DTI-ALPS Index and White Matter Disruption Mediate the Link Between Hydrocephalus and Cognitive Dysfunction: An MRI Study.

RATIONALE AND OBJECTIVES: A better understanding of how ventricular dilatation influences cognition in hydrocephalus might facilitate early intervention and rehabilitation for cognitive decline. We aimed to investigate whether diffusion tensor imaging analysis along the PVS (DTI-ALPS) and white matter (WM) disruption sequentially mediate the association between ventricular dilatation and cognitive decline. MATERIALS AND METHODS: 102 patients with communicating hydrocephalus (median age, 59 years), 100 patients with obstructive hydrocephalus (median age, 50 years), and 79 control subjects (median age, 48 years) were prospectively enrolled. WM alterations were quantified by free-water DTI (FW-DTI) and WMH volume. Cognition was assessed using Montreal cognitive assessment (MoCA), clock drawing test (CDT), and vocabulary fluency test (VFT). DTI-ALPS, WM alterations and cognition scores were compared among the three groups. Association between the ventricular dilatation, DTI-ALPS, WM alterations and cognition was assessed. Chain-mediation analysis was conducted to explore whether DTI-ALPS and WM disruption sequentially mediate the association between ventricular dilatation and cognitive decline. Dominance analysis was performed to determine the importance of variables in influencing cognition. RESULTS: Compared with controls, both hydrocephalus subgroups exhibited reduced DTI-ALPS index, white matter damage, and decreased cognitive performance (P < .05). This study revealed significant associations among ventricular dilatation, ALPS, WM metrics, and cognition (P < .05). Chain-mediation analysis confirmed DTI-ALPS and WM metrics sequentially mediate the association between ventricular dilatation and cognitive scores. The relative influence weight of each factor within the chain pathway on cognition varies slightly among subjects, depending on their pathological stage of WM lesions and the dimensions of cognitive impairment. CONCLUSION: The DTI-ALPS index and WM disruption exert a serial mediation pathway linking ventricular dilatation to cognitive decline.