title: Association of Serum Vitamin D with the Risk of Incident Dementia and Subclinical Indices of Brain Aging: The Framingham Heart Study.
abstract: BACKGROUND
  Identifying nutrition- and lifestyle-based risk factors for cognitive impairment and dementia may aid future primary prevention efforts.
  
  
  OBJECTIVE
  We aimed to examine the association of serum vitamin D levels with incident all-cause dementia, clinically characterized Alzheimer's disease (AD), MRI markers of brain aging, and neuropsychological function.
  
  
  METHODS
  Framingham Heart Study participants had baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations measured between 1986 and 2001. Vitamin D status was considered both as a continuous variable and dichotomized as deficient (<10 ng/mL), or at the cohort-specific 20th and 80th percentiles. Vitamin D was related to the 9-year risk of incident dementia (n = 1663), multiple neuropsychological tests (n = 1291) and MRI markers of brain volume, white matter hyperintensities and silent cerebral infarcts (n = 1139).
  
  
  RESULTS
  In adjusted models, participants with vitamin D deficiency (n = 104, 8% of the cognitive sample) displayed poorer performance on Trail Making B-A (β= -0.03 to -0.05±0.02) and the Hooper Visual Organization Test (β= -0.09 to -0.12±0.05), indicating poorer executive function, processing speed, and visuo-perceptual skills. These associations remained when vitamin D was examined as a continuous variable or dichotomized at the cohort specific 20th percentile. Vitamin D deficiency was also associated with lower hippocampal volumes (β= -0.01±0.01) but not total brain volume, white matter hyperintensities, or silent brain infarcts. No association was found between vitamin D deficiency and incident all-cause dementia or clinically characterized AD.
  
  
  CONCLUSIONS
  In this large community-based sample, low 25(OH)D concentrations were associated with smaller hippocampal volume and poorer neuropsychological function.
authors.affiliation: Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Karakis
authors.affiliation: Framingham Heart Study, Framingham, MA, USA.|Department of Neurology, Boston University School of Medicine, Boston, MA, USA.|Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn, Australia.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Pase
authors.affiliation: Framingham Heart Study, Framingham, MA, USA.|Department of Neurology, Boston University School of Medicine, Boston, MA, USA.|Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Alexa
authors.initials: A
authors.lastname: Beiser
authors.affiliation: Jean Mayer-U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Booth
authors.affiliation: Jean Mayer-U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Jacques
authors.affiliation: Jean Mayer-U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Gail
authors.initials: G
authors.lastname: Rogers
authors.affiliation: Imaging of Dementia and Aging (IDeA) Laboratory, Department of Neurology and Center for Neuroscience, University of California, Davis, CA, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.affiliation: Framingham Heart Study, Framingham, MA, USA.
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.affiliation: Framingham Heart Study, Framingham, MA, USA.|Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Jayandra J
authors.initials: JJ
authors.lastname: Himali
authors.affiliation: Department of Neuroscience, Division of Geriatric Medicine, University of Angers, France.|Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada.
authors.forename: Cedric
authors.initials: C
authors.lastname: Annweiler
authors.affiliation: Framingham Heart Study, Framingham, MA, USA.|Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
mesh_terms: D000328:Adult; D000375:Aging / Q000097:blood / Q000473:pathology; D001921:Brain / Q000000981:diagnostic imaging*; D015331:Cohort Studies; D003704:Dementia / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009483:Neuropsychological Tests; D012044:Regression Analysis; D012306:Risk; D012680:Sensitivity and Specificity; D014807:Vitamin D / Q000097:blood*
chemical_list: D014807:Vitamin D
keywords: Alzheimer’s disease; brain; dementia; diet; lifestyle; magnetic resonance imaging; neuropsychology; nutritional status; risk factors; vitamin D