Vitamin D and the risk of dementia and Alzheimer disease
Littlejohns, Thomas J.
Henley, William E.
Chaves, Paolo H.M.
Kestenbaum, Bryan R.
Kuller, Lewis H.
Lopez, Oscar L.
American Academy of Neurology (AAN) / Lippincott, Williams & Wilkins
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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.
National Heart, Lung, and Blood Institute
National Institute of Neurological Disorders and Stroke
National Institute on Aging
Mary Kinross Charitable Trust
James Tudor Foundation
Age Related Diseases and Health Trust
Norman Family Charitable Trust
UK National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula
Vol. 83 (10), pp. 920 - 928
Place of publication