title: Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial.
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).
  
  
  METHODS
  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.
authors: From the Oxford Project to Investigate Memory and Ageing (OPTIMA), Department of Pharmacology, University of Oxford, Oxford, United Kingdom; fredrik.jerneren@pharm.ox.ac.uk.
authors: Fredrik
authors: F
authors: Jernerén
authors: From the Oxford Project to Investigate Memory and Ageing (OPTIMA), Department of Pharmacology, University of Oxford, Oxford, United Kingdom; Department of Physiology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt;
authors: Amany K
authors: AK
authors: Elshorbagy
authors: Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates;
authors: Abderrahim
authors: A
authors: Oulhaj
authors: Functional Magnetic Resonance Imaging of the Brain Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; and.
authors: Stephen M
authors: SM
authors: Smith
authors: From the Oxford Project to Investigate Memory and Ageing (OPTIMA), Department of Pharmacology, University of Oxford, Oxford, United Kingdom; Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors: Helga
authors: H
authors: Refsum
authors: From the Oxford Project to Investigate Memory and Ageing (OPTIMA), Department of Pharmacology, University of Oxford, Oxford, United Kingdom;
authors: A David
authors: AD
authors: Smith
mesh_terms: D000368:Aged; D001284:Atrophy; D015992:Body Mass Index; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000473:pathology*; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000097:blood*; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000097:blood*; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009752:Nutritional Status; D012189:Retrospective Studies; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000097:blood*
chemical_list: D006710:Homocysteine; D014803:Vitamin B Complex; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid
keywords: B vitamin; brain atrophy; homocysteine; mild cognitive impairment; ω-3