Impairment in Functioning and Quality of Life in Patients with Idiopathic Hypersomnia: The Real World Idiopathic Hypersomnia Outcomes Study (ARISE).

Purpose: Idiopathic hypersomnia is a debilitating neurologic sleep disorder characterized by excessive daytime sleepiness, sleep inertia, and prolonged sleep. Its impact on patients' quality of life and daily functioning has not been fully elucidated. The Real World Idiopathic Hypersomnia Outcomes Study (ARISE) evaluated the daily functioning, relationships, cognition, emotional well-being, and productivity/employment of participants with idiopathic hypersomnia. Patients and Methods: ARISE was a US-based virtual cross-sectional survey comprising multiple patient-reported outcome measures (Functional Outcomes of Sleep Questionnaire, short version [FOSQ-10], Quality of Life in Neurological Disorders [Neuro-QoL] Social Roles and Stigma domains, British Columbia Cognitive Complaints Inventory [BC-CCI], Patient Health Questionnaire [PHQ-9], and the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem [WPAI:SHP]). Participants were adults 21-65 years of age with idiopathic hypersomnia. Data were analyzed for all participants and for subgroups with/without long sleep time (LST; self-reported sleep ≥11 hours in 24 hours). Results: Of 75 participants enrolled, most were female (81.3%) and the mean (SD) age was 34.1 (10.7) years. Participants' scores on the FOSQ-10 (mean [SD] score: 10.7 [2.8]) and the Neuro-QoL Social Roles (43.4 [4.2]) and Stigma (57.3 [5.9]) domains reflected impairments in daily functioning and quality of life. More than half of participants reported moderate to severe cognitive complaints (BC-CCI; 62.7%) and moderate to severe depressive symptoms (PHQ-9; 66.7%). Scores on the WPAI:SHP showed substantial impairments in absenteeism, presenteeism, overall work productivity, and overall regular daily activity (mean percent [SD]: 12.3 [23.6], 47.6 [22.7], 51.4 [24.7], and 64.0 [21.9], respectively). These considerable impairments were found in participants with and without LST. Conclusion: ARISE participants with idiopathic hypersomnia demonstrated poor quality of life and impaired functioning across multiple symptom domains.

Long-Term Treatment of Narcolepsy and Idiopathic Hypersomnia with Low-Sodium Oxybate.

Narcolepsy and idiopathic hypersomnia are chronic conditions that negatively affect alertness, mental and physical energy, functioning, and quality of life (QoL). Calcium, magnesium, potassium, and sodium oxybates (low-sodium oxybate; LXB) is an oxybate formulation with 92% less sodium than sodium oxybate (SXB; a treatment for narcolepsy) and the same active moiety. LXB is approved in the US for treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age or older with narcolepsy, and idiopathic hypersomnia in adults. In Phase 3 clinical trials, LXB exhibited a safety profile consistent with that of SXB in narcolepsy. Besides continued efficacy in treating symptoms, potential benefits of long-term LXB treatment include flexible optimization of dosing and regimen, improvement of QoL and functioning, weight loss, and (relative to SXB in narcolepsy) health benefits of reduced sodium content. Dosing of LXB is twice nightly (for narcolepsy) or once or twice nightly (for idiopathic hypersomnia) based on patient characteristics and response, and individualized titration can be leveraged over the long term as a patient's life circumstances change. Patients with narcolepsy transitioning from SXB initiate LXB at the same dose, and most patients require no further changes to achieve similar efficacy and tolerability. Improvements in functioning and QoL with LXB treatment could have cascading positive effects in multiple domains, particularly in younger patients. In clinical trials, LXB was associated with weight loss in both narcolepsy (in which obesity is a well-established comorbidity) and idiopathic hypersomnia, only occasionally leading participants to be underweight. As both narcolepsy and idiopathic hypersomnia are associated with increased risk of cardiometabolic and cardiovascular comorbidities, limiting medication-related sodium intake with LXB may have significant health benefits, although this has not yet been verified prospectively due to the prolonged follow-up required. LXB is a promising long-term treatment for narcolepsy and idiopathic hypersomnia.

Narcolepsy and idiopathic hypersomnia are disorders that make people feel very sleepy. Low-sodium oxybate (LXB) is a medicine for these disorders. Doctors think LXB works on parts of the brain that keep people awake. LXB may quiet those brain parts down at night by reducing their electrical activity, which helps people sleep better. LXB wears off by the morning, so people can wake up normally and feel more alert the next day. LXB has less sodium (which is part of salt) than a medicine called sodium oxybate. Sodium oxybate has been used for narcolepsy for more than 20 years. LXB has several benefits. First, LXB may be healthier than medicines that contain a lot of sodium, such as a high-sodium oxybate. This is because sodium can increase blood pressure and risk of heart disease. Second, LXB can be taken twice each night for narcolepsy, or once or twice each night for idiopathic hypersomnia. This depends on a person's lifestyle, how well the medicine is working, and side effects. Third, people taking LXB are more able to work and do other activities and have better quality of life. Finally, people taking LXB may lose weight. This can help overweight or obese people.

Symptom Severity and Treatment Satisfaction in Patients with Idiopathic Hypersomnia: The Real World Idiopathic Hypersomnia Outcomes Study (ARISE).

Objective: Idiopathic hypersomnia is a debilitating sleep disorder characterized by excessive daytime sleepiness, sleep inertia, and prolonged sleep duration. The patient burden of idiopathic hypersomnia is poorly understood. The Real World Idiopathic Hypersomnia Outcomes Study (ARISE) evaluated symptoms and treatment effectiveness/satisfaction in participants with idiopathic hypersomnia. Methods: ARISE was a United States-based virtual cross-sectional survey. Participants were adults 21-65 years of age with idiopathic hypersomnia recruited from social media, the Hypersomnia Foundation website, and a patient panel. Self-assessments included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), Treatment Satisfaction Questionnaire for Medication, version II (TSQM-vII), and additional treatment questions. Data were analyzed for all participants and for subgroups with/without long sleep time (LST; ≥11 hours in 24 hours). Results: Of 75 participants enrolled, most were female (81.3%). The mean (SD) age was 34.1 (10.7) years and 49% had LST. Most participants took off-label prescription medications (89.3%) and/or used other measures (93.3%) to manage their symptoms. The mean (SD) ESS score was 14.5 (3.5) and the mean IHSS score was 35.2 (7.6). Treatment satisfaction was low (mean [SD] TSQM-vII score: overall, 61.9 [21.2]; with LST, 57.9 [21.4]; without LST, 66.7 [20.3]), primarily driven by dissatisfaction with treatment effectiveness. The most common classes of prescription medications used were stimulants (61.3%), wake-promoting agents (28.0%), and antidepressants (18.7%); non-prescription measures used to manage symptoms included caffeine (73.3%), planned naps (34.7%), and individual accommodations (32.0%). Conclusion: Overall, participants with idiopathic hypersomnia, with or without LST, had substantial symptom burden despite most of the study population taking off-label medications and using nonprescription measures to manage symptoms.

Sleep and seizure risk in epilepsy: bed and wake times are more important than sleep duration.

Sleep duration, sleep deprivation and the sleep-wake cycle are thought to play an important role in the generation of epileptic activity and may also influence seizure risk. Hence, people diagnosed with epilepsy are commonly asked to maintain consistent sleep routines. However, emerging evidence paints a more nuanced picture of the relationship between seizures and sleep, with bidirectional effects between changes in sleep and seizure risk in addition to modulation by sleep stages and transitions between stages. We conducted a longitudinal study investigating sleep parameters and self-reported seizure occurrence in an ambulatory at-home setting using mobile and wearable monitoring. Sixty subjects wore a Fitbit smartwatch for at least 28 days while reporting their seizure activity in a mobile app. Multiple sleep features were investigated, including duration, oversleep and undersleep, and sleep onset and offset times. Sleep features in participants with epilepsy were compared to a large (n = 37 921) representative population of Fitbit users, each with 28 days of data. For participants with at least 10 seizure days (n = 34), sleep features were analysed for significant changes prior to seizure days. A total of 4956 reported seizures (mean = 83, standard deviation = 130) and 30 485 recorded sleep nights (mean = 508, standard deviation = 445) were included in the study. There was a trend for participants with epilepsy to sleep longer than the general population, although this difference was not significant. Just 5 of 34 participants showed a significant difference in sleep duration the night before seizure days compared to seizure-free days. However, 14 of 34 subjects showed significant differences between their sleep onset (bed) and/or offset (wake) times before seizure occurrence. In contrast to previous studies, the current study found undersleeping was associated with a marginal 2% decrease in seizure risk in the following 48 h (P < 0.01). Nocturnal seizures were associated with both significantly longer sleep durations and increased risk of a seizure occurring in the following 48 h. Overall, the presented results demonstrated that day-to-day changes in sleep duration had a minimal effect on reported seizures, while patient-specific changes in bed and wake times were more important for identifying seizure risk the following day. Nocturnal seizures were the only factor that significantly increased the risk of seizures in the following 48 h on a group level. Wearables can be used to identify these sleep-seizure relationships and guide clinical recommendations or improve seizure forecasting algorithms.

Insomnia: Personalized Diagnosis and Treatment Options.

Chronic insomnia is a clinical diagnosis fulfilled by criteria: (a) difficulty initiating or maintaining sleep, (b) inability to sleep despite having adequate opportunities, (c) having negative daytime effects due to lack of sleep, and (d) sleep difficulty not explained by other disorder-with symptoms at least three times per week during a period of 3 months. Cognitive behavioral therapy is considered a first-line treatment but can be supported with pharmacologic or digital therapeutics. When developing a patient's care plan, we should consider a "personomics" approach in which we personalize care plans as a form of sleep precision medicine.

Sleep architecture is associated with core symptom severity in autism spectrum disorder.

STUDY OBJECTIVES: While caregiver-reported sleep disturbances are common in children and adolescents with autism spectrum disorder (['), few studies have measured objective sleep in ASD compared to controls, and their findings are mixed. We investigated (1) differences in sleep architecture, specifically slow-wave sleep (SWS) and rapid eye movement (REM) sleep, between ASD and typically developing controls (TD); and (2) if any observed differences in sleep were associated with core ASD symptoms. METHODS: We used ambulatory polysomnography (PSG) in 53 participants with ASD (ages 4-18) and 66 age-matched TD in their home sleeping environment. The primary outcome measures were SWS and REM sleep. Core behavioral ASD symptoms were assessed using the Autism Diagnostic Interview-Revised (ADI-R). Spectral power bands during sleep, and additional behavioral measures, were examined in exploratory analyses. RESULTS: Compared to TD, participants with ASD exhibited a higher SWS ratio and lower REM sleep ratio. Within the ASD group, higher SWS was associated with more severe symptoms on the Restricted, Repetitive, and Stereotyped Behaviors subscale of the ADI-R. No association was observed between REM sleep ratio and any ASD symptom. CONCLUSIONS: Increased SWS and reduced REM sleep ratio differentiated ASD from TD. However, only increased SWS was associated with more severe core ASD symptoms. Increased SWS may reflect neuronal immaturity specific to ASD in this age group. These findings may inform the underlying mechanisms of clinical symptoms observed in children and adolescents with ASD.

The genetic etiology of periodic limb movement in sleep.

STUDY OBJECTIVES: Periodic limb movement in sleep is a common sleep phenotype characterized by repetitive leg movements that occur during or before sleep. We conducted a genome-wide association study (GWAS) of periodic limb movements in sleep (PLMS) using a joint analysis (i.e., discovery, replication, and joint meta-analysis) of four cohorts (MrOS, the Wisconsin Sleep Cohort Study, HypnoLaus, and MESA), comprised of 6843 total subjects. METHODS: The MrOS study and Wisconsin Sleep Cohort Study (N = 1745 cases) were used for discovery. Replication in the HypnoLaus and MESA cohorts (1002 cases) preceded joint meta-analysis. We also performed LD score regression, estimated heritability, and computed genetic correlations between potentially associated traits such as restless leg syndrome (RLS) and insomnia. The causality and direction of the relationships between PLMS and RLS was evaluated using Mendelian randomization. RESULTS: We found 2 independent loci were significantly associated with PLMS: rs113851554 (p = 3.51 × 10-12, ß = 0.486), an SNP located in a putative regulatory element of intron eight of MEIS1 (2p14); and rs9369062 (p = 3.06 × 10-22, ß = 0.2093), a SNP located in the intron region of BTBD9 (6p12); both of which were also lead signals in RLS GWAS. PLMS is genetically correlated with insomnia, risk of stroke, and RLS, but not with iron deficiency. Pleiotropy adjusted Mendelian randomization analysis identified a causal effect of RLS on PLMS. CONCLUSIONS: Because PLMS is more common than RLS, PLMS may have multiple causes and additional studies are needed to further validate these findings.

Characterization of autonomic symptom burden in long COVID: A global survey of 2,314 adults.

Background: Autonomic dysfunction is a known complication of post-acute sequelae of SARS-CoV-2 (PASC)/long COVID, however prevalence and severity are unknown. Objective: To assess the frequency, severity, and risk factors of autonomic dysfunction in PASC, and to determine whether severity of acute SARS-CoV-2 infection is associated with severity of autonomic dysfunction. Design: Cross-sectional online survey of adults with PASC recruited through long COVID support groups between October 2020 and August 2021. Participants: 2,413 adults ages 18-64 years with PASC including patients who had a confirmed positive test for COVID-19 (test-confirmed) and participants who were diagnosed with COVID-19 based on clinical symptoms alone. Main measures: The main outcome measure was the Composite Autonomic Symptom 31 (COMPASS-31) total score, used to assess global autonomic dysfunction. Test-confirmed hospitalized vs. test-confirmed non-hospitalized participants were compared to determine if the severity of acute SARS-CoV-2 infection was associated with the severity autonomic dysfunction. Key results: Sixty-six percent of PASC patients had a COMPASS-31 score >20, suggestive of moderate to severe autonomic dysfunction. COMPASS-31 scores did not differ between test-confirmed hospitalized and test-confirmed non-hospitalized participants [28.95 (15.62, 46.60) vs. 26.4 (13.75, 42.10); p = 0.06]. Conclusions: Evidence of moderate to severe autonomic dysfunction was seen in 66% of PASC patients in our study, independent of hospitalization status, suggesting that autonomic dysfunction is highly prevalent in the PASC population and independent of the severity of acute COVID-19 illness.

Proteomic Biomarkers of the Apnea Hypopnea Index and Obstructive Sleep Apnea: Insights into the Pathophysiology of Presence, Severity, and Treatment Response.

Obstructive sleep apnea (OSA), a disease associated with excessive sleepiness and increased cardiovascular risk, affects an estimated 1 billion people worldwide. The present study examined proteomic biomarkers indicative of presence, severity, and treatment response in OSA. Participants (n = 1391) of the Stanford Technology Analytics and Genomics in Sleep study had blood collected and completed an overnight polysomnography for scoring the apnea−hypopnea index (AHI). A highly multiplexed aptamer-based array (SomaScan) was used to quantify 5000 proteins in all plasma samples. Two separate intervention-based cohorts with sleep apnea (n = 41) provided samples pre- and post-continuous/positive airway pressure (CPAP/PAP). Multivariate analyses identified 84 proteins (47 positively, 37 negatively) associated with AHI after correction for multiple testing. Of the top 15 features from a machine learning classifier for AHI ≥ 15 vs. AHI < 15 (Area Under the Curve (AUC) = 0.74), 8 were significant markers of both AHI and OSA from multivariate analyses. Exploration of pre- and post-intervention analysis identified 5 of the 84 proteins to be significantly decreased following CPAP/PAP treatment, with pathways involving endothelial function, blood coagulation, and inflammatory response. The present study identified PAI-1, tPA, and sE-Selectin as key biomarkers and suggests that endothelial dysfunction and increased coagulopathy are important consequences of OSA, which may explain the association with cardiovascular disease and stroke.

A school-based health and mindfulness curriculum improves children's objectively measured sleep: a prospective observational cohort study.

STUDY OBJECTIVES: Poor sleep impedes children's cognitive, emotional, and psychosocial development. Pediatric sleep dysregulation is common, and children who live in communities of low socioeconomic status experience additional risk factors for short sleep duration and poor sleep quality. School-based training in mindfulness and yoga-informed practices can improve children's behavior and well-being, but effects on objectively measured sleep are unknown. METHODS: Effects of a school-based health and mindfulness curriculum, which taught practices such as paced breathing, on sleep and stress were examined in 115 children (49 girls, ages 8 to 11 at baseline). Fifty-eight children in a community of low socioeconomic status received the curriculum twice weekly for 2 years. Fifty-seven children in a socioeconomic status-matched community engaged in their usual physical education class instead. In-home ambulatory polysomnography and perceived social stress were measured in all children at 3 time points: at baseline (ie, prior to curriculum exposure) and at 2 yearly follow-ups. RESULTS: Children receiving the curriculum gained an average of 74 minutes of total sleep time, and 24 minutes of rapid eye movement sleep, per night over the 2-year study period. Children not receiving the curriculum experienced a decrease in total sleep time averaging 64 minutes per night, with no changes in rapid eye movement sleep. Sleep improved within the first 3 months of curriculum exposure, in a dose-dependent fashion. Higher curriculum engagement (eg, using the breathing exercises outside of class) was associated with larger gains in total and rapid eye movement sleep duration. Aggregate within-group changes in social stress were not significant. However, among children receiving the curriculum, those who experienced larger gains in total and rapid eye movement sleep duration also experienced larger increases in perceived social stress. CONCLUSIONS: A school-based health and mindfulness curriculum improved children's objectively measured sleep over 2 years. Social stress did not mediate these effects; instead, mindfulness training may have increased awareness of environmental stressors, while developing tools to reduce stress vulnerability. CITATION: Chick CF, Singh A, Anker LA, et al. A school-based health and mindfulness curriculum improves children's objectively measured sleep: a prospective observational cohort study. J Clin Sleep Med. 2022;18(9):2261-2271.

Genetic risk for subjective reports of insomnia associates only weakly with polygraphic measures of insomnia in 2,770 adults.

STUDY OBJECTIVES: Subjective insomnia complaints and objective sleep changes are mostly studied outside of clinical trial studies. In this study, we tested whether 240 genetic variants associated with subjectively reported insomnia were also associated with objective insomnia parameters extracted from polysomnographic recordings in three studies. METHODS: The study sample (total n = 2,770) was composed of the Wisconsin Sleep Cohort (n = 1,091) and the Osteoporotic Fractures in Men (n = 1,026) study, two population-based studies, and the Stanford Sleep Cohort, a sleep center patient-based sample (n = 653). Seven objective polysomnographic features related to insomnia defined outcome variables, with each variant allele serving as predictor. Meta-regression was performed, accounting for common confounders as well as variance differences between studies. Additionally, a normalized genetic risk score was generated for each subject to serve as a predictor variable in separate linear mixed models assessing objective insomnia features. RESULTS: After correction for multiple testing, single-nucleotide polymorphisms associated with subjective insomnia were not significantly associated with 6 of 7 objective sleep measures. Only periodic limb movement index was significantly associated with rs113851554 (MEIS1), as found in previous studies. The normalized genetic risk score was only weakly associated with arousal index and duration of wake after sleep onset. CONCLUSIONS: Our findings suggest that subjective insomnia does not have a strong genetic signature mapping onto objective (polysomnographic) sleep variables. CITATION: Foldager J, Peppard PE, Hagen EW, et al. Genetic risk for subjective reports of insomnia associates only weakly with polygraphic measures of insomnia in 2,770 adults. J Clin Sleep Med. 2022;18(1):21-29.

Cutaneous α-synuclein is correlated with autonomic impairment in isolated rapid eye movement sleep behavior disorder.

STUDY OBJECTIVES: To define the clinical implications of cutaneous phosphorylated α-synuclein (p-syn) and its association with subjective and objective measures of autonomic impairment and clinical features including antidepressant use in isolated rapid eye movement (REM) sleep behavior disorder (iRBD). METHODS: Twenty-five iRBD patients had quantified neurological and cognitive examinations, olfactory testing, questionnaires, autonomic function testing, and 3 punch skin biopsies (distal thigh, proximal thigh, neck). Skin biopsies were stained for the pan-axonal marker PGP 9.5 and co-stained with p-syn, and results were compared to 28 patients with Parkinson's disease (PD) and 18 healthy controls. Equal numbers of iRBD patients on and off antidepressants were recruited. The composite autonomic severity scale (CASS) was calculated for all patients. RESULTS: P-syn was detected in 16/25 (64%) of iRBD patients, compared to 27/28 (96%) of PD and 0/18 controls. The presence of p-syn at any biopsy site was correlated with both sympathetic (CASS adrenergic r = 0.6, p < 0.05) and total autonomic impairment (CASS total r = 0.6, p < 0.05) on autonomic reflex testing in iRBD patients. These results were independent of the density of p-syn at each site. There was no correlation between p-syn and antidepressant use. CONCLUSIONS: In patients with iRBD, the presence of cutaneous p-syn was detected in most patients and was associated with greater autonomic dysfunction on testing. Longitudinal follow-up will aid in defining the predictive role of both skin biopsy and autonomic testing in determining phenoconversion rates and future disease status.

The impact of student debt on neurological practice.

The median cost of attending medical school is rising annually, and with it, student debt. Neurology residents have stepped up during the pandemic to answer the call of a health system at its breaking point. In this article, we outline how this escalating problem of student debt affects the neurology pipeline, the wellbeing and career decisions of current neurology trainees and practicing neurologists and through it, and the gap in healthcare. We describe currently available options for loan repayment and call for advocacy and legislation to address this mounting burden as a means to improve neurological care in the United States.

Current Status and Future Strategies for Mentoring Women in Neurology.

The American Academy of Neurology's (AAN) 2017 Gender Disparity Report identified improving mentorship as a key intervention to fill the leadership and pay gaps for women in neurology. Here we summarize the literature on mentoring women, provide an outline of ideal components of programs geared toward closing gender gaps, and present a mentoring program for AAN members. The strategies discussed share similarities with those for closing gaps related to race, ethnicity, and religion. Developing effective mentorship and sponsorship programs is essential to ensure a sufficiently diverse pool of academic faculty and private practitioners and to establish equal representation in leadership roles in this field.

Estimation of Apnea-Hypopnea Index Using Deep Learning On 3-D Craniofacial Scans.

Obstructive sleep apnea (OSA) is characterized by decreased breathing events that occur through the night, with severity reported as the apnea-hypopnea index (AHI), which is associated with certain craniofacial features. In this study, we used data from 1366 patients collected as part of Stanford Technology Analytics and Genomics in Sleep (STAGES) across 11 US and Canadian sleep clinics and analyzed 3D craniofacial scans with the goal of predicting AHI, as measured using gold standard nocturnal polysomnography (PSG). First, the algorithm detects pre-specified landmarks on mesh objects and aligns scans in 3D space. Subsequently, 2D images and depth maps are generated by rendering and rotating scans by 45-degree increments. Resulting images were stacked as channels and used as input to multi-view convolutional neural networks, which were trained and validated in a supervised manner to predict AHI values derived from PSGs. The proposed model achieved a mean absolute error of 11.38 events/hour, a Pearson correlation coefficient of 0.4, and accuracy for predicting OSA of 67% using 10-fold cross-validation. The model improved further by adding patient demographics and variables from questionnaires. We also show that the model performed at the level of three sleep medicine specialists, who used clinical experience to predict AHI based on 3D scan displays. Finally, we created topographic displays of the most important facial features used by the model to predict AHI, showing importance of the neck and chin area. The proposed algorithm has potential to serve as an inexpensive and efficient screening tool for individuals with suspected OSA.

Neurobiology and Neuroprotective Benefits of Sleep.

PURPOSE OF REVIEW: This article outlines the neurocircuitry underlying sleep-wake and circadian physiology with a focus on the fundamental roles that sleep and circadian health play in optimal neurologic function. RECENT FINDINGS: The foundation of sleep and wake promotion is laid primarily by the "fast-acting" neurotransmitters: γ-aminobutyric acid (GABA) for sleep and glutamate for wake. External to these primary systems are a host of modulatory systems that are characterized by two flip-flop switches of mutually inhibitory neurotransmitter systems that facilitate transitions between wake and sleep as well as non-rapid eye movement (non-REM) and REM sleep. Additional mechanisms are in place to help coordinate the sleep-wake states with environmental, metabolic, and behavioral demands. The complexity of the evolutionarily preserved sleep-wake and circadian systems, the proportion of the day dedicated to the natural sleeping period, as well as the neurocognitive dysfunction and neurodegeneration caused by deficient sleep highlight the importance of defining, assessing, and optimizing the sleep health of our patients and ourselves. SUMMARY: Exciting discoveries continue to elucidate the underlying mechanisms of sleep and wake state coordination, reinforcing fundamental healthy practices and paving the way for new interventions that preserve and promote optimal neurologic health.

Active and Distance Learning in Neuroscience Education.

With social distancing and uncertainty about the complete re-opening of laboratories and campuses, there is a pressing need for a more flexible educational experience. Seizing this opportunity to integrate active learning into adaptive curricula can fast-forward neuroscience education at every level.

The 5-HTTLPR long allele predicts two-year longitudinal increases in cortisol and declines in verbal memory in older adults.

OBJECTIVES: The short form or s-allele variant of the serotonin transporter polymorphism (5-HTTLPR), as compared with the long-form or l-allele variant, has been associated with the presence of cognitive dysfunction, and particularly memory impairment in older adults. This body of cross-sectional work has culminated in the hypothesis that presence of the s-allele predicts greater memory decline in older adults. Yet, to date, there are no longitudinal studies that have investigated this issue. METHODS/DESIGN: Here, we examine 109 community-dwelling older adults (mean and SD of age = 70.7 ± 8.7 years) who underwent blood draw for genotyping, cognitive, and psychological testing at baseline, 12-, and 24-monthfollow-ups. RESULTS: Multilevel modeling found that s-allele carriers (ss or ls) performed worse than ll homozygotes at baseline on delayed verbal recall. Yet, s-allele carriers' memory performance was stable over the two-yearfollow-up period, while l-allele homozygotes experienced significant memory decline. l-allele homozygote status was associated with both increased cortisol and decreased memory over time, resulting in attenuated verbal memory performance differences compared to s-allele carriers with age. CONCLUSIONS: Overall, our findings do not support the hypothesis that presence of the 5-HTTLPRs-allele is a marker for memory decline in older adults. J Am Geriatr Soc 68:-, 2020.

Active Learning in Psychiatry Education: Current Practices and Future Perspectives.

Over the past few decades, medical education has seen increased interest in the use of active learning formats to engage learners and promote knowledge application over knowledge acquisition. The field of psychiatry, in particular, has pioneered a host of novel active learning paradigms. These have contributed to our understanding of the role of andragogy along the continuum of medical education, from undergraduate to continuing medical education. In an effort to frame the successes and failures of various attempts at integrating active learning into healthcare curricula, a group of educators from the A. B. Baker Section on Neurological Education from the American Academy of Neurology reviewed the state of the field in its partner field of medical neuroscience. Herein we provide a narrative review of the literature, outlining the basis for implementing active learning, the novel formats that have been used, and the lessons learned from qualitative and quantitative analysis of the research that has been done to date. While preparation time seems to present the greatest obstacle to acceptance from learners and educators, there is generally positive reception to the new educational formats. Additionally, most assessments of trainee performance have suggested non-inferiority (if not superiority). However, occasional mixed findings point to a need for better assessments of the type of learning that these new formats engender: knowledge application rather than acquisition. Moreover, this field is relatively nascent and, in order to ascertain how best to integrate active learning into psychiatry education, a framework for quantitative outcome assessments is needed going forward.