Plasma n6 polyunsaturated fatty acid levels and risk for dementia: a prospective observational study from the United Kingdom Biobank

BACKGROUND: Some recent observational studies have linked higher blood linoleic acid (LA) concentration with lower risk of cardiometabolic diseases. However, these associations have not been observed for other n-6 polyunsaturated fatty acids (PUFAs), which, in some settings, have been linked to higher disease risk, and thus the controversy over the health effects of n-6 PUFAs remains. Dementia is a paradigmatic case of it. OBJECTIVES: To investigate the association of LA and non-LA n-6 PUFAs with the risk of incident dementia. METHODS: We included 273,795 participants from the UK Biobank free of dementia at baseline for whom plasma n-6 PUFAs data were available. We modeled the relationships between LA and, separately, non-LA n-6 PUFAs and incident dementia by quintile (Q) and using continuous linear model using Cox proportional hazards models, adjusting for variables reported to relate to incident dementia. RESULTS: percentiles: 14.22 to 15.80 y). Compared with participants at Q1 (lowest quintile) of LA, those at Q5 (highest quintile) showed a lower risk of dementia [adjusted hazard ratio (95% confidence interval) = 0.82 (0.74, 0.91)]. In contrast, participants at Q5 of plasma non-LA n-6 PUFAs were at a higher risk of incident dementia compared with Q1 [1.21 (1.10, 1.33)]. Similar patterns were observed when considering LA and non-LA n-6 PUFAs continuously. CONCLUSIONS: We observed heterogeneous associations between different types of n-6 PUFAs and risk of dementia, supporting the increasing view that n-6 PUFAs should not be treated homogeneously. Future research should investigate whether dietary LA (which drives plasma LA concentrations) may help reduce risk for dementia. REGISTRATION: This research has been conducted using the UK Biobank Resource under Application Number 85092.