Brain Atrophy in Cognitively Impaired Elderly: The Importance of Long-Chain ω-3 Fatty Acids and B Vitamin Status in a Randomized Controlled Trial

Am J Clin Nutr. 2015 Jul;102(1):215-21. doi: 10.3945/ajcn.114.103283. Epub 2015 Apr 15.

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 ω-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 ω-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 μmol/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 ω-3 fatty acids. It is also suggested that the beneficial effect of ω-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. This trial was registered at www.controlled-trials.com as ISRCTN94410159.

Keywords: B vitamin; brain atrophy; homocysteine; mild cognitive impairment; ω-3.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atrophy
  • Body Mass Index
  • Brain / pathology*
  • Cognition Disorders / pathology*
  • Dietary Supplements
  • Docosahexaenoic Acids / administration & dosage
  • Docosahexaenoic Acids / blood*
  • Eicosapentaenoic Acid / administration & dosage
  • Eicosapentaenoic Acid / blood*
  • Female
  • Homocysteine / blood
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Nutritional Status
  • Retrospective Studies
  • Vitamin B Complex / administration & dosage
  • Vitamin B Complex / blood*

Substances

  • Homocysteine
  • Vitamin B Complex
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid

Associated data

  • ISRCTN/ISRCTN94410159