Erythrocyte omega-3 fatty acids are inversely associated with incident dementia: Secondary analyses of longitudinal data from the Women's Health Initiative Memory Study (WHIMS)

Abstract

Objective: To assess whether red blood cell (RBC) docosahexaenoic acid and eicosapentaenoic acid (DHA+EPA) levels have a protective association with the risk of dementia in older women.

Methods: RBC DHA+EPA levels were assessed at baseline, and cognitive status was evaluated annually in a cohort of 6706 women aged ≥65 years who participated in the Women's Health Initiative Memory Study (WHIMS). Cox regression was used to quantify the association between RBC DHA+EPA and the risk of probable dementia, independent of major dementia risk factors.

Results: During a median follow-up period of 9.8 years, 587 incident cases of probable dementia were identified. After adjusting for demographic, clinical, and behavioral risk factors, a one standard deviation increase in DHA+EPA levels was associated with a significantly lower risk of dementia (HR = 0.92, 95% CI: 0.84, 1.00; p < 0.05). This effect estimate did not meaningfully change after further adjustment for baseline cognitive function and APOE genotype. For women with high DHA+EPA exposure (1SD above mean) compared to low exposure (1SD below mean), the adjusted 15-year absolute risk difference for dementia was 2.1% (95% CI: 0.2%, 4.0%). In secondary analyses, we also observed a protective association with longitudinal change in Modified Mini-Mental State (3MS) Exam scores, but no significant association with incident MCI, PD/MCI, or baseline 3MS scores.

Discussion: Higher levels of DHA+EPA may help protect against the development of dementia. Results from prospective randomized controlled trials of DHA+EPA supplementation are needed to help clarify whether this association is causal.

Keywords: All cognitive disorders/dementia; Alzheimer's Disease; Biomarkers; Cohort studies; Omega-3 fatty acids; Women.

Figure 1

Flow diagram showing identification of eligible Women’s Health Initiative Memory Study (WHIMS) participants.

Figure 2. Kaplan-Meier plots of dementia-free survival stratified by red blood cell docosahexaenoic acid and eicosapentaenoic acid (RBC DHA+EPA) tertile

Kaplan-Meier plots of dementia-free survival by RBC DHA+EPA levels at baseline. Incident cases of probable dementia were counted as events. Participants were censored at loss to follow-up, the end of the study period or death. Numbers at the bottom of the graph reflect the number of participants remaining in the risk set at a given follow-up interval.