Imaging study of white matter microstructural damage and glymphatic system dysfunction in patients with primary insomnia: a combined analysis based on PSMD, DTI-ALPS, and EPVS.

Background: Primary insomnia is associated with cognitive impairment and subtle brain structural alterations; however, the relationship between white matter microstructural damage and glymphatic-related imaging changes remains unclear. This study investigated these alterations by jointly assessing peak width of skeletonized mean diffusivity (PSMD), diffusion tensor imaging analysis along the perivascular space (DTI-ALPS), and enlarged perivascular spaces (EPVS). Methods: This retrospective cross-sectional study included 64 right-handed adults, comprising 32 patients with primary insomnia and 32 healthy controls. All participants underwent standardized assessments of sleep, mood, and cognition, as well as 3.0-T magnetic resonance imaging, including diffusion tensor imaging and T2-weighted imaging. PSMD and the DTI-ALPS index were calculated from diffusion data, and EPVS in the basal ganglia and centrum semiovale were visually rated. Between-group differences were evaluated using independent-samples Results: Patients with primary insomnia had higher PSMD values than healthy controls (P=0.047). Basal ganglia EPVS scores were higher in the unadjusted comparison (P=0.040), but this association was attenuated after adjustment for age, education, sex, diabetes, hypertension, smoking, and alcohol consumption (odds ratio =0.329, 95% confidence interval: 0.099-1.091; P=0.069). No significant between-group differences were found in the DTI-ALPS index (P=0.267) or centrum semiovale EPVS scores (false discovery rate-adjusted P=0.211). In the full sample, higher PSMD was associated with lower DTI-ALPS values (r=-0.331, adjusted P=0.019), higher basal ganglia EPVS scores (r=0.456, adjusted P=0.001), and lower Montreal Cognitive Assessment (r=-0.329, adjusted P=0.019) and Mini-Mental State Examination scores (r=-0.440, adjusted P=0.001). These associations remained significant after additional adjustment for depressive and anxiety symptoms. Conclusions: Primary insomnia was associated with greater white matter microstructural heterogeneity, whereas evidence of glymphatic dysfunction was partial and indirect. Higher PSMD was related to glymphatic-related imaging markers and poorer cognitive performance; however, the small sample and cross-sectional design warrant cautious interpretation.