Sleep-Disordered Breathing is frequently associated with idiopathic normal pressure hydrocephalus but not other types of hydrocephalus

Study Objectives Previous studies have shown sleep-disordered breathing (SDB) to be highly prevalent in patients with idiopathic normal pressure hydrocephalus (iNPH). The current study aimed to estimate and compare the prevalence of SDB in patients with different types of hydrocephalus and test if SDB was associated with changed CO2. Methods We investigated the prevalence of SDB in a prospective cohort of 48 hydrocephalus patients with nocturnal polysomnography (PSG). Twenty-three of the patients also had simultaneous CO2 measurements. Results The prevalence of SDB was high in patients with iNPH, with moderate-to-severe SDB in 21/22 (96%) of the patients and an apnea-hypopnea index (AHI) of 43.5 (95% CI 33.8–52.2). Patients with pediatric-onset hydrocephalus had moderate-to-severe SDB in 7/16 (44%), with an AHI of 16.1 (95% CI 8.16-23.8). Except for one patient, all patients with adult-onset obstructive hydrocephalus (9/10) had normal respiration or mild SDB with an AHI of 8.4 (95% CI 5.5-10.5). None of the 23 patients measured with CO2 had elevated CO2 associated with SDB and had normal CO2 during sleep, with 40.8 ± 5.5 mmHg, 42.7 ± 4.1 mmHg, 34.5-45.8 mmHg for patients with iNPH, pediatric-onset, and adult-onset, respectively. Conclusion We found a high prevalence of SDB in patients with iNPH, confirming previous findings. We extended this with the finding that the prevalence of SDB in patients with other types of hydrocephalus is not significantly different from that in the general population. Additionally, we did not find elevations of CO2 associated with SDB or CO2 retention during sleep.

Association between Lower Body Temperature and Increased Tau Pathology in Cognitively Normal Older Adults

Background Rodent model and in vitro studies suggest body temperature (Tb), and consequently brain temperature, has the potential to bidirectionally interact with tau pathology in Alzheimer’s Disease (AD). Tau phosphorylation is substantially increased by small (< 1°C) reductions in temperature within the human physiological range, and lower brain thermoregulatory areas may be among those first affected by AD pathology. Here, we evaluated whether Tb (as a proxy for brain temperature) is cross-sectionally associated with clinically utilized markers of tau pathology in cognitively normal older adults. Methods Tb was measured with ingestible telemetry continuously over 48 hours, including two nights of nocturnal polysomnography to delineate whether tau pathology is differentially associated with Tb during waking vs sleep. Tau pathology was assessed with plasma and cerebrospinal fluid (CSF) tau phosphorylated at threonine 181 (P-tau), sampled the day following Tb measurement, as well as neurofibrillary tangle (NFT) burden in early Braak stage areas, imaged with MR-PET using the [18F]MK-6240 radiotracer on average one month later. Results Plasma and CSF P-tau levels were highly correlated with one another, and with tau tangle radiotracer uptake. Lower Tb, as quantified by lower mean Tb and a greater proportion of time Tb was under 37.0°C, was associated with increased NFT burden and increased plasma and CSF P-tau levels. NFT burden was associated with lower Tb during waking, but not during sleeping intervals. Conclusions Preliminary results suggest that lower Tb in older adults may be associated with increased soluble and aggregated tau pathology.

Clinical and Polysomnographic Characteristics of Patients with Extreme Obstructive Sleep Apnea, AHI > 100: A Case-Control Study

Background: Severe obstructive sleep apnea (OSA), defined by apnea-hypopnea index (AHI) as more than 30 events per hour, was previously related to more comorbidity. However, limited studies separated the patients with AHI > 100 from those with a less severe manifestation of the disease. Objectives: The current study aimed at describing the characteristics of this subgroup and comparing them with less severe conditions. Methods: A retrospective analysis was conducted on 114 patients with OSA. Nocturnal polysomnography was used to diagnose severe OSA. Patients were categorized into two groups: (1) 60 < AHI < 100 (very severe OSA), (2) AHI ≥ 100 (extreme OSA). Demographic, medical history, and polysomnographic variables were evaluated and compared between the two groups. Results: Extreme OSA was diagnosed in 19 patients, the mean body mass index (BMI) was significantly higher in this group (39.26 ± 5.93 vs. 35.68 ± 6.45 kg/m2, P = 0.025). They also had lower minimal O2 saturation (65.68 ± 10.16 vs. 74.10 ± 8.74, P = 0.003) and more time with < 90% O2 saturation (T < 90%) (81.78 ± 22.57 vs. 58.87 ± 33.14, P = 0.01). OHS prevalence was significantly higher in the group with extreme OSA (P = 0.04). The most frequent comorbidity was hypertension, with an incidence of 60.5%, for the extreme group, although there was no significant difference between the two groups in terms of clinical associations. Conclusions: The current study results suggested that greater BMI and lower minimal O2 saturation, as well as increased T < 90%, were associated with extreme OSA, although no differences were observed in the associated diseases between the compared groups.

Association of Central Hypersomnia and Fatigue in Patients With Multiple Sclerosis: A Polysomnographic Study

Objective:To evaluate sleepiness and central hypersomnia in multiple sclerosis (MS) associated fatigue, we performed long term polysomnography in MS patients and healthy controls.Methods:Patients with MS and healthy controls completed questionnaires on sleep, fatigue, sleepiness, and depression. They underwent nocturnal polysomnography, multiple sleep latency tests and bed rest 24-hour polysomnography. Patients were divided into 3 groups (fatigue and sleepiness; fatigue and no sleepiness; neither fatigue nor sleepiness).Results:Among 44 patients with MS, 19 (43.2%) had fatigue and sleepiness, 15 (34%) had only fatigue, and 10 (22.7%) had neither fatigue nor sleepiness. Compared to 24 controls, patients with fatigue and sleepiness had higher REM sleep percentages (median [interquartile range]: 20.5% [19.6-24.7] vs. 18.1% [12.6-20.6]), lower arousal indexes (12.7 [7.5-17.0] vs. 22.4 [14.3-34.4]) and shorter daytime mean sleep latencies (8.6 [6.3-14.3] vs. 16.6 [12.6-19.5] min). Restless leg syndrome, periodic leg movements and sleep apnea had similar frequencies between groups. Central hypersomnia was found in 10 (53%) patients with fatigue and sleepiness (narcolepsy type 2, N=2), in 2 (13%) patients with fatigue only, and in 3 (30%) patients with neither fatigue nor sleepiness. Patients with central hypersomnia were younger and sleepier than those without hypersomnia, but had similar levels of fatigue, disability, depression, cognitive performance and frequencies of the human leukocyte antigen DQB1*0602 genotype. The severity of fatigue increased with higher depression scores, higher sleepiness severity, and lower sleep efficacy.Conclusion:Central hypersomnias are frequent in MS when fatigue and sleepiness are present. Screening them through polysomnography studies is recommended.

ASSOCIATION BETWEEN QUALITY OF SLEEPAND OTHER PARAMETERS IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE.

Background: Night time reux has been shown to be associated with fragmented sleep. However, few studies have assessed the quality of sleep on gastroesophageal reux and the impact of gastroesophageal reux on reported quality of sleep and quality of sleep on gastroesophageal reux. The aims of this study were to evaluate the quality of sleep and other parameters in patients with gastroesophageal reux disease.50 Subjects with typical GERD symptoms ≥3 times a week and All subjects were administered 3 questionnaires: PSQI , ESS, GERD-HRQL . All the subjects underwent nocturnal polysomnography and completed a all 3 questionnaire before NPSG. Results: Overall ,the mean percentage of N1 was 9.10±9.74 ,N2 was 83.97±13.81 , N3 was 3.44±4.16 , N4 was 0.60±2.04 , REM was 2.14±3.79 , PSQI was 12.48±1.23 , ESS was 11.80±0.76 , TST (hr) was 5.19±0.74 , SPT(hr) was 6.58±0.77 , sleep efciency(%) was 52.50±27.16 , Latency (mint) was 22.79±30.85 , REM Latency (mints) was 96.99±151.86 ,and Microarousal index was 36.05±25.93 . To assess the potential impact of sleep quality via nocturnal polysomnography on severity of gastroesophageal reux , we performed correlations between the GERD questionnaire and nocturnal polysomnography reports . We observed that PSQI(r= -0.285, p<0.045) , ESS(r=0.206, p=0.05) , N1(r=0.202 , p>0.160) , N2(r=- 0.045 ,p>0.758) , N3(r=-0.079, p>0.583) , N4(r-0.209 ,p>0.145),REM(r=0.045 ,p>0.756) , TST(r=0.036 ,p>0.803), SPT(r=0.015,p>0.917) , Sleep Efciency (r=-0.113,p>0.435) , Sleep Latency (r=-0.045 ,p>0.756), REM Latency (r=0.165, p >0.253), Microarousal index (r=0.058 , p>0.683). Conclusions: Gastroesophageal reux disease and sleep disorders are extremely prevalent conditions, and it seems intuitive that there must be some overlap between the two. Sleep disorders may in fact be one of the most prevalent of the extraesophageal complications of GERD and often goes unrecognized.

Association of CSF orexin-A levels and nocturnal sleep stability in patients with hypersomnolence

ObjectiveTo evaluate the associations between CSF orexin-A (ORX) levels and markers of nocturnal sleep stability, assessed by polysomnography.MethodsNocturnal polysomnography data and ORX levels of 300 drug-free participants (55% men, 29.9±15.5 years, ORX level 155.1±153.7 pg/mL) with hypersomnolence were collected. Several markers of nocturnal sleep stability were analyzed: sleep and wake bouts and sleep/wake transitions. Groups were categorized according to ORX levels, in 2 categories (deficient ≤110; >110), in tertiles (≤26, 26–254, >254), and compared using logistic regression models. Results were adjusted for age, sex, and body mass index.ResultsWe found higher number of wake bouts (43 vs 25, p < 0.0001), sleep bouts (43 vs 25.5, p < 0.0001), and index of sleep bouts/hour of sleep time, but lower index of wake bouts/hour of wake time (41.4 vs 50.6, p < 0.0001), in patients with ORX deficiency. The percentage of wake bouts <30 seconds was lower (51.3% vs 60.8%, p < 0.001) and of wake bouts ≥1 minutes 30 seconds higher (7.7% vs 6.7%, p = 0.02) when ORX deficient. The percentage of sleep bouts ≤14 minutes was higher (2–5 minutes: 23.7% vs 16.1%, p < 0.0001), and of long sleep bouts lower (>32 minutes 30 seconds: 7.3% vs 18.3%, p < 0.0001), when ORX deficient. These findings were confirmed when groups were categorized according to ORX tertiles, with a dose–response effect of ORX levels in post hoc comparisons, and in adjusted models.InterpretationThis study shows an association between ORX levels and nocturnal sleep stabilization in patients with hypersomnolence. Sleep and wake bouts are reliable markers of nighttime sleep stability that correlate with CSF ORX levels in a dose-dependent manner.

Sleep dysregulation, memory impairment, and CSF biomarkers during different levels of neurocognitive functioning in Alzheimer’s disease course

Background Alzheimer's disease (AD) is frequently accompanied by sleep impairment, which can induce AD-related neurodegeneration. We herein investigated the sleep architecture, cognition, and cerebrospinal fluid (CSF) biomarkers (tau proteins and β-amyloid42) during AD progression from subjective cognitive impairment (SCI) to mild cognitive impairment (MCI) and eventually to AD dementia, and compared the results with cognitively normal (CN) subjects. Methods We included patients affected by SCI, MCI, mild AD, and moderate-to-severe AD in our study along with CN subjects as controls. All the subjects underwent nocturnal polysomnography to investigate sleep, neuropsychological testing to evaluate cognition, and lumbar puncture for CSF AD biomarkers assessment. Results Sleep (both rapid eye movement (REM) and non-REM sleep) and memory function are both progressively impaired during the course of AD from SCI to mild and subsequently to moderate AD. Further, sleep dysregulation appears earlier than cognitive deterioration, with a reduction of CSF β-amyloid42 level. Conclusion Sleep, memory, and CSF AD biomarkers are closely interrelated in AD progression from the earliest asymptomatic and preclinical stages of the disease related in AD since the earliest and preclinical stages of the disease.