Association of Vitamin B12, Folate, and Sulfur Amino Acids With Brain Magnetic Resonance Imaging Measures in Older Adults: A Longitudinal Population-Based Study.
Vitamin B12, folate, and sulfur amino acids may be modifiable risk factors for structural brain changes that precede clinical dementia.



To investigate the association of circulating levels of vitamin B12, red blood cell folate, and sulfur amino acids with the rate of total brain volume loss and the change in white matter hyperintensity volume as measured by fluid-attenuated inversion recovery in older adults.



The magnetic resonance imaging subsample of the Swedish National Study on Aging and Care in Kungsholmen, a population-based longitudinal study in Stockholm, Sweden, was conducted in 501 participants aged 60 years or older who were free of dementia at baseline. A total of 299 participants underwent repeated structural brain magnetic resonance imaging scans from September 17, 2001, to December 17, 2009.



The rate of brain tissue volume loss and the progression of total white matter hyperintensity volume.



In the multi-adjusted linear mixed models, among 501 participants (300 women [59.9%]; mean [SD] age, 70.9 [9.1] years), higher baseline vitamin B12 and holotranscobalamin levels were associated with a decreased rate of total brain volume loss during the study period: for each increase of 1 SD, β (SE) was 0.048 (0.013) for vitamin B12 (P < .001) and 0.040 (0.013) for holotranscobalamin (P = .002). Increased total homocysteine levels were associated with faster rates of total brain volume loss in the whole sample (β [SE] per 1-SD increase, -0.035 [0.015]; P = .02) and with the progression of white matter hyperintensity among participants with systolic blood pressure greater than 140 mm Hg (β [SE] per 1-SD increase, 0.000019 [0.00001]; P = .047). No longitudinal associations were found for red blood cell folate and other sulfur amino acids.



This study suggests that both vitamin B12 and total homocysteine concentrations may be related to accelerated aging of the brain. Randomized clinical trials are needed to determine the importance of vitamin B12 supplementation on slowing brain aging in older adults.
Center for Alzheimer Research-Aging Research Center, Karolinska Institutet, Stockholm University, Stockholm, Sweden2Department of Neurology, Klinikum Augsburg, Augsburg, Germany.
Babak
B
Hooshmand
Center for Alzheimer Research-Aging Research Center, Karolinska Institutet, Stockholm University, Stockholm, Sweden.
Francesca
F
Mangialasche
Center for Alzheimer Research-Aging Research Center, Karolinska Institutet, Stockholm University, Stockholm, Sweden.
Grégoria
G
Kalpouzos
Center for Alzheimer Research-Aging Research Center, Karolinska Institutet, Stockholm University, Stockholm, Sweden.
Alina
A
Solomon
Center for Alzheimer Research-Aging Research Center, Karolinska Institutet, Stockholm University, Stockholm, Sweden3Institute of Gerontology, School of Health and Welfare, Jönköping University, Jönköping, Sweden.
Ingemar
I
Kåreholt
Department of Pharmacology, University of Oxford, Oxford, UK.
A David
AD
Smith
Department of Pharmacology, University of Oxford, Oxford, UK5Institute of Nutrition, University of Oslo, Oslo, Norway.
Helga
H
Refsum
Center for Alzheimer Research-Aging Research Center, Karolinska Institutet, Stockholm University, Stockholm, Sweden.
Rui
R
Wang
Institute for Clinical Radiology, Ludwig-Maximillian University Hospital, Munich, Germany.
Marc
M
Mühlmann
Institute for Clinical Radiology, Ludwig-Maximillian University Hospital, Munich, Germany.
Birgit
B
Ertl-Wagner
Center for Alzheimer Research-Aging Research Center, Karolinska Institutet, Stockholm University, Stockholm, Sweden.
Erika Jonsson
EJ
Laukka
Center for Alzheimer Research-Aging Research Center, Karolinska Institutet, Stockholm University, Stockholm, Sweden.
Lars
L
Bäckman
Center for Alzheimer Research-Aging Research Center, Karolinska Institutet, Stockholm University, Stockholm, Sweden.
Laura
L
Fratiglioni
Center for Alzheimer Research-Aging Research Center, Karolinska Institutet, Stockholm University, Stockholm, Sweden.
Miia
M
Kivipelto
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D000603:Amino Acids, Sulfur / Q000097:blood*; D001284:Atrophy; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013223:Statistics as Topic; D013548:Sweden; D014805:Vitamin B 12 / Q000097:blood*; D066127:White Matter / Q000000981:diagnostic imaging
D000603:Amino Acids, Sulfur; D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12