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 t-tests or Mann-Whitney U tests with false discovery rate correction. Ordinal logistic regression was used to adjust the basal ganglia EPVS comparison for demographic and vascular risk factors. Partial correlations were adjusted for age, sex, and education, with additional analyses further adjusted for depressive and anxiety symptoms. 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.