Brain atrophy in cognitively impaired elderly: The importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial

Fredrik Jernerén, Amany K. Elshorbagy, Abderrahim Oulhaj, Stephen M. Smith, Helga Refsum, A. David Smith

Research output: Contribution to journalArticlepeer-review

115 Citations (Scopus)

Abstract

Background: Increased brain atrophy rates are common in older people with cognitive impairment, particularly in those who eventually convert to Alzheimer disease. Plasma concentrations of omega-3 (ω-3) fatty acids and homocysteine are associated with the development of brain atrophy and dementia. Objective: We investigated whether plasma v-3 fatty acid concentrations (eicosapentaenoic acid and docosahexaenoic acid) modify the treatment effect of homocysteine-lowering B vitamins on brain atrophy rates in a placebo-controlled trial (VITACOG). Design: This retrospective analysis included 168 elderly people (≥70 y) with mild cognitive impairment, randomly assigned either to placebo (n = 83) or to daily high-dose B vitamin supplementation (folic acid, 0.8 mg; vitamin B-6, 20 mg; vitamin B-12, 0.5 mg) (n = 85). The subjects underwent cranial magnetic resonance imaging scans at baseline and 2 y later. The effect of the intervention was analyzed according to tertiles of baseline v-3 fatty acid concentrations. Results: There was a significant interaction (P = 0.024) between B vitamin treatment and plasma combined ω-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates. In subjects with high baseline ω-3 fatty acids (>590 μmol/L), B vitamin treatment slowed the mean atrophy rate by 40.0% compared with placebo (P = 0.023). B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baseline ω-3 fatty acids (<390 mmol/L). High baseline ω-3 fatty acids were associated with a slower rate of brain atrophy in the B vitamin group but not in the placebo group. Conclusions: The beneficial effect of B vitamin treatment on brain atrophy was observed only in subjects with high plasma v-3 fatty acids. It is also suggested that the beneficial effect of v-3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status. The results highlight the importance of identifying subgroups likely to benefit in clinical trials.

Original languageEnglish
Pages (from-to)215-221
Number of pages7
JournalAmerican Journal of Clinical Nutrition
Volume102
Issue number1
DOIs
Publication statusPublished - Jul 1 2015

Keywords

  • B vitamin
  • Brain atrophy
  • Homocysteine
  • Mild cognitive impairment
  • ω-3

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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