Association of fish oil supplementation with risk of incident dementia: A prospective study of 215,083 older adults

Background & aims Evidence linking the use of omega-3 PUFA supplements with incident dementia is scarce. We aim to assess the relationship between fish oil supplementation and incident dementia risk among older adults with different apolipoprotein E (APOE) genotypes in a large population-based cohort. Methods We included 215,083 participants (average age: 64.1 ± 2.9 y) without dementia at baseline from UK Biobank study. Fish oil use was assessed by a touch screen questionnaire at baseline. Dietary intake was assessed by a food frequency questionnaire. The APOE genotypes were determined by allele variations on rs429358 and rs7412 from genome-wide genotyping of blood samples. Dementia was diagnosed using the International Classification of Diseases (ICD-9 and ICD-10). Cox proportional hazards regression models were used to calculate the associations of fish oil supplement use with dementia risk. Results During an average 7.92 years of follow-up, 2054 participants were diagnosed with dementia. After multivariable adjustment for major risk factors, the use of fish oil supplements was significantly associated with a lower risk of all-cause dementia (p for trend = 0.004). Compared with non-users, the multivariable-adjusted hazard ratio (95% confidence interval) of dementia was 0.87 (0.79–0.96) for fish oil users. A marginal interaction was found between fish oil supplementation and APOE gene variants on the risk of dementia (p for interaction = 0.057). However, fish oil supplementation was not associated with the risk of any subtype of dementia, including Alzheimer's disease (AD), vascular dementia (VD), and frontotemporal dementia (FTD). Conclusions Intake of fish oil supplements was associated with lower risk of all-cause dementia among 60–73 y elders. Our findings provide new population-based evidence for linking fish oil supplement use with dementia prevention.