Intakes of fish and polyunsaturated fatty acids and mild-to-severe cognitive impairment risks: a dose-response meta-analysis of 21 cohort studies. 
The intake of fish and polyunsaturated fatty acids (PUFAs) may benefit cognitive function.  However, optimal intake recommendations for protection are unknown.  We systematically investigated associations between fish and PUFA intake and mild-to-severe cognitive impairment risk.  Studies that reported risk estimates for mild cognitive impairment (MCI), cognitive decline, dementia, Alzheimer disease (AD), or Parkinson disease (PD) from fish, total PUFAs, total n-3 (ω-3) PUFAs, or at least one n-3 PUFA were included.  Study characteristics and outcomes were extracted.  The pooled RR was estimated with the use of a random-effects model meta-analysis.  A dose-response analysis was conducted with the use of the 2-stage generalized least-squares trend program.  We included 21 studies (181,580 participants) with 4438 cases identified during follow-up periods (2.1-21 y).  A 1-serving/wk increment of dietary fish was associated with lower risks of dementia (RR: 0.95; 95% CI: 0.90, 0.99; P = 0.042, I(2) = 63.4%) and AD (RR: 0.93; 95% CI: 0.90, 0.95; P = 0.003, I(2) = 74.8%).  Pooled RRs of MCI and PD were 0.71 (95% CI: 0.59, 0.82; P = 0.733, I(2) = 0%) and 0.90 (95% CI: 0.80, 0.99; P = 0.221, I(2) = 33.7%), respectively, for an 8-g/d increment of PUFA intake.  As an important source of marine n-3 PUFAs, a 0.1-g/d increment of dietary docosahexaenoic acid (DHA) intake was associated with lower risks of dementia (RR: 0.86; 95% CI: 0.76, 0.96; P < 0.001, I(2) = 92.7%) and AD (RR: 0.63; 95% CI: 0.51, 0.76; P < 0.001, I(2) = 94.5%).  Significant curvilinear relations between fish consumption and risk of AD and between total PUFAs and risk of MCI (both P-nonlinearity < 0.001) were observed.  Fishery products are recommended as dietary sources and are associated with lower risk of cognitive impairment.  Marine-derived DHA was associated with lower risk of dementia and AD but without a linear dose-response relation.