Objective:

To investigate the associations between plasma levels of different types of polyunsaturated fatty acids (PUFAs), fish oil supplementation and risk of incident dementia.

Background:

Cohort studies report inconsistent associations between omega-3 PUFAs or fish oil and dementia risk. Furthermore, evidence relating omega-6 PUFAs with dementia is scarce.

Design/Methods:

Plasma PUFA levels were measured by nuclear magnetic resonance in blood samples collected at baseline, including total PUFAs, omega-3 PUFAs, docosahexaenoic acid (DHA), omega-6 PUFAs, and linoleic acid (LA). Information on fish oil supplementation was collected through a touchscreen questionnaire at baseline. Multivariable Cox models were used to investigate independent association of plasma PUFA levels and fish oil supplementation with dementia risk. Mediation analyses were conducted to investigate whether plasma PUFA levels mediated the association between fish oil supplementation and dementia. Linear regression models were applied to investigate the associations of plasma PUFA levels and fish oil supplementation with peripheral immunity and brain structure.

Results:

Higher plasma levels of five PUFA measures and fish oil supplementation showed consistent associations with lower dementia risk (hazard ratios [95% confidence intervals]: 0.85 [0.81–0.89] for total PUFAs, 0.90 [0.86–0.95] for omega-3 PUFAs, 0.92 [0.87–0.96] for DHA, 0.86 [0.82–0.90] for omega-6 PUFAs, 0.86 [0.82–0.90] for LA, all p < 0.001; 0.93 [0.89–0.97] for fish oil users versus non-users, p = 0.002). The relationship between fish oil supplementation and dementia was partially mediated by plasma concentrations of omega-3 PUFAs and DHA. Significant associations of plasma PUFA levels and fish oil supplementation with peripheral immune markers that were related to dementia risk, as well as the positive associations of plasma PUFA levels with brain gray matter volumes and white matter microstructural integrity, suggesting they may affect dementia risk through peripheral immunity and brain structure.

Conclusions:

Higher plasma PUFA levels and fish oil supplementation were both associated with lower dementia risk.