Association of Serum Vitamin D with the Risk of Incident Dementia and Subclinical Indices of Brain Aging: The Framingham Heart Study

Article type: Research Article

Authors: Karakis, Ioannis^a | Pase, Matthew P.^{b; c; d; *} | Beiser, Alexa^{b; c; e} | Booth, Sarah L.^f | Jacques, Paul F.^f | Rogers, Gail^f | DeCarli, Charles^g | Vasan, Ramachandran S.^b | Wang, Thomas J.^h | Himali, Jayandra J.^{b; c} | Annweiler, Cedric^{i; j} | Seshadri, Sudha^{b; c; *}

Affiliations: [a] Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA | [b] Framingham Heart Study, Framingham, MA, USA | [c] Department of Neurology, Boston University School of Medicine, Boston, MA, USA | [d] Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn, Australia | [e] Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA | [f] Jean Mayer-U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA | [g] Imaging of Dementia and Aging (IDeA) Laboratory, Department of Neurology and Center for Neuroscience, University of California, Davis, CA, USA | [h] Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA | [i] Department of Neuroscience, Division of Geriatric Medicine, University of Angers, France | [j] Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada

Correspondence: [*] Correspondence to: Dr. Sudha Seshadri and Dr. Matthew P. Pase, Department of Neurology, Boston University School of Medicine, B602, 72 East Concord Street, Boston, MA 02118, USA. Tel.: +1 617 414 1337; Fax: +1 617 638 8086; E-mail: suseshad@bu.edu (Dr. S. Seshadri); Tel.: +1 617 638 8064; Fax: +1 617 638 8086; (Dr. M.P. Pase) E-mail: matthewpase@gmail.com.

Abstract: Background:Identifying nutrition- and lifestyle-based risk factors for cognitive impairment and dementia may aid future primary prevention efforts. Objective:We aimed to examine the association of serum vitamin D levels with incident all-cause dementia, clinically characterized Alzheimer’s disease (AD), MRI markers of brain aging, and neuropsychological function. Methods:Framingham Heart Study participants had baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations measured between 1986 and 2001. Vitamin D status was considered both as a continuous variable and dichotomized as deficient (<10 ng/mL), or at the cohort-specific 20th and 80th percentiles. Vitamin D was related to the 9-year risk of incident dementia (n = 1663), multiple neuropsychological tests (n = 1291) and MRI markers of brain volume, white matter hyperintensities and silent cerebral infarcts (n = 1139). Results:In adjusted models, participants with vitamin D deficiency (n = 104, 8% of the cognitive sample) displayed poorer performance on Trail Making B-A (β= –0.03 to –0.05±0.02) and the Hooper Visual Organization Test (β= –0.09 to –0.12±0.05), indicating poorer executive function, processing speed, and visuo-perceptual skills. These associations remained when vitamin D was examined as a continuous variable or dichotomized at the cohort specific 20th percentile. Vitamin D deficiency was also associated with lower hippocampal volumes (β= –0.01±0.01) but not total brain volume, white matter hyperintensities, or silent brain infarcts. No association was found between vitamin D deficiency and incident all-cause dementia or clinically characterized AD. Conclusions:In this large community-based sample, low 25(OH)D concentrations were associated with smaller hippocampal volume and poorer neuropsychological function.

Keywords: Alzheimer’s disease, brain, dementia, diet, lifestyle, magnetic resonance imaging, neuropsychology, nutritional status, risk factors, vitamin D

DOI: 10.3233/JAD-150991

Journal: Journal of Alzheimer's Disease, vol. 51, no. 2, pp. 451-461, 2016