Disturbance of functional brain networks and cognitive decline in Parkinson?s disease: Severe cerebral small vessel disease aggravates this relationship

Introduction: Several studies have identified a relationship between functional brain network disturbance and cognitive decline in people with Parkinson's disease (PwP); however, few studies have explored whether cerebral small vessel disease (CSVD) burden modifies this relationship. This study aimed to investigate the potential moderating effect of CSVD on the relationship between functional brain network disturbance and cognitive decline in PwP. Methods: We prospectively recruited 61 PwP from Beijing Tiantan Hospital between October 2021 to September 2022. The Montreal Cognitive Assessment (MoCA) score was used to assess cognition. CSVD imaging markers were evaluated following the STandards for ReportIng Vascular changes on nEuroimaging instructions, and the CSVD burden score was calculated. The functional connectivity indicator was obtained and calculated using quantitative electroencephalography examination. The moderating effect of CSVD burden on the relationship between functional brain network disturbance and cognitive decline was examined using hierarchical linear regression. Results: Forty-six of 61 (75.4%) PwP had cognitive impairment. Higher global weighted phase lag index (wPLI) values in beta1 bands were significantly associated with lower adjusted MoCA scores. CSVD burden aggravated the effect of the global wPLI in beta1 bands on adjusted MoCA scores. This effect was reinforced by the high level of CSVD burden. Conclusions: Higher wPLI indicates a possible pathological activation of functional brain networks that are associated with cognitive decline in PwP, and the high level of CSVD burden aggravates this relationship.