Brain atrophy in cognitively impaired elderly: the importance of long-chain v-3 fatty acids and B vitamin status in a randomized controlled trial 1,2 Fredrik Jernerén, 3* Amany K Elshorbagy, 3,4 Abderrahim Oulhaj, 5 Stephen M Smith, 6 Helga Refsum, 3,7 and A David Smith 3 3 From the Oxford Project to Investigate Memory and Ageing (OPTIMA), Department of Pharmacology, University of Oxford, Oxford, United Kingdom; 4 Department of Physiology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt; 5 Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; 6 Functional Magnetic Resonance Imaging of the Brain Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; and 7 Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway 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 (v-3) fatty acids and homocysteine areassociated with the development of brain atrophy and dementia. Objective:We investigated whether plasmav-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).Thesubjects 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 combinedv-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates. In subjects with high baselinev-3 fatty acids (.590mmol/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 baselinev-3 fatty acids (,390mmol/L). High baselinev-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 plasmav-3 fatty acids. It is also suggested that the beneficial effect ofv 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. Am J Clin Nutr 2015;102:215–21.
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