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Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer's Disease: The OmegAD Study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Karolinska Univ Hosp, Theme Ageing, Stockholm, Sweden.ORCID iD: 0000-0003-3705-0725
Univ Oslo, Dept Nutr, Oslo, Norway;Univ Oxford, Dept Pharmacol, Oxford, England.
Univ Oxford, Dept Pharmacol, Oxford, England.
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2019 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 69, no 1, p. 189-197Article in journal (Refereed) Published
Abstract [en]

Background: Trials of supplementation with omega-3 fatty acids (omega 3-FAs) in patients with mild cognitive impairment or Alzheimer's disease (AD) have produced inconsistent effects on cognitive decline. There is evidence of an interaction between B vitamin status and omega 3-FAs in relation to brain atrophy and cognitive decline.

Objective: We investigated whether baseline levels of plasma total homocysteine (tHcy), a marker of B vitamin status, modify the effects of omega 3-FAs supplementation on cognitive performance in moderate AD.

Methods: This post hoc analysis of the OmegAD trial included 171 community-based patients with AD (MMSE >= 15): 88 patients received daily doses of 1.7 g docosahexaenoic acid and 0.6 g eicosapentaenoic acid for 6 months. Treatment outcome on cognition was analyzed according to baseline levels of tHcy using a general linear model and ANCOVA.

Results: We found significant interactions between omega 3-FA supplementation and tHcy on cognition and clinical stage assessed by MMSE (p = 0.040), global CDR (p = 0.059), and CDRsob (p = 0.023), but not on ADAS-cog (p = 0.649). In patients with tHcy levels <11.7 mu mol/L, omega 3-FA supplementation improved cognitive performance as measured by MMSE (+7.1%, 95% CI: 0.59 to 13.7%, p = 0.033) and clinical status as measured by CDRsob (-22.3%, 95% CI: -5.8 to -38.7%, p = 0.009) compared with placebo.

Conclusion: The effect of omega 3-FA supplementation on MMSE and CDR appears to be influenced by baseline tHcy, suggesting that adequate B vitamin status is required to obtain beneficial effects of omega 3-FA on cognition.

Place, publisher, year, edition, pages
2019. Vol. 69, no 1, p. 189-197
Keywords [en]
Alzheimer's disease, B vitamins, cognition, dementia, homocysteine, omega-3 fatty acids
National Category
Neurology
Identifiers
URN: urn:nbn:se:uu:diva-384475DOI: 10.3233/JAD-181148ISI: 000467519100017PubMedID: 30958356OAI: oai:DiVA.org:uu-384475DiVA, id: diva2:1323072
Funder
The Swedish Brain FoundationThe Dementia Association - The National Association for the Rights of the DementedThe Karolinska Institutet's Research FoundationStiftelsen Gamla TjänarinnorÅke Wiberg Foundation, M16-0251Swedish Nutrition Foundation (SNF)Gun och Bertil Stohnes StiftelseSwedish Society of MedicineAvailable from: 2019-06-11 Created: 2019-06-11 Last updated: 2019-06-11Bibliographically approved

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Jernerén, FredrikCederholm, TommyBasun, Hans

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