Science

Thomas J. Littlejohns, MSc; William E. Henley, PhD; Iain A. Lang, PhD; Cedric Annweiler, MD,
PhD; Olivier Beauchet, MD, PhD; Paulo H.M. Chaves, MD, PhD; Linda Fried, MD, MPH; Bryan R. Kestenbaum, MD, MS; Lewis H. Kuller, MD, DrPH; Kenneth M. Langa, MD, PhD; Oscar L. Lopez, MD; Katarina Kos, MD, PhD; Maya Soni, PhD
David J. Llewellyn, PhD

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 Communica- tive 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 multivar- iate adjusted hazard ratios (95% confidence interval [CI]) for incident all-cause dementia in par- ticipants 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.