Author(s): 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
Publication date PMC-release: 2 September 2014
Publisher: Lippincott Williams & Wilkins
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.
(1) UK Medical Research Council, grant number G0902158, Principal Investigator, 2010-2014.
(1) UK National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula (PenCLAHRC), n/a, Senior Lecturer, 2009-2013 and 2014-2018 (2) UK National Institute for Health Research (NIHR) Knowledge Mobilisation Fellowship, n/a, Fellow, 2014-2017
- Travel grant: “Alzheimerï¿½s Association International Conference (AAIC) Fellowship Committee” grant (Vancouver, BC, Canada, July 2012).
- Gï¿½riatrie, Psychologie et Neuropsychiatrie du Vieillissement, Associate Editor, since 2012 - Journal of Alzheimer's Disease, Associate Editor, since 2012
Consultancies for the Korian group,Ipsen Pharma, MSD and ï¿½rontolopï¿½le autonomie longï¿½vitï¿½ des Pays de la Loire
American Journal of Epidemiology, Associate Editor, 2012-present; no compensation Journal of Epidemiology (Japan Epidemiological Association), Associate Editor, 2011-present - no compensation
Employed by nonprofit university: Columbia University, Dean and DeLamar Professor of Public Health
(1) National Institute on Aging, 1U01AG032947-01, Subcontract PI (prime: Johns Hopkins, University), 9/30/08-8/31/2011 (2) National Institute on Aging, 5R37AG019905-10, PI, 9/1/10-8/31/12 (3) National Institute on Aging, 5P01AG027735-05, Subcontract PI (prime: Johns Hopkins University), 8/01/08-6/30/12
Kestenbaum, B., et al. (2009). Epidemiology and biostatistics : an introduction to clinical research. Dordrecht ; New York, Springer.
Daiichi Sankyo Pharmaceuticals Inc. A74915 (Giachelli, PI) 05/01/2012 ï¿½ 04/30/2014 0.1 calendar ï¿½Candidate vascular calcification genes in human smooth muscle tissueï¿½ $227,273 Role: Co-investigator
NIH funding: NIH/NIDDK 1 R01DK094891-01 (Kestenbaum, PI) 09/01/2012 ï¿½ 08/31/2015 3.6 calendar ï¿½Mineral Metabolism disturbances and arteriovenous fistula maturationï¿½ $217,500 Role: Principal investigator This 3-year project will evaluate whether mineral metabolism plays a role in arteriovenous fistula maturation.NIH/NHLBI 1 R01 HL096875 (Kestenbaum, de Boer, Co- PIs) 04/01/2010 ï¿½ 06/30/2014 2.4 calendar ï¿½Phosphorous, vitamin D, and cardiovascular outcomesï¿½ $416,729 Role: Co- Role: Principal Investigator This 4-year project evaluates a comprehensive panel of serum and urine markers of mineral metabolism in association with clinical and subclinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis.NIH/NIDDK 1 R21-DK081315-01A2 (Kestenbaum, PI) 07/01/2011 ï¿½ 08/31/2014 1.2 calendar ï¿½Serum calcification activity in patients with chronic kidney diseaseï¿½ $125,000 Role: Principal investigator This 2-year project will develop a novel serum calcification assay for patients with chronic kidney disease. NIH/NIDDK 1 R01DK087726 (de Boer, PI) 07/01/2010 ï¿½ 07/31/2014 1.2 calendarï¿½Insulin Resistance in chronic kidney diseaseï¿½ $294,202 Role: Key PersonnelThis 4-year project will comprehensively characterize insulin sensitivity, beta-cell function, and glucose tolerance using gold-standard methods among individuals who have moderate-severe chronic kidney disease.NIH/NHLBI R01 DK102134 (Young, PI) 09/01/2013 ï¿½ 08/31/2016 0.6 calendar ï¿½CKD targeted analyses of the Jackson Heart Studyï¿½ Role: Co-investigator This 3-year project will determine novel and traditional risk factors for kidney disease progression and cardiovascular complications of kidney disease among African Americans in the Jackson Heart Study. NIH/NIDDK 1 R01DK094434 (Rosenfeld, PI) 08/01/2012 ï¿½ 06/30/2017 0.6 calendar RANK-RANKL and vascular complications in chronic kidney disease $205,285 Role: Co-investigator This 5-year project combines laboratory and translational methods to determine the role of receptor activator of NFkB ligand (RANKL) in accelerated atherosclerosis of moderate-severe chronic kidney disease.
(1) Roche, conference travel, (2) DSM, workshop travel and speaker honorarium.
(1) Alzheimer's Association (NIRG-11-200737), (2) Norman Family Charitable Trust, (3) Age Related Diseases and Health Trust, (4) Sir Halley Stewart Trust, Lord Clinton's Charitable Trust, (5) RD&E Foundation Trust, (6) UK National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care for the South West Peninsula (PenCLAHRC)
Go to Neurology.org 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.
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