Abstract

Abstract Introduction Previous studies on the implications of benzodiazepine (BZD), a widely prescribed pharmacotherapeutic treatment method for sleep insomnia, on sleep architecture demonstrated significantly reduced EEG activity in low-frequency bands. In this study, we explore the effect of BZD on NREM sleep instability also known as cyclic alternating pattern (CAP) in community-dwelling older men. Methods CAP was scored in overnight EEG recordings from 30 older men on long-acting BZD (LBZD), 35 older men on short-acting BZD (SBZD), and 50 age-matched men who did not use BZD (NBZD), participating in the Osteoporotic Fractures in Men Sleep Study (MrOS sleep). A high performance automated detection system determined the ratio between CAP time and NREM sleep time (CAP rate), the number of A1-phases per hour of NREM sleep (A1 index), and the number of A2+A3-phases per hour of NREM sleep (A2+A3 index). The relationship between CAP parameters and BZD use was determined using the Kruskal-Wallis test by ranks with Bonferroni correction for post-hoc analysis. Results CAP rate was significantly decreased in older men using long-acting BZD (NBZD: 59.6±18.0%, LBZD: 46.9±13.1%, SBZD: 53.0±20.1%) as compared to non-BZD user (p < 0.01). All BZD users demonstrated significantly lower frequencies of A1-phases (NBZD: 19.9±23.0 no./h, LBZD: 6.9±13.3 no./h, SBZD: 4.5±9.9 no./h) as compared to non-BZD users (LBZD: p < 0.01, SBZD: p < 0.001). The A2+A3 index did not show any variations between the three groups. Conclusion Older men using long-acting BZD demonstrate a significantly reduced CAP rate during sleep, particularly less frequent A1-phases, compared to the control group. Moreover, short-acting BZD user show significantly less frequent A1-phases but no difference in CAP rate and A2+A3-phases than older men using no BZD. Hence, BZD usage has a major adverse effect on the occurrence of EEG slow waves. Support The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study “Outcomes of Sleep Disorders in Older Men” under the following grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839.

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