Impact of early glymphatic disorders on the development of vascular dementia

Early treatment can effectively ameliorate cognitive decline and slow disease progression in vascular cognitive impairment (VCI). Glymphatic system dysfunction may significantly contribute to the onset and progression of diverse neurodegenerative diseases. To investigate its influence on VCI, we used dynamic contrast-enhanced magnetic resonance imaging to observe the exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF) in the brains of vascular dementia (VD) model and SHAM rats, and used the Morris water maze and hematoxylin–eosin staining to confirm the predictive value of the glymphatic system for VCI. The clearance rate of the CSF contrast agent, Gd-DOTA, from the brain interstitial space was slower in the VD than in the SHAM group. Behavioral tests showed a robust negative correlation between VCI and retention of Gd-DOTA contrast agents in the hippocampal region of VD rats. Pathology revealed a significant positive correlation between the number of apoptotic neurons in the hippocampal CA1 region and Gd-DOTA retention in the hippocampal region of VD rats. The clearance of brain ISF was hindered in the model rats, indicating that glymphatic system damage contributed to cognitive impairment in this group. Our findings suggest that glymphatic system function may be a predictor of VD development.