DTI-ALPS evidence of glymphatic function enhancement following dexmedetomidine-controlled sleep in patients with insomnia and depression

To investigate glymphatic system alterations in chronic insomnia disorder (CID) patients comorbid with major depressive disorder (MDD) following patient-controlled sleep therapy with dexmedetomidine (Dex-PCSL), and to evaluate the utility of DTI-ALPS parameters in distinguishing patients with high versus low treatment sensitivity. Seventy CID + MDD patients and 36 matched good sleepers (GSs) were enrolled. All patients received sub-anesthetic Dex-PCSL and were categorized as high-sensitivity (HS-case, > 25% PSQI reduction) or low-sensitivity (LS-case, ≤ 25%). MRI scanning was performed before and after treatment. Diffusion-related metrics, including the DTI-ALPS index, were quantified alongside sleep and mood assessments. Group comparisons, correlation analyses, and ROC analysis were used to evaluate glymphatic alterations and predictive performance. At baseline, both hemispheric and total ALPS indices were significantly lower in the LS-case group than in the GS group, whereas the HS-case group showed no significant differences from the GS group. The LS-case group also demonstrated reduced right-hemisphere ALPS compared with the HS-case group. Following treatment, ALPS indices increased in both patient groups; yet, right-hemisphere ALPS in LS-case patients remained lower. The PSQI reduction rate was positively correlated with baseline right-hemisphere ALPS, x_proj_R, and total ALPS. ROC analysis showed that the right-hemisphere ALPS index effectively predicted treatment sensitivity, with an AUC of 0.821 (95% CI: 0.735–0.907, P < 0.001). Dex-PCSL was associated with increased glymphatic-related imaging markers in CID + MDD patients, and right-hemisphere DTI-ALPS may represent a potential biomarker associated with individual treatment responsiveness, providing insights for personalized therapy.