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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References	11476837 - Lancet. 2001 Jul 21;358(9277):201-5 22133718 - Sci Transl Med. 2011 Nov 30;3(111):111cm33 14981176 - Neurology. 2004 Feb 24;62(4):591-600 11844848 - N Engl J Med. 2002 Feb 14;346(7):476-83 12557288 - Ann Neurol. 2003 Feb;53(2):214-21 21415848 - Nat Rev Neurosci. 2011 Apr;12(4):217-30 19357304 - Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7209-14 19277975 - Hum Brain Mapp. 2009 Oct;30(10):3238-53 15324362 - J Intern Med. 2004 Sep;256(3):183-94 18709889 - Food Nutr Bull. 2008 Jun;29(2 Suppl):S143-72 21512418 - Neuroreport. 2011 Jun 11;22(8):391-5 16197296 - Clin Chem Lab Med. 2005;43(10):1048-51 15501092 - Neuroimage. 2004;23 Suppl 1:S208-19 18501637 - Neuroimage. 2009 Jan 1;44(1):83-98 18703672 - FASEB J. 2008 Nov;22(11):3823-35 18672473 - Neurology. 2008 Sep 9;71(11):819-25 17537547 - Neurobiol Aging. 2008 Nov;29(11):1654-65 17698497 - Brain. 2007 Sep;130(Pt 9):2375-86 11747097 - Hum Brain Mapp. 2002 Jan;15(1):1-25 20838622 - PLoS One. 2010;5(9):e12244 19959661 - Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21930-5 19661622 - J Alzheimers Dis. 2009;18(4):819-28 11525331 - Neuroimage. 2001 Jul;14(1 Pt 1):21-36 17514200 - Nat Rev Neurosci. 2007 Jun;8(6):481-8 10746355 - Br Med Bull. 1999;55(3):669-82 23365250 - J Neurosci. 2013 Jan 30;33(5):2147-55 11930016 - Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4703-7 22192775 - Mol Neurodegener. 2011;6:85 18295581 - Cell. 2008 Feb 22;132(4):645-60 9646150 - Int J Geriatr Psychiatry. 1998 Apr;13(4):235-9 18375482 - Clin Chem. 2008 May;54(5):801-13 21784352 - Alzheimers Dement. 2011 Jul;7(4):412-7 18765650 - Neurology. 2008 Sep 2;71(10):743-9 20569758 - Am J Med. 2010 Jun;123(6):522-527.e2 20821056 - Neuropsychol Rev. 2010 Sep;20(3):236-60 19460794 - Brain. 2009 Aug;132(Pt 8):2048-57 9823829 - Arch Neurol. 1998 Nov;55(11):1449-55 20975758 - Nat Neurosci. 2010 Nov;13(11):1338-44 22903991 - Science. 2012 Aug 17;337(6096):790-2 16806314 - Neuropsychologia. 2006;44(12):2189-208 18718572 - Biol Psychiatry. 2008 Nov 15;64(10):842-9 20008648 - Arch Neurol. 2009 Dec;66(12):1447-55 18474741 - Arch Neurol. 2008 May;65(5):642-9 19571149 - J Neurosci. 2009 Jul 1;29(26):8586-94 20005012 - Neurobiol Aging. 2011 Oct;32(10):1733-41 21775213 - Lancet Neurol. 2011 Sep;10(9):819-28 22232016 - J Alzheimers Dis. 2012;29(1):133-49 21780182 - Int J Geriatr Psychiatry. 2012 Jun;27(6):592-600 17240287 - Lancet. 2007 Jan 20;369(9557):208-16 12221169 - Neurology. 2002 Sep 10;59(5):746-8
References_xml	– reference: 22232016 - J Alzheimers Dis. 2012;29(1):133-49 – reference: 9646150 - Int J Geriatr Psychiatry. 1998 Apr;13(4):235-9 – reference: 19460794 - Brain. 2009 Aug;132(Pt 8):2048-57 – reference: 11747097 - Hum Brain Mapp. 2002 Jan;15(1):1-25 – reference: 20821056 - Neuropsychol Rev. 2010 Sep;20(3):236-60 – reference: 17240287 - Lancet. 2007 Jan 20;369(9557):208-16 – reference: 15324362 - J Intern Med. 2004 Sep;256(3):183-94 – reference: 19661622 - J Alzheimers Dis. 2009;18(4):819-28 – reference: 22903991 - Science. 2012 Aug 17;337(6096):790-2 – reference: 21775213 - Lancet Neurol. 2011 Sep;10(9):819-28 – reference: 19357304 - Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7209-14 – reference: 18709889 - Food Nutr Bull. 2008 Jun;29(2 Suppl):S143-72 – reference: 11930016 - Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4703-7 – reference: 11476837 - Lancet. 2001 Jul 21;358(9277):201-5 – reference: 16197296 - Clin Chem Lab Med. 2005;43(10):1048-51 – reference: 18375482 - Clin Chem. 2008 May;54(5):801-13 – reference: 9823829 - Arch Neurol. 1998 Nov;55(11):1449-55 – reference: 20975758 - Nat Neurosci. 2010 Nov;13(11):1338-44 – reference: 20005012 - Neurobiol Aging. 2011 Oct;32(10):1733-41 – reference: 18703672 - FASEB J. 2008 Nov;22(11):3823-35 – reference: 10746355 - Br Med Bull. 1999;55(3):669-82 – reference: 22133718 - Sci Transl Med. 2011 Nov 30;3(111):111cm33 – reference: 15501092 - Neuroimage. 2004;23 Suppl 1:S208-19 – reference: 18295581 - Cell. 2008 Feb 22;132(4):645-60 – reference: 18765650 - Neurology. 2008 Sep 2;71(10):743-9 – reference: 18718572 - Biol Psychiatry. 2008 Nov 15;64(10):842-9 – reference: 18672473 - Neurology. 2008 Sep 9;71(11):819-25 – reference: 19571149 - J Neurosci. 2009 Jul 1;29(26):8586-94 – reference: 16806314 - Neuropsychologia. 2006;44(12):2189-208 – reference: 20838622 - PLoS One. 2010;5(9):e12244 – reference: 23365250 - J Neurosci. 2013 Jan 30;33(5):2147-55 – reference: 19959661 - Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21930-5 – reference: 11525331 - Neuroimage. 2001 Jul;14(1 Pt 1):21-36 – reference: 17514200 - Nat Rev Neurosci. 2007 Jun;8(6):481-8 – reference: 18474741 - Arch Neurol. 2008 May;65(5):642-9 – reference: 17537547 - Neurobiol Aging. 2008 Nov;29(11):1654-65 – reference: 21512418 - Neuroreport. 2011 Jun 11;22(8):391-5 – reference: 21415848 - Nat Rev Neurosci. 2011 Apr;12(4):217-30 – reference: 18501637 - Neuroimage. 2009 Jan 1;44(1):83-98 – reference: 21784352 - Alzheimers Dement. 2011 Jul;7(4):412-7 – reference: 22192775 - Mol Neurodegener. 2011;6:85 – reference: 20008648 - Arch Neurol. 2009 Dec;66(12):1447-55 – reference: 19277975 - Hum Brain Mapp. 2009 Oct;30(10):3238-53 – reference: 17698497 - Brain. 2007 Sep;130(Pt 9):2375-86 – reference: 21780182 - Int J Geriatr Psychiatry. 2012 Jun;27(6):592-600 – reference: 12221169 - Neurology. 2002 Sep 10;59(5):746-8 – reference: 11844848 - N Engl J Med. 2002 Feb 14;346(7):476-83 – reference: 14981176 - Neurology. 2004 Feb 24;62(4):591-600 – reference: 20569758 - Am J Med. 2010 Jun;123(6):522-527.e2 – reference: 12557288 - Ann Neurol. 2003 Feb;53(2):214-21
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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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