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 (omega3), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may have effects in psychiatric and behavioral symptoms in Alzheimer's disease (AD). An association with APOEomega4 carriers and neuropsychiatric symptoms in AD has also been suggested.


OBJECTIVE
To determine effects of dietary omega3 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 0.6 g EPA (omega3 group) or placebo for 6 months. Then, all received the omega3 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 APOEomega4 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 APOEomega4 carriers (p=0.006) and in MADRS scores in non-APOEomega4 carriers (p=0.005) were found.


CONCLUSIONS
Supplementation with omega3 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-APOEomega4 carriers and agitation symptoms (assessed by NPI) in APOEomega4 carriers. ClinicalTrials.gov identifier: NCT00211159
Freund-Levi
Yvonne
Y
Department of NVS, Section of Clinical Geriatrics, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden. Yvonne.Freund-Levi@ki.se
Basun
Hans
H
Cederholm
Tommy
T
Faxén-Irving
Gerd
G
Garlind
Anita
A
Grut
Mikaela
M
Vedin
Inger
I
Palmblad
Jan
J
Wahlund
Lars-Olof
LO
Eriksdotter-Jönhagen
Maria
M
D000203:Activities of Daily Living; D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy; D019587:Dietary Supplements; D000077265:Donepezil; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D005702:Galantamine / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D008297:Male; D048448:Phenylcarbamates / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D000068836:Rivastigmine; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D001057:Apolipoproteins E; D002800:Cholinesterase Inhibitors; D015525:Fatty Acids, Omega-3; D007189:Indans; D048448:Phenylcarbamates; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil; D000068836:Rivastigmine