Association of Seafood Consumption, Brain Mercury Level, and <i>APOE ε4</i> Status With Brain Neuropathology in Older Adults

Morris, Martha Clare; Brockman, John; Schneider, Julie A.; Wang, Yamin; Bennett, David A.; Tangney, Christy; Rest, Ondine van de

doi:10.1001/jama.2015.19451

Cited by 118 publications

(80 citation statements)

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“…The robustness of the current associations is reinforced by our findings in a subsample of deceased participants with autopsy data, in which we recently showed associations between higher seafood consumption with lower levels of Alzheimer disease neuropathology also in APOE e4 carriers only. 25 A very recent study observed associations between fish oil supplement use and less cognitive decline and less brain atrophy in the entire study cohort that, after stratification, remained significant in the APOE e4 noncarriers only. 26 Results from randomized placebo-controlled intervention trials are also mixed, observing positive effects of longchain n-3 fatty acids among APOE e4 carriers 27,28 or in APOE e4 noncarriers.…”

Section: Resultsmentioning

confidence: 98%

APOE ε4 and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline

et al. 2016

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Objective: To examine the association between consumption of seafood and long-chain n-3 fatty acids with change in 5 cognitive domains over an average of 4.9 years.Methods: From an ongoing longitudinal, community-based epidemiologic study of aging and dementia (the Rush Memory and Aging Project), we included 915 participants (age 81.4 6 7.2 years, 25% men) who had completed at least one follow-up cognitive assessment and dietary data. Diet was assessed by semiquantitative food frequency questionnaire. Scores for global cognitive function and 5 cognitive domains (episodic, semantic, and working memory, perceptual speed, and visuospatial ability) were assessed using 19 cognitive tests. Mixed models adjusted for multiple risk factors of cognitive change were used to assess the associations.Results: Consumption of seafood was associated with slower decline in semantic memory (b 5 0.024; p 5 0.03) and perceptual speed (b 5 0.020; p 5 0.05) in separate models adjusted for age, sex, education, participation in cognitive activities, physical activity, alcohol consumption, smoking, and total energy intake. In secondary analyses, APOE e4 carriers demonstrated slower rates of decline in global cognition and in multiple cognitive domains with weekly seafood consumption and with moderate to high long-chain n-3 fatty acid intake from food. These associations were not present in APOE e4 noncarriers. Higher intake levels of a-linolenic acid were associated with slower global cognitive decline, but also only in APOE e4 carriers. Conclusions:These results suggest protective relations of one meal per week of seafood and long-chain n-3 fatty acids against decline in multiple cognitive domains. The role of APOE e4 in this association needs further study. The primary structural component of the brain is the long-chain n-3 fatty acid, docosahexaenoic acid (DHA) (22:6 n-3), of which the direct nutrient source is seafood. DHA is also metabolized in vivo from the n-3 fatty acids eicosapentaenoic acid (EPA) (20:5 n-3) and a-linolenic acid (ALA) (18:3 n-3). The importance of seafood and n-3 fatty acids in the prevention of dementia has been demonstrated through a number of prospective epidemiologic studies, 1,2 most of which reported findings for global cognitive functioning. Few examined associations with specific cognitive domains that may provide clues to the underlying biologic mechanisms of effect. Further, we are not aware of a previous study investigating whether APOE, the gene encoding the lipid protein responsible for intercellular trafficking of cholesterol and other lipids involved in brain composition and functioning, 3 and more specifically the APOE e4 genotype, a major risk factor for dementia, 4 might modify the relations of seafood/n-3 fatty acid intake to domainspecific cognitive decline. We investigated whether APOE e4 modifies the association between seafood and n-3 fatty acid intakes and domain-specific cognitive decline in a community-based, prospective study.

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Section: Resultsmentioning

confidence: 98%

APOE ε4 and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline

et al. 2016

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“…But supplementation with DHA and/or EPA in the healthy elderly, elderly with mild cognitive impairment, and elderly with neurodegenerative disease have shown mixed results regarding improvement or retention of cognitive status (Sydenham et al 2012;Janssen and Kiliaan 2014;Burckhardt et al 2016). More recently it has been suggested that dietary consumption of seafood as a source of DHA may be more important for prevention of AD than supplementation, with APOEε4 carriers who consumed seafood at least once per week showing a lower burden of neuritic plaques and neurofibrillary tangles at death (Morris et al 2016). However, the discrepancies between intervention studies could also be the product of an alteration to DHA metabolism even in normal, healthy adults with advanced age (Astarita et al 2010;Plourde et al 2011).…”

Section: Discussionmentioning

confidence: 99%

The phospholipid composition of the human entorhinal cortex remains relatively stable over 80 years of adult aging

et al. 2017

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Membrane lipid composition is altered in the brain during the pathogenesis of several age-related neurodegenerative diseases, including Alzheimer's disease. The entorhinal cortex is one of the first regions of the brain to display the neuropathology typical of Alzheimer's disease, yet little is known about the changes that occur in membrane lipids within this brain region during normal aging (i.e., in the absence of dementia). In the present study, the phospholipid composition of mitochondrial and microsomal membranes from human entorhinal cortex was examined for any changes over the adult lifespan (18-98 years). Overall, changes in several molecular phospholipids were seen with age in the entorhinal cortex across both membranes. The proportion of total phosphatidylcholine within the mitochondrial fraction increased within the entorhinal cortex with age, while total mitochondrial phosphatidylethanolamine decreased. Many mitochondrial phosphatidylethanolamines containing docosahexaenoic acid increased with age; however, this did not translate into an overall age-related increase in total mitochondrial docosahexaenoic acid. The most abundant phospholipid present within the human brain, PC 16:0_18:1, also increased with age within the mitochondrial membranes of the entorhinal cortex. When compared to other regions of the brain, the phospholipid composition of the entorhinal cortex remains relatively stable in adults over the lifespan in the absence of dementia.

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“…[6] In addition, epidemiologic studies have shown that diets richer in fish are associated with reduced risk for dementia[7, 8] and less neuropathology. [9]…”

Section: Introductionmentioning

confidence: 99%

Erythrocyte omega-3 fatty acids are inversely associated with incident dementia: Secondary analyses of longitudinal data from the Women's Health Initiative Memory Study (WHIMS)

Ammann

Pottala

Robinson

et al. 2017

Prostaglandins, Leukotrienes and Essential Fatty Acids

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OBJECTIVE To assess whether red blood cell (RBC) docosahexaenoic acid and eicosapentaenoic acid (DHA+EPA) levels have a protective association with the risk of dementia in older women. METHODS RBC DHA+EPA levels were assessed at baseline, and cognitive status was evaluated annually in a cohort of 6706 women aged ≥65 years who participated in the Women’s Health Initiative Memory Study (WHIMS). Cox regression was used to quantify the association between RBC DHA+EPA and the risk of probable dementia, independent of major dementia risk factors. RESULTS During a median follow-up period of 9.8 years, 587 incident cases of probable dementia were identified. After adjusting for demographic, clinical, and behavioral risk factors, a one standard deviation increase in DHA+EPA levels was associated with a significantly lower risk of dementia (HR = 0.92, 95% CI: 0.84, 1.00; p < 0.05). This effect estimate did not meaningfully change after further adjustment for baseline cognitive function and APOE genotype. For women with high DHA+EPA exposure (1 SD above mean) compared to low exposure (1 SD below mean), the adjusted 15-year absolute risk difference for dementia was 2.1% (95% CI: 0.2%, 4.0%). In secondary analyses, we also observed a protective association with longitudinal change in Modified Mini-Mental State (3MS) Exam scores, but no significant association with incident MCI, PD/MCI, or baseline 3MS scores. DISCUSSION Higher levels of DHA+EPA may help protect against the development of dementia. Results from prospective randomized controlled trials of DHA+EPA supplementation are needed to help clarify whether this association is causal.

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Association of Seafood Consumption, Brain Mercury Level, and APOE ε4 Status With Brain Neuropathology in Older Adults

Cited by 118 publications

References 50 publications

APOE ε4 and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline

APOE ε4 and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline

The phospholipid composition of the human entorhinal cortex remains relatively stable over 80 years of adult aging

Erythrocyte omega-3 fatty acids are inversely associated with incident dementia: Secondary analyses of longitudinal data from the Women's Health Initiative Memory Study (WHIMS)

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