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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.

Abstract

BACKGROUND

Trials of supplementation with omega-3 fatty acids (ω3-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 ω3-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 ω3-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 ω3-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 <11.7μmol/L, ω3-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 ω3-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 ω3-FA on cognition.

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  • Authors+Show Affiliations

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    Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.

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    Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden. Theme Ageing, Karolinska University Hospital, Stockholm, Sweden.

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    Department of Nutrition, University of Oslo, Oslo, Norway. Department of Pharmacology, University of Oxford, Oxford, United Kingdom.

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    Department of Pharmacology, University of Oxford, Oxford, United Kingdom.

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    Department of Pharmacology, University of Oxford, Oxford, United Kingdom.

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    Departments of Medicine and Hematology, Karolinska University Hospital Huddinge, and the Karolinska Institutet, Stockholm, Sweden.

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    Theme Ageing, Karolinska University Hospital, Stockholm, Sweden. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.

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    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.

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    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.

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    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.

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    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.

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    Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.

    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden. Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden. Department of Psychiatry in Region Örebro County and School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro. Department of Old Age Psychiatry, Psychology & Neuroscience, King's College, London, UK.

    Source

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    30958356

    Citation

    Jernerén, Fredrik, et al. "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." Journal of Alzheimer's Disease : JAD, vol. 69, no. 1, 2019, pp. 189-197.
    Jernerén F, Cederholm T, Refsum H, et al. 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. J Alzheimers Dis. 2019;69(1):189-197.
    Jernerén, F., Cederholm, T., Refsum, H., Smith, A. D., Turner, C., Palmblad, J., ... Freund-Levi, Y. (2019). 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. Journal of Alzheimer's Disease : JAD, 69(1), pp. 189-197. doi:10.3233/JAD-181148.
    Jernerén F, et al. 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. J Alzheimers Dis. 2019;69(1):189-197. PubMed PMID: 30958356.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - 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. AU - Jernerén,Fredrik, AU - Cederholm,Tommy, AU - Refsum,Helga, AU - Smith,A David, AU - Turner,Cheryl, AU - Palmblad,Jan, AU - Eriksdotter,Maria, AU - Hjorth,Erik, AU - Faxen-Irving,Gerd, AU - Wahlund,Lars-Olof, AU - Schultzberg,Marianne, AU - Basun,Hans, AU - Freund-Levi,Yvonne, PY - 2019/4/9/pubmed PY - 2019/4/9/medline PY - 2019/4/9/entrez KW - Alzheimer’s disease KW - B vitamins KW - cognition KW - dementia KW - homocysteine KW - omega-3 fatty acids SP - 189 EP - 197 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 69 IS - 1 N2 - BACKGROUND: Trials of supplementation with omega-3 fatty acids (ω3-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 ω3-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 ω3-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 ω3-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 <11.7μmol/L, ω3-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 ω3-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 ω3-FA on cognition. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/30958356/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_ L2 - https://content.iospress.com/openurl?genre=article&amp;id=doi:10.3233/JAD-181148 DB - PRIME DP - Unbound Medicine ER -