to age cohort effects.
Introduction
Non‐pharmacological treatments (NPTs) have the potential to improve meaningful outcomes for older people at risk of, or living with dementia, but research often lacks methodological ...rigor and continues to produce mixed results.
Methods
In the current position paper, experts in NPT research have specified treatment targets, aims, and ingredients using an umbrella framework, the Rehabilitation Treatment Specification System.
Results
Experts provided a snapshot and an authoritative summary of the evidence for different NPTs based on the best synthesis efforts, identified main gaps in knowledge and relevant barriers, and provided directions for future research. Experts in trial methodology provide best practice principles and recommendations for those working in this area, underscoring the importance of prespecified protocols.
Discussion
We conclude that the evidence strongly supports various NPTs in relation to their primary targets, and discuss opportunities and challenges associated with a unifying theoretical framework to guide future efforts in this area.
Alzheimer's disease (AD) is generally associated with lower omega-3 fatty acid intake from fish but despite numerous studies, it is still unclear whether there are differences in omega-3 fatty acids ...in plasma or brain. In matched plasma and brain samples provided by the Memory and Aging Project, fatty acid profiles were quantified in several plasma lipid classes and in three brain cortical regions. Fatty acid data were expressed as % composition and as concentrations (mg/dL for plasma or mg/g for brain). Differences in plasma fatty acid profiles between AD, mild cognitive impairment (MCI), and those with no cognitive impairment (NCI) were most apparent in the plasma free fatty acids (lower oleic acid isomers and omega-6 fatty acids in AD) and phospholipids (lower omega-3 fatty acids in AD). In brain, % DHA was lower only in phosphatidylserine of mid-frontal cortex and superior temporal cortex in AD compared to NCI (-14% and -12%, respectively; both p < 0.05). The only significant correlation between plasma and brain fatty acids was between % DHA in plasma total lipids and % DHA in phosphatidylethanolamine of the angular gyrus, but only in the NCI group (+0.77, p < 0.05). We conclude that AD is associated with altered plasma status of both DHA and other fatty acids unrelated to DHA, and that the lipid class-dependent nature of these differences reflects a combination of differences in intake and metabolism.
There is considerable interest in the impact of (n-3) long-chain PUFA in mitigating the morbidity and mortality caused by chronic diseases. In 2002, the Institute of Medicine concluded that ...insufficient data were available to define Dietary Reference Intakes (DRI) for eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), noting only that EPA and DHA could contribute up to 10% toward meeting the Adequate Intake for alpha-linolenic acid. Since then, substantial new evidence has emerged supporting the need to reassess this recommendation. Therefore, the Technical Committee on Dietary Lipids of the International Life Sciences Institute North America sponsored a workshop on 4-5 June 2008 to consider whether the body of evidence specific to the major chronic diseases in the United States--coronary heart disease (CHD), cancer, and cognitive decline--had evolved sufficiently to justify reconsideration of DRI for EPA+DHA. The workshop participants arrived at these conclusions: 1) consistent evidence from multiple research paradigms demonstrates a clear, inverse relation between EPA+DHA intake and risk of fatal (and possibly nonfatal) CHD, providing evidence that supports a nutritionally achievable DRI for EPA+DHA between 250 and 500 mg/d; 2) because of the demonstrated low conversion from dietary ALA, protective tissue levels of EPA+DHA can be achieved only through direct consumption of these fatty acids; 3) evidence of beneficial effects of EPA+DHA on cognitive decline are emerging but are not yet sufficient to support an intake level different from that needed to achieve CHD risk reduction; 4) EPA+DHA do not appear to reduce risk for cancer; and 5) there is no evidence that intakes of EPA+DHA in these recommended ranges are harmful.
Clinical evidence points to the premise that caffeine may benefit cognition, but whether these findings extend to real life settings and amidst factors that impact caffeine metabolism is unclear. The ...aim of this study was to investigate the impact of recent caffeine drinking on cognitive ability while additionally accounting for lifestyle and genetic factors that impact caffeine metabolism. We included up to 434,900 UK Biobank participants aged 37-73 years, recruited in 2006-2010, who provided biological samples and completed touchscreen questionnaires regarding sociodemographic factors, medical history, lifestyle, and diet. Recent caffeine drinking (yes/no in the last hour) was recorded during a physical assessment. Participants completed at least one of four self-administered cognitive function tests using the touchscreen system: prospective memory (PM), pairs matching (Pairs), fluid intelligence (FI), and reaction time (RT). Multivariable regressions were used to examine the association between recent caffeine drinking and cognition test scores. We also tested interactions between recent caffeine drinking and a genetic caffeine-metabolism score (CMS) on cognitive function. Among white participants, recent caffeine drinking was associated with higher performance on RT but lower performance on FI, Pairs, and PM (
≤ 0.004). Similar directions of associations for FI (
= 0.09), Pairs (
= 0.03), and PM (
= 0.34) were observed among non-white participants. No significant and consistent effect modification by age, sex, smoking, test time, habitual caffeine intake, or CMS was observed. Caffeine consumed shortly before tasks requiring shorter reaction times may improve task performance. Potential impairments in memory and reasoning tasks with recent caffeine drinking warrant further study.
Randomized trials of α-tocopherol supplements on cognitive decline are negative, whereas studies of dietary tocopherols have shown benefit. We investigated these inconsistencies by analyzing the ...relations of α- and γ-tocopherol brain concentrations to Alzheimer's disease (AD) neuropathology among 115 deceased participants of the prospective Rush Memory and Aging Project. Associations of amyloid load and neurofibrillary tangle severity with brain tocopherol concentrations were examined in separate adjusted linear regression models. γ-Tocopherol concentrations were associated with lower amyloid load (β = ‒2.10, P = .002) and lower neurofibrillary tangle severity (β = ‒1.16, P = .02). Concentrations of α-tocopherol were not associated with AD neuropathology, except as modified by γ-tocopherol: high α-tocopherol was associated with higher amyloid load when γ-tocopherol levels were low and with lower amyloid levels when γ-tocopherol levels were high ( P for interaction = 0.03). Brain concentrations of γ- and α-tocopherols may be associated with AD neuropathology in interrelated, complex ways. Randomized trials should consider the contribution of γ-tocopherol.
CONTEXT Oxidative processes have been suggested as elements in the development
of Alzheimer disease (AD), but whether dietary intake of vitamin E and other
antioxidant nutrients prevents its ...development is unknown. OBJECTIVE To examine whether intake of antioxidant nutrients, vitamin E, vitamin
C, and beta carotene is associated with incident AD. DESIGN, SETTING, AND PARTICIPANTS Prospective study, conducted from 1993 to 2000, of individuals selected
in a stratified random sample of community-dwelling residents. The 815 residents
65 years and older were free of AD at baseline and were followed up for a
mean of 3.9 years. They completed food frequency questionnaires an average
of 1.7 years after baseline. MAIN OUTCOME MEASURE Incident AD diagnosed in clinical evaluations with standardized criteria. RESULTS Increasing vitamin E intake from foods was associated with decreased
risk of developing AD after adjustment for age, education, sex, race, APOE ∊4, and length of follow-up. Relative risks (95%
confidence intervals CIs) from lowest to highest quintiles of intake were
1.00, 0.71 (0.24-2.07), 0.62 (0.26-1.45), 0.71 (0.27-1.88), and 0.30 (0.10-0.92)
(P for trend = .05). The protective association of
vitamin E was observed only among persons who were APOE ∊4 negative. Adjustment for other dietary factors reduced the
protective association. After adjustment for baseline memory score, the risk
was 0.36 (95% CI, 0.11-1.17). Intake of vitamin C, beta carotene, and vitamin
E from supplements was not significantly associated with risk of AD. CONCLUSION This study suggests that vitamin E from food, but not other antioxidants,
may be associated with a reduced risk of AD. Unexpectedly, this association
was observed only among individuals without the APOE ∊4
allele.
Epidemiological studies suggest that certain micronutrients may improve or maintain cognitive function. Consistent demonstration of benefits in intervention trials has been elusive, possibly because ...most intervention trials do not select subjects on the basis of nutrient status and/or intake. The objective of this review was to identify levels of intake or markers of nutrient insufficiency that define at‐risk older adult populations to determine whether these populations will benefit from nutritional intervention. This review examines evidence from interventional and prospective observational studies that evaluated the effects of folate, vitamin B₁₂, and vitamin E on cognitive decline in older populations. The studies suggest that supplementation may protect against cognitive decline when serum folate is <12 nmol/L or vitamin E intake is <6.1 mg/day. The literature is inadequate to define a level for vitamin B₁₂. Epidemiological studies investigating the relations of nutrients to cognitive decline should consider nutrient status in the reporting and interpretation of results. Randomized trials should design inclusion and exclusion criteria to select individuals with low intake and to disallow multivitamin intake. These recommendations may be useful for the design of valid trials and to advance the current understanding of nutrition and neurological diseases.
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