Vitamin D and the risk of dementia and Alzheimer disease



Vitamin D and the risk of dementia and Alzheimer disease

  1. Thomas J. Littlejohns, MSc,
  2. William E. Henley, PhD,
  3. Iain A. Lang, PhD,
  4. Cedric Annweiler, MD, PhD,
  5. Olivier Beauchet, MD, PhD,
  6. Paulo H.M. Chaves, MD, PhD,
  7. Linda Fried, MD, MPH,
  8. Bryan R. Kestenbaum, MD, MS,
  9. Lewis H. Kuller, MD, DrPH,
  10. Kenneth M. Langa, MD, PhD,
  11. Oscar L. Lopez, MD,
  12. Katarina Kos, MD, PhD,
  13. Maya Soni, PhD*and
  14. David J. Llewellyn, PhD*



  1. Correspondence to Dr. Llewellyn:
  1. Published online before print August 6, 2014, doi: 10.1212/WNL.0000000000000755Neurology September 2, 2014 vol. 83 no. 10 920-928
  1. Also available:
  2. Figures Only
  3. Data Supplement
  4. PPT Slides of All Figures


Objective: To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease.

Methods: One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population–based Cardiovascular Health Study between 1992–1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992–1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer’s Disease and Related Disorders Association criteria.

Results: During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25 to <50 nmol/L) were 2.25 (95% CI: 1.23–4.13) and 1.53 (95% CI: 1.06–2.21) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95% CI: 1.02–4.83) and 1.69 (95% CI: 1.06–2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L.

Conclusion: Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions.


  • Go to for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by The National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) South West Peninsula.

  • * These authors contributed equally to the manuscript.

  • Supplemental data at

  • Received February 3, 2014.
  • Accepted in final form May 28, 2014.

This is an open access article distributed under the terms of the Creative Commons Attribution-Noncommercial No Derivative 3.0 License, which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.


  • Vitamin D deficiency and the risk of dementia

    • Robert H Howland

    published online August 28, 2014

  • Disturbed sleep: the trigger for vitamin D deficiency?

    • Sergio Tufik

    published online August 14, 2014


Print ISSN: 0028-3878
Online ISSN: 1526-632X
    • American Academy of Neurology
    • HighWire
    • Wolters Kluwer Lippincott Williams  Wilkins
WriteClick is a trademark of the AAN, registered in the U.S.
© 2014 American Academy of Neurology | Help | Feedback | Advertise
This entry was posted in Aging, China, Complementary - Alternative Medicine, development, dietary, epigenetics, Events, International And Concierge Medicine, metabolic, News, Psychiatry/Neurology and tagged . Bookmark the permalink.

Comments are closed.