Nighttime Restlessness Research Articles

Sleep alterations in treatment-resistant depression patients undergoing ketamine treatment.

This study examines self-reported sleep alterations in treatment-resistant depression (TRD) inpatients following intravenous ketamine administration. This is a post-hoc analysis of a naturalistic observational study, which enrolled 28 inpatients with treatment-resistant major depressive disorder and analyzed self-reported sleep changes (items 1-4; 'insomnia', 'nighttime restlessness', 'early morning waking', 'hypersomnia') in Inventory of Depressive Symptomatology 30-item (IDS SR-30) in responders and non-responders stratified per Montgomery-Åsberg Depression Rating Scale (MADRS) during short-term ketamine treatment. Responders, as well as non-responders, did not experience significant changes in IDS SR-30 sleep items ('insomnia', 'nighttime restlessness', 'early morning waking', 'hypersomnia') (p's > 0.05) at 7-day follow-up after eight intravenous ketamine infusions as compared to baseline. Neither responders, nor non-responders reported any significant alterations in sleep patterns during ketamine infusions. These findings are not in line with current literature, as so far modest improvements in sleep during ketamine treatment have been reported. Results should be interpreted with caution, primarily due to the small sample size.

Nighttime behaviors, but not insomnia, correlates with cognition and biomarkers of dementia

AbstractBackgroundWhile sleep disturbances appear to be risk factors in the progression of Alzheimer’s disease (AD) and other dementias, little is known about the prevalence across dementia severity and the potential influence on the trajectory of cognitive decline.MethodWe used the prospective National Alzheimer Coordinating Center Uniform Data Set to evaluate the hypotheses that the prevalence of insomnia differs by definition and by stage of cognitive impairment, that certain sleep features track with established biomarkers of AD, and that longitudinal changes in sleep disorders affect cognition and AD biomarkers. We conducted cross‐sectional analyses to determine the prevalence of clinician‐determined insomnia and nighttime behaviors (nighttime restlessness, agitation, daytime sleepiness) in normal, mild cognitive impairment (MCI), and demented individuals, as defined by Montreal Cognitive Assessment (MoCA) cut‐off scores obtained during the patient’s first visit. We evaluated mean MoCA scores, hippocampal volumes, and CSF phosphorylated tau:beta amyloid ratios obtained near the first visit using Analysis of Variance (ANOVA) with age as a covariate. In longitudinal evaluations, we classified changes in insomnia and nighttime behaviors as “none”, “remitted”, “acquired”, or “steady” between the first and last visits. Similar changes in MoCA scores and hippocampal volumes were assessed with repeated‐measure ANOVA.ResultThe prevalence of clinician‐identified insomnia at initial visits was 15%, 17%, and 13% for normal, MCI, and dementia groups respectively. Prevalence of clinician‐identified nighttime behaviors was 13%, 19%, and 27% respectively. Insomnia was significantly associated with higher MoCA scores, larger hippocampal volumes, and higher pTau:Beta values, indicating those with clinician‐identified insomnia had better cognition and less neurodegeneration than individuals who clinicians identified to be without insomnia. In contrast, the presence of nighttime behaviors were associated with significantly worse cognition, smaller hippocampal volumes, and lower pTau:Beta. Similar findings were seen between longitudinal associations of sleep disorders and cognition and hippocampal volumes.ConclusionOur findings suggest that the clinician determination of insomnia may be under‐recognized in patients with cognitive impairment seen in memory disorders clinics, and that nighttime behaviors especially when reported by family members may better reflect sleep disturbances, the biological underpinnings of AD, and have diagnostic specificity in AD over insomnia.

Do sleep changes mediate the anti-depressive and anti-suicidal response of intravenous ketamine in treatment-resistant depression?

Sleep disturbances are commonly reported in patients with treatment-resistant depression (TRD). Available data have shown that intravenous (IV) ketamine is an effective treatment for patients with TRD and growing data suggest ketamine may improve overall sleep architecture. In the present study, we evaluated whether changes in sleep symptoms mediated the anti-depressive and/or anti-suicidal effects of IV ketamine and whether improvement in sleep correlated with a higher likelihood of achieving response or remission. Adults with TRD received four infusions of IV ketamine at a community-based clinic. Total depressive symptom severity was measured with the Quick Inventory Depressive Symptoms Self-Report 16-Item (QIDS-SR16 ) at baseline and was repeated across four infusions. Suicidal ideation (SI) and four sleep symptoms were measured using the SI item and the five sleep items on the QIDS-SR16 . A total of 323 patients with TRD received IV ketamine. Self-reported improvements in insomnia, night-time restlessness, hypersomnia, early morning waking, and total sleep were significant partial mediators to the improvements observed in depression severity. Similarly, insomnia, night-time restlessness, early morning waking and total sleep improvements mediated the reduction of IV ketamine on SI. All sleep items, except for hypersomnia, were associated with an increased likelihood of achieving response or remission. Notably, each point improvement in total sleep score was significantly associated with achieving responder/remitter status (odds ratio 3.29, 95% confidence interval 2.00-5.41). Insomnia, sleep restlessness, early morning waking and total sleep improvements were significant mediators of antidepressant and anti-suicidal improvements in patients with TRD receiving IV ketamine.

Regulation of amyloid-β dynamics and pathology by the circadian clock.

Nighttime restlessness and daytime drowsiness are common and early symptoms of Alzheimer's Disease (AD). This symptomology implicates dysfunctional biological timing, yet the role of the circadian system in AD pathogenesis is unknown. To evaluate the role of the circadian clock in amyloid-β (Aβ) dynamics and pathology, we used a mouse model of β-amyloidosis and disrupted circadian clock function either globally or locally in the brain via targeted deletion of the core clock gene Bmal1 Our results demonstrate that loss of central circadian rhythms leads to disruption of daily hippocampal interstitial fluid Aβ oscillations and accelerates amyloid plaque accumulation, whereas loss of peripheral Bmal1 in the brain parenchyma increases expression of Apoe and promotes fibrillar plaque deposition. These results provide evidence that both central circadian rhythms and local clock function influence Aβ dynamics and plaque formation and demonstrate mechanisms by which poor circadian hygiene may directly influence AD pathogenesis.

Sleep and Speech Outcomes After Superior Adenoidectomy in Children with Cleft Palate.

ObjectiveTo describe the sleep and speech outcomes in patients with cleft palate who underwent superior adenoidectomy.Subjectives and methodsThis is a case series with chart review of patients with diagnoses of cleft palate and sleep disordered breathing (SDB), obstructive sleep apnea (OSA) or nasal obstruction treated with superior adenoidectomy from 1991-2015 at the Children’s Hospital of Minnesota. Postoperative clinic notes documented the changes in symptoms following surgery. All speech outcomes were recorded.ResultsFifty patients (23 females, 27 males) aged 11 months to 17 years were included. Forty-six patients (92%) had improvement of sleep symptoms including snoring, nighttime restlessness, and witnessed apnea events, following superior adenoidectomy. Forty-two of the 46 patients (91%) had stable speech postoperatively with either no development or no worsening of velopharyngeal insufficiency (VPI).ConclusionSuperior adenoidectomy is an effective procedure to alleviate symptoms of sleep disordered breathing in patients with cleft palate without significantly affecting speech.

Nighttime restlessness in people with dementia in residential care: an explorative field study

Nighttime restlessness in dementia is an underestimated problem. Although little is known about the prevalence and not every person with dementia struggles with it, nighttime restlessness puts a heavy burden on the persons themselves and their caregivers.This field study explores nighttime restlessness in nursing homes based on two research questions: (1) What is nighttime restlessness according to professional caregivers? and (2) How is nighttime restlessness managed?Data were collected through diaries, interviews with caregivers and one night of observation in eight nursing homes.Wandering and screaming seem to be the most prevalent nighttime agitated behaviours. Caregivers identify many possible causes, but spatial and sensory factors, such as light or noise, were rarely mentioned spontaneously. The observations highlighted that a lot of light and noise is prominent and this might be causing nighttime restlessness.Caregivers try several strategies: for example talking with the resident, put on a light and apply medication or physical restraints.The management of nighttime restlessness requires a holistic approach. Caregivers' attention for and efforts to ameliorate the spatial and sensory environment in the management of nighttime restlessness are limited.

Initial evaluation of nighttime restlessness in a naturally occurring canine model of osteoarthritis pain.

Chronic pain due to osteoarthritis (OA) can lead to significant disruption of sleep and increased restlessness. Our objective was to assess whether naturally occurring canine OA is associated with nighttime restlessness and so has potential as a model of OA-associated sleep disturbance. The study was designed as a two-part prospective masked, placebo-controlled study using client-owned dogs (Part A n = 60; Part B n = 19). Inclusion criteria consisted of OA-associated joint pain and mobility impairment. The primary outcome measure for both parts was nighttime accelerometry. In Part B, quality of sleep was assessed using a clinical metrology instrument (Sleep and Night Time Restlessness Evaluation Score, SNoRE). Part A included dogs receiving two weeks of non-steroidal anti-inflammatory drug (NSAID) preceded with two weeks of no treatment. Part B was a crossover study, with NSAID/placebo administered for two weeks followed by a washout period of one week and another two weeks of NSAID/placebo. Repeated measures analysis of variance was used to assess differences between baseline and treatment. There were no significant changes in accelerometry-measured nighttime activity as a result of NSAID administration. SNoRE measures indicated significant improvements in aspects of the quality of nighttime sleep that did not involve obvious movement. These results reflect the few similar studies in human OA patients. Although accelerometry does not appear to be useful, this model has potential to model the human pain-related nighttime sleep disturbance, and other outcome measures should be explored in this model.

Initial evaluation of nighttime restlessness in a naturally occurring canine model of osteoarthritis pain

Initial evaluation of nighttime restlessness in a naturally occurring canine model of osteoarthritis pain

Testes play a role in termination but not in initiation of the spring migration in the night-migratory blackheaded bunting

Day length regulates the development of seasonal phenotypes linked with both the spring migration (e.g., premigratory body fattening and intense nighttime restlessness, called Zugunruhe, in captive birds) and reproduction (e.g., gonadal growth and maturation). The apparent overlap in these photoinduced seasonal phenotypes could be taken to suggest that they are causally linked. The present study investigates this, using the night-migratory blackheaded bunting (Emberiza melanocephala). We continuously monitored activity of male buntings exposed for 19 weeks to short (8 h light : 16 h darkness; 8L : 16D) and long (16L : 8D) photoperiods. Long, but not short, days induced the spring migratory phenotype. Another experiment investigated the role of testes in spring migration by comparing the development of Zugunruhe between intact and castrated buntings held on natural day lengths, at Meerut (India, 29°01′N, 77°45′E) during the period from March to October, thus covering the times of both the spring and autumn migrations. Testes were not involved in induction of the migratory phenotype but probably influenced the end of the migratory season, since castrates delayed the termination of the Zugunruhe.

Temperature alters the photoperiodically controlled phenologies linked with migration and reproduction in a night-migratory songbird

We investigated the effects of temperature on photoperiodic induction of the phenologies linked with migration (body fattening and premigratory night-time restlessness, Zugunruhe) and reproduction (testicular maturation) in the migratory blackheaded bunting. Birds were exposed for four weeks to near-threshold photoperiods required to induce testicular growth (11.5 L:12.5 D and 12 L:12 D) or for 18 weeks to a long photoperiod (13 L:11 D) at 22°C or 27°C (low) and 35°C or 40°C (high) temperatures. A significant body fattening and half-maximal testicular growth occurred in birds under the 12 L, but not under the 11.5 L photoperiod. Further, one of six birds in both temperature groups on 11.5 L, and four and two of six birds, respectively, in low- and high-temperature groups on 12 L showed the Zugunruhe. Buntings on 13 L in both temperature groups showed complete growth-regression cycles in body fattening, Zugunruhe and testis maturation. In birds on 13 L, high temperature attenuated activity levels, delayed onset of Zugunruhe by about 12 days, reduced body fattening and slowed testicular maturation. The effect of temperature seems to be on the rate of photoperiodic induction rather than on the critical day length. It is suggested that a change in temperature could alter the timing of the development of phenologies linked with seasonal migration and reproduction in migratory songbirds.

Circadian control of nocturnal songbird migration

Bird migration has evolved under the influence of annual and daily fluctuations in resource availability. Numerous passerine migrants migrate exclusively by night, maximizing the time available for foraging and feeding during the day. When held in captivity, and in total absence of environmental cues, nocturnal migrants typically show rhythms of night-time restlessness (Zugunruhe), which persist with a periodicity of about 24 h. Experimental evidence suggests that these circadian rhythms of Zugunruhe may either result from a “redefinition” of the diurnal clock or from changes in the phase relationship between independent endogenous oscillators. The role of melatonin in this control system remains ambiguous. Lowered levels of circulating melatonin found during migratory nights could either be the positive stimulus, a permissive factor or a side effect of nocturnal wakefulness. Although the nutritional state of a migrant is known to strongly influence the incidence of migratory activity, the physiological link between the circadian clock controlling Zugunruhe and the metabolic/hormonal path-ways that regulate the incidence of migration is uncertain. A functional genetic approach promises to bring behavioural and physiological knowledge together. Determining the mechanisms that are involved in the day-to-day scheduling of migration is crucial for understanding the overall control of migration, as the sum of migratory nights determines for how long, and how far, a migrant potentially travels.

Impact of psychiatric symptoms and sleep disorders on the quality of life of patients with Parkinson’s disease

The objective of this study is to assess how the non-motor symptoms of Parkinson's disease (PD), such as depression, cognitive deterioration, neuropsychiatric and sleep disorders, affect the quality of life, and to compare them with the motor symptoms in order to determine their real impact. A cross-sectional study was designed including 99 patients (mean age 68.5 ± 9.9 years, duration of disease 8.7 ± 6.2 years). Demographic data, onset of PD, years on treatment with levodopa (LD), class of dopaminergic drug prescribed, and dosages were obtained. The following scales were used: quality of life (PDQ-39), Unified Parkinson's Disease Rating Scale (UPDRS I-IV), Parkinson Disease Sleep Scale (PDSS) and daytime sleepiness (Epworth), Mini-Mental State Examination, depression (HAM-D), and the neuropsychiatric inventory (NPI-10). The PDQ-39 summary index (PDQ-39 SI) was 24.7 ± 13.2. A linear regression model including all variables showed that four independent variables accounted for 67.2% of the variance in the PDQ-39 SI (F = 33,277; p < 0.001): NPI, PDSS, UPDRS IV, and UPDRS I. When sub-items of the NPI, PDSS and UPDRS IV scales are analyzed, significant correlations (p < 0.001) are found between the PDQ-39 SI and depression, agitation, apathy, anxiety, hallucinations, delusions, incontinence of urine, morning painful posturing, restlessness in bed, morning fatigue, duration of off periods, unpredictable and predictable off periods, early morning dystonia, and sudden off periods. Neuropsychiatric symptoms, especially depression, nighttime sleep disorders such as urinary incontinence, nighttime restlessness, morning fatigue and somnolence, off-period dystonia and motor fluctuations are the variables that most affect the quality of life of patients with PD.

Walking and night-time restlessness in mild-to-moderate dementia: a randomized controlled trial

Walking and night-time restlessness in mild-to-moderate dementia: a randomized controlled trial

Transitions into and out of daylight saving time compromise sleep and the rest-activity cycles

BackgroundThe aim of this study was to analyze the effects of transition out of and into daylight saving time on the rest-activity cycles and sleep. Rest-activity cycles of nine healthy participants aged 20 to 40 years were measured around transitions out of and into daylight saving time on fall 2005 and spring 2006 respectively. Rest-activity cycles were measured using wrist-worn accelerometers. The participants filled in the Morningness-Eveningness and Seasonal Pattern Assessment Questionnaires before starting the study and kept a sleep diary during the study.ResultsFall transition was more disturbing for the more morning type and spring transition for the more evening type of persons. Individuals having a higher global seasonality score suffered more from the transitions.ConclusionTransitions out of and into daylight saving time enhanced night-time restlessness and thereby compromised the quality of sleep.

Response to Clinical Corners case (Sleep Medicine 6/2: 83–4): Pregnancy associated with daytime sleepiness and nighttime restlessness

Response to Clinical Corners case (Sleep Medicine 6/2: 83–4): Pregnancy associated with daytime sleepiness and nighttime restlessness

Response to Clinical Corners case (Sleep Medicine 6/2: 83–4): Pregnancy associated with daytime sleepiness and nighttime restlessness

Response to Clinical Corners case (Sleep Medicine 6/2: 83–4): Pregnancy associated with daytime sleepiness and nighttime restlessness

A circadian pacemaker in free-living chipmunks: essential for survival?

The importance of circadian timing was evaluated for 18 months from late-April 1997 through October 1998 in a high-density population of free-living eastern chipmunks, Tamias striatus, at a 4-ha forest site in the Allegheny Mountains. Included in the radiocollared field group were 30 chipmunks with supra-chiasmatic nucleus-targeted lesions, 24 surgical controls, and 20 intact controls. An additional 17 chipmunks were used in a laboratory study as lesion-calibration controls to correlate degree of circadian arrhythmicity with extent of supra-chiasmatic nucleus deletion. Survival was documented in the field by daily radio tracking and by regular trapping censuses except during winter hibernation. A significantly higher proportion of supra-chiasmatic nucleus-lesioned than surgical control chipmunks or intact controls were killed by weasel predation during the first 80 days after repatriation. A 28-h continuous census found no surface activity of any chipmunks during hours of darkness. However, episodes of nocturnal movement were detected within the permanent dens by radio telemetric data logging, especially in supra-chiasmatic nucleus-lesioned animals. Excavation and mapping of six chipmunk burrow systems aided in the interpretation of the telemetric activity data. Nighttime restlessness of supra-chiasmatic nucleus-lesioned animals may have acted as a clue to the predator for locating its prey.