Akiko Ozaki

The Japanese Centenarian Study: Autonomy Was Associated with Health Practices as Well as Physical Status

OBJECTIVES: To investigate the prevalence of centenarians who have preserved activities of daily living (ADLs) and good cognitive and psychosocial status in Japan.

Factors Associated With Shift Work Disorder in Nurses Working With Rapid-Rotation Schedules in Japan: The Nurses’ Sleep Health Project

Workers who meet the criteria for shift work disorder (SWD) have elevated levels of risk for various health and behavioral problems. However, the impact of having SWD on shiftworkers engaged in rapid-rotation schedules is unknown. Moreover, the risk factors for the occurrence of SWD remain unclear. To clarify these issues, we conducted a questionnaire-based, cross-sectional survey on a sample of shiftworking nurses. Responses were obtained from 1202 nurses working at university hospitals in Tokyo, Japan, including 727 two-shift workers and 315 three-shift workers. The questionnaire included items relevant to age, gender, family structure, work environment, health-related quality of life (QOL), diurnal type, depressive symptoms, and SWD. Participants who reported insomnia and/or excessive sleepiness for at least 1 mo that was subjectively relevant to their shiftwork schedules were categorized as having SWD. The prevalence of SWD in the sampled shiftworking nurses was 24.4%; shiftworking nurses with SWD showed lower health-related QOL and more severe depressive symptoms, with greater rates of both actual accidents/errors and near misses, than those without SWD. The results of logistic regression analyses showed that more time spent working at night, frequent missing of nap opportunities during night work, and having an eveningness-oriented chronotype were significantly associated with SWD. The present study indicated that SWD might be associated with reduced health-related QOL and decreased work performance in shiftworking nurses on rapid-rotation schedules. The results also suggested that missing napping opportunities during night work, long nighttime working hours, and the delay of circadian rhythms are associated with the occurrence of SWD among shiftworking nurses on rapid-rotation schedules. (Author correspondence: yuinoue@tokyo-med.ac.jp)

Circadian fluctuation of time perception in healthy human subjects

Previous studies suggested that various psychophysiological factors have influences on human time perception. In particular, working memory loads, time of day, body temperature, and mood were known as important modifiers of time perception. The purpose of this study is to elucidate factors affecting the short-term time perception under controlled condition. Fourteen healthy young male adults participated in this study. Time perception sessions (TPS) were conducted 4 times at 0900, 1300, 1700 and 2100 h. The TPS consisted of five 10-s time production trials under five different conditions (control trial, those with reward, and 3 different dual-load working memory tasks). Subjective status was assessed using visual analogue scales (VAS). To verify a participants vigilance state, an alpha attenuation coefficient (AAC) was calculated. Two-way repeated measures ANOVA for produced time revealed a significant main effect of session, but no effect of task or interaction. Although produced time was not correlated with AACs or VAS scores, there was a significant negative correlation between produced time and core body temperature. These results suggest that human short-term time perception may be more influenced by circadian rhythm than working memory load or psychophysiological status.

Quality of life in patients with narcolepsy with cataplexy, narcolepsy without cataplexy, and idiopathic hypersomnia without long sleep time: Comparison between patients on psychostimulants, drug-naïve patients and the general Japanese population

OBJECTIVE To assess the quality of life of patients with narcolepsy with cataplexy (NA-CA), narcolepsy without cataplexy (NA w/o CA), and idiopathic hypersomnia without long sleep time (IHS w/o LST) who were taking psychostimulant medication, and to ascertain which factors (including psychosocial and environmental variables) influence quality of life in this population. METHODS In total, 185 patients who had received regular treatment were enrolled in the study (NA-CA, n=83; NA w/o CA, n=48; IHS w/o LST, n=54). Patients were asked to complete questionnaires including the Short Form-36 Health Survey (SF-36), the Epworth Sleepiness Scale (ESS), and items concerning psychosocial and environmental variables. RESULTS All three diagnostic groups had significantly lower scores for most SF-36 domains compared with the Japanese normative data, and the ESS score was significantly reduced with treatment. Multiple logistic regression analyses revealed that several SF-36 domains were associated with the ESS score; autonomy in controlling own job schedule, experience of divorce or break up with a partner due to symptoms, experience of being forced to relocate or being dismissed due to symptoms, and perception of support from others. CONCLUSIONS The severity of subjective sleepiness and psychological and environmental variables influenced quality of life in patients with these hypersomnias of central origin.

Diurnal fluctuation of time perception under 30-h sustained wakefulness.

Previous studies have reported that time perception in humans fluctuates over a 24-h period. Behavioral changes seem to affect human time perception, so that the fluctuation in human time perception may be the result of such changes due to self-determined activities. Recently, we carried out a study in which a healthy human cohort was asked to perform simultaneously loaded cognitive tasks under controlled conditions, and found that time perception decreased linearly from morning to evening. In addition, the variations in time perception were not a consequence of behavioral changes. It remains to be elucidated whether diurnal variations in time perception are a consequence of circadian rhythm or of some homeostatic changes that are attributable to accumulated wake time. The effects of circadian rhythm on time perception were investigated in eight healthy young male volunteers by conducting 10-s time production tasks under 30-h constant-routine conditions. Core body temperature and serum melatonin and cortisol levels were measured during the course of the study. Produced time exhibited a diurnal variation and was strongly correlated with circadian variations in core body temperature and serum melatonin levels. These results suggest that human short-term time perception is under the influence of the circadian pacemaker.

Effects of Oral L-Carnitine Administration in Narcolepsy Patients: A Randomized, Double-Blind, Cross-Over and Placebo-Controlled Trial

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement (REM) sleep abnormalities. A genome-wide association study (GWAS) identified a novel narcolepsy-related single nucleotide polymorphism (SNP), which is located adjacent to the carnitine palmitoyltransferase 1B (CPT1B) gene encoding an enzyme involved in β-oxidation of long-chain fatty acids. The mRNA expression levels of CPT1B were associated with this SNP. In addition, we recently reported that acylcarnitine levels were abnormally low in narcolepsy patients. To assess the efficacy of oral l-carnitine for the treatment of narcolepsy, we performed a clinical trial administering l-carnitine (510 mg/day) to patients with the disease. The study design was a randomized, double-blind, cross-over and placebo-controlled trial. Thirty narcolepsy patients were enrolled in our study. Two patients were withdrawn and 28 patients were included in the statistical analysis (15 males and 13 females, all with HLA-DQB1*06:02). l-carnitine treatment significantly improved the total time for dozing off during the daytime, calculated from the sleep logs, compared with that of placebo-treated periods. l-carnitine efficiently increased serum acylcarnitine levels, and reduced serum triglycerides concentration. Differences in the Japanese version of the Epworth Sleepiness Scale (ESS) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) vitality and mental health subscales did not reach statistical significance between l-carnitine and placebo. This study suggests that oral l-carnitine can be effective in reducing excessive daytime sleepiness in narcolepsy patients. Trial Registration University hospital Medical Information Network (UMIN) UMIN000003760

Time estimation during nocturnal sleep in human subjects

It has been postulated that time estimation during nocturnal sleep in humans can be explained by an interval timing clock inside the brain. However, no systematic investigations have been carried out with respect to how the human brain perceives the passage of time during sleep. The brain mechanisms of over- or underestimation of time spent in sleep have not yet been clarified. Here, we carried out an experimental study in which 11 healthy volunteers participated in time estimation trials scheduled six times during 9 h nocturnal sleep periods, under carefully controlled conditions. The time estimation ratio (TER: a ratio of subjective passage of time to actual time interval) decreased significantly from the first to the sixth trial. Individual TER was positively correlated with slow wave sleep prior to the trial, while it was negatively correlated with REM sleep. Our results indicate that the human brain has an ability to estimate the passage of time during nocturnal sleep without referring to time cues, and that the accuracy of this function fluctuates from overestimation in the early hours of sleep to underestimation in the last hours of sleep.

Circadian rhythms in humans' delta sleep electroencephalogram

Eight healthy young male volunteers entered a 20-40 min ultrashort sleep-wake schedule for 78 h in the time-isolation facility. Rectal temperature was continuously recorded. Sleep electroencephalograms (EEGs) obtained during 20 min nap trials were stored in the computer and later analyzed by fast Fourier transform. A two-way repeated-measures ANOVA (with day and time-of-day as the repeated measures) revealed significant circadian rhythms in the powers of sigma and delta sleep EEGs, and in rectal temperature. These results obtained under conditions in which behavioral confounding factors of retiring and rising were experimentally minimized suggest that the circadian pacemaker contributes to determining the hours of day when one can sleep deeply.