AUTHOR=Lv Lingling , Qin Lixia , Hu Shenglan , Tan Changlian , Liao Haiyan , Zhang Hainan , Ren Feng , Wang Chunyu 

TITLE=Vitamin D-linked vulnerability and functional connectivity alterations in the superior frontal gyrus contributing to cognitive impairment in Parkinson’s disease

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 17 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2025.1657723

DOI=10.3389/fnagi.2025.1657723

ISSN=1663-4365

ABSTRACT=Background and aimsForecasting specific factors influencing cognitive impairment (CI) in Parkinson’s disease (PD) patients can improve clinical outcomes. This study aims to identify brain areas vulnerable to vitamin D deficiency and assess functional integrity in PD patients with and without CI.MethodsThirty-four PD patients [14 with CI (PD-CI), 20 with normal cognition (PD-NC)] and 21 healthy controls (HCs) underwent serum vitamin D testing, T1-weighted MRI, and resting-state functional MRI (rs-fMRI). Voxel-based morphometry (VBM) was used to compare gray matter volume (GMV) between PD patients and HCs. Whole-brain multiple regression analyses, adjusted for age and sex, identified GMV regions associated with vitamin D levels. Resting-state functional connectivity (FC) analyses were performed using vitamin D-related regions as seeds. Correlation and multivariate regression analyses, adjusted for Hoehn and Yahr stage and age, assessed relationships among FC, cognitive performance, and vitamin D levels.ResultsCompared with HCs, PD patients exhibited significant GMV loss, affecting widespread brain regions including the middle frontal gyrus (MFG), superior frontal gyrus (SFG), and hippocampus. Region of interest (ROI)-based analysis revealed that vitamin D levels were associated with GMV in the bilateral MFG and SFG (r = −0.406, p = 0.021). These findings suggest that the MFG and SFG are vulnerable regions in PD patients linked to vitamin D levels. To assess the impact of abnormal vitamin D levels on relevant resting-state networks, clusters encompassing the bilateral SFG were used as ROIs. The intrinsic connectivity network of the vulnerable area, using the bilateral SFG as seed regions, revealed abnormal functional connectivity with several brain networks, including the visual network, the default mode network, the executive control network, the sensorimotor network, and the memory network. Abnormal FC values within the SFG functional network were associated with disease severity, cognitive dysfunction, and vitamin D levels (p < 0.05). Multi-model regression analyses revealed that connectivity in the left SFGmed network was negatively associated with CI in PD, with vitamin D levels showing a potential protective effect.ConclusionThe SFG is associated with vitamin D levels in PD patients, and disruptions in its structural and functional connectivity may link to CI. Future longitudinal studies are necessary to confirm these associations and explore the potential impact of vitamin D supplementation on cognitive function in PD.