Fredrik Jernerén1, Tommy Cederholm2,3, Helga Refsum4,5, A David Smith5, Cheryl Turner5, Jan Palmblad6, Maria Eriksdotter3,7, Erik Hjorth7, Gerd Faxen-Irving7, Lars-Olof Wahlund7, Marianne Schultzberg7, Hans Basun2, Yvonne Freund-Levi7,8,9,10. 1. Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden. 2. Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden. 3. Theme Ageing, Karolinska University Hospital, Stockholm, Sweden. 4. Department of Nutrition, University of Oslo, Oslo, Norway. 5. Department of Pharmacology, University of Oxford, Oxford, United Kingdom. 6. Departments of Medicine and Hematology, Karolinska University Hospital Huddinge, and the Karolinska Institutet, Stockholm, Sweden. 7. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden. 8. Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden. 9. Department of Psychiatry in Region Örebro County and School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro. 10. Department of Old Age Psychiatry, Psychology & Neuroscience, King's College, London, UK.
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 gdocosahexaenoic 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.
RCT Entities:
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.
Authors: Ruth Peters; John Breitner; Sarah James; Gregory A Jicha; Pierre-Francois Meyer; Marcus Richards; A David Smith; Hussein N Yassine; Erin Abner; Atticus H Hainsworth; Patrick G Kehoe; Nigel Beckett; Christopher Weber; Craig Anderson; Kaarin J Anstey; Hiroko H Dodge Journal: Alzheimers Dement (N Y) Date: 2021-12-08
Authors: Isabella C Arellanes; Nicholas Choe; Victoria Solomon; Xulei He; Brian Kavin; Ashley E Martinez; Naoko Kono; David P Buennagel; Nalini Hazra; Giselle Kim; Lina M D'Orazio; Carol McCleary; Abhay Sagare; Berislav V Zlokovic; Howard N Hodis; Wendy J Mack; Helena C Chui; Michael G Harrington; Meredith N Braskie; Lon S Schneider; Hussein N Yassine Journal: EBioMedicine Date: 2020-07-17 Impact factor: 8.143