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

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 subj...

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Veröffentlicht in:	Proceedings of the National Academy of Sciences - PNAS Jg. 110; H. 23; S. 9523
Hauptverfasser:	Douaud, Gwenaëlle, Refsum, Helga, de Jager, Celeste A, Jacoby, Robin, Nichols, Thomas E, Smith, Stephen M, Smith, A David
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 04.06.2013
Schlagworte:	Alzheimer Disease - complications Bayes Theorem England Hippocampus - drug effects Hippocampus - pathology Homocysteine - blood Humans Image Processing, Computer-Assisted Linear Models Longitudinal Studies Magnetic Resonance Imaging Nerve Degeneration - etiology Nerve Degeneration - pathology Nerve Degeneration - prevention & control Temporal Lobe - drug effects Temporal Lobe - pathology Vitamin B Complex - pharmacology Vitamin B Complex - therapeutic use England clinical trial structural neuroimaging hippocampus causal modeling degeneration
ISSN:	1091-6490, 1091-6490
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Abstract	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.
AbstractList	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.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. 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.
Author	Smith, Stephen M Jacoby, Robin Nichols, Thomas E Smith, A David Refsum, Helga de Jager, Celeste A Douaud, Gwenaëlle
Author_xml	– sequence: 1 givenname: Gwenaëlle surname: Douaud fullname: Douaud, Gwenaëlle email: douaud@fmrib.ox.ac.uk organization: Functional Magnetic Resonance Imaging of the Brain (FMRIB) Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. douaud@fmrib.ox.ac.uk – sequence: 2 givenname: Helga surname: Refsum fullname: Refsum, Helga – sequence: 3 givenname: Celeste A surname: de Jager fullname: de Jager, Celeste A – sequence: 4 givenname: Robin surname: Jacoby fullname: Jacoby, Robin – sequence: 5 givenname: Thomas E surname: Nichols fullname: Nichols, Thomas E – sequence: 6 givenname: Stephen M surname: Smith fullname: Smith, Stephen M – sequence: 7 givenname: A David surname: Smith fullname: Smith, A David
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/23690582$$D View this record in MEDLINE/PubMed
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Snippet	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...
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SubjectTerms	Alzheimer Disease - complications Bayes Theorem England Hippocampus - drug effects Hippocampus - pathology Homocysteine - blood Humans Image Processing, Computer-Assisted Linear Models Longitudinal Studies Magnetic Resonance Imaging Nerve Degeneration - etiology Nerve Degeneration - pathology Nerve Degeneration - prevention & control Temporal Lobe - drug effects Temporal Lobe - pathology Vitamin B Complex - pharmacology Vitamin B Complex - therapeutic use
Title	Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment
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