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Biomedical subjects

Eus J W Van Someren

Publications and source records attributed to Eus J W Van Someren.

At least 19 recordsLinked to original sources

Skin temperature and sleep-onset latency: changes with age and insomnia.

Throughout the 24-hour day, the occurrence of sleep and wakefulness is closely related to changes in body temperatures. Changes in skin temperature may causally affect the ability to initiate and maintain sleep. First, we briefly summarize a previously proposed neurobiological mechanism that couples skin temperature to sleep propensity. Next we review previous findings on the relation between skin temperature and sleep-onset latency, indicating that sleep propensity can be enhanced by warming the skin to the level that normally occurs prior to--and during--sleep. Finally, we present new data indicating age- and insomnia-related changes in the sleep-onset latency response to foot warming, and evaluate whether different methods of foot warming could provide an applicable strategy to address sleep complaints. Foot temperature manipulations included footbaths before sleep onset (1), and heatable bed socks applied either before (2) or after lights-off (3). In adults, sleep-onset was accelerated by warm and neutral bed socks after lights-off and correlated to the increase in foot temperature. This increase was attenuated in elderly subjects. In elderly subjects without sleep difficulties, sleep onset could be accelerated with neutral bed socks after lights-off and a warm footbath prior to lights-off. In elderly insomniacs, none of the treatments accelerated sleep onset. We illustrate that elderly subjects show an attenuated increase in foot temperature after lights-off and lose the relationship between pre-sleep heat-loss activation and sleep latency. The sensitivity of sleep propensity to foot warming changes with age and is attenuated in age-related insomnia.

Adult↗

Evaluation of wireless determination of skin temperature using iButtons.

Measurements of skin temperatures are often complicated because of the use of wired sensors. This is so in field studies, but also holds for many laboratory conditions. This article describes a wireless temperature system for human skin temperature measurements, i.e. the Thermochron iButton DS1291H. The study deals with validation of the iButton and its application on the human skin, and describes clinical and field measurements. The validation study shows that iButtons have a mean accuracy of -0.09 degrees C (-0.4 degrees C at most) with a precision of 0.05 degrees C (0.09 degrees C at most). These properties can be improved by using calibration. Due to the size of the device the response time is longer than that of conventional sensors, with a tau in water of 19 s. On the human skin under transient conditions the response time is significantly longer, revealing momentary deviations with a magnitude of 1 degrees C. The use of iButtons has been described in studies on circadian rhythms, sleep and cardiac surgery. With respect to circadian rhythm and sleep research, skin temperature assessment by iButtons is of significant value in laboratory, clinical and home situations. We demonstrate that differences in laboratory and field measurements add to our understanding of thermophysiology under natural living conditions. The advantage of iButtons in surgery research is that they are easy to sterilize and wireless so that they do not hinder the surgical procedure. In conclusion, the application of iButtons is advantageous for measuring skin temperatures in those situations in which wired instruments are unpractical and fast responses are not required.

Adult↗

New actigraph for long-term tremor recording.

A new method of movement analysis is validated, allowing an actigraph to discriminate tremor from other movements and store duration and intensity measures of both movement types. For algorithm optimization, wrist acceleration was recorded in nine controls and nine Parkinson's disease patients, while simultaneously rating their observed tremor minute by minute on item 20 of the Unified Parkinson's Disease Rating Scale. An optimization procedure to minimize false positives in controls while maximizing tremor detection in patients resulted in false positive tremor classification in 2.4% +/- 2.5% of the movement time of control subjects (range, 0%-7%), while providing tremor classification in 82.1% +/- 15.4% of the movement time in patients (range, 55%-100%), correlating r = 0.93 with their averaged observed tremor score. A second, generalizability study showed that application of the optimized algorithm resulted in accurate classification of 71% +/- 14% of the observed tremor time (range, 46%-90%) in another 9 patients and in a false positive classification in only 0.5% +/- 0.8% of the time in another 10 controls (range, 0%-2.4%). The commercial availability of this actigraph now for the first time makes it possible to investigate tremor fluctuations over several weeks. An example is given of how long-term monitoring can be of use in evaluation of symptom management.

Aged↗

Mechanisms and functions of coupling between sleep and temperature rhythms.

Energy metabolism is strongly linked to the circadian rhythms in sleep and body temperature. Both heat production and heat loss show a circadian modulation. Sleep preferably occurs during the circadian phase of decreased heat production and increased heat loss, the latter due to a profound increase in skin blood flow and, consequently, skin warming. The coupling of these rhythms may differ depending on whether they are assessed in experimental laboratory studies or in habitual sleeping conditions. In habitual sleeping conditions, skin blood flow is for a prolonged time increased to a level hardly ever seen during wakefulness. Possible mechanisms linking the rhythms in sleep and core body and skin temperature are discussed, with a focus on causal effects of changes in core and skin temperature on sleep regulation. It is shown that changes in skin temperature rather than in core temperature causally affect sleep propensity. Contrary to earlier suggestions of a functional role of sleep in heat loss, it is argued that sleep facilitates a condition of increased skin blood flow during a prolonged circadian phase, yet limits heat loss and the risk of hypothermia. Sleep-related behavior including the creation of an isolated microclimate of high temperature by means of warm clothing and bedding in humans and the curling up, huddling and cuddling in animals all help limit heat loss The increase in skin blood flow that characterizes the sleeping period may thus not primarily reflect a thermoregulatory drive. There is indirect support for an alternative role of the prolonged period of increased skin blood flow: it may support maintenance of the skin as a primary barrier in host defense.

Animals↗

Altered skin-temperature regulation in narcolepsy relates to sleep propensity.

STUDY OBJECTIVES: In healthy subjects, sleep propensity increases when the distal skin temperature increases relative to the proximal skin temperature. This increase results from increased blood flow in the skin of the extremities and is, among other factors, controlled by the hypothalamic circadian clock, as is sleep. Because narcolepsy is characterized by hypothalamic alterations, we studied skin temperature in narcoleptic patients in relation to their characteristically increased sleep propensity during the day. DESIGN: Distal and proximal skin temperature and their gradient (DPG) were measured during a Multiple Sleep Latency Test. This allowed temperature to be studied during wakefulness, at sleep onset and during sleep. SETTING: Tertiary narcolepsy referral center in a university hospital. PATIENTS: Fifteen unmedicated narcolepsy patients with cataplexy and 15 controls. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: In subjects in the waking state, DPG was higher in narcoleptics than in controls throughout the day (time by group interaction, p < .0001), due to increased distal skin temperature and decreased proximal skin temperature. The increase in DPG was related to a shorter subsequent sleep-onset latency (p = .02). Once asleep, narcoleptics maintained their elevated distal skin temperature and DPG (p < .0001), whereas proximal skin temperature increased to reach normal levels. CONCLUSIONS: This is the first demonstration of a dramatic alteration of daytime skin temperature control in narcolepsy. Even awake narcoleptic patients showed a DPG higher than that which healthy controls achieve when asleep. This observation suggests that hypocretin deficiency in narcolepsy affects skin-temperature regulation and invites further examination. Skin-temperature control might ultimately even have therapeutic implications for the alleviation of narcoleptic symptoms.

Adult↗

Comparison between informant-observed and actigraphic assessments of sleep-wake rhythm disturbances in demented residents of homes for the elderly.

OBJECTIVE: Sleep-wake rhythm disturbances frequently occur in demented elderly and are of clinical relevance because they herald accelerated functional decline and institutionalization. Assessment of sleep-wake rhythm disorders is therefore of significant importance and can be performed by questionnaires or actigraphy, i.e., the recording of wrist activity. The present study investigates the relation of these two types of measurement by simultaneously assessing actigraphy and the Circadian Sleep Inventory for Normal and Pathological States (CSINAPS). METHODS: Seventy-eight elderly subjects, mean age 85+/-6 years, living in group care facilities of 12 homes for the elderly, wore an actigraph for two weeks. Caregivers completed the nurse informant CSINAPS. Spearman rank correlations and Mann-Whitney U tests were calculated over the equivalent sleep-wake rhythm parameters as derived from actigraphy and from the CSINAPS. RESULTS: Good correlations were found between questionnaire items about habitual timing of sleep and wakefulness and their actigraphic counterparts. Caregivers overestimated the actual sleep time between sleep onset and offset by 96 minutes. Questionnaire reports of sleep disturbances like wandering at night were also reflected in actigraphy parameters. However, the questionnaire and actigraphy variables correlate only modestly and may complement each other. In our study, both actigraphy and the CSINAPS seemed to miss the previously established high prevalence of sleep-disordered breathing (SDB) and leg movements during sleep (LM). CONCLUSION: The assessment of sleep and wake disturbances in demented elderly is best served by parallel use of a questionnaire like the CSINAPS and actigraphy. Moreover, if SDB and LM are a focus of interest, additional assessments are needed.

Aged↗

Peripheral electrical nerve stimulation and rest-activity rhythm in Alzheimer's disease.

Rest-activity rhythm disruption is a prominent clinical feature of Alzheimer's disease (AD). The origin of the altered rest-activity rhythm is believed to be degeneration of the suprachiasmatic nucleus (SCN). In accordance with the 'use it or lose it' hypothesis of Swaab [Neurobiol Aging 1991, 12: 317-324] stimulation of the SCN may prevent age-related loss of neurons and might reactivate nerve cells that are inactive but not lost. Previous studies with relatively small sample sizes have demonstrated positive effects of peripheral electrical nerve stimulation on the rest-activity rhythm in AD patients. The present randomized, placebo-controlled, parallel-group study was meant to replicate prior findings of electrical stimulation in AD in a substantially larger group of AD patients. The experimental group (n = 31) received peripheral electrical nerve stimulation and the placebo group (n = 31) received sham stimulation. Effects of the intervention on the rest-activity rhythm were assessed by using wrist-worn actigraphs. Near-significant findings on the rest-activity rhythm partially support the hypothesis that neuronal stimulation enhances the rest-activity rhythm in AD patients. Interestingly, post-hoc analyses revealed significant treatment effects in a group of patients who were not using acetylcholinesterase inhibitors concomitantly. We conclude that more research is needed before firm general conclusions about the effectiveness of electrical stimulation as a symptomatic treatment in AD can be drawn. In addition, the present post-hoc findings indicate that future studies on non-pharmacological interventions should take medication use into account.

Activity Cycles↗

Colocalization of corticotropin-releasing hormone and oestrogen receptor-alpha in the paraventricular nucleus of the hypothalamus in mood disorders.

Oestrogens may modulate the activity of the hypothalamic-pituitary-adrenal (HPA) axis. The present study was to investigate whether the activity of the HPA axis in mood disorders might be directly modulated by oestrogens via oestrogen receptors (ORs) in the corticotropin-releasing hormone (CRH) neurons of the human hypothalamic paraventricular nucleus (PVN). Brains of 13 subjects ranging in age between 45 and 79 years suffering from major depression/major depressive disorder (eight cases) or bipolar disorder (five cases) and of 13 controls, matched for sex, age, brain weight, post-mortem delay, fixation time and season and clock time at death, were studied with double-label immunocytochemistry. The total number of CRH-immunoreactive (IR) neurons, CRH neurons that colocalized ORalpha in the neuronal nucleus and the number of only nuclear ORalpha-containing neurons in the PVN were measured using an image analysis system. In addition, the volume of the PVN delineated on the basis of CRH neurons was determined. It was found that the total number of CRH-IR neurons in patients with mood disorders was nearly 1.7 times higher than in controls (P = 0.034). A novel finding was that the total number of CRH-IR neurons and the number of CRH-nuclear ORalpha double-staining neurons in the PVN were strongly correlated both in controls and in patients with mood disorders (P < 0.001 and P = 0.022, respectively). The ratio of the CRH-nuclear-ORalpha double-staining neurons to the total CRH-IR neurons in patients with mood disorders was similar to that in the controls (P = 0.448). The volume of the sub-region of the PVN that was delineated on the basis of CRH neurons was significantly larger in patients with mood disorders than in controls (P = 0.022). Another novel finding was the large population of extra-hypothalamic CRH neurons that was found in the thalamus. In summary, oestrogens may directly influence CRH neurons in the human PVN. The increased numbers of neurons expressing CRH in mood disorders is accompanied by increased ORalpha colocalization in the nucleus of these neurons. These changes seem to be trait- rather than state-related.

Aged↗

Cutaneous warming promotes sleep onset.

Sleep occurs in close relation to changes in body temperature. Both the monophasic sleep period in humans and the polyphasic sleep periods in rodents tend to be initiated when core body temperature is declining. This decline is mainly due to an increase in skin blood flow and consequently skin warming and heat loss. We have proposed that these intrinsically occurring changes in core and skin temperatures could modulate neuronal activity in sleep-regulating brain areas (Van Someren EJW, Chronobiol Int 17: 313-54, 2000). We here provide results compatible with this hypothesis. We obtained 144 sleep-onset latencies while directly manipulating core and skin temperatures within the comfortable range in eight healthy subjects under controlled conditions. The induction of a proximal skin temperature difference of only 0.78 +/- 0.03 degrees C (mean +/- SE) around a mean of 35.13 +/- 0.11 degrees C changed sleep-onset latency by 26%, i.e., by 3.09 minutes [95% confidence interval (CI), 1.91 to 4.28] around a mean of 11.85 min (CI, 9.74 to 14.41), with faster sleep onsets when the proximal skin was warmed. The reduction in sleep-onset latency occurred despite a small but significant decrease in subjective comfort during proximal skin warming. The induction of changes in core temperature (delta = 0.20 +/- 0.02 degrees C) and distal skin temperature (delta = 0.74 +/- 0.05 degrees C) were ineffective. Previous studies have demonstrated correlations between skin temperature and sleep-onset latency. Also, sleep disruption by ambient temperatures that activate thermoregulatory defense mechanisms has been shown. The present study is the first to experimentally demonstrate a causal contribution to sleep-onset latency of skin temperature manipulations within the normal nocturnal fluctuation range. Circadian and sleep-appetitive behavior-induced variations in skin temperature might act as an input signal to sleep-regulating systems.

Adult↗

Effect of morning bright light treatment for rest-activity disruption in institutionalized patients with severe Alzheimer's disease.

BACKGROUND: Disturbances in rest-activity rhythm are prominent and disabling symptoms in Alzheimer's disease (AD). Nighttime sleep is severely fragmented and daytime activity is disrupted by multiple napping episodes. In most institutional environments, light levels are very low and may not be sufficient to enable the circadian clock to entrain to the 24-hour day. The purpose of this randomized, placebo-controlled, clinical trial was to test the effectiveness of morning bright light therapy in reducing rest-activity (circadian) disruption in institutionalized patients with severe AD. METHOD: Subjects (n = 46, mean age 84 years) meeting the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke--the Alzheimer's Disease and Related Disorders Association) AD diagnostic criteria were recruited from two large, skilled nursing facilities in San Francisco, California. The experimental group received one hour (09:30-10:30) of bright light exposure (> or = 2500 lux in gaze direction) Monday through Friday for 10 weeks. The control group received usual indoor light (150-200 lux). Nighttime sleep efficiency, sleep time, wake time and number of awakenings and daytime wake time were assessed using actigraphy. Circadian rhythm parameters were also determined from the actigraphic data using cosinor analysis and nonparametric techniques. Repeated measures analysis of variance (ANOVA) was used to test the primary study hypotheses. RESULTS AND CONCLUSION: Although significant improvements were found in subjects with aberrant timing of their rest-activity rhythm, morning bright light exposure did not induce an overall improvement in measures of sleep or the rest-activity in all treated as compared to control subjects. The results indicate that only subjects with the most impaired rest-activity rhythm respond significantly and positively to a brief (one hour) light intervention.

Aged↗

Idiopathic chronic sleep onset insomnia in attention-deficit/hyperactivity disorder: a circadian rhythm sleep disorder.

To investigate whether ADHD-related sleep-onset insomnia (SOI) is a circadian rhythm disorder, we compared actigraphic sleep estimates, the circadian rest-activity rhythm, and dim light melatonin onset (DLMO) in ADHD children having chronic idiopathic SOI with that in ADHD children without sleep problems. Participants were 87 psychotropic-medication-naïve children, aged 6 to 12 yrs, with rigorously diagnosed ADHD and SOI (ADHD-SOI) and 33 children with ADHD without SOI (ADHD-noSOI) referred from community mental health institutions and pediatric departments of non-academic hospitals in The Netherlands. Measurements were 1 wk, 24 h actigraphy recordings and salivary DLMO. The mean (+/-SD) sleep onset time was 21:38 +/- 0:54 h in ADHD-SOI, which was significantly (p < 0.001) later than that of 20:49 +/- 0:49 h in ADHD-noSOI. DLMO was significantly later in ADHD-SOI (20:32 +/- 0:55 h), compared with ADHD-noSOI (19:47 +/- 0:49 h; p < 0.001). Wake-up time in ADHD-SOI was later than in ADHD-noSOI (p = 0.002). There were no significant between-group differences in sleep maintenance, as estimated by number of wake bouts and activity level in the least active 5 h period, or inter- and intradaily rhythm variability. We conclude that children with ADHD and chronic idiopathic sleep-onset insomnia show a delayed sleep phase and delayed DLMO, compared with ADHD children without SOI.

Attention Deficit Disorder with Hyperactivity↗

Diurnal rhythms of free estradiol and cortisol during the normal menstrual cycle in women with major depression.

To investigate whether depression is accompanied by changes in diurnal rhythms of free estradiol and cortisol in different phases of the menstrual cycle, we measured these two hormone levels in saliva samples collected every 2 h for 24 h from 15 healthy normally cycling women and 12 age-matched normally cycling women suffering from major depression taking antidepressants. The assessments were repeated four times over one menstrual cycle: during menstruation and in the late follicular/peri-ovulating, early to mid-luteal and late luteal phases, respectively. Quantification with a nonlinear periodic regression model revealed distinct diurnal rhythms in free estradiol and free cortisol in all subjects. For the diurnal cortisol rhythm, significant differences were found in the peak-width and ultradian amplitude among different menstrual phases, both in controls and depressed patients, while no significant differences were found between the two groups. The diurnal estradiol rhythm, on the other hand, was quite consistent among different menstrual phases within both groups, while the depressed patients had overall larger amplitudes than controls, which is negatively correlated with disease duration. Significant positive correlations between the two hormone rhythms were found for 24-h mean level (mesor), peak, and trough in late luteal phase, and for ultradian harmonics in early to mid-luteal phase in controls, but only for ultradian harmonics in late follicular/peri-ovulating phase and for acrophase in the menstruation phase in depressed patients. A sub-analysis was also performed in patients who received Fluoxetine (n = 7). The findings implicate a close correlation between the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis, both of which may be involved in depression.

Adult↗

Changes in diurnal rhythms of free cortisol secretion during different phases of menstrual cycle.

The effect of the menstrual cycle on the diurnal cortisol rhythm was investigated in 15 normally cyclic healthy women during reproductive life. Salivary cortisol was measured by radioimmunoassay in samples collected every 2 h for 24 h during the four phases of the menstrual cycle: menstrual phase, late follicular/peri-ovulation phase, early to mid luteal phase and late luteal phase, respectively. Distinct diurnal rhythms of free cortisol were found throughout the menstrual cycle by using a nonlinear periodic regression model. The model was characterized by an asymmetrically peaked diurnal cycle and ultradian harmonics. There was a trend to higher troughs and significantly shorter peak-width in phase II and phase IV compared to phase I. The ultradian amplitude in phase IV was significantly lower compared with phase I and showed a trend of decrease compared with phase II. The results suggest that the daily cortisol secretion is modulated by the phase of the menstrual cycle.

Adult↗

Non-pharmacological interventions in cognitively impaired and demented patients--a comparison with cholinesterase inhibitors.

The present paper reviews studies examining the effects of non-pharmacological stimulation, i.e. bright light, physical activity and tactile stimulation (touch), on cognition, affective behaviour, and the sleep-wake rhythm of impaired and demented elderly, both in a qualitative (narrative) and quantitative (meta-analytic) manner. An extensive search through eight bibliographic data bases (PubMed, Web of Science, ERIC, PsychINFO, Psyndex, Cinahl, Biological Abstracts and Rehabdata) was performed up to August 2002. The primary criterion for inclusion in this review was that studies provided sufficient data to calculate effect-sizes. In the qualitative analysis, all three types of stimulation appeared to improve cognitive functioning. Disturbances in behaviour react positively to bright light and tactile stimulation. Bright light was also beneficial to sleep. Tactile stimulation had, moreover, a beneficial influence on the patient-caretaker relationship. A comparison was made with several representative papers published since 1991 on the effects of acetylcholinesterase inhibitors on cognition and behaviour with representative papers on non-pharmacological stimulation interventions. Data indicated that improvements in cognition and affective behaviour by non-pharmacological interventions (d' = 0.32) and by cholinesterase inhibitors (d' = 0.31) were of similar effect-size. Possible mechanisms underlying the non-pharmacological stimulation effects are discussed and suggestions offered for future research.

Affect↗

Human basal cortisol levels are increased in hospital compared to home setting.

The impact of study-environment on experimental outcome is mostly not realized and certainly not demonstrated. In the present study, a comparison was made between free salivary cortisol levels in healthy young men in a carefully controlled hospital setting versus a home setting. Cortisol levels during rest were increased in hospital compared to home environment: 2-fold at awakening, 3-fold at the morning peak, and 5-fold late in the evening. Early morning light increased cortisol concentrations only in the home setting, while this effect was absent in the hospital setting. The data of the present study show that study-environment has a major impact on basal hypothalamo-pituitary-adrenal (HPA)-axis activity, which is of particular relevance in future studies in which small changes in HPA-axis activity are subject of study.

Adrenocorticotropic Hormone↗

Age-associated difference in circadian sleep-wake and rest-activity rhythms.

Using actigraphic monitoring of wrist activity, we investigated the sleep and rest-activity patterns of 65 young, middle-aged, old and the oldest subjects in their natural environmental conditions. To assess the effects of age and gender on sleep and circadian rhythms in activity, multivariate analyses were performed. Age significantly affected circadian sleep and rest-activity rhythms. In the old and oldest groups, the actigraphic estimates of "actual sleep time" and "sleep efficiency" decreased significantly. The estimates of "sleep latency," the number of "nighttime awakening," sleep fragmentation and daytime naps significantly increased in the old and oldest groups. Concerning the circadian patterning of rest and activity, the interdaily stability (IS) was similar in the four age groups, while the old and oldest subjects showed significant increases in intradaily variability (IV) and nighttime activity and a decrease in amplitude (AMP). The present study demonstrated weakened and fragmented circadian sleep and rest-activity rhythms during aging. However, no gender-related difference was found.

Adult↗