Objective: Long-chain omega-3 polyunsaturated fatty acids (PUFAs) have been identified as a potential protective factor for vascular events and cognitive impairment. However, few prospective studies have so far explored the impact of PUFAs on dementia while simultaneously controlling for MRI-findings, such as cerebral small-vessel disease (SVD) and brain atrophy.
Methods: Within a cohort of Japanese participants with vascular risk factors and free of dementia, we evaluated the association between PUFAs levels, MRI-findings at baseline, and incident all-cause dementia. Circulating plasma levels of omega-3 (ie, eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA]) and omega-6 (ie, dihomo-γ-linolenic acid [DGLA], arachidonic acid [AA]) PUFAs were measured at baseline. Baseline brain MRI was used to determine SVD (lacunas, white matter hyperintensities and cerebral microbleeds) and atrophy (medial-temporal lobe atrophy and bicaudate ratio). Logistic regression analyses were used to estimate the cross-sectional association between tertile of each PUFAs and MRI-findings. Cox proportional hazards analyses were performed to estimate the longitudinal association between PUFAs and dementia, adjusting for age, sex, APOEε4, educational level, vascular risk factors, cerebrovascular events, estimated glomerular filtration rate, and MRI-findings.
Results: In the 613 subjects (age: 67.3 ± 8.4 years, male: 59%), multivariable analyses adjusted for potential confounders showed that any PUFAs was not significantly associated with each of SVD. During the mean 7.5-year follow-up (range: 3-13), 48 subjects were diagnosed with dementia (Alzheimer’s disease:24; vascular dementia:18; mixed-type:4; other: 2). In multivariable Cox models adjusted for confounders, the relative risk of all-cause dementia was 0.42 (95%CI, 0.17-0.96, p=0.040) in the highest versus lowest tertile of DHA levels. However, no significant associations with dementia were observed for circulating EPA, EPA/AA ratio, or omega-6 PUFAs.
Conclusions: Our results provide additional evidence of DHA may be associated with lower risk of dementia.