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Eicosapentaenoic Acid Is Associated with Decreased Incidence of Alzheimer’s Dementia in the Oldest Old

van Lent DM, Egert S, Wolfsgruber S, Kleineidam L, Weinhold L, Wagner-Thelen H, Maier W, Jessen F, Ramirez A, Schmid M, Scherer M, Riedel-Heller SG, Wagner M (2021) Nutrients 13(2) 461. doi: 10.3390/nu13020461. 

Web URL: View this and related abstracts via Pubmed here. Free full text of this article is available online



Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) may have different effects on cognitive health due to their anti- or pro-inflammatory properties.


We aimed to prospectively examine the relationships between n-3 and n-6 PUFA contents in serum phospholipids with incident all-cause dementia and Alzheimer's disease dementia (AD). We included 1264 non-demented participants aged 84 ± 3 years from the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) multicenter-cohort study. We investigated whether fatty acid concentrations in serum phospholipids, especially eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), linoleic acid (LA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA), were associated with risk of incident all-cause dementia and AD.


During the follow-up window of seven years, 233 participants developed dementia. Higher concentrations of EPA were associated with a lower incidence of AD (hazard ratio (HR) 0.76 (95% CI 0.63; 0.93)). We also observed that higher concentrations of EPA were associated with a decreased risk for all-cause dementia (HR 0.76 (95% CI 0.61; 0.94)) and AD (HR 0.66 (95% CI 0.51; 0.85)) among apolipoprotein E ε4 (APOE ε4) non-carriers but not among APOE ε4 carriers. No other fatty acids were significantly associated with AD or dementia.


Higher concentrations of EPA were associated with a lower risk of incident AD. This further supports a beneficial role of n-3 PUFAs for cognitive health in old age.


Previous studies have reported low dietary intakes and blood levels of the long-chain omega-3 EPA and DHA - found in fish and seafood - as risk factors for a wide range of mental health disorders, including age-related cognitive decline and dementia.

Adequate supplies of both these omega-3 long-chain polyunsaturated fats (LC-PUFA) - toether with some omega-6 LC-PUFA (notably AA and DGLA) are vital for normal brain structure and function, but are relatively lacking from modern, western-type diets.

In this study, higher initial blood levels of EPA, but no other fatty acid, predicted a significantly lower risk of developing Alzheimers disease in a community-based sample of 1250 older adults, who were initially assessed at around 84 years of age, and were then followed up for 7 years.

Other research has shown that EPA, rather than DHA, appears to be more effective in reducing depressive symptoms in patients with major depression, although both these omega-3 have multiple potentially beneficial actions that are relevant to maintaining brain health.

The current study is purely observational, so cannot address any questions of cause and effect. The findings do, however, support the case for further investigations of omega-3, and possibly EPA in particular, for the prevention of age-related cognitive decline and dementia.

To date, findings from clinical trials of dietary supplementation with omega-3 LC-PUFA alone for the prevention or managment of age-related cognitive impairment or dementia have been mixed and inconclusive.  However, trials of supplementation with omega-3 EPA/DHA together with other micronutrients have shown more promise, both in slowing age-related cognitive decline, and reducing physical brain shrinkage.