0052 Zolpidem and Infraslow Oscillations in Human Sleep: A Retrospective Matched Case-Control Study

Abstract Introduction Although zolpidem is a widely prescribed non-benzodiazepine hypnotic that acts through GABA-A receptors. Emerging evidence shows that zolpidem dampens noradrenergic infraslow oscillations (ISO) and vascular vasomotion during non-rapid eye movement (NREM) sleep, thereby reducing glymphatic clearance in mice. Whether analogous changes in sleep microstructure occur in humans taking zolpidem is unknown. Methods We analyzed data from 8,180 adults who underwent overnight polysomnography (PSG) at the Massachusetts General Hospital site in the Human Sleep Project. 105 (1.3%) participants had zolpidem, defined as prescription(s) within 15 days before PSG. Electroencephalography (EEG) was used to quantify the ISO during NREM using Luna software. We first generated timeseries of band powers for different frequency bands, and then the 0.005-0.03Hz relative band power of ISO (%) was computed from these timeseries. We used optimal propensity-score matching to compare zolpidem users with non-users and conducted stratified analyses by sex and apnea-hypopnea index (AHI). Results Compared with matched non-users, individuals with zolpidem prescriptions within 15 days before PSG had a slightly lower occipital beta-band ISO power (-1.1%, p=0.011). In males, zolpidem was associated with higher delta-band ISO power (1.2%, p=0.045) and lower beta-band ISO power (-1.4%, p=0.023) in central regions, while females had higher theta-band ISO powers across all regions (1.2-1.4%, p< 0.05). In people without apnea (AHI< 5), zolpidem was associated with lower frontal and central alpha-band ISO power (-1.1 to -1.6%, p < 0.01). Meanwhile, in participants with at least moderate apnea (AHI>15), zolpidem was associated with a higher occipital delta-band ISO power (1.8%, p< 0.001) and 1/f-corrected slow sigma-band ISO power (1.5%, p< 0.001). Conclusion Zolpidem was associated with reduced fast-band (alpha and beta) ISO and elevated slow-band (delta and theta) ISO, but was not associated with the spindle/sigma-band ISO that has been described in mice. In severe sleep apnea, zolpidem is associated with beneficial ISO changes, including delta-band and spindle/sigma-band ISO powers. The limitations include unknown actual zolpidem use on the night of PSG, lack of external validation, and use of a clinical population. Support (if any) AASM Foundation 370-SR-25.