Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon4

Neurology. 2005 Nov 8;65(9):1409-14. doi: 10.1212/01.wnl.0000183148.34197.2e.


Objective: To compare associations of lean fish vs fatty fish (tuna or other fish) intake with dementia, Alzheimer disease (AD), and vascular dementia (VaD) and in relation to APOE epsilon4 status in the Cardiovascular Health Cognition Study (CHCS).

Methods: Fish intake was assessed by food frequency questionnaires. Incident dementia, AD, and VaD were determined through a series of cognitive tests, physician's assessment, and committee consensus. We used Cox proportional hazards regression to calculate hazard ratios of dementia, AD, and VaD with lean fried fish, fatty fish, or total fish intake, which were then stratified by the presence of APOE epsilon4.

Results: Although consumption of lean fried fish had no protective effect, consumption of fatty fish more than twice per week was associated with a reduction in risk of dementia by 28% (95% CI: 0.51 to 1.02), and AD by 41% (95% CI: 0.36 to 0.95) in comparison to those who ate fish less than once per month. Stratification by APOE epsilon4 showed this effect to be selective to those without the epsilon4 allele. Adjustment by education and income attenuated the effect.

Conclusion: In the Cardiovascular Health Cognition Study, consumption of fatty fish was associated with a reduced risk of dementia and Alzheimer disease for those without the APOE epsilon4 allele.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / genetics
  • Alzheimer Disease / prevention & control*
  • Apolipoprotein E4
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Cohort Studies
  • Dementia / epidemiology
  • Dementia / genetics
  • Dementia / prevention & control*
  • Dietary Fats, Unsaturated / metabolism
  • Dietary Fats, Unsaturated / therapeutic use*
  • Fatty Acids, Omega-3 / metabolism
  • Fatty Acids, Omega-3 / therapeutic use
  • Feeding Behavior / physiology
  • Female
  • Fish Oils / metabolism
  • Fish Oils / therapeutic use*
  • Fish Products*
  • Food, Formulated / standards
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Incidence
  • Male
  • Risk Factors
  • Socioeconomic Factors
  • Surveys and Questionnaires


  • Apolipoprotein E4
  • Apolipoproteins E
  • Dietary Fats, Unsaturated
  • Fatty Acids, Omega-3
  • Fish Oils