Vitamin D, Folate, and Cobalamin Serum Concentrations Are Related to Brain Volume and White Matter Integrity in Urban Adults

May A Beydoun; Danielle Shaked; Sharmin Hossain; Hind A Beydoun; Leslie I Katzel; Christos Davatzikos; Rao P Gullapalli; Stephen L Seliger; Guray Erus; Michele K Evans; Alan B Zonderman; Shari R Waldstein

doi:10.3389/fnagi.2020.00140

Vitamin D, Folate, and Cobalamin Serum Concentrations Are Related to Brain Volume and White Matter Integrity in Urban Adults

Front Aging Neurosci. 2020 May 25:12:140. doi: 10.3389/fnagi.2020.00140. eCollection 2020.

Authors

May A Beydoun¹, Danielle Shaked^{1

2}, Sharmin Hossain¹, Hind A Beydoun³, Leslie I Katzel^{4

5}, Christos Davatzikos⁶, Rao P Gullapalli⁷, Stephen L Seliger⁸, Guray Erus⁶, Michele K Evans¹, Alan B Zonderman¹, Shari R Waldstein^{2

4

5}

Affiliations

¹ Laboratory of Epidemiology and Population Sciences, The National Institute on Aging (NIA) The Intramural Research Program (IRP), The National Institutes of Health (NIH), Baltimore, MD, United States.
² Department of Psychology, University of Maryland, Baltimore County, MD, United States.
³ Department of Research Programs, Fort Belvoir Community Hospital, Fort Belvoir, VA, United States.
⁴ Geriatric Research Education and Clinical Center, Baltimore VA Medical Center, Baltimore, MD, United States.
⁵ Division of Gerontology & Geriatric Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States.
⁶ Section for Biomedical Image Analysis, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States.
⁷ Department of Diagnostic Radiology, University of Maryland School of Medicine, Baltimore, MD, United States.
⁸ Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States.

Abstract

Background and objectives: Lower vitamin status has been linked to cognitive deficits, pending mechanistic elucidation. Serum 25-hydroxyvitamin D [25(OH)D], folate and cobalamin were explored against brain volumes and white matter integrity (WMI). Methods: Three prospective waves from Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study were used [Baltimore, City, MD, 2004-2015, N = 183-240 urban adults (Age_v1: 30-64 years)]. Serum vitamin 25-hydroxyvitamin D [25(OH)D], folate and cobalamin concentrations were measured at visits 1 (v₁: 2004-2009) and 2 (v₂: 2009-2013), while structural and diffusion Magnetic Resonance Imaging (sMRI/dMRI) outcomes were measured at v_scan: 2011-2015. Top 10 ranked adjusted associations were corrected for multiple testing using familywise Bonferroni (FWER <0.05) and false discovery rates (FDR, q-value < 0.10). Results: We found statistically significant (FWER < 0.05; β±SE) direct associations of 25(OH)D(v₁) with WM volumes [overall: +910 ± 336/males: +2,054 ± 599], occipital WM; [overall: +140 ± 40, males: +261 ± 67 and Age_v1 > 50 years: +205 ± 54]; parietal WM; [overall: +251 ± 77, males: +486 ± 129 and Age_v1 > 50 years: +393 ± 108] and left occipital pole volume [overall: +15.70 ± 3.83 and above poverty: 19.0 ± 4.3], findings replicated for 25(OH)D (v₂-v₁) annualized exposure, which was also linked with greater WMI (fractional anisotropy, FA) in the anterior limb of the internal capsule (ALIC); FWER < 0.05 [Overall: +0.0020 ± 0.0004; Whites: +0.0024 ± 0.0004] and in the cingulum (hippocampus) [Overall: +0.0016 ± 0.0004]. Only trends were detected for cobalamin exposures (q < 0.10), while serum folate (v₁) was associated with lower mean diffusivity (MD) in ALIC, reflecting greater WMI, overall. Conclusions: Among urban adults, serum 25(OH)D status and increase were consistently linked to larger occipital and parietal WM volumes and greater region-specific WMI. Pending longitudinal replication of our findings, randomized controlled trials of vitamin D supplementation should be conducted against brain marker outcomes.

Keywords: 25-hydroxyvitamin D; brain volumes; cobalamin; cognitive aging; folate; health disparities; white matter integrity.

Abstract

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