ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Parkinson’s Disease and Aging-related Movement Disorders
This article is part of the Research TopicVitamin D and Aging: Associations with Mortality, Cognition, Chronic Diseases, and Metabolic Conditions in Elderly IndividualsView all 5 articles
Vitamin D-Linked Vulnerability and Functional Connectivity Alterations in the Superior Frontal Gyrus Contributing to Cognitive Impairment in Parkinson's Disease
Provisionally accepted
- Second Xiangya Hospital, Central South University, Changsha, China
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Background &Aims Forecasting 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. Methods Thirty-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. Results Compared 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. Conclusion The 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.
Keywords: Parkinson's disease, cognitive impairment, Vitamin D, gray matter volume, superior frontal gyrus
Received: 01 Jul 2025; Accepted: 29 Oct 2025.
Copyright: © 2025 Lv, Qin, Hu, Tan, Liao, Zhang, Ren and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Feng Ren, renfeng@csu.edu.cn
Chunyu Wang, wangchunyu@csu.edu.cn
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