Association of serum Vitamin D with the risk of incident dementia and subclinical indices of brain aging: The framingham heart study

Ioannis Karakis, Matthew P. Pase, Alexa Beiser, Sarah L. Booth, Paul F. Jacques, Gail Rogers, Charles DeCarli, Ramachandran S. Vasan, Thomas J. Wang, Jayandra J. Himali, Cedric Annweiler, Sudha Seshadri

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


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 (<10ng/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.

Original languageEnglish (US)
Pages (from-to)451-461
Number of pages11
JournalJournal of Alzheimer's Disease
Issue number2
StatePublished - Mar 15 2016
Externally publishedYes


  • Alzheimer's disease
  • Vitamin D
  • brain
  • dementia
  • diet
  • lifestyle
  • magnetic resonance imaging
  • neuropsychology
  • nutritional status
  • risk factors

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Clinical Psychology
  • General Neuroscience


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