Validation and performance of the sleep inertia questionnaire in central disorders of hypersomnolence.

BACKGROUND: Optimal measurement tools for problematic sleep inertia, common in some central disorders of hypersomnolence (CDH), have not yet been determined. We evaluated the performance of the Sleep Inertia Questionnaire (SIQ) in CDH, and how well it distinguished hypersomnolent groups from controls, and IH (idiopathic hypersomnia) from narcolepsy type 1 (NT1). METHODS: This prospective, bi-centric study included 63 control, 84 IH, 16 NT1, 18 narcolepsy type 2 (NT2), and 88 subjective excessive daytime sleepiness (sEDS) participants, using ICSD-3 criteria. 126 (47.2 %) participants were on any medication at the time of SIQ completion. We assessed construct validity of SIQ scores, and sleep inertia duration (SID), and compared them across diagnoses, controlling for age and center. We derived cutpoints to distinguish hypersomnolent patients from controls and IH from NT1. Sensitivity analyses for depression, chronotype, and medication were performed. RESULTS: The SIQ sum and composite score were significantly lower in controls than in other groups (p < 0.0001), demonstrating outstanding ability to distinguish patients from controls (AUCs 0.92), without differences among hypersomnolent groups. SID (AUC 0.76) was significantly shorter in controls than in all hypersomnolent groups except NT1, and was shorter in NT1 than in IH or sEDS. Optimal SIQ sum cutpoint was 42 (J = 0.71) for patients versus controls. Optimal SID cutpoint in distinguishing IH from NT1 was 25 min (J = 0.39). CONCLUSION: The SIQ has excellent ability to distinguish hypersomnolent patients from healthy controls, after controlling for depression, eveningness, and medication. SID is best at distinguishing IH from NT1.

Prevalence and Course of Idiopathic Hypersomnia in the Wisconsin Sleep Cohort Study.

BACKGROUND AND OBJECTIVES: Idiopathic hypersomnia (IH) is a CNS disorder of hypersomnolence of unknown etiology. Due to the requirement for objective sleep testing to diagnose the disorder, there are currently no population-based estimates of the prevalence of IH nor data regarding the longitudinal course of IH in naturalistic settings. METHODS: Subjective and objective data from the Wisconsin Sleep Cohort study were used to identify cases with probable IH from participants with polysomnography and multiple sleep latency test data. Demographic, polysomnographic, and symptom-level data were compared between those with and without IH. Longitudinal trajectories of daytime sleepiness among those with IH were assessed to evaluate symptom persistence or remission over time. RESULTS: From 792 cohort study participants with available polysomnography and multiple sleep latency test data, 12 cases with probable IH were identified resulting in an estimated prevalence of IH of 1.5% (95% CI 0.7-2.5, p < 0.0001). Consistent with inclusion/exclusion criteria, cases with IH had more severe sleepiness and sleep propensity, despite similar or longer sleep times. Longitudinal data (spanning 12.1 ± 4.3 years) demonstrated a chronic course of sleepiness for most of the cases with IH, though pathologic somnolence remitted in roughly 40% of cases. DISCUSSION: These results demonstrate IH is more common in the working population than generally assumed with a prevalence on par with other common neurologic and psychiatric conditions. Further efforts to identify and diagnose those impaired by unexplained daytime somnolence may help clarify the causes of IH and the mechanisms underlying symptomatic remission.

Associations of sleep duration and daytime sleepiness with plasma amyloid beta and cognitive performance in cognitively unimpaired, middle-aged and older African Americans.

STUDY OBJECTIVES: Given the established racial disparities in both sleep health and dementia risk for African American populations, we assess cross-sectional and longitudinal associations of self-report sleep duration (SRSD) and daytime sleepiness with plasma amyloid beta (Aß) and cognition in an African American (AA) cohort. METHODS: In a cognitively unimpaired sample drawn from the African Americans Fighting Alzheimer's in Midlife (AA-FAiM) study, data on SRSD, Epworth Sleepiness Scale, demographics, and cognitive performance were analyzed. Aß40, Aß42, and the Aß42/40 ratio were quantified from plasma samples. Cross-sectional analyses explored associations between baseline predictors and outcome measures. Linear mixed-effect regression models estimated associations of SRSD and daytime sleepiness with plasma Aß and cognitive performance levels and change over time. RESULTS: One hundred and forty-seven participants comprised the cross-sectional sample. Baseline age was 63.2 ±â€…8.51 years. 69.6% self-identified as female. SRSD was 6.4 ±â€…1.1 hours and 22.4% reported excessive daytime sleepiness. The longitudinal dataset included 57 participants. In fully adjusted models, neither SRSD nor daytime sleepiness is associated with cross-sectional or longitudinal Aß. Associations with level and trajectory of cognitive test performance varied by measure of sleep health. CONCLUSIONS: SRSD was below National Sleep Foundation recommendations and daytime sleepiness was prevalent in this cohort. In the absence of observed associations with plasma Aß, poorer self-reported sleep health broadly predicted poorer cognitive function but not accelerated decline. Future research is necessary to understand and address modifiable sleep mechanisms as they relate to cognitive aging in AA at disproportionate risk for dementia. CLINICAL TRIAL INFORMATION: Not applicable.

Don't hold PAT: watch for and correct oximetry artifact.

This study evaluated the accuracy of the algorithmic oxygen saturation (SpO2) nadir detection of WatchPAT (Zoll/Itamar, Caesarea, Israel) compared with visual inspection in a real-world setting. SpO2 tracings for 209 consecutive adult WatchPAT recordings were reviewed for SpO2 artifact, with erroneous SpO2 data removed manually. Error rates for SpO2 minima were determined across all studies, and relationships between correct and erroneous studies examined. The overall error rate for SpO2 nadir was 22.5%. Erroneous studies had overall less time spent at SpO2 ≤ 88%, higher true SpO2 nadir, lower mean body mass index, and greater artifact time; however, these variables were not associated with the magnitude of discrepancy between manual and algorithmically derived SpO2 minima. These data demonstrate that SpO2 nadir determined by WatchPAT algorithms should not be considered universally accurate. Like other home sleep apnea tests, visual inspection and manual correction of the study data are often required to derive accurate clinical results. CITATION: Plante DT, Rumble ME. Don't hold PAT: watch for and correct oximetry artifact. J Clin Sleep Med. 2023;19(12):2113-2116.

Cardiorespiratory Fitness Attenuates the Deleterious Effects of Sleep Apnea on Cerebral Structure and Perfusion in the Wisconsin Sleep Cohort Study.

BACKGROUND: Emerging evidence suggests that age-related changes in cerebral health may be sensitive to vascular risk modifiers, such as physical activity and sleep. OBJECTIVE: We examine whether cardiorespiratory fitness modifies the association of obstructive sleep apnea (OSA) severity with MRI-assessed measures of cerebral structure and perfusion. METHODS: Using data from a cross-sectional sample of participants (n = 129, 51% female, age range 49.6-85.3 years) in the Wisconsin Sleep Cohort study, we estimated linear models of MRI-assessed total and regional gray matter (GM) and white matter (WM) volumes, WM hyperintensity (WMH:ICV ratio), total lesion volume, and arterial spin labeling (ASL) cerebral blood flow (CBF), using an estimated measure of cardiorespiratory fitness (CRF) and OSA severity as predictors. Participants' sleep was assessed using overnight in-laboratory polysomnography, and OSA severity was measured using the apnea-hypopnea index (AHI), or the mean number of recorded apnea and hypopnea events per hour of sleep. The mean±SD time difference between PSG data collection and MRI data collection was 1.7±1.5 years (range: [0, 4.9 years]). RESULTS: OSA severity was associated with reduced total GM volume (ß=-0.064; SE = 0.023; p = 0.007), greater total WM lesion volume (interaction p = 0.023), and greater WMHs (interaction p = 0.017) in less-fit subjects. Perfusion models revealed significant differences in the association of AHI and regional CBF between fitness groups (interaction ps < 0.05). CONCLUSION: This work provides new evidence for the protective role of cardiorespiratory fitness against the deleterious effects of OSA on brain aging in late-middle age to older adults.

Associations between self-reported sleep patterns and health, cognition and amyloid measures: results from the Wisconsin Registry for Alzheimer's Prevention.

Previous studies suggest associations between self-reported sleep problems and poorer health, cognition, Alzheimer's disease pathology and dementia-related outcomes. It is important to develop a deeper understanding of the relationship between these complications and sleep disturbance, a modifiable risk factor, in late midlife, a time when Alzheimer's disease pathology may be accruing. The objectives of this study included application of unsupervised machine learning procedures to identify distinct subgroups of persons with problematic sleep and the association of these subgroups with concurrent measures of mental and physical health, cognition and PET-identified amyloid. Dementia-free participants from the Wisconsin Registry for Alzheimer's Prevention (n = 619) completed sleep questionnaires including the Insomnia Severity Index, Epworth Sleepiness Scale and Medical Outcomes Study Sleep Scale. K-means clustering analysis identified discrete sleep problem groups who were then compared across concurrent health outcomes (e.g. depression, self-rated health and insulin resistance), cognitive composite indices including episodic memory and executive function and, in a subset, Pittsburgh Compound B PET imaging to assess amyloid burden. Significant omnibus tests (P < 0.05) were followed with pairwise comparisons. Mean (SD) sample baseline sleep assessment age was 62.6 (6.7). Cluster analysis identified three groups: healthy sleepers [n = 262 (42.3%)], intermediate sleepers [n = 229 (37.0%)] and poor sleepers [n = 128 (20.7%)]. All omnibus tests comparing demographics and health measures across sleep groups were significant except for age, sex and apolipoprotein E e4 carriers; the poor sleepers group was worse than one or both of the other groups on all other measures, including measures of depression, self-reported health and memory complaints. The poor sleepers group had higher average body mass index, waist-hip ratio and homeostatic model assessment of insulin resistance. After adjusting for covariates, the poor sleepers group also performed worse on all concurrent cognitive composites except working memory. There were no differences between sleep groups on PET-based measures of amyloid. Sensitivity analyses indicated that while different clustering approaches resulted in different group assignments for some (predominantly the intermediate group), between-group patterns in outcomes were consistent. In conclusion, distinct sleep characteristics groups were identified with a sizable minority (20.7%) exhibiting poor sleep characteristics, and this group also exhibited the poorest concurrent mental and physical health and cognition, indicating substantial multi-morbidity; sleep group was not associated with amyloid PET estimates. Precision-based management of sleep and related factors may provide an opportunity for early intervention that could serve to delay or prevent clinical impairment.

Physical Activity and Physical and Mental Health in Middle-Aged Adults with Down Syndrome.

Background: Adults with Down syndrome have an increased risk of aging-related physical and mental health conditions and experience them at an earlier age than the general population. There is a need to investigate modifiable lifestyle factors that may reduce risk for these conditions. Method: The present study investigated the associations between physical activity (i.e., sedentary behavior and moderate-to-vigorous activity) assessed via accelerometer across 7 days and caregiver-reported physical and mental health of 66 non-demented middle-aged adults with Down Syndrome aged 25-55 years (52% female). Results: Regression analyses indicated that more time spent in moderate intensity physical activity was associated with less risk of sleep apnea (b = -.031 p = .004) and endocrine/metabolic conditions (b = -.046 p = .009), and lower total number of physical health conditions (b = -.110 p =.016) and anxiety disorders (b = -.021 p =.049) after controlling for relevant sociodemographics. After also adjusting for BMI, the association between time spent in moderate intensity physical activity and sleep apnea (b=-.035, p = .002), endocrine/metabolic conditions (b=-.033, p = .045) and total physical health (b=-.091, p =.026) remained significant Unexpectedly, time spent in sedentary behavior was negatively associated with musculoskeletal conditions (b=-.017, p = .044). Conclusion: Findings indicate important associations between physical activity in everyday life and the physical and mental health of adults with Down syndrome. Social policies and interventions aimed at reducing time spent sitting around (i.e., sedentary behavior) and encouraging moderate-to-vigorous activity may be a low-burden and low-cost mechanism for fostering healthy physical and mental aging in the Down syndrome population.

Mastery learning program to teach sleep study scoring.

STUDY OBJECTIVES: Scoring a polysomnogram is an essential skill for sleep medicine trainees to meet Accreditation Council for Graduate Medical Education Sleep Medicine Milestones. Appraisal is based on faculty evaluation rather than objective competency assessment. We developed a computer-based polysomnogram scoring curriculum, utilizing the mastery learning method, then compared achievement of competency using the new curriculum against standard institutional training. METHODS: The scoring program consisted of a pretest assessment, sequential acquisition of knowledge utilizing online modules, a posttest, and competency assessment. Fellows needed to demonstrate mastery of each module before moving ahead. Competency was demonstrating ≥ 90% on interscorer reliability assessment on 5 studies (out of up to 10 attempts). Participating fellows were assigned to Mastery Learning Participants (MLP) or Traditional Learning Participants (TLP) groups and completed the program within the first 1-3 months of training. RESULTS: Of 87 fellows enrolled in the program, 75 participants completed the program (40 MLP and 35 TLP). Among completers, there was no difference in the proportion that achieved competency (MLP 90.0% vs TLP 97.1%; P = .36) or studies needed to achieve competency (MLP 7.25 ± 1.3 vs TLP 7.41 ± 1.3; P = .60). Pretest scores were not significantly different between groups (MLP 61.2% ± 15.9 vs TLP 57.6% ± 16.6; P = .35), but MLP posttest scores were higher than TLP (MLP 80.9% ± 8.8 vs TLP 76.4% ± 9.8; P = .04). CONCLUSIONS: We demonstrated similar outcomes utilizing a novel, computer-based modular interactive course compared to traditional methods of teaching polysomnogram scoring. We used a mastery learning paradigm and set specific objective competency levels for this skill. CITATION: Epstein LJ, Plante DT, Rosen IM. Mastery learning program to teach sleep study scoring. J Clin Sleep Med. 2022;18(12):2745-2750.

Sleep and White Matter in Adults with Down Syndrome.

Adults with Down syndrome are at a high risk for disordered sleep. These sleep problems could have marked effects on aging and Alzheimer's disease, potentially altering white matter integrity. This study examined the associations between disordered sleep assessed via an actigraph accelerometer worn on 7 consecutive nights, presence of diagnosis of obstructive sleep apnea, and diffusion tensor imaging indices of white matter integrity in 29 non-demented adults with Down Syndrome (48% female, aged 33-54 years). Average total sleep time was associated with lower mean diffusivity in the left superior longitudinal fasciculus (r = -0.398, p = 0.040). Average sleep efficiency, length of awakenings, and movement index were related to fractional anisotropy in the right inferior longitudinal fasciculus (r = -0.614 to 0.387, p ≤ 0.050). Diagnosis of obstructive sleep apnea was associated with fractional anisotropy in the right inferior longitudinal fasciculus (r = -0.373, p = 0.050). Findings suggest that more disrupted sleep is associated with lower white matter integrity in the major association tracts in middle-aged adults with Down syndrome. Longitudinal work is needed to confirm the directionally of associations. Sleep interventions could be an important component for promoting optimal brain aging in the Down syndrome population.

The Evolving Nexus of Sleep and Depression.

Sleep disturbances and depression are closely linked and share a bidirectional relationship. These interconnections can inform the pathophysiology underlying each condition. Insomnia is an established and modifiable risk factor for depression, the treatment of which offers the critical opportunity to prevent major depressive episodes, a paradigm-shifting model for psychiatry. Identification of occult sleep disorders may also improve outcomes in treatment-resistant depression. Sleep alterations and manipulations may additionally clarify the mechanisms that underlie rapid-acting antidepressant therapies. Both sleep disturbance and depression are heterogeneous processes, and evolving standards in psychiatric research that consider the transdiagnostic components of each are more likely to lead to translational progress at their nexus. Emerging tools to objectively quantify sleep and its disturbances in the home environment offer great potential to advance clinical care and research, but nascent technologies require further advances and validation prior to widespread application at the interface of sleep and depression.

Cerebrospinal fluid orexin in Alzheimer's disease: a systematic review and meta-analysis.

OBJECTIVE/BACKGROUND: A growing body of evidence suggests that sleep and Alzheimer's disease (AD) have a bi-directional relationship. Emerging research also suggests that orexin, a key neurotransmitter involved in sleep-wake regulation, may be altered in persons with AD, however results have not been consistent across prior studies. This investigation was conducted to both evaluate the aggregate literature to minimize the risk of bias and identify potential factors associated with heterogeneity across studies. METHODS: Systematic review identified relevant investigations that compared cerebrospinal fluid orexin in persons with AD and controls. Meta-analysis (random effects model) compared effect size (Hedge's g) for orexin between AD and controls. Meta-regression was additionally performed for key variables of interest to evaluate potential causes of heterogeneity among studies. RESULTS: 17 studies were identified that met inclusion/exclusion criteria. Evidence of publication bias was not identified. Non-significant increases in orexin were observed in AD relative to controls, with moderate to large heterogeneity among studies (Hedge's g = 0.20, p = 0.136, I2 = 72.6%). Meta-regression demonstrated both year of publication (ß = 0.055, p = 0.020) and effect size for phosphorylated tau in AD versus controls (ß = 0.417, p = 0.031) were associated with differences in orexin. CONCLUSIONS: Results do not support broad differences in orexin in AD compared to controls, however, evolving diagnostic criteria may have affected findings across studies. Future research that examines orexin in AD over the longitudinal course of the disorder and explores potential links between phosphorylated tau and orexin are indicated.

Physical activity and cognitive and imaging biomarkers of Alzheimer's disease in down syndrome.

Adults with Down syndrome (DS) are at risk for Alzheimer's disease. Despite sharing trisomy 21, however, there is variability in the age of disease onset. This variability may mean that other factors, such as lifestyle, influence cognitive aging and disease timing. The present study assessed the association between everyday life physical activity using an actigraph accelerometer and cognitive functioning and early Alzheimer's disease pathology via positron emission tomography amyloid-ß and tau and diffusion tension imaging measures of white matter integrity in 61 non-demented adults with DS. Percent time in sedentary behavior and in moderate-to-vigorous activity were associated (negatively and positively, respectively) with cognitive functioning (r = -.472 to .572, p < 0.05). Neither sedentary behavior nor moderate-to-vigorous activity were associated with amyloid-ß or tau, but both were associated with white matter integrity in the superior and inferior longitudinal fasciculus (Fractional Anisotropy: r = -.397 to -.419, p < 0.05; Mean Diffusivity: r = .400, p < 0.05). Longitudinal studies are needed to determine if physical activity promotes healthy aging in DS.

PAX8/PAX8-AS1 DNA methylation levels are associated with objective sleep duration in persons with unexplained hypersomnolence using a deep phenotyping approach.

STUDY OBJECTIVES: Patients with unexplained hypersomnolence have significant impairment related to daytime sleepiness and excessive sleep duration, the biological bases of which are poorly understood. This investigation sought to examine relationships between objectively measured hypersomnolence phenotypes and epigenetic modification of candidate hypersomnolence genes to advance this line of inquiry. METHODS: Twenty-eight unmedicated clinical patients with unexplained hypersomnolence were evaluated using overnight ad libitum polysomnography, multiple sleep latency testing, infrared pupillometry, and the psychomotor vigilance task. DNA methylation levels on CpG sites annotated to 11 a priori hypersomnolence candidate genes were assessed for statistical association with hypersomnolence measures using independent regression models with adjusted local index of significance (aLIS) P-value threshold of 0.05. RESULTS: Nine CpG sites exhibited significant associations between DNA methylation levels and total sleep time measured using ad libitum polysomnography (aLIS p-value < .05). All nine differentially methylated CpG sites were annotated to the paired box 8 (PAX8) gene and its related antisense gene (PAX8-AS1). Among these nine differentially methylated positions was a cluster of five CpG sites located in the body of the PAX8 gene and promoter of PAX8-AS1. CONCLUSIONS: This study demonstrates that PAX8/PAX8-AS1 DNA methylation levels are associated with total sleep time in persons with unexplained hypersomnolence. Given prior investigations that have implicated single nucleotide polymorphisms in PAX8/PAX8-AS1 with habitual sleep duration, further research that clarifies the role of DNA methylation levels on these genes in the phenotypic expression of total sleep time is warranted.

The Hypersomnia Severity Index: reliability, construct, and criterion validity in a clinical sample of patients with sleep disorders.

STUDY OBJECTIVES: The Hypersomnia Severity Index (HSI) was designed to assess the severity and impairment of hypersomnolence and has been validated in persons with psychiatric disorders. Little is known about its psychometric properties in clinical samples of patients with sleep disorders. METHODS: One hundred fifty-eight patients (aged 44.1 ± 16.4 years, 29.1% male, 19.6% racial/ethnic minority) evaluated at the Behavioral Sleep Medicine program of the Penn State Health Sleep Research and Treatment Center completed the HSI and other patient-reported outcomes. We examined the HSI's reliability and factorial, construct, and criterion validity. RESULTS: The HSI showed satisfactory internal consistency (α = 0.79). A 2-factor structure, reflecting symptoms (HSI-S) and impairment, explained 56.2% of the variance. Convergent validity with the Epworth Sleepiness Scale was optimal (r = .65) but greater for HSI-S (r = .69) than for impairment (r = .39). Divergent validity was optimal for HSI-S against unrelated measures of sleep effort, reactivity, and incompatible behaviors (r ≤ .02). Construct validity showed higher scores in patients with central disorders of hypersomnolence and lower scores in patients with chronic insomnia disorder compared to those with other sleep disorders; however, these divergent scores were primarily driven by HSI-S rather than impairment. Criterion validity showed that an HSI-S cutoff score ≥ 8 provided the best balance in sensitivity/specificity (0.82/0.78) to identify central disorders of hypersomnolence (area under the curve, 0.85). CONCLUSIONS: The HSI shows satisfactory indices of reliability and validity in a clinical patient sample. Its construct and criterion validity are supported by its divergent association with other patient-reported outcomes and central disorders of hypersomnolence vs chronic insomnia disorder diagnoses and the adequate sensitivity/specificity of its HSI-S cutoff score to reliably identify central disorders of hypersomnolence. CITATION: Fernandez-Mendoza J, Puzino K, Amatrudo G, et al. The Hypersomnia Severity Index: reliability, construct, and criterion validity in a clinical sample with sleep disorders. J Clin Sleep Med. 2021;17(11):2249-2256.

A high-density electroencephalography study reveals abnormal sleep homeostasis in patients with rapid eye movement sleep behavior disorder.

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by disrupting motor enactments during REM sleep, but also cognitive impairments across several domains. In addition to REM sleep abnormalities, we hypothesized that RBD patients may also display EEG abnormalities during NREM sleep. We collected all-night recordings with 256-channel high-density EEG in nine RBD patients, predominantly early-onset medicated individuals, nine sex- and age- matched healthy controls, and nine additional controls with matched medications and comorbidities. Power spectra in delta to gamma frequency bands were compared during both REM and NREM sleep, between phasic and tonic REM sleep, and between the first versus last cycle of NREM sleep. Controls, but not RBD patients, displayed a decrease in beta power during phasic compared to tonic REM sleep. Compared to controls, RBD patients displayed a reduced decline in SWA from early to late NREM sleep. Overnight changes in the distribution of the amplitude of slow waves were also reduced in RBD patients. Without suppression of beta rhythms during phasic REM sleep, RBD patients might demonstrate heightened cortical arousal, favoring the emergence of behavioral episodes. A blunted difference between REM sleep sub-stages may constitute a sensitive biomarker for RBD. Moreover, reduced overnight decline in SWA suggests a reduced capacity for synaptic plasticity in RBD patients, which may favor progression towards neurodegenerative diseases.

Disease symptomatology and response to treatment in people with idiopathic hypersomnia: initial data from the Hypersomnia Foundation registry.

OBJECTIVE/BACKGROUND: Knowledge of idiopathic hypersomnia symptomatology derives from clinical case series. Web-based registries provide complementary information by allowing larger sample sizes, with greater geographic and social diversity. PATIENTS/METHODS: Data were obtained from the Hypersomnia Foundation's online registry. Common clinical features of idiopathic hypersomnia and other central disorders of hypersomnolence were queried, for the last thirty days and when symptoms were most severe. Symptoms were compared between idiopathic hypersomnia participants with and without long sleep durations and between participants with idiopathic hypersomnia and those with either form of narcolepsy. Frequency of medication use and residual symptoms on medication were evaluated. RESULTS: Five-hundred sixty-three registry respondents were included, with idiopathic hypersomnia (n = 468), narcolepsy type 2 (n = 44), and narcolepsy type 1 (n = 51). "Brain fog," poor memory, and sleep drunkenness were all present in most idiopathic hypersomnia respondents, with brain fog and sleep drunkenness more commonly endorsed by those with long sleep durations. Eighty-two percent of participants with idiopathic hypersomnia were currently treated with medication, most commonly traditional psychostimulants such as amphetamine salts. Among treated patients, symptoms improved while on medication, but substantial residual hypersomnia symptoms remained. Participants with narcolepsy type 1 were more likely than those with idiopathic hypersomnia to endorse intentional and unintentional daytime naps and automatic behaviors. CONCLUSIONS: Symptoms of idiopathic hypersomnia extend well beyond excessive daytime sleepiness, and these symptoms frequently persist despite treatment. These findings highlight the importance of online registries in identifying gaps in the use and effectiveness of current treatments.

Association of sleep with cognition and beta amyloid accumulation in adults with Down syndrome.

Adults with Down syndrome have an increased risk for both disordered sleep and Alzheimer's disease (AD). In the general population, disrupted sleep has been linked to beta amyloid accumulation, an early pathophysiologic feature of AD. In this study, the association among sleep, beta amyloid, and measures of AD-related cognitive decline was examined in 47 non-demented adults with Down syndrome (aged 26-56 years). Sleep was measured using actigraphy over 7 nights. Pittsburgh Compound B positron emission tomography was used to assess global and striatal beta amyloid burden. Participants had the following clinical AD status: 7 (15%) mild cognitive impairment and 40 (85%) cognitively unaffected. Average length of night-time awakenings was significantly positively associated with striatal beta amyloid and decreased cognitive performance in executive functioning and motor planning and coordination. Findings suggest that disrupted sleep is associated with beta amyloid accumulation and cognitive features of preclinical AD in Down syndrome. Early identification and treatment of sleep problems could be a lifestyle intervention that may delay beta amyloid accumulation and cognitive decline in this AD vulnerable group.

Multimodal assessment increases objective identification of hypersomnolence in patients referred for multiple sleep latency testing.

STUDY OBJECTIVES: The multiple sleep latency test (MSLT) has limitations when evaluating disorders of hypersomnolence with unknown etiology. Alternative measures of hypersomnolence may objectively identify pathology in patients with complaints of daytime sleepiness that may not be captured by the MSLT alone. This study evaluated the impact of a multimodal hypersomnolence assessment relative to MSLT in patients with unexplained hypersomnolence. METHODS: Seventy-five patients with unexplained hypersomnolence were included in the analyzed sample. Polysomnography was performed without prescribed wake time, and the psychomotor vigilance task and pupillographic sleepiness test were completed between MSLT nap opportunities. Presence or absence of hypersomnolence for each assessment was defined using a priori cutpoints. Proportions of patients identified as hypersomnolent using the multimodal assessment relative to MSLT alone were evaluated, as well as the sensitivity and specificity of ancillary hypersomnolence measures relative to MSLT as a gold standard. RESULTS: The multimodal assessment more than doubled the proportion of patients identified as having objective deficits relative to MSLT ≤ 8 minutes alone. The combination of excessive sleep duration, lapses on the psychomotor vigilance task, and impairments on the pupillographic sleepiness test also had perfect sensitivity in identifying all patients identified as sleepy by the MSLT across 3 different MSLT cutpoints (5, 8, and 10 minutes). CONCLUSIONS: These data demonstrate the insufficiency of the MSLT as a singular tool to identify objective pathology in persons with unexplained hypersomnolence. Further efforts to refine and standardize multimodal assessments will likely improve diagnostic acumen and research into the causes of these disorders.