Effect of chronic benzodiazepine and benzodiazepine receptor agonist use on sleep architecture and brain oscillations in older adults with chronic insomnia

Study Objectives: Insomnia in older adults is associated with widespread benzodiazepine (BZD) and benzodiazepine receptor agonist (BZRA) use despite evidence that chronic use disrupts sleep regulation and cognition. Little is known about BZD/BZRA effects on Non-rapid eye movement (NREM) slow oscillations (SO), spindles and their coupling, which is crucial for memory in older adults. Our objective was to investigate the effects of chronic BZD/BZRA use on sleep macro-architecture, electroencephalogram (EEG) relative power, SO and spindle characteristics and coupling. Methods: After habituation polysomnography, second-night data were analyzed from 101 participants (66.05 ± 5.84 years, range: 55–80 years, 73 per cent female) were categorized into three groups: good sleepers (GS, n = 28), individuals with insomnia (INS, n = 26) or individuals with insomnia who chronically use BZD/BZRA (MED, n = 47; diazepam equivalent: 6.1 ± 3.8 mg per use; >3 nights/week). We performed a comprehensive comparison of sleep architecture, EEG relative spectrum, and associated brain oscillatory activities, focusing on SO and spindles and their temporal coupling. Results: MED showed disrupted sleep architecture with lower N3 and higher N1 duration and spectral activity and altered sleep-related brain oscillations synchrony, compared to INS and GS. An exploratory interaction model suggested that chronic use of higher doses (mg per use) correlated with more pronounced disruptions in sleep micro-architecture and EEG spectrum. Conclusions: Our results suggest that chronic BZD and BZRA use is associated with poorer sleep quality. Such alteration of sleep regulation—at the macro and micro-architectural levels—may contribute to the reported association between BZD/BZRA use and cognitive impairment in older adults.