Backgrounds &aims: Previous studies have shown that marine omega-3 PUFAs (fish oil) supplements was associated with improved cognitive function, whereas the association between use of fish oil supplements and risk of incident dementia was still unclear. We aimed to prospectively assess the relations between use of fish oil supplements and risks of all-cause and disease-specific dementia according to the apolipoprotein E (APOE) ε4 dosage.

Methods: A total of 445,961 participants from UK biobank, who were free of dementia at baseline and completed data on supplement use and genetic information were analyzed in this study. Cox proportional hazards models were used to calculate the hazard ratios (HRs) comparing incident dementia rates in participants who did and did not use fish oil.

Results: During a median of 12.2 years of follow-up, a total of 5795 incident cases of dementia were documented, including 1266 cases of vascular dementia and 2382 cases of AD. After adjustment for covariates, use of fish oil supplements was significantly associated with lower risks of all-cause dementia (Hazard ratios, HR, 95% CI, 0.90, 0.85-0.96) and vascular dementia (HR, 0.85; 95% CI, 0.75-0.97), but not AD (HR, 0.99; 95% CI, 0.91-1.09). For all-cause dementia and vascular dementia, we found that the protective associations appeared to be attenuated by the increasing APOE ε4 dosage (P-interaction = 0.002 and 0.002, respectively). Notably, the use of fish oil supplements was significantly associated with an 86.0% higher risk of vascular dementia in participants with two APOE-ε4 alleles (HR, 1.86, 95%CI, 1.23-2.80).

Conclusions: Our results indicate that use of fish oil supplements is differently associated with risks of all-cause dementia and vascular dementia according to the APOE ε4 dosage.