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The Lancet. Neurology May 2022Insomnia is a frequent complaint of patients with Parkinson's disease, and it negatively affects quality of life. Drugs that improve both sleep and parkinsonism would be... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and efficacy of subcutaneous night-time only apomorphine infusion to treat insomnia in patients with Parkinson's disease (APOMORPHEE): a multicentre, randomised, controlled, double-blind crossover study.
BACKGROUND
Insomnia is a frequent complaint of patients with Parkinson's disease, and it negatively affects quality of life. Drugs that improve both sleep and parkinsonism would be of major benefit to patients with Parkinson's disease-related insomnia. We aimed to test the safety and efficacy of subcutaneous night-time only apomorphine infusion in patients with Parkinson's disease and insomnia.
METHODS
We did a randomised, multicentre, double-blind, placebo-controlled, crossover trial in 11 expert centres in Parkinson's disease and sleep centres in France. Participants aged 35-90 years with fluctuating Parkinson's disease and moderate to severe insomnia (Insomnia Severity Index score ≥15) were randomly assigned to either first receive night-time subcutaneous apomorphine (up to 5 mg/h) or matching placebo. Randomisation was done using a computer-generated plan in blocks of four, stratified by centre. This first intervention was followed by a 14-night washout period, then crossover to the other intervention. The treatment periods consisted of a 10-night titration phase followed by a 7-night fixed-dose phase. The dose was adjusted during the titration phase on the basis of a daily telephone call assessing sleep quality and treatment tolerability. The primary efficacy endpoint was the difference in Parkinson's disease sleep scale (PDSS) scores from the beginning to the end of each treatment period. Analysis was done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT02940912.
FINDINGS
Between Jan 31, 2017, and Jan 29, 2021, 46 participants were enrolled. 25 (54%) patients were randomly assigned to receive apomorphine first and 21 (46%) patients to receive placebo first. Mean change in PDSS score was significantly greater with night-time apomorphine infusion (15·18 [SD 24·34]) compared with placebo (5·23 [21·52]; treatment effect 9·95 [95% CI 0·88-19·03]; p=0·041). Adverse events were reported in 25 (54%) participants during the apomorphine period and in 17 (37%) participants during the placebo period (p=0·16). Apomorphine was associated with more frequent dizziness than was placebo (seven [15%] vs 0; p=0·041).
INTERPRETATION
Subcutaneous night-time only apomorphine infusion improved sleep disturbances according to difference on PDSS score, with an overall safety profile consistent with previous studies in Parkinson's disease. This treatment might be useful to manage sleep disturbances in patients with advanced Parkinson's disease and moderate to severe insomnia.
FUNDING
Orkyn and Aguettant Pharma.
TRANSLATION
For the French translation of the abstract see Supplementary Materials section.
Topics: Adult; Aged; Aged, 80 and over; Apomorphine; Cross-Over Studies; Double-Blind Method; Humans; Middle Aged; Parkinson Disease; Quality of Life; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders; Treatment Outcome
PubMed: 35429481
DOI: 10.1016/S1474-4422(22)00085-0 -
Longitudinal analysis and treatment of neuropsychiatric symptoms in post-acute sequelae of COVID-19.Journal of Neurology Oct 2023Persistent neuropsychiatric symptoms following acute COVID-19 infection are frequently reported. These include anxiety, depression, difficulty concentrating, fatigue,...
BACKGROUND
Persistent neuropsychiatric symptoms following acute COVID-19 infection are frequently reported. These include anxiety, depression, difficulty concentrating, fatigue, and insomnia. The longitudinal evolution of this neuropsychiatric burden is poorly understood and clinical guidelines concerning treatment are lacking.
OBJECTIVE
We sought to describe the longitudinal evolution of neuropsychiatric symptoms in the post-acute sequelae of COVID-19 (PASC) syndrome and examine symptom treatment at a single center.
METHODS
Consecutive participants experiencing persistent neurologic symptoms after acute COVID-19 infection were recruited from October 2020 to July 2022. Data collected included COVID-19 infection history, neurological exam and review of systems, Montreal Cognitive Assessment (MoCA), and self-reported surveys concerning neuropsychiatric symptoms and treatment. Data were collected at baseline and at 1-year follow-up.
RESULTS
A total of 106 participants (mean age 48.6, females 67%) were included in the study. At 1-year follow-up, 72.5% of participants reported at least one neuropsychiatric symptom. Over half (52.5%) of participants reported persistent fatigue. At baseline, 38.8% of all participants had met the established MoCA cut-off score of < 26 for mild cognitive impairment; this decreased to 20.0% at 1 year. COVID-19 infection severity was associated with neuro-PASC symptoms (including fatigue and anxiety) at 1 year. Overall, 29% of participants started at least one new medication for COVID-19-associated neuropsychiatric symptoms. Of the participants who started new medications, fatigue was the most common indication (44.8%) followed by insomnia (27.6%).
CONCLUSIONS
Neuropsychiatric symptoms related to neuro-PASC improve over time but can persist for over a year post-recovery. Most treatment modalities targeted neuro-PASC fatigue.
Topics: Female; Humans; Middle Aged; Anxiety; COVID-19; Fatigue; Post-Acute COVID-19 Syndrome; Sleep Initiation and Maintenance Disorders; Male
PubMed: 37493802
DOI: 10.1007/s00415-023-11885-x -
Sleep Medicine Mar 2024Chronic insomnia impairs the glymphatic system and may lead to cognitive impairment and dementia in elderly population. The diffusion tensor image analysis along the...
Glymphatic system dysfunction in middle-aged and elderly chronic insomnia patients with cognitive impairment evidenced by diffusion tensor imaging along the perivascular space (DTI-ALPS).
BACKGROUND
Chronic insomnia impairs the glymphatic system and may lead to cognitive impairment and dementia in elderly population. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) has been proposed as a non-invasive method to measure the activity of human brain glymphatic. We aim to explore whether glymphatic function is impaired in middle-aged and elderly chronic insomnia individuals and to identify the relationships between glymphatic dysfunction and cognitive impairment.
METHODS
A total of 33 chronic insomnia patients (57.36 ± 5.44 years, 30 females) and 20 age- and sex-matched healthy controls (57.95 ± 5.78 years, 16 females) were prospectively enrolled between May 2022 and January 2023. All participants completed MRI screening, cognition and sleep assessments, and DTI-ALPS index analysis.
RESULTS
Our findings revealed that the DTI-ALPS index was significantly difference among the chronic insomnia patients with impaired cognition group (1.32 ± 0.14), with normal cognition group (1.46 ± 0.09), and healthy controls (1.61 ± 0.16) (p = 0.0012, p < 0.0001, p = 0.0008, respectively). Mini-Mental State Examination (MMSE) scores of chronic insomnia patients with cognitive impairment were positively correlated with the DTI-ALPS index (Partial correlation analyses after correction for age, sex, education level and duration of chronic insomnia: r = 0.78, p = 0.002). DTI-ALPS had moderate accuracy in distinguishing chronic insomnia patients with cognitive impairment from those with normal cognition.
DATA CONCLUSION
The glymphatic system dysfunction is involved in chronic insomnia among middle-aged and elderly individuals, and it has been found to be correlated with cognitive decline.
Topics: Female; Middle Aged; Humans; Aged; Glymphatic System; Sleep Initiation and Maintenance Disorders; Diffusion Tensor Imaging; Cognitive Dysfunction; Cognition
PubMed: 38364456
DOI: 10.1016/j.sleep.2024.01.028 -
BMC Endocrine Disorders Sep 2022Epidemiological evidence suggests that inadequate sleep duration and insomnia may be associated with increased risk of metabolic syndrome (MetS). However, longitudinal...
BACKGROUND
Epidemiological evidence suggests that inadequate sleep duration and insomnia may be associated with increased risk of metabolic syndrome (MetS). However, longitudinal data with repeated measures of sleep duration and insomnia and of MetS are limited. We examined the association of sleep duration and insomnia with MetS and its components using longitudinal data from the Women's Health Initiative (WHI).
METHODS
The study included postmenopausal women (ages 50-79 years) diabetes-free at enrollment in the WHI, with baseline data on sleep duration (n = 5,159), insomnia (n = 5,063), MetS, and its components. Repeated measures of self-reported sleep duration and insomnia were available from years 1 or 3 of follow-up and of the MetS components from years 3, 6 and 9. Associations were assessed using logistic regression and generalized estimating equations models, and odds ratios and 95% confidence intervals (CI) adjusted for major risk factors were calculated.
RESULTS
In cross-sectional analysis, baseline sleep duration ≥ 9 h was positively associated with MetS (OR = 1.51; 95%CI 1.12-2.04), while sleep duration of 8- < 9 h was associated with waist circumference > 88 cm and triglycerides ≥ 150 mg/dL (OR = 1.18; 95%CI 1.01-1.40 and OR = 1.23; 95%CI 1.05-1.46, respectively). Insomnia had a borderline positive association with MetS (OR = 1.14; 95%CI 0.99-1.31), and significant positive associations with waist circumference > 88 cm and glucose ≥ 100 mg/dL (OR = 1.18; 95%CI 1.03-1.34 and OR = 1.17; 95%CI 1.02-1.35, respectively). In the longitudinal analysis, change from restful sleep to insomnia over time was associated with increased odds of developing MetS (OR = 1.40; 95%CI 1.01-1.94), and of a triglyceride level ≥ 150 mg/dL (OR = 1.48; 95%CI 1.08-2.03).
CONCLUSIONS
Among postmenopausal women in the WHI, sleep duration and insomnia were associated with current and future risk of MetS and some of its components.
Topics: Aged; Cross-Sectional Studies; Female; Humans; Metabolic Syndrome; Middle Aged; Sleep; Sleep Initiation and Maintenance Disorders; Women's Health
PubMed: 36104689
DOI: 10.1186/s12902-022-01138-9 -
Behavioral Sleep Medicine 2021This pilot study explored the efficacy of a novel forehead cooling device for perceived sleep difficulties and hot flashes in menopausal-age women.
OBJECTIVE/BACKGROUND
This pilot study explored the efficacy of a novel forehead cooling device for perceived sleep difficulties and hot flashes in menopausal-age women.
PARTICIPANTS
20 women (55.1 ± 4.2 years; 19 post-menopausal) with insomnia symptoms and self-reported two or more hot flashes per day.
METHODS
Participants completed daily assessments of sleep and hot flashes (via diaries) across 1 baseline week and 4 weeks of open-label, in-home, nightly treatment with a forehead cooling device (15-18°C) along with sleep hygiene instructions. They also completed ratings of insomnia and menopausal symptoms using standardized questionnaires.
RESULTS
Women reported reductions in sleep onset latency (SOL), wakefulness after sleep onset (WASO), and nocturnal hot flash severity during the first week of treatment (SOL: 25.7 ± 18.4 min; WASO: 36.3 ± 27.3 min; hot flash severity: 3.0 ± 2.8) compared with baseline (SOL: 38 ± 26.3 min; WASO: 52.2 ± 35.6 min; hot flash severity: 6.8 ± 3.7), with further improvements after 2-4 weeks of use ( < .001). There were also clinically meaningful reductions in insomnia severity and hot flash-related daily interference and lower psychological and physical symptom scores on the Greene climacteric scale after treatment (all p's<0.001).
CONCLUSIONS
This exploratory, naturalistic, pilot study shows that nightly use of a forehead cooling device produces improvements in self-reported sleep and reductions in insomnia, hot flash, and other menopausal, symptoms. Controlled studies are warranted to determine the role of this therapy in the management of sleep difficulties and menopausal symptoms in women. Further mechanistic studies are needed to understand the physiological impact of forehead cooling on sleep and menopausal symptoms.
Topics: Cryotherapy; Female; Forehead; Hot Flashes; Humans; Menopause; Middle Aged; Pilot Projects; Sleep Initiation and Maintenance Disorders
PubMed: 33040586
DOI: 10.1080/15402002.2020.1826484 -
Sleep Medicine Nov 2020Sleep bruxism (SB) is characterized by recurrent masticatory muscle activity during sleep with occasional tooth grinding. SB can be concomitant with sleep apnea although...
UNLABELLED
Sleep bruxism (SB) is characterized by recurrent masticatory muscle activity during sleep with occasional tooth grinding. SB can be concomitant with sleep apnea although its association with insomnia is understudied.
STUDY OBJECTIVE
Assess the strength of the associations between SB, insomnia and sleep apnea in a general population.
METHODS
Data from the 2007 EPISONO general population study (n = 1042; Sao Paulo, Brazil) were reused for the present analyses. The data was collected from polysomnography (PSG) and from a questionnaire. SB could only be assessed as "possible" with self-report questionnaires, but as "definitive" with both self-reports and PSG. Logistic regression and decision tree analyses were performed.
RESULTS
Logistic regression analyses revealed that being male, overweight, obese, having an apnea/hypopnea index (AHI) above 30 and insomnia syndrome are among risk factors for SB (prevalence ratio (PR): 1.5-3.3). A high AHI and insomnia syndrome had similar PRs, 2.7 and 2.8, respectively. Decision tree analysis showed that insomnia syndrome contributed to the predictive accuracy of SB self-report (88%). A similar estimate (91%) was observed with SB PSG data. Correspondence analysis illustrated three age profiles in participants: (1) good sleepers aged 20-35 years, (2) females aged 35-50 years with SB and concomitant insomnia syndrome, and (3) participants aged ≥ 50 years with obesity and sleep apnea.
CONCLUSIONS
Insomnia is likely a condition associated with SB, especially in middle-age females, while sleep apnea seems age and gender dependent. Such overlap may influence the treatment decision to achieve best outcomes.
CLINICAL TRIAL REGISTRATION
EPISONO study; Clinical trials.gov ID # NCT00596713.
Topics: Adult; Brazil; Female; Humans; Male; Middle Aged; Polysomnography; Sleep Apnea, Obstructive; Sleep Bruxism; Sleep Initiation and Maintenance Disorders; Young Adult
PubMed: 32858352
DOI: 10.1016/j.sleep.2020.06.016 -
Cerebral Cortex (New York, N.Y. : 1991) May 2023Normal sleepers may be at risk for insomnia during COVID-19. Identifying psychological factors and neural markers that predict their insomnia risk, as well as...
Normal sleepers may be at risk for insomnia during COVID-19. Identifying psychological factors and neural markers that predict their insomnia risk, as well as investigating possible courses of insomnia development, could lead to more precise targeted interventions for insomnia during similar public health emergencies. Insomnia severity index of 306 participants before and during COVID-19 were employed to determine the development of insomnia, while pre-COVID-19 psychometric and resting-state fMRI data were used to explore corresponding psychological and neural markers of insomnia development. Normal sleepers as a group reported a significant increase in insomnia symptoms after COVID-19 outbreak (F = 4.618, P = 0.0102, df = 2, 609.9). Depression was found to significantly contribute to worse insomnia (β = 0.066, P = 0.024). Subsequent analysis found that functional connectivity between the precentral gyrus and middle/inferior temporal gyrus mediated the association between pre-COVID-19 depression and insomnia symptoms during COVID-19. Cluster analysis identified that postoutbreak insomnia symptoms followed 3 courses (lessened, slightly worsened, and developed into mild insomnia), and pre-COVID-19 depression symptoms and functional connectivities predicted these courses. Timely identification and treatment of at-risk individuals may help avoid the development of insomnia in the face of future health-care emergencies, such as those arising from COVID-19 variants.
Topics: Humans; Sleep Initiation and Maintenance Disorders; COVID-19; Depression; Emergencies; SARS-CoV-2; Brain
PubMed: 36749000
DOI: 10.1093/cercor/bhad016 -
Psychiatry Research Apr 2020Posttraumatic stress disorder (PTSD) and insomnia are comorbid clinical conditions that are thought to result from genetic and environmental effects. Though studies have...
Posttraumatic stress disorder (PTSD) and insomnia are comorbid clinical conditions that are thought to result from genetic and environmental effects. Though studies have established the heritability of these disorders independently, no study to date has examined the genetic contributions to the relation between insomnia and PTSD symptoms (PTSS). The present study assessed this gap in the literature using a behavioral genetics approach to symptom dimensions. The sample consisted of 242 twin pairs who endorsed lifetime trauma exposure. Insomnia symptoms were assessed with the Women's Health Initiative Survey, and intrusion and avoidance PTSS were assessed with the Impact of Events Scale. Structural equation modeling was then employed to test the relative contributions of genetic, shared environmental, and nonshared environmental components to the relations between insomnia symptoms and intrusions and avoidance. Results indicated a significant association between insomnia symptoms and intrusions (r = 0.33, p < 0.01) and insomnia symptoms and avoidance (r = 0.20, p < 0.01), and 36-44% of phenotypic variance was accounted for by genetic contributions. These findings highlight a significant role for genetic factors in the mechanisms underlying the comorbidity between insomnia and PTSS. The implications for current etiological models of PTSD and insomnia are discussed.
Topics: Adult; Aged; Comorbidity; Diseases in Twins; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Registries; Sleep Initiation and Maintenance Disorders; Stress Disorders, Post-Traumatic; Twins; Twins, Dizygotic; Twins, Monozygotic; Washington
PubMed: 31495512
DOI: 10.1016/j.psychres.2019.112548 -
International Journal of Environmental... Sep 2022Insomnia disorder is considered a public health problem and additional studies should investigate predisposing and perpetuating factors. This study examined the...
Insomnia disorder is considered a public health problem and additional studies should investigate predisposing and perpetuating factors. This study examined the relationship between Big Five personality traits, time perspective, and insomnia. In a cross-sectional study, 400 participants (227 women; age range 18-74 years) were administered the Big Five Inventory-10 items, the Zimbardo Time Perspective Inventory, and the Insomnia Severity Index (ISI). A measure of chronotype was also included for control purposes. The results show that insomniacs reported lower scores for conscientiousness and extraversion, and for past-positive (PP) and future (F) perspectives, whereas they obtained higher scores for past-negative (PN) perspectives and deviation from a balanced time perspective. The correlations confirmed these findings, but negative correlations between present-hedonistic (PH) perspective and ISI score, and between emotional stability and ISI score, were also found. The mediation analyses showed that F played an indirect role in the relationship between consciousness and ISI score, PN had an indirect effect on the relationship between emotional stability and ISI or between extraversion and insomnia, and PH had an indirect effect on the relationship between extraversion and ISI score. The current outcomes shed light on the mechanisms which serve to mediate the relationship between insomnia and personality traits.
Topics: Adolescent; Adult; Aged; Cross-Sectional Studies; Extraversion, Psychological; Female; Humans; Middle Aged; Personality; Sleep Initiation and Maintenance Disorders; Young Adult
PubMed: 36078734
DOI: 10.3390/ijerph191711018 -
Behavior Genetics Mar 2021Twin studies have provided data about the relative weight of genetic and environmental factors on sleep variables over the last few decades. However, heritability is a...
STUDY OBJECTIVES
Twin studies have provided data about the relative weight of genetic and environmental factors on sleep variables over the last few decades. However, heritability is a non-intuitive concept and it is often misunderstood even amongst the scientific community. This study aimed to analyze: (1) understanding of the meaning of heritability of insomnia; (2) the accuracy of estimations of heritability in the general population regarding three sleep traits (sleep duration, sleep quality and insomnia); (3) perceptions of the effectiveness of different treatments for insomnia depending on how the disorder is presented (i.e. having an environmental or genetic etiology) and whether the subject's estimate of genetic influence on sleep traits impacted beliefs about the effectiveness of different treatments.
METHODS
Participants (N = 3658) completed a survey which included: questions about general genetic knowledge; a specific question about the meaning of heritability; estimates of heritability of three different sleep traits; and the effectiveness of different treatments for insomnia depending on how the etiology of this condition was presented.
RESULTS
Fewer than 25% of the participants selected the correct description of the heritability of insomnia. Almost half of the sample incorrectly believed that heritability refers to the chance of passing a disorder onto their children. We also found that participants provided different estimates for the effectiveness of different treatments depending on the presumed etiology of the disorder.
CONCLUSION
Most people do not have accurate knowledge about the concept of heritability. People's assumptions about the etiology of a disorder may influence which treatments they consider most effective.
Topics: Adult; Aged; Female; Genotype; Health Knowledge, Attitudes, Practice; Humans; Male; Middle Aged; Phenotype; Sleep; Sleep Initiation and Maintenance Disorders; Surveys and Questionnaires
PubMed: 33486622
DOI: 10.1007/s10519-021-10041-3