An inverse association of cerebral amyloid-β deposition and serum docosahexaenoic acid levels in cognitively normal older adults in Japan

Abstract

Background

Alzheimer's disease (AD) is driven by amyloid-β (Aβ) plaque accumulation, but the mechanisms behind this process remain unclear. Omega-3 fatty acids, particularly docosahexaenoic acid (DHA), may offer protective effects, though their relationship with Aβ accumulation is not fully understood.

Objective

This study investigated whether serum DHA and eicosapentaenoic acid (EPA) levels, measured 6–9 years before imaging, were inversely associated with cerebral Aβ deposition in cognitively normal older adults in Japan, a population known for high omega-3 intake. We focused on individuals identified as Aβ-positive based on positron emission tomography (PET) scans, as they are at higher risk for AD progression, to assess DHA's potential in mitigating early amyloid pathology.

Methods

An analytical sample of 97 older adults (75–89 years) from the Suita Study was analyzed. Serum DHA and EPA levels were assessed between 2008 and 2012, and amyloid PET was performed between 2016 and 2019. Multiple regression analyses were conducted, adjusting for age, sex, APOE4 status, and cardiometabolic disease.

Results

Among 97 participants (49% males, 8.2% APOE4 carriers), 37.1% (n = 36) had cardiometabolic disease, and 29.8% (n = 29) were Aβ positive. In Aβ-positive individuals, higher serum DHA levels were significantly associated with lower Aβ deposition independent of age, sex and APOE4 status (standardized β = -0.423, p = 0.030). This became non-significant after additionally adjusting for cardiometabolic disease (β = -0.382, p = 0.059). No significant association was found between EPA and Aβ deposition.

Conclusions

Higher long-term DHA levels may help reduce Aβ accumulation in those at risk for AD, supporting its potential role in early prevention.