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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:  Two prospective waves from Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study were primarily 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 (v 1 : 2004–2009), while structural and diffusion Magnetic Resonance Imaging (sMRI/dMRI) outcomes were measured at vscan: 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(v 1 ) 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]. Only trends were detected for cobalamin exposures ( q  < 0.10), while serum folate (v 1 ) was associated with lower mean diffusivity (MD) in the Anterior Limb of the Internal Capsule (ALIC), reflecting greater WMI, overall, while regional FA (e.g., cingulum gyrus) was associated with greater 25(OH)D concentration.   Conclusions:  Among urban adults, serum 25(OH)D status was 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.

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