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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.AJ

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.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Jernerén F
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.
Elshorbagy AK
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;
Oulhaj A
Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates;
Smith SM
Functional Magnetic Resonance Imaging of the Brain Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; and.
Refsum H
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.
Smith AD
From the Oxford Project to Investigate Memory and Ageing (OPTIMA), Department of Pharmacology, University of Oxford, Oxford, United Kingdom;

MeSH

AgedAtrophyBody Mass IndexBrainCognition DisordersDietary SupplementsDocosahexaenoic AcidsEicosapentaenoic AcidFemaleHomocysteineHumansMagnetic Resonance ImagingMaleNutritional StatusRetrospective StudiesVitamin B Complex

Pub Type(s)

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

Language

eng

PubMed ID

25877495

Citation

Jernerén, Fredrik, et al. "Brain Atrophy in Cognitively Impaired Elderly: the Importance of Long-chain Ω-3 Fatty Acids and B Vitamin Status in a Randomized Controlled Trial." The American Journal of Clinical Nutrition, vol. 102, no. 1, 2015, pp. 215-21.
Jernerén F, Elshorbagy AK, Oulhaj A, et al. 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;102(1):215-21.
Jernerén, F., Elshorbagy, A. K., Oulhaj, A., Smith, S. M., Refsum, H., & Smith, A. D. (2015). Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial. The American Journal of Clinical Nutrition, 102(1), 215-21. https://doi.org/10.3945/ajcn.114.103283
Jernerén F, et al. 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;102(1):215-21. PubMed PMID: 25877495.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial. AU - Jernerén,Fredrik, AU - Elshorbagy,Amany K, AU - Oulhaj,Abderrahim, AU - Smith,Stephen M, AU - Refsum,Helga, AU - Smith,A David, Y1 - 2015/04/15/ PY - 2014/11/18/received PY - 2015/03/19/accepted PY - 2015/4/17/entrez PY - 2015/4/17/pubmed PY - 2015/9/12/medline KW - B vitamin KW - brain atrophy KW - homocysteine KW - mild cognitive impairment KW - ω-3 SP - 215 EP - 21 JF - The American journal of clinical nutrition JO - Am J Clin Nutr VL - 102 IS - 1 N2 - 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. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/25877495/Brain_atrophy_in_cognitively_impaired_elderly:_the_importance_of_long_chain_ω_3_fatty_acids_and_B_vitamin_status_in_a_randomized_controlled_trial_ DB - PRIME DP - Unbound Medicine ER -