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

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.

To investigate the association of LA and non-LA n-6 PUFAs with the risk of incident dementia.

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.

A total of 5799 incident dementia cases were ascertained (median follow-up: 15.06 y; 25^th and 75^th 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.

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.

This research has been conducted using the UK Biobank Resource under Application Number 85092.