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

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 (beta = -0.03 to -0.05 +/- 0.02) and the Hooper Visual Organization Test (beta = -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 (beta = -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.