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      Vitamin D and the risk of dementia and Alzheimer disease

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          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.

          Related collections

          Most cited references27

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          Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain.

          Darryl W. Eyles, Steven Smith, Robert Kinobe … (2005)
          Despite a growing body of evidence that Vitamin D is involved in mammalian brain functioning, there has been a lack of direct evidence about its role in the human brain. This paper reports, for the first time, the distribution of the 1,25-dihydroxyvitamin D3 receptor (VDR), and 1alpha-hydroxylase (1alpha-OHase), the enzyme responsible for the formation of the active vitamin in the human brain. The receptor and the enzyme were found in both neurons and glial cells in a regional and layer-specific pattern. The VDR was restricted to the nucleus whilst 1alpha-OHase was distributed throughout the cytoplasm. The distribution of the VDR in human brain was strikingly similar to that reported in rodents. Many regions contained equivalent amounts of both the VDR and 1alpha-OHase, however the macrocellular cells within the nucleus basalis of Meynert (NBM) and the Purkinje cells in the cerebellum expressed 1alpha-OHase in the absence of VDR. The strongest immunohistochemical staining for both the receptor and enzyme was in the hypothalamus and in the large (presumably dopaminergic) neurons within the substantia nigra. The observed distribution of the VDR is consistent with the proposal that Vitamin D operates in a similar fashion to the known neurosteroids. The widespread distribution of 1alpha-OHase and the VDR suggests that Vitamin D may have autocrine/paracrine properties in the human brain.
          Article 0 comments Cited 426 times – based on 0 reviews     Review now
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            Is Open Access

            2013 Alzheimer's disease facts and figures.

            (2013)
            This report provides information to increase understanding of the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality rates, health expenditures and costs of care, and effect on caregivers and society in general. It also explores the roles and unique challenges of long-distance caregivers, as well as interventions that target those challenges. An estimated 5.2 million Americans have AD. Approximately 200,000 people younger than 65 years with AD comprise the younger onset AD population; 5 million comprise the older onset AD population. Throughout the coming decades, the baby boom generation is projected to add about 10 million to the total number of people in the United States with AD. Today, someone in America develops AD every 68 seconds. By 2050, one new case of AD is expected to develop every 33 seconds, or nearly a million new cases per year, and the total estimated prevalence is expected to be 13.8 million. AD is the sixth leading cause of death in the United States and the fifth leading cause of death in Americans age 65 years or older. Between 2000 and 2010, the proportion of deaths resulting from heart disease, stroke, and prostate cancer decreased 16%, 23%, and 8%, respectively, whereas the proportion resulting from AD increased 68%. The number of deaths from AD as determined by official death certificates (83,494 in 2010) likely underrepresents the number of AD-related deaths in the United States. A projected 450,000 older Americans with AD will die in 2013, and a large proportion will die as a result of complications of AD. In 2012, more than 15 million family members and other unpaid caregivers provided an estimated 17.5 billion hours of care to people with AD and other dementias, a contribution valued at more than $216 billion. Medicare payments for services to beneficiaries age 65 years and older with AD and other dementias are three times as great as payments for beneficiaries without these conditions, and Medicaid payments are 19 times as great. Total payments in 2013 for health care, long-term care, and hospice services for people age 65 years and older with dementia are expected to be $203 billion (not including the contributions of unpaid caregivers). An estimated 2.3 million caregivers of people with AD and other dementias live at least 1 hour away from the care recipient. These "long-distance caregivers" face unique challenges, including difficulty in assessing the care recipient's true health condition and needs, high rates of family disagreement regarding caregiving decisions, and high out-of-pocket expenses for costs related to caregiving. Out-of-pocket costs for long-distance caregivers are almost twice as high as for local caregivers. Copyright © 2013. Published by Elsevier Inc.
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              The Cardiovascular Health Study: design and rationale.

              L P Fried, N O Borhani, P. Enright … (1991)
              The Cardiovascular Health Study (CHS) is a population-based, longitudinal study of coronary heart disease and stroke in adults aged 65 years and older. The main objective of the study is to identify factors related to the onset and course of coronary heart disease and stroke. CHS is designed to determine the importance of conventional cardiovascular disease (CVD) risk factors in older adults, and to identify new risk factors in this age group, especially those that may be protective and modifiable. The study design called for enrollment of 1250 men and women in each of four communities: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. Eligible participants were sampled from Medicare eligibility lists in each area. Extensive physical and laboratory evaluations were performed at baseline to identify the presence and severity of CVD risk factors such as hypertension, hypercholesterolemia and glucose intolerance; subclinical disease such as carotid artery atherosclerosis, left ventricular enlargement, and transient ischemia; and clinically overt CVD. These examinations in CHS permit evaluation of CVD risk factors in older adults, particularly in groups previously under-represented in epidemiologic studies, such as women and the very old. The first of two examination cycles began in June 1989. A second comprehensive examination will be repeated three years later. Periodic interim contacts are scheduled to ascertain and verify the incidence of CVD events, the frequency of recurrent events, and the sequellae of CVD.
              Article 0 comments Cited 201 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Thomas J. Littlejohns:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                William E. Henley:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. (1) UK Medical Research Council, grant number G0902158, Principal Investigator, 2010-2014.

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Iain A. Lang:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. (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

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

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                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Cedric Annweiler:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. - Travel grant: “Alzheimer�s Association International Conference (AAIC) Fellowship Committee” grant (Vancouver, BC, Canada, July 2012).

                Editorial Boards:

                1. - G�riatrie, Psychologie et Neuropsychiatrie du Vieillissement, Associate Editor, since 2012 - Journal of Alzheimer's Disease, Associate Editor, since 2012

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

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                1. NONE

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                1. NONE

                Legal Proceedings:

                1. NONE

                Olivier Beauchet:
                Comment :

                Scientific Advisory Boards:

                1. NONE

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                1. NONE

                Editorial Boards:

                1. editorial advisory board member of Geriatr Psychol Neuropsychiatr Vieil

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. Consultancies for the Korian group,Ipsen Pharma, MSD and �rontolop�le autonomie long�vit� des Pays de la Loire

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

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                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

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                1. NONE

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                Paulo H.M. Chaves:
                Comment :

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                1. NONE

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                1. NONE

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                1. NONE

                Editorial Boards:

                1. American Journal of Epidemiology, Associate Editor, 2012-present; no compensation Journal of Epidemiology (Japan Epidemiological Association), Associate Editor, 2011-present - no compensation

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

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                1. NONE

                Legal Proceedings:

                1. NONE

                Linda Fried:
                Comment :

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. Employed by nonprofit university: Columbia University, Dean and DeLamar Professor of Public Health

                Consultancies:

                1. Sanofi-Aventis

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. Sanofi-Aventis (consulting)

                Research Support, Government Entities:

                1. (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

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

                Bryan R. Kestenbaum:
                Comment :

                Scientific Advisory Boards:

                1. NONE

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                1. NONE

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                1. NONE

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. Kestenbaum, B., et al. (2009). Epidemiology and biostatistics : an introduction to clinical research. Dordrecht ; New York, Springer.

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. Daiichi Sankyo Pharmaceuticals Inc. A74915 (Giachelli, PI) 05/01/2012 � 04/30/2014 0.1 calendar �Candidate vascular calcification genes in human smooth muscle tissue� $227,273 Role: Co-investigator

                Research Support, Government Entities:

                1. NIH funding: NIH/NIDDK 1 R01DK094891-01 (Kestenbaum, PI) 09/01/2012 � 08/31/2015 3.6 calendar �Mineral Metabolism disturbances and arteriovenous fistula maturation� $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 � 06/30/2014 2.4 calendar �Phosphorous, vitamin D, and cardiovascular outcomes� $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 � 08/31/2014 1.2 calendar �Serum calcification activity in patients with chronic kidney disease� $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 � 07/31/2014 1.2 calendar�Insulin Resistance in chronic kidney disease� $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 � 08/31/2016 0.6 calendar �CKD targeted analyses of the Jackson Heart Study� 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 � 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.

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

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                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

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                Lewis H. Kuller:
                Comment :

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                1. NONE

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                1. NONE

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                1. NONE

                Editorial Boards:

                1. NONE

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                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                Kenneth M. Langa:
                Comment :

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

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                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NIH, AG009740, Co-Investigator

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                Oscar L. Lopez:
                Comment :

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                1. NONE

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                1. NONE

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                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. Lundbeck,Lilly,Baxter, Grifols,Cognoptix

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

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                1. NONE

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                1. NONE

                Research Support, Government Entities:

                1. NIA: P50 AG05133-27

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

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                1. NONE

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                Katarina Kos:
                Comment :

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                1. NONE

                Gifts:

                1. NONE

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                1. NONE

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

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                Maya Soni:
                Comment :

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                1. NONE

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                1. NONE

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                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

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                1. NONE

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                1. NONE

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                David J. Llewellyn:
                Comment :

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                1. NONE

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                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. (1) Roche, conference travel, (2) DSM, workshop travel and speaker honorarium.

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. (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)

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Journal
                Journal ID (nlm-ta): Neurology
                Journal ID (iso-abbrev): Neurology
                Journal ID (hwp): neurology
                Journal ID (publisher-id): neur
                Journal ID (pmc): neurology
                Journal ID (publisher-id): NEUROLOGY
                Title: Neurology
                Publisher: Lippincott Williams & Wilkins (Hagerstown, MD )
                ISSN (Print): 0028-3878
                ISSN (Electronic): 1526-632X
                Publication date (Print): 2 September 2014
                Publication date PMC-release: 2 September 2014
                Volume: 83
                Issue: 10
                Pages: 920-928
                Affiliations
                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.
                Author notes
                Correspondence to Dr. Llewellyn: david.llewellyn@ 123456exeter.ac.uk

                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.

                [*]

                These authors contributed equally to the manuscript.

                Article
                Publisher ID: NEUROLOGY2014574723
                DOI: 10.1212/WNL.0000000000000755
                PMC ID: 4153851
                PubMed ID: 25098535
                SO-VID: 22843ccb-9f62-46a7-b097-38ca863253ae
                Copyright © © 2014 American Academy of Neurology
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-Noncommercial No Derivative 3.0 License, which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.

                History
                Date received : 03 February 2014
                Date accepted : 28 May 2014
                Categories
                Subject: 25
                Subject: 26
                Subject: Article

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