Faculty Bibliography

STUDY OBJECTIVES:Phenotyping using polysomnography (PUP) is an algorithmic method to quantify physiologic mechanisms underlying obstructive sleep apnea (OSA): loop gain (LG1), arousal threshold (ArTH), and upper airway collapsibility (Vpassive) and muscular compensation (Vcomp). The consecutive-night test-retest reliability and agreement of PUP-derived estimates are unknown. From a cohort of elderly (age ≥55 years), largely non-sleepy, community-dwelling volunteers who underwent in-lab polysomnography (PSG) on 2 consecutive nights, we determined the test-retest reliability and agreement of PUP-estimated physiologic factors. METHODS:Participants who had an apnea-hypopnea index (AHI3A) of at least 15 events per hour on the first night were included. PUP analyses were performed on each of the two PSGs from each participant. Physiologic factor estimates were derived from NREM sleep and compared across nights using intraclass correlation coefficients for reliability and smallest real differences (SRD) for agreement. RESULTS:Two PSGs from each of 43 participants (86 total) were analyzed. A first-night effect was evident with increased sleep time and stability and decreased OSA severity on the second night. LG1, ArTH, and Vpassive demonstrated good reliability (ICC > 0.80). Vcomp had modest reliability (ICC = 0.67). For all physiologic factors, SRD values were approximately 20% or more of the observed ranges, suggesting limited agreement of longitudinal measurements for a given individual. CONCLUSIONS:For NREM sleep in cognitively normal elderly individuals with OSA, PUP-estimated LG1, ArTH, and Vpassive demonstrated consistent relative ranking of individuals (good reliability) on short-term repeat measurement. For all physiologic factors, longitudinal measurements demonstrated substantial intraindividual variability across nights (limited agreement).

BACKGROUND:Down syndrome (DS) population has a very high prevalence of obstructive sleep apnoea (OSA), but this remains underdiagnosed. Hence, we aimed to evaluate caregiver's knowledge of OSA and related sociodemographic factors that could contribute to OSA screening patterns in this population. METHODS:An online survey though the LuMind IDSC Foundation focused on OSA diagnosis, treatments and the number of sleep studies performed. Data were compared between subjects born before and after the American Academy of Pediatrics (AAP) recommendations for OSA screening. RESULTS:Of the caregivers, 724 (parents 96.3%), responded to the survey. The median [interquartile (IQR)] age of the subjects with DS was 12 [20;7] years. The majority (84.3%) had sleep apnoea diagnosis, and half of them were initially referred for a sleep study due to disturbed sleep symptoms. Only 58.7% of the responders were aware of the AAP recommendations. This was linked to higher socioeconomic and/or educational level and to an earlier OSA diagnosis. The median (IQR) age of OSA diagnosis was lowered after the AAP guidelines publication compared with before its publication (3 [4;2] years vs. 10 [18;5] years, P < 0.000). Adenotonsillectomy (81.9%) and continuous positive airway pressure (61.5%) were the most commonly prescribed treatments. Few had discussed other new therapies such as hypoglossal nerve stimulation (16.0%). Only 16.0% of the subjects repeated the sleep study to monitor OSA with ageing, and 30.2% had to wait more than 4 years between studies. CONCLUSIONS:This study reinforces the need to improve OSA knowledge of caregivers and clinicians of individuals with DS to promote an earlier diagnosis and optimal treatment of OSA in this population.

There is emerging evidence that obstructive sleep apnea (OSA) is a risk factor for preclinical Alzheimer's disease (AD). An American Thoracic Society workshop was convened that included clinicians, basic scientists, and epidemiologists with expertise in OSA, cognition, and dementia, with the overall objectives of summarizing the state of knowledge in the field, identifying important research gaps, and identifying potential directions for future research. Although currently available cognitive screening tests may allow for identification of cognitive impairment in patients with OSA, they should be interpreted with caution. Neuroimaging in OSA can provide surrogate measures of disease chronicity, but it has methodological limitations. Most data on the impact of OSA treatment on cognition are for continuous positive airway pressure (CPAP), with limited data for other treatments. The cognitive domains improving with CPAP show considerable heterogeneity across studies. OSA can negatively influence risk, manifestations, and possibly progression of AD and other forms of dementia. Sleep-dependent memory tasks need greater incorporation into OSA testing, with better delineation of sleep fragmentation versus intermittent hypoxia effects. Plasma biomarkers may prove to be sensitive, feasible, and scalable biomarkers for use in clinical trials. There is strong biological plausibility, but insufficient data, to prove bidirectional causality of the associations between OSA and aging pathology. Engaging, recruiting, and retaining diverse populations in health care and research may help to decrease racial and ethnic disparities in OSA and AD. Key recommendations from the workshop include research aimed at underlying mechanisms; longer-term longitudinal studies with objective assessment of OSA, sensitive cognitive markers, and sleep-dependent cognitive tasks; and pragmatic study designs for interventional studies that control for other factors that may impact cognitive outcomes and use novel biomarkers.

INTRODUCTION/BACKGROUND:Tumor necrosis factor (TNF) inhibitors are widely used to treat rheumatoid arthritis (RA) and their potential to retard Alzheimer's disease (AD) progression has been reported. However, their long-term effects on the dementia/AD risk remain unknown. METHODS:A propensity scored matched retrospective cohort study was conducted among 40,207 patients with RA within the US Veterans Affairs health-care system from 2000 to 2020. RESULTS:A total of 2510 patients with RA prescribed TNF inhibitors were 1:2 matched to control patients. TNF inhibitor use was associated with reduced dementia risk (hazard ratio [HR]: 0.64, 95% confidence interval [CI]: 0.52-0.80), which was consistent as the study period increased from 5 to 20 years after RA diagnosis. TNF inhibitor use also showed a long-term effect in reducing the risk of AD (HR: 0.57, 95% CI: 0.39-0.83) during the 20 years of follow-up. CONCLUSION/CONCLUSIONS:TNF inhibitor use is associated with lower long-term risk of dementia/AD among US veterans with RA.