Vitamin D deficiency is associated with reduced hippocampal volume and disrupted structural connectivity in patients with mild cognitive impairment

Abstract

Vitamin D deficiency may exacerbate adverse neurocognitive outcomes in the progression of diseases such as Parkinson's, Alzheimer's, and other dementias. Mild cognitive impairment (MCI) is prodromal for these neurocognitive disorders and neuroimaging studies suggest that, in the elderly, this cognitive impairment is associated with a reduction in hippocampal volume and white matter structural integrity. To test whether vitamin D is associated with neuroanatomical correlates of MCI, we analyzed an existing structural and diffusion MRI dataset of elderly patients with MCI. Based on serum 25‐OHD levels, patients were categorized into serum 25‐OHD deficient (<12 ng/mL, n = 27) or not‐deficient (>12 ng/mL, n = 29). Freesurfer 6.0 was used to parcellate the whole brain into 164 structures and segment the hippocampal subfields. Whole‐brain structural connectomes were generated using probabilistic tractography with MRtrix. The network‐based statistic (NBS) was used to identify subnetworks of connections that significantly differed between the groups. We found a significant reduction in total hippocampal volume in the serum 25‐OHD deficient group especially in the CA1, molecular layer, dentate gyrus, and fimbria. We observed a connection deficit in 13 regions with the right hippocampus at the center of the disrupted network. Our results demonstrate that low vitamin D is associated with reduced volumes of hippocampal subfields and connection deficits in elderly people with MCI, which may exacerbate neurocognitive outcomes. Longitudinal studies are now required to determine if vitamin D can serve as a biomarker for Alzheimer's disease and if intervention can prevent the progression from MCI to major cognitive disorders.

Vitamin D deficiency as a risk factor for dementia and Alzheimer’s disease: an updated meta-analysis

“…In summary, the results of this meta-analysis should be interpreted with caution due to the methodological differences and the confounding factors among the included studies. In the early stages of dementia, for example, mild cognitive impairment is more likely to benefit from therapeutic intervention; thus, more data on the association between mild cognitive impairment and vitamin D would be helpful [46]. Therefore, future prospective studies should examine the association between vitamin D deficiency and the early stages of AD and dementia (e.g., mild cognitive impairment).…”

Low Vitamin D and Its Association with Cognitive Impairment and Dementia

“…Neuroimaging has suggested a positive association between low vitamin D levels, white matter hyperintensities, and enlarged frontal horn of the lateral ventricle [15]. Significant positive correlation of serum 25(OH)D with total hippocampus volume and disrupted structural connectivity between hippocampus, cortical, and subcortical areas in the right hemisphere was found in patients with mild cognitive impairment [16]. However, small sample size, cross-sectional design, and lack of detailed data on potential covariates (hypertension and diabetes) were the limitations of the study.…”

Vitamin D concentration and focal brain atrophy in older adults: a voxel‐based morphometric study

“…The identification of focal brain atrophy related to vitamin D has received little attention to date. Previous studies mostly focused on the changes of whole‐brain volume, ventricular volume, and hippocampal volume according to the vitamin D status.…”