Prolonged Sleep Duration Research Articles

Total daily sleep duration and the risk of dementia: a prospective population‐based study

We determined in a population-based study whether sleep duration was associated with an increased risk of incident dementia. In a population-based study in central Spain, participants were evaluated at baseline and 3 years later. Baseline demographic variables were recorded and participants indicated their daily sleep duration as the sum of night-time sleep and daytime napping. The average daily total sleep duration was grouped into five categories: < or = 5 (short sleepers), 6, 7 (reference), 8, and > or = 9 h (long sleepers). We identified all cases with incident dementia, diagnosed using DSM-IV criteria. Three thousand two hundred eighty six participants with baseline information about sleep duration had a median duration of follow-up of 3.2 years. There were 140 incident cases of dementia. The relative risks (RR) for short sleepers and for long sleepers were 2.36 (95% CI = 1.07-5.21, P = 0.03) and 2.40 (95% CI = 1.20-4.81, P = 0.01), respectively. After adjustment for potential confounders, the RR was only marginally increased for short sleepers (1.87, 95% CI = 0.85-4.15, P = 0.12) but remained increased for long sleepers (2.18; 95% CI = 1.09-4.37, P = 0.03). Prolonged sleep duration (night-time sleep and daytime napping) may be associated with an increased risk of dementia.

Sleep homeostasis: A role for adenosine in humans?

Sleep is not the mere absence of wakefulness, but an active state which is finely regulated. The homeostatic facet of sleep–wake regulation is keeping track of changes in ‘sleep propensity’ (or ‘sleep need’), which increases during wakefulness and decreases during sleep. Increased sleep propensity following extended prior wakefulness (sleep deprivation) is counteracted by prolonged sleep duration, but also by enhanced non-rapid-eye-movement (nonREM) sleep intensity as measured by electroencephalographic (EEG) slow-wave activity (SWA, power within ∼1–4Hz). This highly reliable regulatory feature of nonREM sleep may be the most important aspect of sleep in relation to its function. The neurochemical mechanisms underlying nonREM sleep homeostasis are poorly understood. Here we provide compelling and convergent evidence that adenosinergic neurotransmission plays a role in nonREM sleep homeostasis in humans. Specifically, a functional polymorphism in the adenosine metabolizing enzyme, adenosine deaminase, contributes to the high inter-individual variability in deep slow-wave sleep duration and intensity. Moreover, the adenosine receptor antagonist, caffeine, potently attenuates the EEG markers of nonREM sleep homeostasis during sleep, as well as during wakefulness. Finally, adenosinergic mechanisms modulate individual vulnerability to the detrimental effects of sleep deprivation on neurobehavioral performance, and EEG indices of disturbed sleep after caffeine consumption. While these convergent findings strongly support an important contribution of adenosine and adenosine receptors to nonREM sleep homeostasis, further research is needed to elucidate the underlying mechanisms that mediate the actions of adenosine on sleep and the sleep EEG.

Sleep Duration as a Risk Factor for Diabetes Incidence in a Large US Sample

To explore the relationship between sleep duration and diabetes incidence over an 8- to 10-year follow-up period in data from the First National Health and Nutrition Examination Survey (NHANES I). We hypothesized that prolonged short sleep duration is associated with diabetes and that obesity and hypertension act as partial mediators of this relationship. The increased load on the pancreas from insulin resistance induced by chronically short sleep durations can, over time, compromise beta-cell function and lead to type 2 diabetes. No plausible mechanism has been identified by which long sleep duration could lead to diabetes. Multivariate longitudinal analyses of the NHANES I using logistic regression models. Probability sample (n=8992) of the noninstitutionalized population of the United States between 1982 and 1992. Subjects between the ages of 32 and 86 years. Between 1982 and 1992, 4.8% of the sample (n=430) were determined by physician diagnosis, hospital record, or cause of death to be incident cases of diabetes. Subjects with sleep durations of 5 or fewer hours (odds ratio = 1.47, 95% confidence interval 1.03-2.09) and subjects with sleep durations of 9 or more hours (odds ratio = 1.52, 95% confidence interval 1.06-2.18) were significantly more likely to have incident diabetes over the follow-up period after controlling for covariates. Short sleep duration could be a significant risk factor for diabetes. The association between long sleep duration and diabetes incidence is more likely to be due to some unmeasured confounder such as poor sleep quality.

Repeated dose effects of lormetazepam and flurazepam upon driving performance

The residual effects of lormetazepam 1 mg and 2 mg in soft gelatine capsules on driving performance were assessed and compared to those of flurazepam 30 mg, which is also a powerful hypnotic, but possesses a far less favourable pharmacokinetic profile with a long-acting sedative metabolite. Driving performance was tested 10 to 11 h and 16 to 17 h post administration, after 2 days on placebo (baseline), and 2, 4 and 7 days of drug treatment (active), and after 1 and 3 days following the resumption of placebo (washout). The driving test consisted of operating an instrumented motor-vehicle over a 72 km highway circuit in light traffic. Flurazepam 30 mg significantly impaired the ability to control the lateral position of the vehicle compared to placebo baseline measurements. The degree of impairment was substantial in the female subjects and was greater in the morning than in the afternoon. Lormetazepam 1 mg showed no residual effect on driving performance. Lormetazepam 2 mg impaired driving performance to some extent on the following morning, 10 to 11 h post administration, but no residual effect was found in the afternoon. All drugs improved sleep quality and prolonged sleep duration to more or less the same extent.

Effect of gradual withdrawal on the rebound sleep disorder after discontinuation of triazolam

Sixty volunteers with insomnia participated in a randomized, double-blind, controlled clinical trial. After an initial six nights of placebo, 30 subjects (the abrupt-withdrawal group) received 0.5 mg of triazolam nightly for 7 to 10 nights, after which they received placebo. The other 30 subjects (the tapered-dosage group) received the same initial placebo treatment, then triazolam at 0.5 mg for seven nights, at 0.25 mg for two nights, and at 0.125 mg for two nights, and then placebo. As compared with the initial placebo period, the triazolam period significantly reduced the interval before the onset of sleep (sleep latency), and it prolonged sleep duration, reduced the number of awakenings, and improved the self-rated soundness of sleep in all cohorts. In the abrupt-withdrawal group, plasma levels of triazolam were undetectable the morning after the first night of placebo substitution, and subjects reported prolongation of sleep latency (57 minutes longer than base line), reduction in sleep duration (1.4 hours less than base line), and increased awakenings (1.2 per night above base line). The symptoms of rebound sleep disorder lasted one or possibly two nights, and there was a reversion toward base line on subsequent placebo nights. In the tapered-dosage group, however, plasma triazolam levels fell gradually to zero, and rebound symptoms were decreased or eliminated. Thus, rebound sleep disorder following abrupt discontinuation of triazolam can be attenuated by a regimen of tapering.

Effect of Gradual Withdrawal on the Rebound Sleep Disorder after Discontinuation of Triazolam

Sixty volunteers with insomnia participated in a randomized, double-blind, controlled clinical trial. After an initial six nights of placebo, 30 subjects (the abrupt-withdrawal group) received 0.5 mg of triazolam nightly for 7 to 10 nights, after which they received placebo. The other 30 subjects (the tapered-dosage group) received the same initial placebo treatment, then triazolam at 0.5 mg for seven nights, at 0.25 mg for two nights, and at 0.125 mg for two nights, and then placebo. As compared with the initial placebo period, the triazolam period significantly reduced the interval before the onset of sleep (sleep latency), and it prolonged sleep duration, reduced the number of awakenings, and improved the self-rated soundness of sleep in all cohorts. In the abrupt-withdrawal group, plasma levels of triazolam were undetectable the morning after the first night of placebo substitution, and subjects reported prolongation of sleep latency (57 minutes longer than base line), reduction in sleep duration (1.4 hours less than base line), and increased awakenings (1.2 per night above base line). The symptoms of rebound sleep disorder lasted one or possibly two nights, and there was a reversion toward base line on subsequent placebo nights. In the tapered-dosage group, however, plasma triazolam levels fell gradually to zero, and rebound symptoms were decreased or eliminated. Thus, rebound sleep disorder following abrupt discontinuation of triazolam can be attenuated by a regimen of tapering.

Augmented depression and reduced excitability of the central nervous system (CNS) by cadmium in the rat

Reports indicating that low doses of cadmium caused vasolidation, but that larger quantities elicited a pressor response, apparently mediated by a CNS reflex, prompted an examination of cadmium-induced changes in CNS responsiveness and activity. Rats were injected intraperitoneally with either 2 mg/kg or 4 mg/kg of CdCl 2 solution, after which the CNS was either depressed by pentobarbital or excited by strychine at different dose levels. Cadmium treatment, administered before pentobarbital, decreased the time required for sleep induction and prolonged sleep duration at doses of either 20 mg/kg or 30 mg/kg: at 40 mg/kg only induction was affected and at 60 mg/kg neither was influenced. At a dosage of 60 μg/kg, strychnine caused convulsions in all control animals, but in none pretreated with CdCl 2. When either 75 or 120 mg/kg of strychnine was used, cadmium at either dosage failed to prevent convulsions, although the onset was delayed and duration curtailed. The rapidity with which Cd modified CNS activity indicated that the effect can not depend upon cadmium- induced synthesis of metallothionine, but represents a direct effect of Cd on the CNS. Cadmium treatment did not substantially improve the survival of rats that convulsed when treated with strychnine.