Mid-life serum Vitamin D concentrations were associated with incident dementia but not late-life neuropsychological performance in the Atherosclerosis Risk in Communities (ARIC) Study

• Type of Material: Article
• Authors: Oluwaseun E. Fashanu, Johns Hopkins University; Di Zhao, Johns Hopkins University; Andrea L. C. Schneider, Johns Hopkins University; Andreaa M. Rawlings, Johns Hopkins University; A. Richey Sharrett, Johns Hopkins University; Pamela L. Lutsey, University of Minnesota; Rebecca F. Gottesman, Johns Hopkins University; Alden L. Gross, Johns Hopkins University; Eliseo Guallar, Johns Hopkins University; Alvaro Alonso, Emory University; Thomas H. Mosley, University of Mississippi; Erin D. Michos, Johns Hopkins University
• Language: English
• Date: 2019-10-22
• Publisher: BMC (part of Springer Nature)
• Publication Version: Final Published Version
• Copyright Statement: © 2019 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12883-019-1483-3
• Title of Journal or Parent Work: BMC Neurology
• ISSN: 1471-2377
• Volume: 19
• Issue: 1
• Start Page: 244
• End Page: 244
• Grant/Funding Information: This work was supported by grant R01NS072243 to Dr. Michos from the National Institute of Neurologic Disorders and Stroke (NINDS) at the National Institutes of Health (NIH).; This TSH measurements was made possible by a NIH/NIDDK grant R01DK089174 to Dr. Elizabeth Selvin.; This work was also supported by R01HL103706 from the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health; and R01HL103706-S1 from the NIH Office of Dietary Supplements, both to Dr. Lutsey.; Drs. Michos and Zhao are also supported by the Blumenthal Scholars Fund for Preventive Cardiology research.; Dr. Gross was supported by K01-AG050699 from the National Institute on Aging at the National Institute of Health.; Reagents for the thyroid assays were donated by Roche Diagnostics.; The ARIC-NCS was funded by U01 HL096812, HL096814, HL096899, HL096902, and HL096917; with additional support from the National Institute of Neurologic Disorders and Stroke.; Dr. Schneider was supported by National Institute of Neurologic Disorders and Stroke through an administrative supplement to award R25NS065729.; The ARIC Study is a collaborative research supported by National Heart, Lung, and Blood Institute contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C.
• Keywords: Cognitive function; Vitamin D; Life Sciences & Biomedicine; 25-HYDROXYVITAMIN D; PARATHYROID-HORMONE; COGNITIVE DECLINE; Cerebrovascular disease; DISEASE; Science & Technology; PRIMARY PREVENTION; D SUPPLEMENTATION; Neurosciences & Neurology; Clinical Neurology; HEALTH; RANDOMIZED CONTROLLED-TRIAL; CALCIUM; DEPRESSION; Vascular risk factors
• Research Categories: Health Sciences, Epidemiology; Biology, Neuroscience; Health Sciences, Medicine and Surgery

Abstract

Background: Activated Vitamin D has anti-inflammatory properties and adequate 25-hydroxyvitamin D [25(OH)D] concentrations may be important for neurocognitive function and protection against neurologic injury. We examined whether mid-life 25(OH) D concentrations were associated with later-life performance on neuropsychological testing, functional ability, depressive symptoms, and incident dementia. Methods: We studied 13,039 white and black ARIC participants who had serum 25(OH) D measured mid-life at visit 2 (1990-1992). Over the next ~ 20 years through visit 5 (2011-2013), participants underwent 3 additional in-person visits, annual telephone calls, and hospitalization surveillance. An extensive battery of neuropsychological outcomes were assessed at visit 5 using standardized protocols. Incident dementia was ascertained through a formal algorithm that included data from in-person cognitive testing, telephone interviews, hospital discharge codes, and death certificate codes. Diagnoses of dementia were adjudicated by expert clinician committee. For the primary cognitive analyses, we imputed for missing covariates and outcomes and used linear regression to evaluate non-concurrent cross-sectional associations of mid-life 25(OH) D (visit 2) with late-life neuropsychological outcomes (visit 5). We also used Cox regression models to examine associations of mid-life 25(OH) D and incident dementia. Results: In mid-life, the mean (SD) age of participants was 57 (6) years, 57% were women, and 24% black. Mean (SD) 25(OH) D was 24.3 (8.6) ng/mL; 33% had deficient (< 20 ng/mL), 44% intermediate (20- < 30 ng/mL), and 23% sufficient (≥30 ng/mL) 25(OH) D concentrations. Association between mid-life 25(OH) D and late-life performance on neuropsychological testing were mostly null. There was no significant association with functional ability or depressive symptoms. Results were similar in a sensitivity analysis using complete-case data (no imputation). However, after a median follow-up of 20 years, low 25(OH) D concentrations were associated with increased risk for incident dementia (p = 0.01 for trend across categories), with HR of 1.26 (95% CI 1.06, 1.49) for participants with deficient 25(OH) D, compared to sufficient concentrations. Conclusion: In this community cohort, mid-life serum 25(OH) D concentrations were associated with incident dementia but not with performance on neuropsychological testing, functional ability, or depressive symptoms, 20 years later. Whether serum 25(OH) D concentrations are causally related to dementia or confounded by poorer health status remains uncertain.