Journal Article

Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment

de Jager, Celeste A., Smith, Stephen M., Jacoby, Robin, Refsum, Helga, Douaud, Gwenaëlle, Nichols, Thomas E., Smith, A. David

2013

Overview

Is it possible to prevent atrophy of key brain regions related to cognitive decline and Alzheimer’s disease (AD)? One approach is to modify nongenetic risk factors, for instance by lowering elevated plasma homocysteine using B vitamins. In an initial, randomized controlled study on elderly subjects with increased dementia risk (mild cognitive impairment according to 2004 Petersen criteria), we showed that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0.5 mg) slowed shrinkage of the whole brain volume over 2 y. Here, we go further by demonstrating that B-vitamin treatment reduces, by as much as seven fold, the cerebral atrophy in those gray matter (GM) regions specifically vulnerable to the AD process, including the medial temporal lobe. In the placebo group, higher homocysteine levels at baseline are associated with faster GM atrophy, but this deleterious effect is largely prevented by B-vitamin treatment. We additionally show that the beneficial effect of B vitamins is confined to participants with high homocysteine (above the median, 11 µmol/L) and that, in these participants, a causal Bayesian network analysis indicates the following chain of events: B vitamins lower homocysteine, which directly leads to a decrease in GM atrophy, thereby slowing cognitive decline. Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline. Further B-vitamin supplementation trials focusing on elderly subjets with high homocysteine levels are warranted to see if progression to dementia can be prevented.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Alzheimer disease / Alzheimer Disease - complications / Alzheimer's disease / Alzheimers disease / atrophy / Bayes Theorem / Bayesian theory / Biological and medical sciences / Biological Sciences / Brain / Cerebellum / Clinical trials / Cognitive ability / Cognitive impairment / Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases / Dementia / Dementia disorders / Dietary supplements / Disease prevention / elderly / England / Entorhinal cortex / Folic acid / Fundamental and applied biological sciences. Psychology / Genetics / Hippocampus / Hippocampus - drug effects / Hippocampus - pathology / homocysteine / Homocysteine - blood / Humans / Image Processing, Computer-Assisted / Linear Models / Longitudinal Studies / Magnetic Resonance Imaging / Medical sciences / Memory / Nerve Degeneration - etiology / Nerve Degeneration - pathology / Nerve Degeneration - prevention & control / Neurology / Older adults / Placebos / pyridoxine / Risk factors / Temporal Lobe - drug effects / Temporal Lobe - pathology / Vertebrates: nervous system and sense organs / Vitamin B / Vitamin B Complex - pharmacology / Vitamin B Complex - therapeutic use / vitamin B12 / Vitamins