Association between cerebrovascular imaging markers and glymphatic function in a large-scale cognitively normal population

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Abstract
Purpose This study aimed to investigate the association between cerebrovascular imaging markers and glymphatic function in cognitively normal individuals. Methods This retrospective study included 574 cognitively normal participants who underwent brain magnetic resonance imaging from January to October 2023. Glymphatic function was assessed using diffusion tensor image analysis along the perivascular space index (ALPS-index). Cerebrovascular imaging markers, including white matter hyperintensity (WMH) burden, cerebral microbleeds (CMBs), and choroid plexus volume (CPV), were quantified using automated segmentation methods. The presence of lacunes in the basal ganglia or old infarcts in other areas was visually determined. Associations between cerebrovascular markers and ALPS-index were analyzed using multivariable regression and partial correlation analyses. Results The mean age of the included participants was 68.9 ± 10.4 years (male, 40.9%; hypertension, 43.7%; diabetes, 20.4%; Mini-Mental State Examination [MMSE] score, 27.6 ± 1.6). A lower ALPS-index, reflecting impaired glymphatic clearance, was significantly associated with higher WMH burden (β=–0.231, p < 0.001), increased CPV fraction (β=–0.234, p < 0.001), and a greater number of deep CMBs (β=–0.087, p = 0.038). The participants with basal ganglia lacunes (ALPS-index: 1.32 ± 0.19), old infarcts other than basal ganglia (ALPS-index: 1.34 ± 0.19), or both (ALPS-index: 1.27 ± 0.19) had significantly lower ALPS-indices than those without these conditions (ALPS-index: 1.43 ± 0.21; all, p < 0.001). Conclusion Cerebrovascular imaging findings are significantly associated with glymphatic dysfunction in cognitively normal individuals, highlighting the need for further studies on glymphatic-targeted interventions in cerebrovascular disease prevention.

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