Investigating light sensitivity in bipolar disorder (HELIOS-BD).

Many people with bipolar disorder have disrupted circadian rhythms. This means that the timing of sleep and wake activities becomes out-of-sync with the standard 24-hour cycle. Circadian rhythms are strongly influenced by light levels and previous research suggests that people with bipolar disorder might have a heightened sensitivity to light, causing more circadian rhythm disruption, increasing the potential for triggering a mood switch into mania or depression. Lithium has been in clinical use for over 70 years and is acknowledged to be the most effective long-term treatment for bipolar disorder. Lithium has many reported actions in the body but the precise mechanism of action in bipolar disorder remains an active area of research. Central to this project is recent evidence that lithium may work by stabilising circadian rhythms of mood, cognition and rest/activity. Our primary hypothesis is that people with bipolar disorder have some pathophysiological change at the level of the retina which makes them hypersensitive to the visual and non-visual effects of light, and therefore more susceptible to circadian rhythm dysfunction. We additionally hypothesise that the mood-stabilising medication lithium is effective in bipolar disorder because it reduces this hypersensitivity, making individuals less vulnerable to light-induced circadian disruption. We will recruit 180 participants into the HELIOS-BD study. Over an 18-month period, we will assess visual and non-visual responses to light, as well as retinal microstructure, in people with bipolar disorder compared to healthy controls. Further, we will assess whether individuals with bipolar disorder who are being treated with lithium have less pronounced light responses and attenuated retinal changes compared to individuals with bipolar disorder not being treated with lithium. This study represents a comprehensive investigation of visual and non-visual light responses in a large bipolar disorder population, with great translational potential for patient stratification and treatment innovation.

Bed partner perception of CPAP therapy on relationship satisfaction and intimacy-A European perspective from the ESADA network.

Obstructive sleep apnea increases morbidity and mortality risks. The most common treatment is continuous positive airway pressure, with nasal mask usage being important, but not always optimal. While most research on treatment adherence focuses on the patient, the bed partner's involvement may be detrimental. Our study aim is to obtain a European-wide picture of the bed partner's attitude and support towards continuous positive airway pressure therapy, including effects on relationship satisfaction and intimacy. The English translation of a German bed partner questionnaire, assessing relationship satisfaction and three major components (general attitude, perceived mask looks, intimacy effects) was distributed within the European Sleep Apnea Database Network and translated in participating countries' local language. Data were collected for 2 years. In total, 10 European countries (13 sleep centres) participated with 1546 questionnaires. Overall, 91% of bed partners had a positive attitude towards continuous positive airway pressure therapy, 86% perceived mask looks not negative, 64% stated no negative intimacy effects. More specifically, 71% mentioned improved sleep quality, 68% supported nightly device usage. For 41% of bed partners, relationship satisfaction increased (no change for 47%). These results were significantly more pronounced in Eastern/Southern Europe compared with Middle Europe, especially regarding intimacy effects. However, increased continuous positive airway pressure therapy length affected attitude negatively. These results provide necessary information to improve treatment strategies by including educational couple-focused approaches. Among others, we revealed that negative intimacy effects are not considered a barrier to continuous positive airway pressure adherence. These results may inspire more research identifying regional gaps with need for treatment adjustments.

Update on the genetic basis of obstructive sleep apnoea - hype or hope?

PURPOSE OF REVIEW: The obstructive sleep apnoea syndrome (OSAS) is a chronic, common condition in western societies which can lead to adverse cardiometabolic effects if left untreated and is one of the commonest causes of excessive daytime somnolence. RECENT FINDINGS: The presentation of OSAS is diverse and is thought to comprise of different intermediate phenotypes and endotypes in varying proportions in each individual. Unfortunately, due to its heterogeneity and the changing definitions of the disorder by workers in the field, attempts at revealing the genetic basis of OSAS has been fraught with difficulty. SUMMARY: This brief review presents a short update on the achievements of the past three decades in this understudied and underfunded area of endeavour in respiratory sleep medicine. The genetic underpinnings of OSAS remain elusive.

Sleep quality, perivascular spaces and brain health markers in ageing - A longitudinal study in the Lothian Birth Cohort 1936.

BACKGROUND: Sleep is thought to play a major role in brain health and general wellbeing. However, few longitudinal studies have explored the relationship between sleep habits and imaging markers of brain health, particularly markers of brain waste clearance such as perivascular spaces (PVS), of neurodegeneration such as brain atrophy, and of vascular disease, such as white matter hyperintensities (WMH). We explore these associations using data collected over 6 years from a birth cohort of older community-dwelling adults in their 70s. METHOD: We analysed brain MRI data from ages 73, 76 and 79 years, and self-reported sleep duration, sleep quality and vascular risk factors from community-dwelling participants in the Lothian Birth Cohort 1936 (LBC1936) study. We calculated sleep efficiency (at age 76), quantified PVS burden (at age 73), and WMH and brain volumes (age 73 to 79), calculated the white matter damage metric, and used structural equation modelling (SEM) to explore associations and potential causative pathways between indicators related to brain waste cleaning (i.e., sleep and PVS burden), brain and WMH volume changes during the 8th decade of life. RESULTS: Lower sleep efficiency was associated with a reduction in normal-appearing white matter (NAWM) volume (ß = 0.204, P = 0.009) from ages 73 to 79, but not concurrent volume (i.e. age 76). Increased daytime sleep correlated with less night-time sleep (r = -0.20, P < 0.001), and with increasing white matter damage metric (ß = -0.122, P = 0.018) and faster WMH growth (ß = 0.116, P = 0.026). Shorter night-time sleep duration was associated with steeper 6-year reduction of NAWM volumes (ß = 0.160, P = 0.011). High burden of PVS at age 73 (volume, count, and visual scores), was associated with faster deterioration in white matter: reduction of NAWM volume (ß = -0.16, P = 0.012) and increasing white matter damage metric (ß = 0.37, P < 0.001) between ages 73 and 79. On SEM, centrum semiovale PVS burden mediated 5% of the associations between sleep parameters and brain changes. CONCLUSION: Sleep impairments, and higher PVS burden, a marker of impaired waste clearance, were associated with faster loss of healthy white matter and increasing WMH in the 8th decade of life. A small percentage of the effect of sleep in white matter health was mediated by the burden of PVS consistent with the proposed role for sleep in brain waste clearance.

A case-control study of sexualised behaviour in sleep: A strong association with psychiatric comorbidity and relationship difficulties.

Sexualised behaviour in sleep (SBS) is a relatively rare parasomnia consisting of instinctive behaviours of a sexual nature occurring during non-rapid-eye movement (NREM) sleep. Little information exists at present regarding the clinical features and onset of this condition as well as its link to psychiatric comorbidity, other sleep disorders and history of adverse early life experience. Aims were to typify the condition further and compare features of SBS patients to those with other NREM parasomnias. METHODS: Details of 335 consecutive patients presenting to a single tertiary sleep centre with non-rapid eye movement (NREM)-parasomnias over a 15-year period (2005-2020) were examined. Data were collated by reviewing case-notes for anthropometric data, past medical history, clinical findings, and video polysomnography. SBS patients were compared to a cohort of 270 non-SBS, NREM-sleep disorder patients (case-control) to ascertain whether they had any distinguishing features from other parasomnias classified in this group. RESULTS: Sixty-five patients with SBS were identified: 58 males, 7 females (comprising 19.4% of the cohort overall). Mean age at presentation was 33(±9.5) years. Onset of behaviours was commoner in adulthood in the SBS cohort, whereas non-SBS, NREM-parasomnia onset (n = 270) was commoner in childhood: 61.1% and 52.9% respectively (p = 0.007). An association was identified between the presence of psychiatric diagnoses and onset of SBS (p = 0.028). Significant triggers for SBS behaviours included alcohol consumption (p < 0.001), intimate relationship difficulties (p = 0.009) and sleep deprivation (p = 0.028). Patients with SBS were significantly more likely to report sleepwalking as an additional NREM behaviour (p < 0.001). Males were more likely to present at clinic together with their bedpartner and females presented alone. A history of SBS appeared to be more common in those working in the armed forces or the police compared to those presenting with non-SBS, NREM-parasomnias (p = 0.004). CONCLUSIONS: SBS is more common in clinical practice than previously described and presents with some distinguishing features within the NREM disorder category. This study is the first to identify that onset in childhood or lack of amnesia does not preclude the condition and that patterns of presentation differ between men and women. Sleepwalkers particularly should be asked about SBS. Comorbid psychiatric conditions, profession and intimate partner difficulties are strong determinants of the presentation.

ERS technical standards for using type III devices (limited channel studies) in the diagnosis of sleep disordered breathing in adults and children.

For more than three decades, type III devices have been used in the diagnosis of sleep disordered breathing in supervised as well as unsupervised settings. They have satisfactory positive and negative predictive values for detecting obstructive and central sleep apnoea in populations with moderately high pre-test probability of symptoms associated with these events. However, standardisation of commercially available type III devices has never been undertaken and the technical specifications can vary widely. None have been subjected to the same rigorous processes as most other diagnostic modalities in the medical field. Although type III devices do not include acquisition of electroencephalographic signals overnight, the minimum number of physical sensors required to allow for respiratory event scoring using standards outlined by the American Academy of Sleep Medicine remains debatable. This technical standard summarises data on type III studies published since 2007 from multiple perspectives in both adult and paediatric sleep practice. Most importantly, it aims to provide a framework for considering current type III device limitations in the diagnosis of sleep disordered breathing while raising research- and practice-related questions aimed at improving our use of these devices in the present and future.

Floppy eyelid syndrome and obstructive sleep apnea: a unique phenotype?

INTRODUCTION: Floppy eyelid syndrome (FES) is an underdiagnosed condition stereotypically found in obese, middle-aged men, characterized by a lax eyelid tarsus which readily everts without excess mechanical manipulation. Obstructive sleep apnoea (OSA) is the most frequently reported comorbidity in patients suffering from FES. The aim of this study was to determine whether or not individuals with FES present with distinct anthropometric characteristics in comparison to patients without FES suspected of having OSA. METHODS: A retrospective case-control study in which FES patients and controls all referred for investigation of suspected OSA, matched for sex, ethnicity, residential location, age (± 2 years), date of sleep study (± 1 month), and type of sleep study were compared for anthropometric, comorbidity, and sleep data differences. RESULTS: OSA prevalence and severity, assessed by apnoea-hypopnea index (AHI), revealed no significant differences between patients with FES (n = 39) and those without (n = 75), (85% vs 88%, p = 0.91 and 31.9 ± 28.7 vs 28.5 ± 16.6, p = 0.81 respectively), despite patients with FES being more obese (p = 0.02). Patients with FES had significantly lower Epworth sleepiness scale (ESS) scores after treatment with CPAP (5.3 ± 4.1 vs 9.4 ± 5.0, p = 0.028). Patients with FES exhibited increased prevalence of hernias (15% vs 4%, p = 0.032), dermatological (41% vs 17%, p = 0.006) and rheumatological (15% vs 3%, p = 0.012) comorbidities. CONCLUSION: FES patients appear to exhibit a distinct phenotype with increased prevalence of comorbidities related to matrix metalloproteinase dysfunction and significant improvement of daytime hypersomnolence with continuous positive airway pressure (CPAP) treatment.

NREM Sleep Parasomnias Commencing in Childhood: Trauma and Atopy as Perpetuating Factors.

Objective/Background: Phenotyping of non-rapid-eye-movement (NREM) parasomnias is currently poorly undertaken. This study aimed to determine whether there are differences phenotypically among childhood-, adolescent-, and adult-onset NREM parasomnias continuing into and presenting in adulthood. Patients/Methods: A retrospective, cohort study of patients presenting with NREM parasomnia between 2008 and 2019 (n = 307) was conducted. Disorders included sleepwalking (n = 231), night terrors (n = 150), sexualised behaviour in sleep (n = 50), and sleep-related eating disorder (n = 28). Results: Compared to the adult-onset NREM behaviours group, the childhood- and adolescent-onset groups were more likely to have a family history of NREM behaviours (p < 0.001), experience a greater spectrum of NREM disorders (p = 0.001), and report a history of sleep-talking significantly more frequently (p = 0.014). Atopy was most prevalent in the childhood-onset group (p = 0.001). Those with childhood-onset NREM parasomnias were significantly more likely to arouse from N3 sleep on video polysomnography (p = 0.0003). Psychiatric disorders were more likely to be comorbid in the adult-onset group (p = 0.012). A history of trauma coinciding with onset of NREM behaviours was significantly more common in the childhood- and adolescent-onset groups (p < 0.001). Conclusions: Significant differences exist across childhood-, adolescent-, and adult-onset NREM parasomnia presenting in adulthood. This study suggests that adult-onset slow-wave sleep disorders may be confounded by psychiatric disorders resulting in nocturnal sleep disruption and that unresolved traumatic life experiences perpetuate NREM disorders arising in childhood and comprise one of the strongest external risk factors for triggering and perpetuating these disorders in adolescence.

Management of obstructive sleep apnea in Europe - A 10-year follow-up.

OBJECTIVE: In 2010, a questionnaire-based study on obstructive sleep apnea (OSA) management in Europe identified differences regarding reimbursement, sleep specialist qualification, and titration procedures. Now, 10 years later, a follow-up study was conducted as part of the ESADA (European Sleep Apnea Database) network to explore the development of OSA management over time. METHODS: The 2010 questionnaire including questions on sleep diagnostic, reimbursement, treatment, and certification was updated with questions on telemedicine and distributed to European Sleep Centers to reflect European OSA management practice. RESULTS: 26 countries (36 sleep centers) participated, representing 20 ESADA and 6 non-ESADA countries. All 21 countries from the 2010 survey participated. In 2010, OSA diagnostic procedures were performed mainly by specialized physicians (86%), whereas now mainly by certified sleep specialists and specialized physicians (69%). Treatment and titration procedures are currently quite homogenous, with a strong trend towards more Autotitrating Positive Airway Pressure treatment (in hospital 73%, at home 62%). From 2010 to 2020, home sleep apnea testing use increased (76%-89%) and polysomnography as sole diagnostic procedure decreased (24%-12%). Availability of a sleep specialist qualification increased (52%-65%) as well as the number of certified polysomnography scorers (certified physicians: 36%-79%; certified technicians: 20%-62%). Telemedicine, not surveyed in 2010, is now in 2020 used in diagnostics (8%), treatment (50%), and follow-up (73%). CONCLUSION: In the past decade, formal qualification of sleep center personnel increased, OSA diagnostic and treatment procedures shifted towards a more automatic approach, and telemedicine became more prominent.

Treating sleep disorders following traumatic brain injury in adults: Time for renewed effort?

Traumatic brain injury (TBI) disrupts normal brain function and can lead to chronic symptoms of sleep disturbance, pain, irritability, and depression. Sleep disorders occur in 30-70% of individuals who have experienced TBI. Disturbed sleep impairs the recovery process and may exacerbate other issues that arise because of brain injury (e.g., headaches, depression). Noticeable benefits have been reported when sleep problems due to TBI are addressed and treated; for instance, treating post-TBI insomnia reduces the expression of inflammatory genes, potentially reducing ongoing neurological damage. In this review, we discuss twenty-four randomised clinical trials (RCT) published to date (August 2021), exploring interventions for sleep disturbances resulting from TBI. Treatment effects were observed for insomnia, circadian rhythm disorders, hypersomnia, and general sleep disturbance. However, the evidence remains limited and significant methodological issues are discussed with a recommendation for further research.

Gene expression profiling of placentae from women with obesity and obstructive sleep apnoea.

INTRODUCTION: Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. The biological mechanisms of these associations are poorly understood. The impact of OSA on placental function has not been well characterised. METHODS: We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9). RESULTS: After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). In unadjusted analyses, 101 genes were differentially expressed in OSA compared to no OSA placentae (p < 0.01). In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. In gene set enrichment analysis, genes within 24 pathways had a non-random distribution in OSA compared to no OSA placentae (adjusted p < 0.05). This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA. DISCUSSION: There is overall similarity in the placental transcriptome of women with obesity who do and do not have OSA during pregnancy. Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts.

Haematocrit level in obesity hypoventilation syndrome: a predictor of mortality?

BACKGROUND: The connection between obstructive sleep apnea and secondary erythrocytosis is controversial. We hypothesised that there may be a higher prevalence of erythrocytosis in patients with obesity hypoventilation syndrome (OHS) due to persistent hypoxemia. METHODS: The study was a retrospective, cross-sectional review of patients with OHS derived from an established cohort of "non-invasive ventilation" patients at the Department of Sleep Medicine at the Royal Infirmary Medical Centre, Edinburgh (2004-2017). Relevant clinical data were obtained from patient records. RESULTS: The cohort comprised 74 patients with OHS, 44 men (60%), mean age at diagnosis 54 ± 10 years. The mean haematocrit level for the group overall was 0.44, in men 0.45, and in women 0.41. Of 11 patients with erythrocytosis (15%), 7 were men. Thirteen patients (18%) died during follow-up (2004-2017). There was a statistically significant increase in risk of death in patients with higher and lower haematocrit levels compared to that in patients with OHS who had normal haematocrits. CONCLUSIONS: This is the first study showing increased prevalence of erythrocytosis in OHS patients. There was a "U"-shaped correlation with mortality according to haematocrit levels.

High prevalence of obstructive sleep apnea in pregnant women with class III obesity: a prospective cohort study.

STUDY OBJECTIVES: To determine the prevalence of obstructive sleep apnea (OSA) in a cohort of women with class III obesity, and a comparator lean group, in the second and third trimesters of pregnancy. Secondary objectives were to compare characteristics of women with obesity with and without OSA and to assess factors that were predictive of OSA. METHODS: We performed a prospective cohort study involving 33 women with class III obesity (mean body mass index 43.5 ± 3.9 kg/m2) and 39 lean women (body mass index 22.0 ± 1.7 kg/m2) with singleton pregnancies. Participants completed 2 level 3 sleep studies between 12-22 weeks and 32-38 weeks gestation. OSA was defined as a respiratory event index ≥ 5 events/h (≥ 3% desaturation criteria). Levels of interleukin-6, glucose, and C-peptide were quantified in maternal blood. Logistic regression analysis was performed to determine predictors of OSA. RESULTS: OSA was identified in 12 (37.5%) and 14 (50.0%) women with obesity and in 1 (2.6%) and 3 (9.1%) lean women in the second and third trimesters, respectively. Women with obesity with OSA were older than those with no OSA but otherwise had similar characteristics. In unadjusted analysis of women with obesity, increased age, body mass index, homeostatic model assessment of insulin resistance, and history of nonsmoking were associated with increased odds of OSA. In multivariable analysis, only increased age remained significantly associated with OSA. CONCLUSIONS: OSA is highly prevalent in pregnant women with class III obesity. Further research is required to establish effective management strategies for the growing number of women in this high-risk group. CITATION: Johns EC, Hill EA, Williams S, et al. High prevalence of obstructive sleep apnea in pregnant women with class III obesity: a prospective cohort study. J Clin Sleep Med. 2022;18(2):423-432.

Trauma Immediately Preceding REM-Behavior Disorder: A Valuable Prognostic Marker?

Background: The definition of rapid eye movement (REM) sleep behavior disorder (RBD) has varied over the years. Rapid eye movement sleep behavior disorder can be considered isolated or idiopathic or can occur in the context of other disorders, including trauma-associated sleep disorder (TSD) and overlap parasomnia. However, whether trauma in RBD carries any prognostic specificity is currently unknown. Study Objectives: To test the hypothesis that RBD secondary to trauma is less likely to result in the development of neurodegeneration compared to idiopathic RBD (iRBD) without trauma in the general population. Methods: A retrospective cohort study of 122 consecutive RBD patients (103 males) at two tertiary sleep clinics in Europe between 2005 and 2020 was studied. Patients were diagnosed as having iRBD by video polysomnography (vPSG) and had a semi-structured interview at presentation, including specifically eliciting any history of trauma. Patients with secondary RBD to recognized causes were excluded from the study. Patients with iRBD were categorized into three groups according to reported trauma history: (1) No history of trauma, (2) traumatic experience at least 12 months prior to RBD symptom onset, and (3) traumatic experience within 12 months of RBD symptom onset. Idiopathic RBD duration was defined as the interval between estimated onset of RBD symptoms and last hospital visit or death. Follow-up duration was defined as the interval between iRBD diagnosis and last hospital visit or death. Results: In a follow-up period of up to 18 years, no patient who experienced trauma within 12 months preceding their iRBD diagnosis received a diagnosis of a neurodegenerative disorder (n = 35), whereas 38% of patients without trauma within the 12 months of symptom onset developed a neurodegenerative illness. These patients were also significantly more likely to have a family history of α-synucleinopathy or tauopathy. Conclusions: The development of RBD within 12 months of experiencing a traumatic life event, indistinguishable clinically from iRBD, did not lead to phenoconversion to a neurodegenerative disorder even after 18 years (mean follow up 6 years). We suggest that a sub-type of RBD be established and classified as secondary RBD due to trauma. Additionally, we advocate that a thorough psychological and trauma history be undertaken in all patients presenting with dream enactment behaviors (DEB).

Objective and Subjective Prevalence of Obstructive Sleep Apnoea/Hypopnoea Syndrome in UK Adults with Down Syndrome: A Strong Marker for Diurnal Behavioural Disturbances.

Prior to this study, the prevalence of obstructive sleep apnoea/hypopnoea syndrome (OSAHS) in adults with Down syndrome was unknown. We hypothesized that unrecognised OSAHS could have an additional deleterious impact on mood and behavioural disturbances in this group of people. AIMS: To assess the prevalence of OSAHS in adults with Down syndrome in the United Kingdom, subjectively and objectively, and ascertain its association with diurnal behavioural disturbances. METHOD: Cross-sectional questionnaire study with home sleep apnoea testing (HSAT) during 2011-2015 across the four nations of the United Kingdom. Participants were adults aged ≥16 years with Down syndrome. Main outcome measures were: self- or caregiver-completed questionnaire data, including the Pictorial Epworth Sleepiness Scale (pESS), selected domains of the Developmental Behavioural Checklist for Adults (DBC-A), anthropometric measures, and symptoms of OSAHS. Objective prevalence was undertaken in a sample of responders using HSAT. RESULTS: Responses were received from 1321/5270 participants (25%), with 1105 valid responses (21%). Eighty-one participants (7%) reported a prior diagnosis of OSA, of whom 38 were receiving therapy. Using validated algorithms, a diagnosis of OSAHS was probable in 366 participants (35%), who were younger, with higher BMI and higher mean total pESS (p < 0.0001). A total of 23% of participants had a pESS > 10. OSAHS was a strong marker for behavioural disturbances on the DBC-A depression, disruption and anti-social subscales (p < 0.001). Of 149 individuals who underwent HSAT, 42% were diagnosed with OSAHS. CONCLUSIONS: Untreated OSAHS in Down syndrome is common and associated with behavioural and mood disturbances. Improving awareness of OSAHS amongst adults with Down syndrome, their families and healthcare professionals is essential.

Impact of temperature on obstructive sleep apnoea in three different climate zones of Europe: Data from the European Sleep Apnoea Database (ESADA).

Recent studies indicate that ambient temperature may modulate obstructive sleep apnoea (OSA) severity. However, study results are contradictory warranting more investigation in this field. We analysed 19,293 patients of the European Sleep Apnoea Database (ESADA) cohort with restriction to the three predominant climate zones according to the Köppen-Geiger climate classification: Cfb (warm temperature, fully humid, warm summer), Csa (warm temperature, summer dry, hot summer), and Dfb (snow, fully humid, warm summer). Average outside temperature values were obtained and several hierarchical regression analyses were performed to investigate the impact of temperature on the apnea-hypopnea index (AHI), oxygen desaturation index (ODI), time of oxygen saturation <90% (T90) and minimum oxygen saturation (MinSpO2 ) after controlling for confounders including age, body mass index, gender, and air conditioning (A/C) use. AHI and ODI increased with higher temperatures with a standardised coefficient beta (ß) of 0.28 for AHI and 0.25 for ODI, while MinSpO2 decreased with a ß of -0.13 (all results p < .001). When adjusting for climate zones, the temperature effect was only significant in Cfb (AHI: ß = 0.11) and Dfb (AHI: ß = 0.08) (Model 1: p < .001). The presence of A/C (3.9% and 69.3% in Cfab and Csa, respectively) demonstrated only a minor increase in the prediction of the variation (Cfb: AHI, R2 +0.003; and Csa: AHI, R2 +0.007; both p < .001). Our present study indicates a limited but consistent influence of environmental temperature on OSA severity and this effect is modulated by climate zones.

Detection of α-synuclein in CSF by RT-QuIC in patients with isolated rapid-eye-movement sleep behaviour disorder: a longitudinal observational study.

BACKGROUND: Isolated rapid-eye-movement (REM) sleep behaviour disorder (IRBD) can be part of the prodromal stage of the α-synucleinopathies Parkinson's disease and dementia with Lewy bodies. Real-time quaking-induced conversion (RT-QuIC) analysis of CSF has high sensitivity and specificity for the detection of misfolded α-synuclein in patients with Parkinson's disease and dementia with Lewy bodies. We investigated whether RT-QuIC could detect α-synuclein in the CSF of patients with IRBD and be used as a biomarker of prodromal α-synucleinopathy. METHODS: In this longitudinal observational study, CSF samples were obtained by lumbar puncture from patients with video polysomnography-confirmed IRBD recruited at a specialised sleep disorders centre in Barcelona, Spain, and from controls free of neurological disease. CSF samples were stored until analysed using RT-QuIC. After lumbar puncture, participants were assessed clinically for neurological status every 3-12 months. Rates of neurological disease-free survival were estimated using the Kaplan-Meier method. Disease-free survival rates were assessed from the date of lumbar puncture to the date of diagnosis of any neurodegenerative disease, or to the last follow-up visit for censored observations. FINDINGS: 52 patients with IRBD and 40 healthy controls matched for age (p=0·20), sex (p=0·15), and duration of follow-up (p=0·27) underwent lumbar puncture between March 23, 2008, and July 16, 2017. The CSF α-synuclein RT-QuIC assay was positive in 47 (90%) patients with IRBD and in four (10%) controls, resulting in a sensitivity of 90·4% (95% CI 79·4-95·8) and a specificity of 90·0% (95% CI 76·9-96·0). Mean follow-up from lumbar puncture until the end of the study (July 31, 2020) was 7·1 years (SD 2·8) in patients with IRBD and 7·7 years (2·9) in controls. During follow-up, 32 (62%) patients were diagnosed with Parkinson's disease or dementia with Lewy bodies a mean 3·4 years (SD 2·6) after lumbar puncture, of whom 31 (97%) were α-synuclein positive at baseline. Kaplan-Meier analysis showed that patients with IRBD who were α-synuclein negative had lower risk for developing Parkinson's disease or dementia with Lewy bodies at 2, 4, 6, 8, and 10 years of follow-up than patients with IRBD who were α-synuclein positive (log-rank test p=0·028; hazard ratio 0·143, 95% CI 0·019-1·063). During follow-up, none of the controls developed an α-synucleinopathy. Kaplan-Meier analysis showed that participants who were α-synuclein negative (ie, five patients with IRBD plus 36 controls) had lower risk of developing Parkinson's disease or dementia with Lewy bodies at 2, 4, 6, 8 and 10 years after lumbar puncture than participants who were α-synuclein positive (ie, 47 patients with IRBD plus four controls; log-rank test p<0·0001; hazard ratio 0·024, 95% CI 0·003-0·177). INTERPRETATION: In patients with IRBD, RT-QuIC detects misfolded α-synuclein in the CSF with both sensitivity and specificity of 90%, and α-synuclein positivity was associated with increased risk of subsequent diagnosis of Parkinson's disease or dementia with Lewy bodies. Detection of α-synuclein in the CSF represents a potential prodromal marker of Parkinson's disease and dementia with Lewy bodies. If these findings are replicated in additional cohorts, detection of CSF α-synuclein by RT-QuIC could be used to enrich IRBD cohorts in neuroprotective trials, particularly when assessing interventions that target α-synuclein. FUNDING: Department of Health and Social Care Policy Research Programme, the Scottish Government, and the Weston Brain Institute.