Omega-3 fatty acids and Alzheimer’s disease-related brain biomarkers in older adults enriched for preclinical Alzheimer’s disease

BACKGROUND: Preclinical and limited human data suggest long-chain omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may be protective of brain volume and amyloid-beta (Aβ) accumulation, hallmarks of Alzheimer's disease (AD), which may be modulated by Apolipoprotein E ε4 (APOE4) carriage. METHODS: This cross-sectional study was conducted using baseline data from a clinical trial at the University of Kansas Medical Center that included cognitively normal older adults, enriched for preclinical AD. We investigated serum DHA+EPA's (% total triacylglycerol fatty acids) relationship with MRI-derived gray matter volume and PET-derived Aβ burden (Florbetapir F18) overall and by APOE4 carriage status. RESULTS: Among all participants (n = 104, 67.3% female, 69.2% preclinical AD, 44.2% APOE4), higher DHA+EPA was related to larger gray matter volume in a left precuneus/postcentral gyrus cluster, with similar relationships between APOE4 carriers and non-carriers. Higher DHA+EPA was also related to lower brain Aβ in the frontoparietal cortex, bilaterally. In APOE sensitivity analyses, higher DHA+EPA was related to lower global and AD-related regional brain Aβ among APOE4 carriers . CONCLUSIONS: Higher DHA+EPA was associated with larger gray matter volume and lower Aβ in AD-susceptible regions, especially among APOE4 carriers. These findings are consistent with the hypothesis that omega-3 fatty acids influence brain volume and Aβ. Well-designed DHA+EPA supplementation RCTs are needed as DHA supplementation RCTs have inconsistently impacted brain volume and no RCTs investigating the impact of omega-3 on brain Aβ have been reported. TRIAL REGISTRATION: NCT02000583 (https://clinicaltrials.gov/study/NCT02000583?term=NCT02000583&viewType=Card&rank=1) registered on November 26, 2013.