Glymphatic dysfunction impairs cognitive function via disrupted white matter network efficiency in primary insomnia:...

Primary insomnia (PI) is increasingly recognized as a brain network disorder associated with cognitive impairment. Emerging evidence suggests that glymphatic system dysfunction may underlie these deficits by impairing brain clearance mechanisms during sleep. However, the interplay between glymphatic activity, structural brain network efficiency, and cognitive function in PI remains poorly understood.

Thirty-six PI patients and 36 matched healthy controls underwent diffusion tensor imaging (DTI). Glymphatic function was quantified using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Structural white matter networks were constructed using probabilistic tractography and analyzed via graph-theoretical metrics. Psychomotor Vigilance Task (PVT) was used to assess sustained attention. Group differences, correlations, and mediation analyses were conducted to examine the relationships among sleep quality, glymphatic function, network properties, and cognitive performance.

Compared with healthy controls (HC), PI patients showed a significantly lower DTI-ALPS index (PI: 1.24 ± 0.18 vs. HC: 1.41 ± 0.17; p = 0.003; Bonferroni-corrected p = 0.036). In addition, PVT reaction times were significantly prolonged in the PI group (PI: 445.89 ± 67.62 ms vs. HC: 405.17 ± 61.32 ms; p = 0.009), and PSQI scores were markedly higher (PI: 12.78 ± 3.70 vs. HC: 2.72 ± 1.34; p < 0.001). Partial correlation analyses revealed that the ALPS index was positively associated with global efficiency and negatively associated with both PSQI scores and PVT reaction times. Mediation analyses showed that (1) ALPS mediated the effect of sleep quality on global efficiency, and (2) global efficiency mediated the association between ALPS and PVT performance.

Our findings reveal a novel mechanistic pathway in which glymphatic dysfunction contributes to attention impairment in PI via disruption of structural network integration. These results suggest that targeting glymphatic health and white matter network integrity may offer new strategies for mitigating insomnia-related cognitive decline.