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Vitamin D and the risk of dementia and Alzheimer disease.

Abstract

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.

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    ,

    From the University of Exeter Medical School (T.J.L., W.E.H., I.A.L., K.K., M.S., D.J.L.), Exeter, UK; Department of Internal Medicine and Geriatrics (C.A., O.B.), Angers University Hospital, Angers, France; Herbert Wertheim College of Medicine (P.H.M.C.), Florida International University, Miami; Mailman School of Public Health (L.F.), Columbia University, New York; Kidney Research Institute, Division of Nephrology (B.R.K.), University of Washington, Seattle; Departments of Epidemiology (L.H.K.) and Neurology and Psychiatry (O.L.L.), University of Pittsburgh, PA; Division of General Medicine (K.M.L.), Veterans Affairs Ann Arbor Center for Clinical Management Research, Ann Arbor, MI; and the Institute for Social Research and the Institute for Healthcare Policy and Innovation (K.M.L.), University of Michigan, Ann Arbor.

    ,

    From the University of Exeter Medical School (T.J.L., W.E.H., I.A.L., K.K., M.S., D.J.L.), Exeter, UK; Department of Internal Medicine and Geriatrics (C.A., O.B.), Angers University Hospital, Angers, France; Herbert Wertheim College of Medicine (P.H.M.C.), Florida International University, Miami; Mailman School of Public Health (L.F.), Columbia University, New York; Kidney Research Institute, Division of Nephrology (B.R.K.), University of Washington, Seattle; Departments of Epidemiology (L.H.K.) and Neurology and Psychiatry (O.L.L.), University of Pittsburgh, PA; Division of General Medicine (K.M.L.), Veterans Affairs Ann Arbor Center for Clinical Management Research, Ann Arbor, MI; and the Institute for Social Research and the Institute for Healthcare Policy and Innovation (K.M.L.), University of Michigan, Ann Arbor.

    ,

    From the University of Exeter Medical School (T.J.L., W.E.H., I.A.L., K.K., M.S., D.J.L.), Exeter, UK; Department of Internal Medicine and Geriatrics (C.A., O.B.), Angers University Hospital, Angers, France; Herbert Wertheim College of Medicine (P.H.M.C.), Florida International University, Miami; Mailman School of Public Health (L.F.), Columbia University, New York; Kidney Research Institute, Division of Nephrology (B.R.K.), University of Washington, Seattle; Departments of Epidemiology (L.H.K.) and Neurology and Psychiatry (O.L.L.), University of Pittsburgh, PA; Division of General Medicine (K.M.L.), Veterans Affairs Ann Arbor Center for Clinical Management Research, Ann Arbor, MI; and the Institute for Social Research and the Institute for Healthcare Policy and Innovation (K.M.L.), University of Michigan, Ann Arbor.

    ,

    From the University of Exeter Medical School (T.J.L., W.E.H., I.A.L., K.K., M.S., D.J.L.), Exeter, UK; Department of Internal Medicine and Geriatrics (C.A., O.B.), Angers University Hospital, Angers, France; Herbert Wertheim College of Medicine (P.H.M.C.), Florida International University, Miami; Mailman School of Public Health (L.F.), Columbia University, New York; Kidney Research Institute, Division of Nephrology (B.R.K.), University of Washington, Seattle; Departments of Epidemiology (L.H.K.) and Neurology and Psychiatry (O.L.L.), University of Pittsburgh, PA; Division of General Medicine (K.M.L.), Veterans Affairs Ann Arbor Center for Clinical Management Research, Ann Arbor, MI; and the Institute for Social Research and the Institute for Healthcare Policy and Innovation (K.M.L.), University of Michigan, Ann Arbor.

    ,

    From the University of Exeter Medical School (T.J.L., W.E.H., I.A.L., K.K., M.S., D.J.L.), Exeter, UK; Department of Internal Medicine and Geriatrics (C.A., O.B.), Angers University Hospital, Angers, France; Herbert Wertheim College of Medicine (P.H.M.C.), Florida International University, Miami; Mailman School of Public Health (L.F.), Columbia University, New York; Kidney Research Institute, Division of Nephrology (B.R.K.), University of Washington, Seattle; Departments of Epidemiology (L.H.K.) and Neurology and Psychiatry (O.L.L.), University of Pittsburgh, PA; Division of General Medicine (K.M.L.), Veterans Affairs Ann Arbor Center for Clinical Management Research, Ann Arbor, MI; and the Institute for Social Research and the Institute for Healthcare Policy and Innovation (K.M.L.), University of Michigan, Ann Arbor.

    ,

    From the University of Exeter Medical School (T.J.L., W.E.H., I.A.L., K.K., M.S., D.J.L.), Exeter, UK; Department of Internal Medicine and Geriatrics (C.A., O.B.), Angers University Hospital, Angers, France; Herbert Wertheim College of Medicine (P.H.M.C.), Florida International University, Miami; Mailman School of Public Health (L.F.), Columbia University, New York; Kidney Research Institute, Division of Nephrology (B.R.K.), University of Washington, Seattle; Departments of Epidemiology (L.H.K.) and Neurology and Psychiatry (O.L.L.), University of Pittsburgh, PA; Division of General Medicine (K.M.L.), Veterans Affairs Ann Arbor Center for Clinical Management Research, Ann Arbor, MI; and the Institute for Social Research and the Institute for Healthcare Policy and Innovation (K.M.L.), University of Michigan, Ann Arbor.

    ,

    From the University of Exeter Medical School (T.J.L., W.E.H., I.A.L., K.K., M.S., D.J.L.), Exeter, UK; Department of Internal Medicine and Geriatrics (C.A., O.B.), Angers University Hospital, Angers, France; Herbert Wertheim College of Medicine (P.H.M.C.), Florida International University, Miami; Mailman School of Public Health (L.F.), Columbia University, New York; Kidney Research Institute, Division of Nephrology (B.R.K.), University of Washington, Seattle; Departments of Epidemiology (L.H.K.) and Neurology and Psychiatry (O.L.L.), University of Pittsburgh, PA; Division of General Medicine (K.M.L.), Veterans Affairs Ann Arbor Center for Clinical Management Research, Ann Arbor, MI; and the Institute for Social Research and the Institute for Healthcare Policy and Innovation (K.M.L.), University of Michigan, Ann Arbor.

    ,

    From the University of Exeter Medical School (T.J.L., W.E.H., I.A.L., K.K., M.S., D.J.L.), Exeter, UK; Department of Internal Medicine and Geriatrics (C.A., O.B.), Angers University Hospital, Angers, France; Herbert Wertheim College of Medicine (P.H.M.C.), Florida International University, Miami; Mailman School of Public Health (L.F.), Columbia University, New York; Kidney Research Institute, Division of Nephrology (B.R.K.), University of Washington, Seattle; Departments of Epidemiology (L.H.K.) and Neurology and Psychiatry (O.L.L.), University of Pittsburgh, PA; Division of General Medicine (K.M.L.), Veterans Affairs Ann Arbor Center for Clinical Management Research, Ann Arbor, MI; and the Institute for Social Research and the Institute for Healthcare Policy and Innovation (K.M.L.), University of Michigan, Ann Arbor.

    ,

    From the University of Exeter Medical School (T.J.L., W.E.H., I.A.L., K.K., M.S., D.J.L.), Exeter, UK; Department of Internal Medicine and Geriatrics (C.A., O.B.), Angers University Hospital, Angers, France; Herbert Wertheim College of Medicine (P.H.M.C.), Florida International University, Miami; Mailman School of Public Health (L.F.), Columbia University, New York; Kidney Research Institute, Division of Nephrology (B.R.K.), University of Washington, Seattle; Departments of Epidemiology (L.H.K.) and Neurology and Psychiatry (O.L.L.), University of Pittsburgh, PA; Division of General Medicine (K.M.L.), Veterans Affairs Ann Arbor Center for Clinical Management Research, Ann Arbor, MI; and the Institute for Social Research and the Institute for Healthcare Policy and Innovation (K.M.L.), University of Michigan, Ann Arbor.

    ,

    From the University of Exeter Medical School (T.J.L., W.E.H., I.A.L., K.K., M.S., D.J.L.), Exeter, UK; Department of Internal Medicine and Geriatrics (C.A., O.B.), Angers University Hospital, Angers, France; Herbert Wertheim College of Medicine (P.H.M.C.), Florida International University, Miami; Mailman School of Public Health (L.F.), Columbia University, New York; Kidney Research Institute, Division of Nephrology (B.R.K.), University of Washington, Seattle; Departments of Epidemiology (L.H.K.) and Neurology and Psychiatry (O.L.L.), University of Pittsburgh, PA; Division of General Medicine (K.M.L.), Veterans Affairs Ann Arbor Center for Clinical Management Research, Ann Arbor, MI; and the Institute for Social Research and the Institute for Healthcare Policy and Innovation (K.M.L.), University of Michigan, Ann Arbor.

    ,

    From the University of Exeter Medical School (T.J.L., W.E.H., I.A.L., K.K., M.S., D.J.L.), Exeter, UK; Department of Internal Medicine and Geriatrics (C.A., O.B.), Angers University Hospital, Angers, France; Herbert Wertheim College of Medicine (P.H.M.C.), Florida International University, Miami; Mailman School of Public Health (L.F.), Columbia University, New York; Kidney Research Institute, Division of Nephrology (B.R.K.), University of Washington, Seattle; Departments of Epidemiology (L.H.K.) and Neurology and Psychiatry (O.L.L.), University of Pittsburgh, PA; Division of General Medicine (K.M.L.), Veterans Affairs Ann Arbor Center for Clinical Management Research, Ann Arbor, MI; and the Institute for Social Research and the Institute for Healthcare Policy and Innovation (K.M.L.), University of Michigan, Ann Arbor.

    ,

    From the University of Exeter Medical School (T.J.L., W.E.H., I.A.L., K.K., M.S., D.J.L.), Exeter, UK; Department of Internal Medicine and Geriatrics (C.A., O.B.), Angers University Hospital, Angers, France; Herbert Wertheim College of Medicine (P.H.M.C.), Florida International University, Miami; Mailman School of Public Health (L.F.), Columbia University, New York; Kidney Research Institute, Division of Nephrology (B.R.K.), University of Washington, Seattle; Departments of Epidemiology (L.H.K.) and Neurology and Psychiatry (O.L.L.), University of Pittsburgh, PA; Division of General Medicine (K.M.L.), Veterans Affairs Ann Arbor Center for Clinical Management Research, Ann Arbor, MI; and the Institute for Social Research and the Institute for Healthcare Policy and Innovation (K.M.L.), University of Michigan, Ann Arbor.

    ,

    From the University of Exeter Medical School (T.J.L., W.E.H., I.A.L., K.K., M.S., D.J.L.), Exeter, UK; Department of Internal Medicine and Geriatrics (C.A., O.B.), Angers University Hospital, Angers, France; Herbert Wertheim College of Medicine (P.H.M.C.), Florida International University, Miami; Mailman School of Public Health (L.F.), Columbia University, New York; Kidney Research Institute, Division of Nephrology (B.R.K.), University of Washington, Seattle; Departments of Epidemiology (L.H.K.) and Neurology and Psychiatry (O.L.L.), University of Pittsburgh, PA; Division of General Medicine (K.M.L.), Veterans Affairs Ann Arbor Center for Clinical Management Research, Ann Arbor, MI; and the Institute for Social Research and the Institute for Healthcare Policy and Innovation (K.M.L.), University of Michigan, Ann Arbor.

    From the University of Exeter Medical School (T.J.L., W.E.H., I.A.L., K.K., M.S., D.J.L.), Exeter, UK; Department of Internal Medicine and Geriatrics (C.A., O.B.), Angers University Hospital, Angers, France; Herbert Wertheim College of Medicine (P.H.M.C.), Florida International University, Miami; Mailman School of Public Health (L.F.), Columbia University, New York; Kidney Research Institute, Division of Nephrology (B.R.K.), University of Washington, Seattle; Departments of Epidemiology (L.H.K.) and Neurology and Psychiatry (O.L.L.), University of Pittsburgh, PA; Division of General Medicine (K.M.L.), Veterans Affairs Ann Arbor Center for Clinical Management Research, Ann Arbor, MI; and the Institute for Social Research and the Institute for Healthcare Policy and Innovation (K.M.L.), University of Michigan, Ann Arbor. david.llewellyn@exeter.ac.uk.

    Source

    Neurology 83:10 2014 Sep 02 pg 920-8

    MeSH

    Aged
    Alzheimer Disease
    Dementia
    Female
    Follow-Up Studies
    Humans
    Incidence
    Male
    Proportional Hazards Models
    Risk Factors
    United States
    Vitamin D
    Vitamin D Deficiency

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    25098535

    Citation

    Littlejohns, Thomas J., et al. "Vitamin D and the Risk of Dementia and Alzheimer Disease." Neurology, vol. 83, no. 10, 2014, pp. 920-8.
    Littlejohns TJ, Henley WE, Lang IA, et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology. 2014;83(10):920-8.
    Littlejohns, T. J., Henley, W. E., Lang, I. A., Annweiler, C., Beauchet, O., Chaves, P. H., ... Llewellyn, D. J. (2014). Vitamin D and the risk of dementia and Alzheimer disease. Neurology, 83(10), pp. 920-8. doi:10.1212/WNL.0000000000000755.
    Littlejohns TJ, et al. Vitamin D and the Risk of Dementia and Alzheimer Disease. Neurology. 2014 Sep 2;83(10):920-8. PubMed PMID: 25098535.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Vitamin D and the risk of dementia and Alzheimer disease. AU - Littlejohns,Thomas J, AU - Henley,William E, AU - Lang,Iain A, AU - Annweiler,Cedric, AU - Beauchet,Olivier, AU - Chaves,Paulo H M, AU - Fried,Linda, AU - Kestenbaum,Bryan R, AU - Kuller,Lewis H, AU - Langa,Kenneth M, AU - Lopez,Oscar L, AU - Kos,Katarina, AU - Soni,Maya, AU - Llewellyn,David J, Y1 - 2014/08/06/ PY - 2014/8/8/entrez PY - 2014/8/8/pubmed PY - 2014/12/30/medline SP - 920 EP - 8 JF - Neurology JO - Neurology VL - 83 IS - 10 N2 - 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. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/25098535/Vitamin_D_and_the_risk_of_dementia_and_Alzheimer_disease_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&amp;pmid=25098535 DB - PRIME DP - Unbound Medicine ER -