Long‐chain omega‐3 polyunsaturated fatty acids, brain atrophy, cognitive decline and dementia risk

Abstract Background Long‐chain omega‐3 polyunsaturated fatty acids (n‐3 PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mainly provided together by fish intake in the human diet, are important constituents of neural membranes. Epidemiological studies reported associations between long‐chain n‐3 PUFA intakes or blood concentrations, and lower risks of dementia and related outcomes (cognitive decline, brain atrophy). However, evidence has been inconsistent according to the type (e.g., EPA, DHA or total n‐3 PUFA) and/or the exposures (intake versus blood status) investigated. Moreover, previous studies displayed short follow‐up periods (generally less than 5 years). In this study, we took advantage of the long follow‐up for dementia and related outcomes in a large cohort of older persons, the Three‐City (3C) study, to look for robust associations of an omega‐3 index in plasma (EPA+DHA), with the long‐term evolution of three complementary outcomes: atrophy of the medial temporal lobe (MTL, a biomarker of dementia), cognitive decline and incidence of dementia. Method We included 1279 participants (aged ≥65) from the 3C study, non‐demented at the time of blood measurements at baseline. Face‐to‐face neuropsychological assessments at baseline and follow‐up visits (7 visits over 17 years) were used to evaluate global cognitive decline (n=1185), memory decline (n=1039), and for the systematic detection of incident dementia. An ancillary study included 467 participants with up to three repeated brain imaging exams over 10 years (FreeSurfer 5.1 segmentation). Linear mixed models were used to assess the associations between plasma EPA+DHA and trajectories of global cognition, memory and MTL volumes. The association between EPA+DHA and the risk of dementia was estimated by a Cox model. Result Higher levels of plasma EPA+DHA were associated with a lower risk of dementia (HR for 1SD = 0.87 [95% CI, 0.76‐0.98]), and a lower decline in global cognition ( P = .04 for change over time), memory ( P = .06) and MTL volume ( P = .02). Conclusion The consistency of the long‐term associations found between higher levels of plasma EPA+DHA and three dementia related outcomes in this large cohort of older adults provides compelling evidence for the interest of long‐chain n‐3 PUFA in dementia and cognitive decline prevention.