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Biomedical subjects

W C Dement

Publications and source records attributed to W C Dement.

At least 145 records · Page 8Linked to original sources

Effect of age on the circadian pattern of sleep and wakefulness in the mouse.

In elderly humans, daytime naps are common, nocturnal sleep is poorly consolidated, and the sleep period often begins and ends earlier than in young adults. Because previous work has suggested that rodents may provide a useful animal model for these changes, we conducted a detailed investigation of sleep patterns in 11 young adult and 9 old mice. Mice were surgically implanted for chronic EEG recording, and sleep state was monitored over multiple circadian cycles. During the active phase, old mice spent more time asleep and had shorter wake episodes compared with young mice. During the rest phase, old mice spent more time awake than young mice, and tended to have shorter episodes of sleep. No evidence was found, however, for earlier timing of sleep in older mice. These results suggest that the mouse may provide a suitable animal model for further study of certain age-related changes in temporal distribution of sleep and wakefulness.

Aging↗

Muscarinic cholinergic receptors and the canine model of narcolepsy.

The role of the muscarinic cholinergic receptor in narcolepsy was examined using radioligand binding to various brain regions of normal and genetically narcoleptic Doberman pinschers. In this multi-litter study, a previous report of a proliferation of muscarinic cholinergic receptors in the brainstem was confirmed, and the concentration of the M2 receptor subtype, in particular, was elevated. This up-regulation of brainstem cholinergic receptors suggests a problem with release of acetylcholine, which, together with previous reports of an impairment of dopamine release, may be indicative of a fundamental membrane problem in narcolepsy.

Amygdala↗

Brain benzodiazepine receptor characteristics in canine narcolepsy.

A regional analysis of brain benzodiazepine (BDZ) receptors was conducted in narcoleptic and normal dogs to determine whether these sites are altered in narcolepsy. It was postulated that BDZ receptors play a role in the excessive sleepiness of narcolepsy because activation of these sites in freely behaving normal animals is hypnogenic. [3H]Flunitrazepam binding sites were assessed in 11 discrete areas of the forebrain and brainstem. No consistent or statistically significant group differences in either receptor densities (Bmax) or binding affinities (Kd) were found. These findings do not support the assertion that BDZ receptors are involved in the pathogenesis of canine narcolepsy.

Animals↗

Sleep fragmentation in canine narcolepsy.

Genetically narcoleptic dogs were recorded continuously for 24 h to examine their sleep-wake patterns and to evaluate the extent of sleep fragmentation. Three narcoleptic and three control dogs from each of two affected breeds (Labrador retrievers and Doberman pinschers) were surgically implanted with electrodes for recording standard sleep parameters. Recordings were scored in 30-s epochs for the states of active waking, drowsiness, light sleep, deep slow wave sleep, REM sleep, and cataplexy. All affected dogs displayed marked fragmentation and disruption of the sleep-wake cycle characterized by repeated awakenings, frequent shifts in sleep stages, numerous attacks of cataplexy occurring from active waking, and a disturbance of the normal REM-NREM periodicity. This sleep disruption was reflected in significantly greater numbers of episodes of each behavioral state as well as in a 38% increase in the total number of all states. These results demonstrate a severe disturbance of the normal sleep pattern in canine narcoleptics. The possibility of a general dysfunction of circadian organization is discussed.

Animals↗

Circadian timekeeping in narcoleptic dogs.

Anatomical and functional aspects of the circadian timekeeping system containing the suprachiasmatic nucleus (SCN) were compared in normal and genetically narcoleptic dogs. The retinohypothalamic tract was delineated by tritiated amino acid autoradiography, the SCN was identified and examined by morphological techniques, and the circadian rhythm of melatonin concentrations in cerebrospinal fluid was measured by radioimmunoassay. Results suggest that the retinal input, cytoarchitecture, and essential timekeeping function of the SCN are intact in narcoleptic dogs.

Animals↗

Heart rate and blood pressure changes associated with cataplexy in canine narcolepsy.

Blood pressure and heart rate were monitored in narcoleptic dogs by means of a chronically implanted catheter placed in the descending aorta. Changes in these variables were recorded during spontaneously occurring cataplectic episodes. We found no reliable change in blood pressure associated with cataplexy onset. However, heart rate showed a marked increase prior to the onset of cataplexy, with peak heart rates being reached at or shortly after the disappearance of muscle tone. Autonomic events correlated with increased heart rate may contribute to the triggering of cataplexy in narcoleptics.

Animals↗

Comparative polysomnographic study of narcolepsy and idiopathic central nervous system hypersomnia.

Patients with a primary diagnosis of narcolepsy or idiopathic CNS hypersomnia seen at Stanford University Sleep Disorders Clinic over a 5-year period were studied retrospectively. The two patient groups were compared with respect to blood pressure, Minnesota Multiphasic Personality Inventory (MMPI) psychological profile, nocturnal sleep structure, prevalence and severity of sleep apnea and periodic leg movements in sleep, and daytime sleep tendency. Narcoleptic patients tended to have higher blood pressure, higher prevalence of abnormally elevated MMPI scores, more abbreviated and more disrupted sleep at night, and greater daytime sleep tendency. Sleep apnea and periodic leg movements were more prevalent in narcoleptic patients, but only periodic leg movements in sleep were more prevalent in narcoleptic patients than in the general population. Periodic leg movements during REM sleep were observed in more than one-third of narcoleptic patients, which may be an important pathophysiologic feature of this disorder.

Adolescent↗

Normal sleep, disturbed sleep, transient and persistent insomnia.

There are three fundamental principles for understanding sleep; the sleeping brain is not a resting brain, the sleeping brain functions in a different manner from the waking brain and the activity and work of the sleeping brain are purposeful. The sleeping brain does fail and this failure is manifest in a variety of clinical symptoms; all sleep complaints should be taken seriously and investigated. Transient insomnia is uniformly associated with objective sleep disturbances which have been documented following phase shifts of the major sleep period such as that caused by transmeridian travel. However, the degree to which the individual responds to these factors is variable. There is a consensus that sleep medications are indicated for transient and short-term insomnia. Benzodiazepine hypnotics are commonly used to induce and maintain sleep, and improve daytime alertness.

Anti-Anxiety Agents↗

Self-reported excessive daytime somnolence and impaired respiration in sleep.

The purpose of this study was to determine which measures of impaired respiration in sleep relate to self-reported excessive daytime somnolence (EDS). Previous studies conflict regarding the relative importance of arterial hypoxemia and brief awakenings in relating to EDS. A group of 37 elderly clinic patients with complaints of snoring, a clinical diagnosis of sleep apnea, and varying degrees of self-reported somnolence were evaluated polysomnographically and psychometrically. Results showed that a subgroup of somnolent patients were characterized by more severe oxygen desaturations relative to nonsomnolent patients. These differences were obtained even when obesity was controlled. Psychologic symptoms related to the symptom of EDS but not to the sleep measures. This suggested that patients were clearly distressed by their hypersomnolence, but that individual differences played a major role in how the distress was manifested.

Aged↗

International cooperative study of aircrew layover sleep: operational summary.

The findings of this cooperative study of layover sleep have direct implications for flight operations. In the consensus view of the principal investigators, these can be divided into their relevance for eastward or westward flight. Eastward flight produced more sleep disruption than westward. Different sleep and scheduling strategies are recommended for each flight direction, and the importance of individual crewmember factors is discussed in relation to age and circadian type. Despite the limitations of this study with regard to trip simplicity and the baseline data, the results for each airline are highly consistent and should be applicable to a wide range of long-haul crewmembers and carriers.

Adult↗

Sleep and wakefulness in aircrew before and after transoceanic flights.

Aircrew were studied before and after flying one of two routes: San Francisco (SFO) to London (LHR) or SFO to Tokyo (NRT). After an adaptation night, sleep and daytime sleepiness were objectively measured in SFO and during the first layover (L/O) of the target trip. Baseline sleep was slightly shorter than normally reported for similar age subjects and, for several reasons, is not an ideal basis for subsequent comparison. Nevertheless, L/O sleep periods tended to provide either less total sleep or less efficient sleep. Crewmembers' estimates of their sleep duration correlated well with objective measures, but their estimates of daytime sleepiness correlated poorly with objectively measured sleepiness. During baseline there was a significant midday sleep tendency as measured by the Multiple Sleep Latency Test. This tendency occurred at almost the same time (GMT) on the second L/O day in LHR. Since sleepiness has a persistent rhythm which is maximal twice per day, it is suggested that L/O sleep periods be taken at these times of maximal sleepiness and that peak workload should coincide with the subsequent periods of maximal alertness. Although the overall quality of sleep diminished only slightly on this L/O, it is possible that if this relatively small loss accumulated over successive L/Os, the effects on daytime sleepiness could be measurable.

Aerospace Medicine↗

Membrane potential and input resistance in alpha motoneurons of hindlimb extensors during isolated and clustered episodes of phasic events in REM sleep.

The function of motoneurons during the phasic events of REM sleep was investigated in cats. The membrane potential, synaptic activity, input resistance and rheobase were measured in hindlimb extensor motoneurons during periods of concentrated phasic events (Type II) in REM sleep in undrugged, minimally restrained cats. During Type II episodes in REM sleep, motoneurons depolarized 3 mV on the average, reduced in input resistance by 20%, and had distinct increases in spontaneous synaptic activity, as compared with periods of REM sleep between episodes (i.e. Type I). This constellation of properties is explained by increased frequencies of both unitary EPSPs and IPSPs in motoneurons. Myoclonic jerks in Type II episodes do not appear to arise because of a temporary withdrawal of the tonic motoneuron inhibition found in REM sleep. Instead, large increases in excitatory synaptic activity overcome the inhibition, giving rise to motoneuron discharges.

Animals↗

EEG spindle activity as a function of age: relationship to sleep continuity.

This study assessed sleep spindle activity and its relationship to transient EEG activation in young adult and aged cats. Sleep-wake variables were monitored polygraphically for 12 h in 5 young adult (2-4 years) and five aged (9-11 years) animals. Recordings were scored for behavioral state. Then, using bandpass frequency analysis, sensorimotor cortical spindles were evaluated in three, 5-min segments of the NREM sleep EEG. Both the incidence of transient arousals (TA) and spindle (much greater than 25 microV) densities were significantly higher in the aged animals than in the young adults. In the young animals only, spindle densities reliably predicted the incidence of TAs. We suggest that spindle expression varies in relation to ascending reticular activating system tone, constituting a functionally-inhibitory thalamocortical response to neurophysiological conditions which promote central activation.

Adult↗

Effects of alprazolam and diazepam on the daytime sleepiness of non-anxious subjects.

Eighteen non-anxious volunteers underwent sleep recordings and daytime tests of sleepiness, performance, and mood while receiving, either alprazolam 0.5 mg b.i.d. or diazepam 5 mg b.i.d. for 7 consecutive days. Recordings and tests were done before treatment and on the 1st and 7th days of treatment. Nocturnal sleep changes were similar for both groups; there were no statistically significant changes in mood. However, levels of daytime sleepiness differed. Alprazolam subjects showed more daytime sedation than diazepam subjects on treatment day 1, but showed a significant decrease in Day 1-7 daytime sedation. Although diazepam subjects were less sedated at the onset, they showed no tolerance to this effect; thus by treatment day 7, the two groups did not differ in levels of daytime sleepiness. Results suggested that tolerance to alprazolam's sedative effects (which develops during the 1st week of treatment) may be separable from tolerance to its antianxiety effects (which develops after at least 4 weeks). As daytime sedation is common and potentially dangerous with most anxiolytics, selective tolerance to this side effect is highly desirable.

Adult↗

Buspirone: an anxiolytic without sedative effect.

Twelve volunteers with a complaint of chronic insomnia participated in a placebo-controlled, double-blind, crossover study of the effects of buspirone t.i.d. on sleep pattern and daytime function. The drug was tested alone and in combination with flurazepam or triazolam. Buspirone alone did not impair objective measures of daytime wakefulness or performance. Impaired alertness was seen the day after bedtime administration of flurazepam but not after triazolam; buspirone did not alter these effects. Buspirone did not affect the Multiple Sleep Latency Test, a sensitive measure of changes in daytime alertness.

Adult↗

Electroencephalographic correlates of cataplectic attacks in narcoleptic canines.

Cataplectic attacks were monitored behaviorally and polygraphically in 4 narcoleptic dogs, of which three inherited the disorder. The recorded EEG signals were evaluated by power spectral analysis. We found 3 distinct stages of cataplexy: an initial stage which resembled wakefulness with tonic suppression of EMG activity, a later stage which was highly similar to REM sleep, and a final transitional stage to wakefulness or NREM sleep. The first stage of cataplexy was characterized by full postural collapse, a waking-like EEG spectrum, visual tracking, and a hypotonic EMG. The second stage of cataplexy differed electrographically from the previous stage by the onset of hypersynchronous hippocampal theta activity, a REM-like EEG spectrum, larger amplitude EEG signals, and a higher peak theta frequency. Glazed eyes, sporadic rapid eye movements and muscle twitches were also present. The final stage of cataplexy was characterized by mixed amplitude, mixed frequency EEG activity, and by the absence of rapid eye movements, visual tracking, directed movements, and muscle twitches. The EEG spectra of two other narcoleptic phenomena, sleep-onset REM periods and NREM sleep onsets from cataplexy, were nearly identical to the spectra of the normally occurring REM and NREM sleep periods.

Alpha Rhythm↗