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

• Published in: The American journal of clinical nutrition Vol. 102; no. 1; pp. 215 - 221
• Main Authors: Jernerén, Fredrik, Elshorbagy, Amany K, Oulhaj, Abderrahim, Smith, Stephen M, Refsum, Helga, Smith, A David
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Nutrition 01.07.2015
• Subjects: Aged; Alzheimer disease; Atrophy; B vitamin; Body Mass Index; brain; Brain - pathology; brain atrophy; Cognition Disorders - pathology; Dietary Supplements; docosahexaenoic acid; Docosahexaenoic Acids - administration & dosage; Docosahexaenoic Acids - blood; eicosapentaenoic acid; Eicosapentaenoic Acid - administration & dosage; Eicosapentaenoic Acid - blood; elderly; Female; folic acid; homocysteine; Homocysteine - blood; Humans; Magnetic Resonance Imaging; Male; mild cognitive impairment; Nutritional Status; omega-3 fatty acids; people; placebos; pyridoxine; randomized clinical trials; Retrospective Studies; Vitamin B Complex - administration & dosage; Vitamin B Complex - blood; vitamin B12; vitamin status; vitamin supplements; ω-3; homocysteine; ω-3; B vitamin; mild cognitive impairment; brain atrophy
• ISSN: 0002-9165; 1938-3207; 1938-3207
• DOI: 10.3945/ajcn.114.103283

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.