Decrease In Slow Wave Sleep Research Articles

Recent Progressions on Peripheral Hypotheses of Hypothalamic Aging

Background: It is well known that the changes of hypothalamus in control of hormones determine the chronological manifestations of aging in mammals.Aim: It is aimed to review the progressions on recently hypothesized peripheral mechanisms responsible for the senescent changes of the hypothalamic nuclei and secretion.Methods: It was searched the papers from Pubmed and Baidu, and then analyzed and summarized.Results and Discussions: (a) It was proposed by Cai that the decrease in slow-wave sleep (SWS) resulting from continual skin aging cause both decrease in secretion of growth hormone (GH) and degeneration of suprachiasmatic nucleus(SCN) for hypothalamus. (b) It was soon hypothesized by the Europeans that the increase in body fat be responsible for the degeneration of male hypothalamic preoptic sexually dimorphic nucleus (SDN-POA), which was supported by the increment of aromatase converting testosterone to estradiol as proposed by Cohen, with testosterone required to maintain SDN-POA. In parallel, it was speculated the aging of female ovary toward menopause as acceleration and precocity similarly in association with the corresponding senescent changes in lipid, aromatase and estradiol. (c) It was the hypothalamic paraventricular nucleus (PVN) that retained neuron number unchanged during aging for psychological stress..Conclusion: It is summarized that the hypothalamic senescence resulting from these peripheral mechanisms shifts the functional balance among these three hypothalamic systems toward aging.

Effect of Intravenous Delivery of N,N Dimethyltryptamine on Sleep-Wake States in Rat

Psychedelics, including N, N, Dimethyltryptamine (DMT), are being increasingly explored for therapeutic potential to treat psychiatric disorders such as depression, anxiety, and post-traumatic stress disorder. These and other psychiatric conditions have a bidirectional relationship with sleep patterns but the impact of psychedelics, particularly DMT, on sleep architecture is incompletely understood. Therefore, in this study, we determined the effect of intravenous DMT administration on sleep-wake states in male and female rats. Under surgical isoflurane anesthesia, adult Sprague Dawley rats (n=10, 5 male, 5 female) were instrumented with electrodes to record electroencephalogram (EEG) from across the cortex and electromyogram (EMG) from dorsal nuchal muscles. In addition, a chronic catheter was positioned in jugular vein for the infusion of DMT or 0.9% saline (as vehicle control). Each rat received an intravenous bolus (100 uL/min over 5 min) of either one of two doses of DMT (low dose: 3.75 mg/kg, high dose: 7.5 mg/kg) or 0.9% saline. The DMT and saline infusions were performed 30-minutes after the start of the lights-ON period (8:00 am) after which EEG and EMG data were recorded for 24h across the light and dark cycle. EEG and EMG data were manually scored (SleepSign, Kissei Comtec) in 4-second intervals and classified as wakefulness, slow-wave sleep, or rapid eye movement sleep, then averaged in 3h bins across the 24h recording period. A linear mixed model was used to compare the changes in percent time spent in each state, mean duration per episode for each state, and mean number of episodes for each state, between vehicle control and DMT infusion sessions. There was a statistically significant increase in the time spent in wakefulness in the first 3h bin after DMT infusion (p<0.02 for low dose, p<0.03 for high dose). In the same 3h bin, a significant decrease in slow-wave sleep (p<0.02 for low and high dose DMT) was observed. DMT infusion produced a significant increase in the latency to the onset of rapid eye movement sleep (p<0.01), but no statistical effect was observed on the time spent in rapid eye movement sleep during the light period. Our results with DMT align with previous reports showing an increase in wakefulness after administration of serotonergic psychedelics. Further analysis of neurophysiologic data is needed to understand the neural dynamics associated with DMT-induced increases in wakefulness. Department of Anesthesiology, University of Michigan. RS was partly supported by Magnificent Michigan Summer Undergraduate Research fellowship, University of Michigan. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Experimental Study of the Effects of Siestas on the Nocturnal Sleep Quality and Thermal Comfort Levels under Thermoneutral Environment in Summer

It has been determined that siestas could potentially have both mental and physical influences on the human body. However, the effects of siestas on the nocturnal sleep quality and thermal comfort levels under thermoneutral environment had not yet been examined in detail. In order to explore the potential influences of siestas on nocturnal sleep, twenty subjects were recruited and divided into two groups based on whether they took siestas or not. During this study's experiment, the temperature was maintained at 25°C, and sleep duration was recorded throughout the night. In addition, thermal comfort votes (TCV) and thermal satisfaction votes (TSV) were obtained both before and after the nocturnal sleep. Furthermore, dopamine (DA) levels, which played important roles in emotional regulation, were measured after the nocturnal sleep. Results showed that the siesta group had a significant increase in self-reported nocturnal sleep quality (p < 0.05), although slight decreases in slow-wave sleep (SWS) duration and rapid eye movement (REM) duration were observed. Additionally, higher TCV and TSV values were reported in the siesta group (p < 0.05). Higher DA concentration was also detected in the siesta group after the nocturnal sleep. Furthermore, some correlations were illustrated between the thermal voting values and the sleep duration, as well as the DA concentration levels. Results implied that siestas could have an influence on the nocturnal sleep quality and thermal comfort levels under thermoneutral environment. Besides, DA concentration levels played an important role in the thermal comfort evaluations when exploring the influences of siestas on nocturnal sleep.

Association Between Slow-Wave Sleep Loss and Incident Dementia

Slow-wave sleep (SWS) supports the aging brain in many ways, including facilitating the glymphatic clearance of proteins that aggregate in Alzheimer disease. However, the role of SWS in the development of dementia remains equivocal. To determine whether SWS loss with aging is associated with the risk of incident dementia and examine whether Alzheimer disease genetic risk or hippocampal volumes suggestive of early neurodegeneration were associated with SWS loss. This prospective cohort study included participants in the Framingham Heart Study who completed 2 overnight polysomnography (PSG) studies in the time periods 1995 to 1998 and 2001 to 2003. Additional criteria for individuals in this study sample were an age of 60 years or older and no dementia at the time of the second overnight PSG. Data analysis was performed from January 2020 to August 2023. Changes in SWS percentage measured across repeated overnight sleep studies over a mean of 5.2 years apart (range, 4.8-7.1 years). Risk of incident all-cause dementia adjudicated over 17 years of follow-up from the second PSG. From the 868 Framingham Heart Study participants who returned for a second PSG, this cohort included 346 participants with a mean age of 69 years (range, 60-87 years); 179 (52%) were female. Aging was associated with SWS loss across repeated overnight sleep studies (mean [SD] change, -0.6 [1.5%] per year; P < .001). Over the next 17 years of follow-up, there were 52 cases of incident dementia. In Cox regression models adjusted for age, sex, cohort, positivity for at least 1 APOE ε4 allele, smoking status, sleeping medication use, antidepressant use, and anxiolytic use, each percentage decrease in SWS per year was associated with a 27% increase in the risk of dementia (hazard ratio, 1.27; 95% CI, 1.06-1.54; P = .01). SWS loss with aging was accelerated in the presence of Alzheimer disease genetic risk (ie, APOE ε4 allele) but not hippocampal volumes measured proximal to the first PSG. This cohort study found that slow-wave sleep percentage declined with aging and Alzheimer disease genetic risk, with greater reductions associated with the risk of incident dementia. These findings suggest that SWS loss may be a modifiable dementia risk factor.

Effects of emerging alcohol use on developmental trajectories of functional sleep measures in adolescents.

Adolescence is characterized by significant brain development, accompanied by changes in sleep timing and architecture. It also is a period of profound psychosocial changes, including the initiation of alcohol use; however, it is unknown how alcohol use affects sleep architecture in the context of adolescent development. We tracked developmental changes in polysomnographic (PSG) and electroencephalographic (EEG) sleep measures and their relationship with emergent alcohol use in adolescents considering confounding effects (e.g. cannabis use). Adolescents (n = 94, 43% female, age: 12-21 years) in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study had annual laboratory PSG recordings across 4-years. Participants were no/low drinkers at baseline. Linear mixed effect models showed developmental changes in sleep macrostructure and EEG, including a decrease in slow wave sleep and slow wave (delta) EEG activity with advancing age. Emergent moderate/heavy alcohol use across three follow-up years was associated with a decline in percentage rapid eye movement (REM) sleep over time, a longer sleep onset latency (SOL) and shorter total sleep time (TST) in older adolescents, and lower non-REM delta and theta power in males. These longitudinal data show substantial developmental changes in sleep architecture. Emergent alcohol use during this period was associated with altered sleep continuity, architecture, and EEG measures, with some effects dependent on age and sex. These effects, in part, could be attributed to the effects of alcohol on underlying brain maturation processes involved in sleep-wake regulation.

OR14-4 Acute sleep disruption does not diminish pulsatile growth hormone secretion in pubertal children

Abstract Context: Growth hormone (GH) plays a critical role in glucose homeostasis and linear growth during childhood. GH secretion is controlled by multiple neurotransmitters and hormones. Sleep is also a powerful stimulus for GH secretion. In children, GH pulses occur after sleep onset in association with slow-wave sleep (SWS), but it is unclear if undisrupted sleep is required for normal GH secretion. Given the rising incidence of pediatric sleep disorders such as obstructive sleep apnea (OSA) that cause sleep fragmentation, it is critical to determine whether sleep fragmentation during childhood may dysregulate the somatotropic axis. Objective To quantify how undisrupted vs fragmented sleep affects GH secretion in children. Methods Pubertal subjects (10 M, 9 F; 9.1-14.4 yrs) were randomized to two overnight polysomnographic studies with frequent blood sampling (q10min) to measure GH: fourteen were healthy subjects studied with or without SWS disruption via auditory stimuli (3 sec, 1500 Hz tones, 40-100 dB followed by 18 sec of a 75 dB noise simulating a knock on the door) and five were subjects with OSA studied with or without prescribed continuous positive airway pressure (CPAP); the latter condition was expected to have sleep fragmentation due to untreated OSA. GH pulses were identified using sparse deconvolution. Studies without auditory stimuli or when using CPAP were combined and analyzed as 'undisrupted sleep'. The relationship between GH pulse rate per hour and sleep stage was evaluated using Poisson generalized estimating equations. Results In SWS disruption studies, an average of 77.51 ± 13.61 (range 23-190) auditory stimuli were delivered, causing a 40.02 ± 7.78% decrease in SWS in favor of lighter sleep stages. In subjects with OSA, CPAP withdrawal caused a slight increase in the apnea hypopnea index (1.08 ± 0.10 vs. 2.20 ± 1.70 events/hour of sleep, p=0.07) with no change in sleep stage durations. During undisrupted sleep, subjects had an average of 0.91 ± 0.067 GH pulses/hour with a mean pulse amplitude of 10.03 ± 1.00 ng/mL and mean basal secretion rate of 0.26 ± 0.10 ng/ml per min. GH pulses occurred more frequently during SWS (2.3 pulses/hour SWS, amplitude 9.92 ± 2.59 ng/mL) than during any other sleep stage (P &amp;lt; 0.001). Neither form of sleep disruption affected the distribution of GH pulses across sleep stages, GH pulse amplitude and frequency, nor basal GH secretion. Conclusion In children, nocturnal GH pulses are temporally associated with SWS. However, neither acute fragmentation of SWS nor nocturnal arousals from OSA altered basal or pulsatile GH secretion, indicating that somatotrophic axis activity is preserved in the face of acute sleep disruption in children. Presentation: Sunday, June 12, 2022 11:45 a.m. - 12:00 p.m.

Acute Sleep Disruption Does Not Diminish Pulsatile Growth Hormone Secretion in Pubertal Children.

In children, growth hormone (GH) pulses occur after sleep onset in association with slow-wave sleep (SWS). There have been no studies in children to quantify the effect of disrupted sleep on GH secretion. This study aimed to investigate the effect of acute sleep disruption on GH secretion in pubertal children. Fourteen healthy individuals (aged 11.3-14.1 years) were randomly assigned to 2 overnight polysomnographic studies, 1 with and 1 without SWS disruption via auditory stimuli, with frequent blood sampling to measure GH. Auditory stimuli delivered during the disrupted sleep night caused a 40.0 ± 7.8% decrease in SWS. On SWS-disrupted sleep nights, the rate of GH pulses during N2 sleep was significantly lower than during SWS (IRR = 0.56; 95% CI, 0.32-0.97). There were no differences in GH pulse rates during the various sleep stages or wakefulness in disrupted compared with undisrupted sleep nights. SWS disruption had no effect on GH pulse amplitude and frequency or basal GH secretion. In pubertal children, GH pulses were temporally associated with episodes of SWS. Acute disruption of sleep via auditory tones during SWS did not alter GH secretion. These results indicate that SWS may not be a direct stimulus of GH secretion.

Benefit of a healing garden on sleep in neurocognitive diseases

Progressive neurocognitive pathologies frequently alter the architecture of sleep with: advanced sleep phase or phase delay, sleep fragmentation, decrease of slow-wave sleep, REM sleep, nocturnal agitation and wandering or even complete reversal of the nycthemeral rhythm. This has a clear impact on the health and quality of life of the patient. Hospitalization increases the risk of sleep disturbances due to inactivity, some sensory deprivation and daytime hypovigilance. The therapeutic gardens offer in an attractive, sensorially stimulating setting and exposed to natural light, the possibility of an adapted physical exercise. Their impact on the quality and quantity of sleep in cognitive-behavioral units has been evaluated in an exploratory manner. The hypnogram of two groups of 30 patients was compared depending on whether they used the garden (weather permitting, in summer) or not (in winter). The results show that the patients who use the garden are significantly more active during the day, have a longer nighttime sleep duration and are less restless at night. In addition, patients who use and walk longer in the garden benefit from an increase in their sleep time. In view of their multiple interests, therapeutic gardens, if they meet validated design criteria, should be integrated more widely into establishments welcoming people with neurocognitive diseases.

Cannabidiol (CBD) and Insomnia : Literature review

IntroductionCannabidiol (CBD) is one of 113 cannabinoids identified in cannabis plants. Considered as a psycho-inactive component, recently, the Court of Justice of the European Union published a ruling in which it establishes that cannabidiol extracted from the cannabis plant should not be considered a drug under the United Nations Single Convention on Narcotic Drugs of 1961. Due to increased publicity on social media of the supposed benefits of this product, in addition to the lack of clear regulations, it is becoming a widely used treatment for sleep disorders.ObjectivesTo analyse literature for the effect of CBD in sleep disturbances, emphasizing advantages and disadvantages of its use.MethodsWe carried out a literature review in Pubmed choosing those articles focused on effect of CBD in sleep disturbances.ResultsThe review of the effect of CBD on sleep cycle suggest that medium to high doses increased REM sleep latency, and medium-low doses decreased REM sleep latency. No evidence of withdrawal syndrome was found with abrupt discontinuation of short-term treatment with CBD.ConclusionsMost of the literature revised shows that the data was taken by self-questionares to CBD users. Studies suggest that a short use of medium to hight doses of CBD may improve insomnia, however, combined use with THC may result in a decrease in slow wave sleep. Longitudinal research should be done in order to understand the clinical impact of CBD on sleep.DisclosureNo significant relationships.

0241 N3 Slow Wave Duration Correlates with Next-Day Savoring Behavior in Pre-pubertal Children

Abstract Introduction Recent meta-analysis (Tomaso et al., 2020) indicates sleep loss to have more profound adverse effects on positive than negative emotion, and experimental studies in adults suggest disruption of slow wave sleep (SWS) in particular mediates these effects (Finan et al., 2015; 2017). In pre-pubertal children, greater SWS has been shown to protect against next day negative affect (Palmer &amp; Alfano, 2017) as well as the development of depression years later (Silk et al., 2007); however specific emotion-based mechanisms underlying these effects have rarely been explored. Pre-pubertal years especially represent a critical developmental window for probing these relationships due to dramatic decreases in SWS that occur during pubertal transition (Carskadon &amp; Dement, 2011). Methods We detected slow waves (0.5 – 4 Hz) during N3 sleep using an automated algorithm among N=18 pre-pubertal children (7-11 years) during a night of normal sleep in relation to next-day savoring; a positive emotion regulation strategy that includes using thoughts and actions to increase the intensity, duration, and appreciation of positive experiences and emotions. Healthy children without any psychiatric disorders completed a night of at-home PSG monitoring (10 hr sleep opportunity). The next morning at 11:00, children returned to the clinic for an in-lab emotional assessment. Before and during the assessment, children were told/reminded that they would be given a piece of chocolate to enjoy at the end of the assessment. After children consumed the chocolate, they were asked several questions about how much they ‘savored’ the experience. All analyses controlled for total sleep time on the PSG night and there were no differences in SWA based on gender. Results Results indicated that the average duration of detected N3 SWs (F3/F4) correlated significantly with the extent to which children enjoyed the chocolate overall (r =.50, p &amp;lt;.05), felt they did a good job enjoying the chocolate while eating it (r =.44-.49, p &amp;lt;.05) and looked forward to eating the chocolate during the assessment (r =.46-.50, p &amp;lt;.05). Conclusion Although preliminary, these novel findings suggest that greater intensity of SWS may have a modulatory effect on subsequent emotional responses to positive experiences/events, which could be protective for longer term affective health. Support (If Any)

0648 Decreased Slow-Wave Sleep May Exacerbate Anxiety in Individuals with Low Anxiety

Abstract Introduction Evidence suggests that individuals with generalized anxiety disorder exhibit decreases in slow-wave sleep (SWS). Because SWS has been shown to be modifiable, it is imperative to better understand the relationship between symptoms of anxiety and amount of SWS to inform treatment development. This study aimed to explore the relationship between anxiety and SWS, and to investigate the impact of slow-wave sleep disruption on state anxiety. Methods Twenty-seven participants’ (mean age 30.9) were recruited as part of an ongoing study examining the relationship between SWS and depression. Participants spent two nights in the laboratory: baseline (BL) and slow-wave disruption (SWD), where SWS was disrupted using auditory stimulation. Anxiety was measured using the State-Trait Anxiety Inventory (STAI). Both trait and state anxiety (BL, SWD) measures were collected. Repeated measures ANOVA was used to determine the impact of SWD on state anxiety. Results Participants’ trait anxiety scores were significantly correlated with percent N3, such that greater anxiety was associated with less N3 (r = -0.43; p&amp;lt;0.05). Individuals were then categorized as either high-anxiety (HA) or low-anxiety (LA) by median split (M=46.5). Results of the repeated measures showed a significant main effect of group (F=43.963; p&amp;lt;0.001), with HA individuals showing greater state anxiety than LA individuals. A significant interaction of group*condition was also found (F(1,24)=4.703; p=0.40). LA participants showed a significant increase in state anxiety following SWD (t=-2.539; p=0.028), while HA participants showed no change. Conclusion The current findings replicate previous research showing that anxious individuals have a reduced amount of SWS and demonstrate that decreases in SWS may exacerbate anxiety in individuals with low anxiety. Further, this work suggests that individuals with high anxiety may be more resilient to changes in anxiety state than individuals with low anxiety when SWS is reduced. Support (If Any) Goldschmied: K23MH118580 (NIMH)

Altered sleep during spontaneous cannabinoid withdrawal in male mice.

Cessation of cannabinoid use in humans often leads to a withdrawal state that includes sleep disruption. Despite important health implications, little is known about how cannabinoid abstention affects sleep architecture, in part because spontaneous cannabinoid withdrawal is difficult to model in animals. In concurrent work we report that repeated administration of the high-efficacy cannabinoid 1 (CB1) receptor agonist AM2389 to mice for 5 days led to heightened locomotor activity and paw tremor following treatment discontinuation, potentially indicative of spontaneous cannabinoid withdrawal. Here, we performed parallel studies to examine effects on sleep. Using implantable electroencephalography (EEG) and electromyography (EMG) telemetry we examined sleep and neurophysiological measures before, during, and after 5 days of twice-daily AM2389 injections. We report that AM2389 produces decreases in locomotor activity that wane with repeated treatment, whereas discontinuation produces rebound increases in activity that persist for several days. Likewise, AM2389 initially produces profound increases in slow-wave sleep (SWS) and decreases in rapid eye movement (REM) sleep, as well as consolidation of sleep. By the third AM2389 treatment, this pattern transitions to decreases in SWS and total time sleeping. This pattern persists following AM2389 discontinuation and is accompanied by emergence of sleep fragmentation. Double-labeling immunohistochemistry for hypocretin/orexin (a sleep-regulating peptide) and c-Fos (a neuronal activity marker) in lateral hypothalamus revealed decreases in c-Fos/orexin+ cells following acute AM2389 and increases following discontinuation, aligning with the sleep changes. These findings indicate that AM2389 profoundly alters sleep in mice and suggest that sleep disruption following treatment cessation reflects spontaneous cannabinoid withdrawal.

Acupuncture stimulation at HT7 as a non-pharmacological therapy for sleep disorder caused by caffeine administration in rats.

Insomnia is one of the most common sleep disorders and is difficult to completely treat because of the undesirable side effects of hypnotics. The present study was designed to investigate the hypnotic effect of acupuncture stimulation at HT7 on caffeine-induced sleep disorders and locomotor activity in rats. We also evaluated neuronal activity changes in the arousal region of the basal forebrain. Rats received intraperitoneal injections of caffeine, and then electroencephalogram power spectrum analysis and locomotor activity measurements were performed. Stimulation at HT7 was performed using a mechanical acupuncture instrument (MAI) before caffeine injection, and its effects on caffeine-induced changes in sleep architecture, locomotor activity and c-Fos expression were examined. Caffeine injection (7.5 mg/kg) produced a significant decrease in slow-wave sleep and an increase in wake time compared with saline injection. Caffeine injection also increased locomotor activity and c-Fos expression in the medial septum-vertical limb of the diagonal band of Broca (MS-VDB), one of the arousal regions of the basal forebrain. Stimulation at HT7 with the MAI alleviated the caffeine-induced sleep disturbance and the increase in locomotor activity. In addition, MAI treatment at HT7, compared with treatment at a location not corresponding to any traditional acupuncture point, reduced the caffeine-induced increase in c-Fos expression. These results indicate that the hypnotic effect of HT7 acupuncture stimulation on caffeine-induced insomnia was associated with suppression of neuronal activity in the basal forebrain.

Insomnia in Patients with Borderline Personality Disorder.

ObjectiveBoth sleep disorders and BPD are prevalent in the population, and one is often a comorbidity of the other. This narrative review aims to assess contemporary literature and scientific databases to provide the current state of knowledge about sleep disorders in patients with borderline personality disorder (BPD) and clinical suggestions for managing sleep disorders in BPD patients and future research direction.MethodsArticles were acquired via PubMed and Web of Science, and papers published between January 1980 and October 2020 were extracted. Authors made a series of literature searches using the keywords: Sleep problems, Insomnia, Nightmares, Obstructive sleep apnea, Borderline personality disorder. The inclusion criteria were: published in peer-reviewed journals; studies in humans; or reviews on the related topic; English language. The exclusion criteria were: abstracts from conferences; commentaries; subjects younger than 18 years. After an inspection of the full texts, 42 papers from 101 were selected. Secondary documents from the reference lists of the primary designated papers were searched, assessed for suitability, and included. In total, 71 papers were included in the review process.ResultsSleep disturbance is common among patients with BPD. Nevertheless, the number of investigations is limited, and the prevalence differs between 5–45%. Studies assessing objective changes in sleep architecture in BPD show inconsistent results. Some of them identify REM sleep changes and a decrease in slow-wave sleep, while other studies found no objective sleep architecture changes. There is also a higher prevalence of nightmares in patients with BPD. Untreated insomnia can worsen BPD symptoms via interference with emotional regulation. BPD itself seems to influence the subjective quality of sleep significantly. Proper diagnosis and treatment of sleep disorders in patients with BPD could lead to better results in therapy. Psychotherapeutic approaches can improve both sleep disorders and BPD symptoms.ConclusionRecognising and managing sleep disorders in patients with BPD may help alleviate the disorder’s symptoms. Treatment of people with BPD may be more effective if the treatment plan explicitly addresses sleep problems. Further research is needed to reach reliable conclusions.

Hypothalamic aging and hormones.

It is the heterogeneous changes of hypothalamic functions that determine the chronological sequence of aging in mammals. Recently, it was hypothesized by Cai the decrease in slow-wave sleep (SWS) resulting from skin aging as responsible for the degeneration of hypothalamic suprachiasmatic nucleus (SCN). It was soon hypothesized by the European people in television that the increase in body fat as responsible for the degeneration of male preoptic sexually dimorphic nucleus (SDN-POA), via the aromatase converting testosterone to estradiol as proposed by Cohen. It is the hypothalamic paraventricular nucleus (PVN) that remains unchanged in neuron number during aging for psychological stress. In this chapter, it is briefly reviewed more manifestations of hypothalamic related mammalian aging processes, including (1) the aging of ovary by lipid, estradiol and hypothalamus; (2) the aging of muscle, stomach, intestine, thymus, and the later aging of brain, regulated by growth hormone/insulin-like growth factor 1(GH/IGF1); (3) the cardiovascular hypertension from PVN activation, the bone and other peripheral aging by psychological stress, and that of kidney by vasopressin. It is classified these aging processes by the primary regulation from one of the three hypothalamic nuclei, although still necessary to investigate and supplement their secondary regulation by the hypothalamic nuclei in future. It is the hypothalamic structural changes that shift the functional balance among these three hypothalamic systems toward aging.

Decreases in slow wave sleep associate with a higher risk of incident Alzheimer’s disease dementia in a community sample

AbstractBackgroundSleep disturbance is common in dementia, although it is unclear whether changes in sleep architecture precede dementia onset. We examined the prospective association of changes in sleep architecture with the risk of incident Alzheimer’s disease (AD) dementia in the community‐based Framingham Heart Study (FHS).MethodsOur sample comprised a subset of 294 FHS Offspring participants who participated in the Sleep Heart Health Study Visit 1 (1995‐1998) and Visit 2 (2001‐2003), were dementia‐free and aged over 60 years at the time of Visit 2. Stages of sleep were quantified using home‐based overnight polysomnography. Annualized change in the sleep metrics were computed by subtracting Visit 1 from Visit 2 measures divided by the time interval (in years) between the two visits. Surveillance for incident AD dementia commenced at visit 2 and continued for up to 17 years (mean follow‐up 11 (SD, 4)). We used a series of proportional hazards models to relate changes in sleep to the risk of incident AD dementia, adjusting for age, sex, APOE ε4 allele status, smoking status, and sleeping medication, antidepressant and anxiolytic use.ResultsParticipant mean age was 69 years (SD, 6, 49% male). Over 17‐years follow‐up, we observed 27 cases of AD dementia. The two sleep assessments were separated by a mean of 5.2 years (SD, 0.4). Levels of wake after sleep onset increased by a mean of 4.8 minutes (SD, 11.7) per year whereas both sleep efficiency and the percentage of slow‐wave sleep declined by 0.4% (SD, 2.3) and 0.6% (SD, 1.5) per year, respectively. Each percentage reduction in slow‐wave sleep associated with a 30% increase in the risk of incident AD dementia (HR, 0.70; 95% CI: 0.54, 0.91, P=0.007). Changes in other stages of sleep (stage 1, 2 and REM), sleep fragmentation (sleep efficiency and wake after sleep onset), and respiratory disturbances (apnea‐hypopnea index) did not associate with dementia risk.ConclusionsBy linking decreases in slow‐wave sleep to the risk of clinical AD up to 17 years later, our results extend observations suggesting that slow‐wave sleep is important for synaptic plasticity underlying memory and for glymphatic clearance of neurotoxins that potentially lead to AD dementia.

Activity–Rest and Body Temperature Rhythms in Mice with Knockout of the Panx1 Gene

Pannexins are a family of three proteins which play an important role in intercellular communications. This study shows that mice with knockout of the Panx1 gene(Panx1–/–) have elevated levels of movement activity and increased proportions of waking, due to decreases in slow-wave sleep, as compared with control animals, as a result of decreases in the adenosine content of the brain. We suggest that these mice may also show impairments to thermoregulation and the daily temperature curve rhythm. To test this suggestion, eight adult male C57BL/6J mice and eight adult male Panx1–/– mice, derived from them, underwent i.p. implantation of autonomous temperature and movement activity sensors. Recordings were made over several months at an environmental temperature of 23 ± 1°C. The results confirmed our previous data indicating higher movement activity in Panx1–/– mice compared with controls. The daily body temperature rhythm in Panx1–/– mice persisted and was no different from that in control animals. The first series of experiments showed an increased tendency to fall into torpor in Panx1–/– mice as compared with controls. However, no onset of torpor occurred in the next series, using a further four pairs of animals. Thus, the role of the Panx1 gene in the diurnal activity-rest rhythm was confirmed, while its role in the temperature rhythm and thermoregulatory reactions remains unclear and requires further study.

Alcohol use disorder and sleep disturbances: a feed-forward allostatic framework.

The development of alcohol use disorder (AUD) involves binge or heavydrinking to high levels of intoxication that leads to compulsive intake, the loss of control in limiting intake, and a negative emotional state when alcohol is removed. This cascade of events occurs over an extended period within a three-stage cycle: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. These threeheuristic stages map onto the dysregulation of functional domains of incentive salience/habits, negative emotional states, and executive function, mediated by the basal ganglia, extended amygdala, and frontal cortex, respectively. Sleep disturbances, alterations of sleep architecture, and the development of insomnia are ubiquitous in AUD and also map onto the three stages of the addiction cycle. During the binge/intoxication stage, alcohol intoxication leads to a faster sleep onset, but sleep quality is poor relative to nights when no alcohol is consumed. The reduction of sleep onset latency and increase in wakefulness later in the night may be related to the acute effects of alcohol on GABAergic systems that are associated with sleep regulation and the effects on brain incentive salience systems, such as dopamine. During the withdrawal/negative affect stage, there is a decrease in slow-wave sleep and some limited recovery in REM sleep when individuals with AUD stop drinking. Limited recovery of sleep disturbances is seen in AUD within the first 30 days of abstinence. The effects of withdrawal on sleep may be related to the loss of alcohol as a positive allosteric modulator of GABAA receptors, a decrease in dopamine function, and the overactivation of stress neuromodulators, including hypocretin/orexin, norepinephrine, corticotropin-releasing factor, and cytokines. During the preoccupation/anticipation stage, individuals with AUD who are abstinent long-term present persistent sleep disturbances, including a longer latency to fall asleep, more time awake during the night, a decrease in slow-wave sleep, decreases in delta electroencephalogram power and evoked delta activity, and an increase in REM sleep. Glutamatergic system dysregulation that is observed in AUD is a likely substrate for some of these persistent sleep disturbances. Sleep pathology contributes to AUD pathology, and vice versa, possibly as a feed-forward drive to an unrecognized allostatic load that drives the addiction process.

Sleep, insomnia, and depression.

Since ancient times it is known that melancholia and sleep disturbances co-occur. The introduction of polysomnography into psychiatric research confirmed a disturbance of sleep continuity in patients with depression, revealing not only a decrease in Slow Wave Sleep, but also a disinhibition of REM (rapid eye movement) sleep, demonstrated as a shortening of REM latency, an increase of REM density, as well as total REM sleep time. Initial hopes that these abnormalities of REM sleep may serve as differential-diagnostic markers for subtypes of depression were not fulfilled. Almost all antidepressant agents suppress REM sleep and a time-and-dose-response relationship between total REM sleep suppression and therapeutic response to treatment seemed apparent. The so-called Cholinergic REM Induction Test revealed that REM sleep abnormalities can be mimicked by administration of cholinomimetic agents. Another important research avenue is the study of chrono-medical timing of sleep deprivation and light exposure for their positive effects on mood in depression. Present day research takes the view on insomnia, i.e., prolonged sleep latency, problems to maintain sleep, and early morning awakening, as a transdiagnostic symptom for many mental disorders, being most closely related to depression. Studying insomnia from different angles as a transdiagnostic phenotype has opened many new perspectives for research into mechanisms but also for clinical practice. Thus, the question is: can the early and adequate treatment of insomnia prevent depression? This article will link current understanding about sleep regulatory mechanisms with knowledge about changes in physiology due to depression. The review aims to draw the attention to current and future strategies in research and clinical practice to the benefits of sleep and depression therapeutics.

Abstract TMP47: Sleep and Endocrine Disturbances Are Associated With Poorer Outcomes During the Post-Acute Phase of Stroke Recovery

Introduction: Sleep disturbances, including decreases in slow wave sleep (SWS) are common following stroke. In this study, we sought to identify the implications of decreased slow wave sleep on endocrine function and cognitive/outcome measures in the post-acute phase of stroke recovery. Methods: Adult stroke patients (n=44) were assessed via overnight polysomnography (PSG). The mean age was 50 ± 1.8 years and mean latency from stroke was 126 ± 16 days. Sleep measures included total sleep time (TST), sleep and REM latency, percent time in sleep stages, apnea/hypopnea index (AHI), wake after sleep onset (WASO), and arousal index. Hormone levels were analyzed within 10 days of PSG. The primary outcome measures were as follows: California Verbal Learning Test (CVLT), Montreal Cognitive Assessment (MoCA), Trails A and B, Mayo Portland Adaptability Inventory (MPAI), and NeuroQOL. Sex differences were also analyzed. Results: Age and BMI were positively correlated with subjective daytime sleepiness using the Epworth Sleepiness Scale (p&lt;.05); however, while BMI was positively correlated with the arousal index (p&lt;.01), it was not correlated with AHI. TST was negatively correlated with subscales of the MPAI (p&lt;.05). Time spent in SWS was associated with decreases in self reported anxiety, fatigue, and sleep disturbances on the NeuroQOL (p&lt;.01). Increases in SWS were also correlated with higher scores on the MoCA (p&lt;.05). Increases in sex hormone binding globulin (SHBG) were associated with decreases in TST (p&lt;.05) and increased percent WASO (p&lt;.01). Additionally, SHBG was negatively associated with the CVLT list B (p&lt;.05). For men, SHBG is positively associated with the number of repetitions on the CVLT (p&lt;.01). As expected, men had a higher arousal index and higher AHI than women. Conclusion: Time spent in SWS is associated with better subjective well-being and improved performance on cognitive measures. Hormone levels, especially SHBG, may serve as early biomarkers for sleep disturbances after stroke and are associated with negative performance on some measures of cognition.