Wei · The American journal of clinical nutrition 2023 · Systematic review, meta-analysis, and prospective cohort study · n=103,651 participants (48 studies) in meta-analysis; 1,135 in ADNI cohort

The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers.

Cited 158 times in the scientific literature.

Level 3 - non-randomized controlled study

Meta-analysis of prospective cohort studies combined with an individual longitudinal cohort analysis.

PubMed 37028557 · doi:10.1016/j.ajcnut.2023.04.001 · record verified 2026-08-29

What was done

Longitudinal data from 1,135 participants without dementia (mean age 73 years) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed across 6 years of follow-up to assess associations of omega-3 supplementation and blood biomarkers with incident Alzheimer's disease (AD). In addition, a meta-analysis and robust error meta-regression dose-response analysis of 48 published prospective cohort studies (103,651 total participants) evaluated longitudinal relationships of dietary omega-3 intake and peripheral blood markers with all-cause dementia or cognitive decline.

What was found

In the ADNI cohort, long-term omega-3 supplement users had a 64% lower risk of AD (HR 0.36, 95% CI: 0.18 to 0.72, P = 0.004). In the meta-analysis of 48 cohorts, dietary omega-3 intake was associated with an approximately 20% lower risk of all-cause dementia or cognitive decline, particularly for DHA intake (RR 0.82, I2 = 63.6%, P = 0.001) and in studies adjusting for APOE ε4 status (RR 0.83, I2 = 65%, P = 0.006). Each 0.1 g/day increment of DHA or EPA intake was associated with an 8% to 9.9% lower risk of cognitive decline (P linear < 0.0005). Higher plasma EPA (RR 0.88, I2 = 38.1%) and erythrocyte membrane DHA (RR 0.94, I2 = 0.4%) were also associated with reduced cognitive decline.

Why it matters

This study combines large prospective cohort data with dose-response modeling and objective blood biomarkers, reinforcing observational evidence that sustained EPA and DHA intake may reduce the risk of cognitive decline and dementia.

Limits

The findings are observational, leaving potential for residual confounding by overall diet quality or lifestyle factors. Moderate-to-high heterogeneity was present across dietary intake analyses (I2 > 60%). The abstract does not detail specific supplement formulations, doses, or adherence metrics in the ADNI cohort.

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