Effect of chronic sedative-hypnotic use on sleep architecture and brain oscillations in older adults with chronic insomnia.

Rationale: High rates of insomnia in older adults lead to widespread benzodiazepine (BZD) and benzodiazepine receptor agonist (BZRA) use, even though chronic use has been shown to disrupt sleep regulation and impact cognition. Little is known about sedative-hypnotic effects on NREM slow oscillations (SO) and spindles, including their coupling, which is crucial for memory, especially in the elderly. Objectives: Our objective was to investigate the effect of chronic sedative-hypnotic use on sleep macro-architecture, EEG relative power, as well as SO and spindle characteristics and coupling. Methods: One hundred and one individuals (66.05 +/- 5.84 years, 73% female) completed a one-night study and were categorized into three groups: good sleepers (GS, n=28), individuals with insomnia (INS, n=26) or individuals with insomnia who chronically use either BZD or BZRA to manage their insomnia difficulties (MED, n=47; dose equivalent in Diazepam: 6.1 +/- 3.8 mg/week). We performed a comprehensive comparison of sleep architecture, EEG relative spectrum, and associated brain oscillatory activities, focusing on NREM brain oscillations crucial for sleep-dependent memory consolidation (i.e., SO and spindles) and their temporal coupling. Results: Chronic use of BZD/BZRA worsened sleep architecture and spectral activity compared to older adults with and without insomnia disorder. The use of BZD/BZRAs also altered the characteristics of sleep-related brain oscillations and their synchrony. An exploratory interaction model suggested that BZD use exacerbated sleep alterations compared to BZRA, and higher BZD/BZRA dosage worsened alteration in sleep micro-architecture and EEG spectrum. Conclusions: Our results suggest that chronic use of sedative-hypnotics is detrimental to sleep when compared to drug-free GS and INS. Such alteration of sleep regulation; at the macro and micro-architectural levels; may contribute to the reported association between sedative-hypnotic use and cognitive impairment in older adults. Keywords: benzodiazepine, sleep, brain oscillation, ageing