Association of Seafood Consumption, Brain Mercury Level, and APOE ε4 Status With Brain Neuropathology in Older Adults.
Level 4 - case-series / case-control
Cross-sectional postmortem clinicopathological study
PubMed 26836731 · doi:10.1001/jama.2015.19451
What was done
Cross-sectional postmortem analysis of 286 autopsied brains from deceased participants (mean age at death 89.9 years, 67% women, 14.6 years mean education) in the Chicago Memory and Aging Project (2004–2013). Dietary consumption of seafood and n-3 fatty acids was assessed annually before death using food frequency questionnaires (first measured a mean of 4.5 years before death). Brain tissue concentrations of mercury and selenium were measured using instrumental neutron activation analyses. Analyses evaluated correlations between seafood consumption, brain mercury levels, APOE ε4 status, and neuropathologies (Alzheimer disease pathology, Lewy bodies, macroinfarctions, and microinfarctions), adjusted for age, sex, education, and total energy intake.
What was found
Brain mercury levels positively correlated with weekly seafood meals (ρ = 0.16; P = .02), but higher brain mercury was not significantly correlated with increased neuropathology. Seafood intake (≥1 meal/week) was significantly correlated with less Alzheimer disease pathology specifically among APOE ε4 carriers: lower neuritic plaque density (β = -0.69 score units [95% CI, -1.34 to -0.04]), less severe neurofibrillary tangles (β = -0.77 score units [95% CI, -1.52 to -0.02]), and lower neuropathologically defined Alzheimer disease (β = -0.53 score units [95% CI, -0.96 to -0.10]). Higher α-linolenic acid intake was correlated with lower odds of cerebral macroinfarctions (tertiles 3 vs 1 OR = 0.51 [95% CI, 0.27 to 0.94]). Fish oil supplementation showed no significant correlation with neuropathologic markers.
Why it matters
This study shows that moderate seafood consumption correlates with reduced Alzheimer-type neuropathology in genetically vulnerable individuals, without evidence that associated brain mercury accumulation causes neuropathologic harm.
Limits
Cross-sectional observational postmortem design prevents establishing causality. Dietary data relied on self-reported food frequency questionnaires. The cohort comprised very elderly individuals (mean age ~90 years) from Chicago retirement communities and subsidized housing, with autopsies available for only 51.6% of deceased participants.
Cited by
- supports Dietary fish consumption protects APOE4 carriers against Alzheimer's disease, whereas isolated DHA supplementation does not show the same protective benefit in APOE4 carriers.