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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 \u00b5mol\/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.<\/jats:p>","DOI":"10.1073\/pnas.1301816110","type":"journal-article","created":{"date-parts":[[2013,5,21]],"date-time":"2013-05-21T01:03:59Z","timestamp":1369098239000},"page":"9523-9528","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":470,"title":["Preventing Alzheimer\u2019s disease-related gray matter atrophy by B-vitamin treatment"],"prefix":"10.1073","volume":"110","author":[{"given":"Gwena\u00eblle","family":"Douaud","sequence":"first","affiliation":[{"name":"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;"},{"name":"Department of Pharmacology, University of Oxford, Oxford OX1 3QT, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helga","family":"Refsum","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford, Oxford OX1 3QT, United Kingdom;"},{"name":"Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;"},{"name":"Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celeste A.","family":"de Jager","sequence":"additional","affiliation":[{"name":"Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Jacoby","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford OX3 7JX, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"E. Nichols","sequence":"additional","affiliation":[{"name":"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;"},{"name":"Department of Statistics and"},{"name":"Warwick Manufacturing Group, University of Warwick, Coventry CV4 7AL, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Smith","sequence":"additional","affiliation":[{"name":"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;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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