Glymphatic system dysfunction in obstructive sleep apnea with mild cognitive impairment evidenced by DTI-ALPS

This study employed diffusion tensor image analysis along the perivascular space (DTI-ALPS) to investigate alterations in the glymphatic system function and its relationship with cognitive function in obstructive sleep apnea with mild cognitive impairment (OSA-MCI).

We further classified OSA subtypes, enrolling 27 untreated OSA-MCI patients, 27 untreated OSA patients without mild cognitive impairment (OSA-nMCI), and 20 good sleeper (GS). All participants underwent Montreal Cognitive Assessment (MoCA), 3.0T head diffusion magnetic resonance imaging (dMRI), and polysomnography (PSG). After measuring diffusion rates (Dxx, Dyy, Dzz) along the X-, Y-, and Z-axes in bilateral projection and association fibers, ALPS indices were calculated and compared across groups. Finally, correlations between bilateral ALPS indices and MoCA scores, apnea-hypopnea index (AHI), and minimal oxygen saturation (MinSpO₂) were analyzed in OSA patients.

Compared to the OSA-nMCI group, the OSA-MCI group exhibited decreased Dyyproj_L (P = 0.001), Dyyproj_R (P = 0.042), ALPS_L (P < 0.001), and ALPS_R (P = 0.010). Relative to the GS group, the OSA-MCI group showed reductions in Dyyproj_L (P < 0.001), Dyyproj_R (P = 0.019), Dzzproj_R (P = 0.021), ALPS_L (P < 0.001), and ALPS_R (P = 0.006), while the OSA-nMCI group demonstrated only decreased Dzzproj_R (P = 0.005). After adjusting for sex, age, years of education, and BMI, mediation analysis revealed three neural pathways through which OSA severity significantly increased cognitive impairment, as mediated by the ALPS indexs. For distinguishing OSA and OSA-MCI, ALPS_L yielded higher AUC values of 0.687 (95% CI: 0.552-0.822) and 0.775 (95% CI: 0.750-0.800), with optimal cutoff values of 1.60 and 1.56, corresponding sensitivities of 0.556 and 0.706, and specificities of 0.800 and 0.816, respectively.

OSA-MCI patients demonstrated glymphatic dysfunction, which was associated with OSA severity and cognitive impairment. Mediation analysis showed that OSA severity effectively increased cognitive impairment, an effect mediated by the ALPS indexs. These exploratory findings revealed that the ALPS index, a measure reflecting glymphatic function, has preliminary discriminative ability in distinguishing between OSA and OSA-MCI patients, particularly for the index in the dominant left cerebral hemisphere.