Associations of vitamin D deficiency with MRI markers of brain health in a community sample

Background & aim: Vitamin D deficiency has been linked to an increased risk of dementia. To strengthen this evidence and establish whether vitamin D can indeed play a role in early prevention of neurodegeneration, knowledge on underlying pathways is crucial. Therefore, we aimed to investigate the association of vitamin D status with brain tissue volumes, hippocampus volume, white matter integrity, and markers of cerebral small vessel disease (CSVD) in a dementia-free population. Methods: In this cross-sectional analysis, 2,716 participants free of dementia from the population-based Rotterdam Study underwent serum 25(OH)D concentration assessment and brain magnetic resonance imaging (MRI) scanning between 2006 and 2009. Outcomes of interest included brain tissue volume (total, white matter, grey matter and hippocampus volume), white matter integrity (fractional anisotropy (FA) and mean diffusivity (MD)), and markers of CSVD (white matter hyper intensity (WMH) volume, presence of lacunes and microbleeds). Associations between vitamin D status, both in categories and continuous, and these brain measurements were assessed using multivariable linear and logistic regression models, adjusting for lifestyle and other disease risk factors. Results: We observed that vitamin D deficiency (25(OH)D < 30 nmol/L) was independently associated with smaller brain tissue volume, smaller white matter volume and smaller hippocampus volume as compared to a sufficient vitamin D status (≥50 nmol/L). Vitamin D per 10 nmol/L increment and an insufficient (30–50 nmol/L) as compared to sufficient vitamin D status were not associated with the brain measures of interest. Moreover, vitamin D status was not associated with grey matter volume, white matter integrity or CSVD markers. Conclusions: In this dementia-free population, vitamin D deficiency was associated with a smaller brain tissue volume and hippocampus volume. More research, in particular with a longitudinal design, is needed to further elucidate the role of vitamin D in neurodegeneration.