Omega-3 supplementation in mild to moderate Alzheimer's disease:: effects on neuropsychiatric symptoms

Background Epidemiological and animal studies have suggested that dietary fish or fish oil rich in omega-3 fatty acids (omega 3), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may have effects in psychiatric and behavioral symptoms in Alzheimer's disease (AD). An association with APOE omega A carriers and neuropsychiatric symptoms in AD has also been suggested. Objective To determine effects of dietary omega 3 supplementation to AD patients with mild to moderate disease on psychiatric and behavioral symptoms, daily functions and a possible relation to APOEgenotype. Methods Randomized, double-blind, placebo-controlled clinical trial where 204 AD patients (74 +/- 9 years) with acetylcholine esterase inhibitor treatment and a MMSE > 15 points were randomized to daily intake of 1.7 g DHA and 0.6g EPA (omega 3 group) or placebo for 6 months. Then, all received the 0 supplementation for 6 more months. Neuropsychiatric symptoms were measured with Neuropsychiatric Inventory (NPI) and Montgomery Asberg Depression Scale (MADRS). Caregivers burden and activities of daily living (Disability Assessment for Dementia, DAD) were also assessed. Results One hundred and seventy-four patients fulfilled the trial. 72% were APOE omega A carriers. No significant overall treatment effects on neuropsychiatric symptoms, on activities of daily living or on caregiver's burden were found, However, significant positive treatment effects on the scores in the NPI agitation domain in APOE omega 4 carriers (p=0.006) and in MADRS scores in non-APOE omega A carriers (p=0.005) were found. Conclusions Supplementation with omega 3 in patients with mild to moderate AD did not result in marked effects on neuropsychiatric symptoms except for possible positive effects on depressive symptoms (assessed by MADRS) in non-APOE omega A carriers and agitation symptoms (assessed by NPI) in APOE omega A carriers. ClinicalTrials.gov identifier: NCT00211159. Copyright (c) 2007 John Wiley & Sons, Ltd.