Influence of Zolpidem and Sleep Inertia on Balance and Cognition During Nighttime Awakening: A Randomized Placebo-Controlled Trial
ABSTRACT To determine whether sleep inertia (grogginess upon awakening from sleep) with or without zolpidem impairs walking stability and cognition during awakenings from sleep.
Three within-subject conditions hypnotic medication (zolpidem), placebo (sleep inertia), and wakefulness control randomized using balanced Latin square design.
Twelve older and 13 younger healthy adults.
Five milligrams of zolpidem or placebo 10 minutes before scheduled sleep (double-blind: zolpidem or sleep inertia); placebo before sitting in bed awake for 2 hours after their habitual bedtime (single-blind: wakefulness control).
Tandem walk on a beam and cognition, measured using computerized performance tasks, approximately 120 minutes after treatment.
No participants stepped off the beam on 10 practice trials. Seven of 12 older adults stepped off the beam after taking zolpidem, compared with none after sleep inertia and three after wakefulness control. Fewer young adults stepped off the beam: three after taking zolpidem, one after sleep inertia, and none after wakefulness control. Number needed to harm analyses showed one tandem walk failure for every 1.7 (95% confidence interval (CI)=1.4-2.0) older and 5.5 (95% CI=5.2-5.8) younger adults treated with zolpidem. Cognition was significantly more impaired after zolpidem exposure than with wakefulness control in older and younger participants (working memory: older, -4.3 calculations, 95% CI=-7.0 to -1.7; younger, -12.4 calculations, 95% CI=-18.2 to -6.7; Stroop: older, 76-ms increase (95% CI=13.5-138.4 ms); younger, 126-ms increase, 95% CI=34.7-217.5 ms), whereas sleep inertia significantly impaired cognition in younger but not older participants.
Zolpidem produced clinically significant balance and cognitive impairments upon awakening from sleep. Because impaired tandem walk predicts falls and hip fractures and because impaired cognition has important safety implications, use of nonbenzodiazepine hypnotic medications may have greater consequences for health and safety than previously recognized.
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ABSTRACT: Background Sleep deprivation and fatigue are common subjective complaints among astronauts. Previous studies of sleep and hypnotic drug use in space have been limited to post-flight subjective survey data or in-flight objective data collection from a small number of crew members. We aimed to characterise representative sleep patterns of astronauts on both short-duration and long-duration spaceflight missions. Methods For this observational study, we recruited crew members assigned to Space Transportation System shuttle flights with in-flight experiments between July 12, 2001, and July 21, 2011, or assigned to International Space Station (ISS) expeditions between Sept 18, 2006, and March 16, 2011. We assessed sleep–wake timing objectively via wrist actigraphy, and subjective sleep characteristics and hypnotic drug use via daily logs, in-flight and during Earth-based data-collection intervals: for 2 weeks scheduled about 3 months before launch, 11 days before launch until launch day, and for 7 days upon return to Earth. Findings We collected data from 64 astronauts on 80 space shuttle missions (26 flights, 1063 in-flight days) and 21 astronauts on 13 ISS missions (3248 in-flight days), with ground-based data from all astronauts (4014 days). Crew members attempted and obtained significantly less sleep per night as estimated by actigraphy during space shuttle missions (7·35 h [SD 0·47] attempted, 5·96 h [0·56] obtained), in the 11 days before spaceflight (7·35 h [0·51], 6·04 h [0·72]), and about 3 months before spaceflight (7·40 h [0·59], 6·29 h [0·67]) compared with the first week post-mission (8·01 h [0·78], 6·74 h [0·91]; p<0·0001 for both measures). Crew members on ISS missions obtained significantly less sleep during spaceflight (6·09 h [0·67]), in the 11 days before spaceflight (5·86 h [0·94]), and during the 2-week interval scheduled about 3 months before spaceflight (6·41 h [SD 0·65]) compared with in the first week post-mission (6·95 h [1·04]; p<0·0001). 61 (78%) of 78 shuttle-mission crew members reported taking a dose of sleep-promoting drug on 500 (52%) of 963 nights; 12 (75%) of 16 ISS crew members reported using sleep-promoting drugs. Interpretation Sleep deficiency in astronauts was prevalent not only during space shuttle and ISS missions, but also throughout a 3 month preflight training interval. Despite chronic sleep curtailment, use of sleep-promoting drugs was pervasive during spaceflight. Because chronic sleep loss leads to performance decrements, our findings emphasise the need for development of effective countermeasures to promote sleep. Funding The National Aeronautics and Space Administration.The Lancet Neurology 09/2014; 13(9). DOI:10.1016/S1474-4422(14)70122-X · 21.82 Impact Factor
Article: The burden of insomnia in Japan[Show abstract] [Hide abstract]
ABSTRACT: Several studies have suggested that patients who experience insomnia report a number of significant impairments. However, despite this literature, fewer studies have focused on the burden of insomnia among patients in Japan. The objective of the current study is to extend this work in Japan to further understand the effect of insomnia on health-related quality of life (hrQOL). Further, another objective is to understand general predictors of hrQOL among patients with insomnia. Data from the 2012 Japan National Health and Wellness Survey, an annual, cross-sectional study of adults aged 18 years or older, were used (N=30,000). All National Health and Wellness Survey respondents were categorized based on the incidence of self-reported insomnia diagnosis and prescription medication usage (clinical insomniacs under treatment versus [vs] good sleepers without insomnia or insomnia symptoms). Comparisons among different groups were made using multiple regression models controlling for demographics and health history. Clinical insomniacs (n=1,018; 3.4%) reported significantly worse hrQOL compared with good sleepers (n=20,542) (mental component summary: 34.2 vs 48.0; physical component summary: 48.0 vs 52.8; health utilities: 0.61 vs 0.76; all P<0.05). Health behaviors (smoking, exercise, alcohol use) and comorbidities were the strongest predictors of health utilities for clinical insomniacs. For all three clinical insomniac subgroups of interest, those with a physical comorbidity but not a psychiatric one, those with a psychiatric comorbidity but not a physical one, and those without either a physical or psychiatric comorbidity, large decrements in health utilities were observed for respondents who did not engage in any positive health behaviors (0.61, 0.57, 0.64, respectively) relative to good sleepers (0.78). However, the gap in health utility scores between these subgroups and good sleepers diminishes with an increasing number of positive health behaviors (eg, clinical insomniacs with a physical comorbidity but not a psychiatric comorbidity performing all three positive health behaviors =0.67 vs good sleepers =0.78). A significant burden remains for those with insomnia who are treated. Given the particularly low levels of hrQOL among treated insomnia patients who have poor health behavior profiles and have psychiatric comorbidities, physicians should place particular emphasis on these patients who are most in need of intervention. Improved treatments may help to address the unmet needs of these patient populations.Nature and Science of Sleep 01/2015; 7:1-11. DOI:10.2147/NSS.S73437
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ABSTRACT: Sleep inertia, sleep homeostatic and circadian processes modulate cognition, including reaction time, memory, mood and alertness. How these processes influence higher-order cognitive functions is not well known. Six participants completed a 73-day-long study that included two 14-day-long 28-h forced desynchrony protocols to examine separate and interacting influences of sleep inertia, sleep homeostasis and circadian phase on higher-order cognitive functions of inhibitory control and selective visual attention. Cognitive performance for most measures was impaired immediately after scheduled awakening and improved during the first ~2-4 h of wakefulness (decreasing sleep inertia); worsened thereafter until scheduled bedtime (increasing sleep homeostasis); and was worst at ~60° and best at ~240° (circadian modulation, with worst and best phases corresponding to ~09:00 and ~21:00 hours, respectively, in individuals with a habitual wake time of 07:00 hours). The relative influences of sleep inertia, sleep homeostasis and circadian phase depended on the specific higher-order cognitive function task examined. Inhibitory control appeared to be modulated most strongly by circadian phase, whereas selective visual attention for a spatial-configuration search task was modulated most strongly by sleep inertia. These findings demonstrate that some higher-order cognitive processes are differentially sensitive to different sleep-wake regulatory processes. Differential modulation of cognitive functions by different sleep-wake regulatory processes has important implications for understanding mechanisms contributing to performance impairments during adverse circadian phases, sleep deprivation and/or upon awakening from sleep. © 2015 European Sleep Research Society.Journal of Sleep Research 03/2015; DOI:10.1111/jsr.12291 · 2.95 Impact Factor