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Littlejohns, Thomas J; Henley, William E; Lang, Iain A; Annweiler, Cedric; Beauchet, Olivier; Chaves, Paulo H M; Fried, Linda; Kestenbaum, Bryan R; Kuller, Lewis H; Langa, Kenneth M; Lopez, Oscar L; Kos, Katarina; Soni, Maya; Llewellyn, David J
Neurology, 2014-September-2, Volume: 83, Issue: 10Journal Article
To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease. 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. 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. 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.
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