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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
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; Theme Ageing, Karolinska University Hospital, Stockholm, Sweden.
Department of Nutrition, University of Oslo, Oslo, Norway; Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
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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
IOS Press, 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:oru:diva-74426DOI: 10.3233/JAD-181148ISI: 000467519100017PubMedID: 30958356Scopus ID: 2-s2.0-85065659695OAI: oai:DiVA.org:oru-74426DiVA, id: diva2:1318532
Funder
Stockholm County CouncilThe Karolinska Institutet's Research FoundationThe Dementia Association - The National Association for the Rights of the DementedStiftelsen Gamla TjänarinnorThe Swedish Brain FoundationSwedish Nutrition Foundation (SNF)Gun och Bertil Stohnes StiftelseÅke Wiberg Foundation
Note

Funding Agencies:

Funds of Capio

Swedish Alzheimer Foundation  

Norwegian Research Council  

Odd Fellows 

Swedish Society of Physicians  

Lion's Sweden 

Available from: 2019-05-28 Created: 2019-05-28 Last updated: 2019-05-28Bibliographically approved

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Freund-Levi, Yvonne

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