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

• Published in: The American journal of clinical nutrition 2023-06, Vol.117 (6), p.1096-1109
• Main Authors: Wei, Bao-Zhen, Li, Lin, Dong, Cheng-Wen, Tan, Chen-Chen, Xu, Wei
• Format: Article
• Language: English
• Subjects: Aged; Alzheimer Disease - prevention & control; Alzheimer's disease; Apolipoprotein E; biomarker; Biomarkers; Blood; Cognitive ability; cognitive decline; Cognitive Dysfunction - prevention & control; Cohort analysis; Cohort Studies; Dementia; Dementia disorders; Diet; dietary; Dietary intake; Dietary Supplements; Docosahexaenoic acid; Docosahexaenoic Acids; Eating; Eicosapentaenoic Acid; Fatty acids; Fatty Acids, Omega-3; Food intake; Humans; Longitudinal studies; Medical imaging; Neurodegenerative diseases; Neuroimaging; omega-3 fatty acid; Omega-3 fatty acids; Original; Polyunsaturated fatty acids; Prospective Studies; Regression models; Risk management; Robustness (mathematics); Statistical analysis
• ISSN: 0002-9165; 1938-3207
• DOI: 10.1016/j.ajcnut.2023.04.001

Previous data have linked omega-3 fatty acids with risk of dementia. We aimed to assess the longitudinal relationships of omega-3 polyunsaturated fatty acid intake as well as blood biomarkers with risk of Alzheimer’s disease (AD), dementia, or cognitive decline. Longitudinal data were derived from 1135 participants without dementia (mean age = 73 y) in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort to evaluate the associations of omega-3 fatty acid supplementation and blood biomarkers with incident AD during the 6-y follow-up. A meta-analysis of published cohort studies was further conducted to test the longitudinal relationships of dietary intake of omega-3 and its peripheral markers with all-cause dementia or cognitive decline. Causal dose–response analyses were conducted using the robust error meta-regression model. In the ADNI cohort, long-term users of omega-3 fatty acid supplements exhibited a 64% reduced risk of AD (hazard ratio: 0.36, 95% confidence interval: 0.18, 0.72; P = 0.004). After incorporating 48 longitudinal studies involving 103,651 participants, a moderate-to-high level of evidence suggested that dietary intake of omega-3 fatty acids could lower risk of all-cause dementia or cognitive decline by ∼20%, especially for docosahexaenoic acid (DHA) intake (relative risk [RR]: 0.82, I2 = 63.6%, P = 0.001) and for studies that were adjusted for apolipoprotein APOE ε4 status (RR: 0.83, I2 = 65%, P = 0.006). Each increment of 0.1 g/d of DHA or eicosapentaenoic acid (EPA) intake was associated with an 8% ∼ 9.9% (Plinear < 0.0005) lower risk of cognitive decline. Moderate-to-high levels of evidence indicated that elevated levels of plasma EPA (RR: 0.88, I2 = 38.1%) and erythrocyte membrane DHA (RR: 0.94, I2 = 0.4%) were associated with a lower risk of cognitive decline. Dietary intake or long-term supplementation of omega-3 fatty acids may help reduce risk of AD or cognitive decline.