Context Sleep-disordered breathing (SDB), characterized by recurrent arousals from sleep and intermittent hypoxemia, is common among older adults. Cross-sectional studies have linked SDB to poor cognition; however, it remains unclear whether sleep disordered breathing precedes cognitive impairment in older adults. Objectives To determine the prospective relationship between sleep disordered breathing and cognitive impairment and to investigate potential mechanisms of this association. Design, Setting, and Participants Prospective sleep and cognition study of 298 women without dementia (mean [SD] age: 82.3 [3.2] years) who had overnight polysomnography (PSG) measured between January 2002 and April 2004 in a substudy of the Study of Osteoporotic Fractures. Sleep disordered breathing was defined as an apnea-hypopnea index of 15 or more events per hour of sleep. Multivariate logistic regression was used to determine the independent association of sleep disordered breathing with risk of mild cognitive impairment or dementia and adjustments were made for age, race, body mass index, education, smoking status, presence of diabetes, presence of hypertension, medication use (antidepressants, benzodiazepines, or non-benzodiazepine anxiolytics), and baseline cognitive scores. Measures of hypoxia, sleep fragmentation, and sleep duration were investigated as underlying mechanisms for this relationship. Main Outcome Measures Adjudicated cognitive status (normal, dementia, or mild cognitive impairment [MCI]) based on data collected between November 2006 and September 2008 Results Compared with the 193 women without sleep disordered breathing, the 105 women (35.2%) with SDB were more likely to develop MCI/dementia (n=60 (31.1%) vs n=47 (44.8%)) even after multivariate adjustment (adjusted OR=1.85, 95% CI 1.11-3.08). Elevated oxygen desaturation index (≥15 events/hour) and high percentage (>7%) of sleep time in apnea or hypopnea, both measures of disordered breathing, were associated with risk of developing MCI/dementia (adjusted OR=1.71, 95% CI 1.04 − 2.83 and adjusted OR=2.04, 95% CI 1.10 − 3.78, respectively). Measures of sleep fragmentation (arousal index and wake after sleep onset) or sleep duration (total sleep time) were not associated with risk of cognitive impairment. Conclusions Among older women, those with sleep disordered breathing, compared with those without SDB, were associated with an increased risk of developing cognitive impairment.

Obstructive sleep apnea is a common disorder whose prevalence is linked to an epidemic of obesity in Western society. Sleep apnea is due to recurrent episodes of upper airway obstruction during sleep that are caused by elevations in upper airway collapsibility during sleep. Collapsibility can be increased by underlying anatomic alterations and/or disturbances in upper airway neuromuscular control, both of which play key roles in the pathogenesis of obstructive sleep apnea. Obesity and particularly central adiposity are potent risk factors for sleep apnea. They can increase pharyngeal collapsibility through mechanical effects on pharyngeal soft tissues and lung volume, and through central nervous system-acting signaling proteins (adipokines) that may affect airway neuromuscular control. Specific molecular signaling pathways encode differences in the distribution and metabolic activity of adipose tissue. These differences can produce alterations in the mechanical and neural control of upper airway collapsibility, which determine sleep apnea susceptibility. Although weight loss reduces upper airway collapsibility during sleep, it is not known whether its effects are mediated primarily by improvement in upper airway mechanical properties or neuromuscular control. A variety of behavioral, pharmacologic, and surgical approaches to weight loss may be of benefit to patients with sleep apnea, through distinct effects on the mass and activity of regional adipose stores. Examining responses to specific weight loss strategies will provide critical insight into mechanisms linking obesity and sleep apnea, and will help to elucidate the humoral and molecular predictors of weight loss responses.

There were modest cross-sectional associations of WASO and self-reported long sleep with cognition among older community-dwelling men. EDS and PSQI were not related to cognition.

Frailty is a common clinical syndrome in older adults that carries an increased risk for poor health outcomes. Little is known about the behavioral antecedents of frailty. In this study, the authors hypothesized that constriction of life space identifies older adults at risk for frailty, potentially a marker of already-decreased physiologic reserve. The authors analyzed the 3-year (1992-1995) cumulative incidence of frailty using a previously validated clinical phenotype in relation to baseline life-space constriction among 599 community-dwelling women aged 65 years or older who were not frail at baseline. Frailty-free mortality (i.e., death prior to observation of frailty) was treated as a competing risk. Multivariate survival models showed that, compared with women who left the neighborhood four or more times per week, those who left the neighborhood less frequently were 1.7 times (95% confidence interval: 1.1, 2.4; p < 0.05) more likely to become frail, and those who never left their homes experienced a threefold increase in frailty-free mortality (95% confidence interval: 1.4, 7.7; p < 0.01), after adjustment for chronic disease, physical disability, and psychosocial factors. Together, these data suggest that a slightly constricted life space may be a marker and/or risk factor for the development of frailty that may prove useful as a screening tool or a target of intervention.

Male sex, obesity, and age are risk factors for obstructive sleep apnea, although the mechanisms by which these factors increase sleep apnea susceptibility are not entirely understood. This study examined the interrelationships between sleep apnea risk factors, upper airway mechanics, and sleep apnea susceptibility. In 164 (86 men, 78 women) participants with and without sleep apnea, upper airway pressure-flow relationships were characterized to determine their mechanical properties [pharyngeal critical pressure under hypotonic conditions (passive Pcrit)] during non-rapid eye movement sleep. In multiple linear regression analyses, the effects of body mass index and age on passive Pcrit were determined in each sex. A subset of men and women matched by body mass index, age, and disease severity was used to determine the sex effect on passive Pcrit. The passive Pcrit was 1.9 cmH(2)O [95% confidence interval (CI): 0.1-3.6 cmH(2)O] lower in women than men after matching for body mass index, age, and disease severity. The relationship between passive Pcrit and sleep apnea status and severity was examined. Sleep apnea was largely absent in those individuals with a passive Pcrit less than -5 cmH(2)O and increased markedly in severity when passive Pcrit rose above -5 cmH(2)O. Passive Pcrit had a predictive power of 0.73 (95% CI: 0.65-0.82) in predicting sleep apnea status. Upper airway mechanics are differentially controlled by sex, obesity, and age, and partly mediate the relationship between these sleep apnea risk factors and obstructive sleep apnea.

Rationale: Obstructive sleep apnea is associated with insulin resistance and liver injury. It is unknown whether apnea contributes to insulin resistance and steatohepatitis in severe obesity. Objectives: To examine whether sleep apnea and nocturnal hypoxemia predict the severity of insulin resistance, systemic inflammation, and steatohepatitis in severely obese individuals presenting for bariatric surgery. Methods: We performed sleep studies and measured fasting blood glucose, serum insulin, C-reactive protein, and liver enzymes in 90 consecutive severely obese individuals, 75 women and 15 men, without concomitant diabetes mellitus or preexistent diagnosis of sleep apnea or liver disease. Liver biopsies (n 5 20) were obtained during bariatric surgery. Measurements and Main Results: Obstructive sleep apnea with a respiratory disturbance index greater than 5 events/hour was diagnosed in 81.1% of patients. The median respiratory disturbance index was 15 6 29 events/hour and the median oxygen desaturation during apneic events was 4.6 6 1.8%. All patients exhibited high serum levels of C-reactive protein, regardless of the severity of apnea, whereas liver enzymes were normal. Oxygen desaturation greater than 4.6% was associated with a 1.5-fold increase in insulin resistance, according to the homeostasis model assessment index. Histopathology data suggested that significant nocturnal desaturation might predispose to hepatic inflammation, hepatocyte ballooning, and liver fibrosis. Fasting blood glucose levels and steatosis scores were not affected by nocturnal hypoxia. There was no relationship between the respiratory disturbance index and insulin resistance or liver histopathology. Conclusions: Hypoxic stress of sleep apnea may be implicated in the development of insulin resistance and steatohepatitis in severe obesity.Keywords: hypoxemia; fatty liver disease; metabolic syndrome; sleepdisordered breathing; liver injury Obstructive sleep apnea (OSA) is a complex disorder consisting of upper airway obstruction, chronic intermittent hypoxia (CIH), and sleep fragmentation (1). Epidemiologic studies have demonstrated that OSA is associated with insulin resistance and glucose intolerance, independent of obesity (2-4). Clinical investigations have also shown that OSA results in low-grade systemic inflammation (5, 6). Both insulin resistance and systemic inflammation may contribute to the increased cardiovascular risk in patients with OSA (7-9). Insulin resistance, systemic inflammation, and OSA are particularly prevalent in patients with severe obesity defined as a body mass index (BMI) exceeding 40 kg/m 2 (2, 10-12). While obesity causes systemic inflammation, insulin resistance, and sleep apnea (12-15), sleep apnea may further exacerbate the inflammatory and metabolic disturbances (2, 3, 6). Nevertheless, it is not known whether concomitant OSA is implicated in metabolic dysregulation and systemic inflammation in severe obesity.One of the consequences of obesity and insulin resistance is nonalcoholic fatty liver disease (N...

OBJECTIVES To examine the association of sleep architecture, sleep disordered breathing, and cognition in older men. DESIGN A population-based cross-sectional study. SETTING 6 sites in the United States. PARTICIPANTS 2,909 community-dwelling men age 67 or older who were not selected on the basis of sleep problems or cognitive impairment. MEASUREMENTS Predictors were measured with in-home polysomnography: sleep architecture, nocturnal hypoxemia (any sleep time with SaO2<80%), apnea-hypopnea index (AHI), and arousal index. Cognitive outcomes were measured by the Modified Mini-Mental State Examination (3MS), Trails B test, and the Digit Vigilance Test (DVT). RESULTS Analyses adjusted by age, race, education, BMI, lifestyle, comorbidities and medication use show that those who spent less percent of time in rapid eye movement (REM) sleep had worse levels of cognition: compared to the highest quartile (≥23.7%), those in the lowest quartile (<14.8%) took an average of 5.9 seconds longer on the Trails B and 20.1 seconds longer on the DVT. Similarly, increased percent time spent in stage 1 sleep was related to poorer cognitive function. Those in the highest quartile of stage 1 sleep (≥8.6%) had worse cognitive scores on average compared to those in the lowest quartile (<4.0%). Those with nocturnal hypoxemia took longer to complete the DVT by an average of 22.3 seconds compared to those without, but no associations were found with 3MS or Trails B. CONCLUSION Spending less percent of time spent in REM sleep, more percent of time spent in stage 1 sleep, and having higher levels of nocturnal hypoxemia were associated with poorer cognition in older men. Further studies are needed to clarify the direction of these associations and to explore potential mechanisms.

Purpose: Data on the health and well-being of the transgender population are limited. However, using claims data we can identify transgender Medicare beneficiaries (TMBs) with high confidence. We seek to describe the TMB population and provide comparisons of chronic disease burden between TMBs and cisgender Medicare beneficiaries (CMBs), thus laying a foundation for national level TMB health disparity research. Methods: Using a previously validated claims algorithm based on ICD-9-CM codes relating to transsexualism and gender identity disorder, we identified a cohort of TMBs using Medicare Fee-for-Service (FFS) claims data. We then describe the demographic characteristics and chronic disease burden of TMBs (N = 7454) and CMBs (N = 39,136,229). Results: Compared to CMBs, a greater observed proportion of TMBs are young (under age 65) and Black, although these differences vary by entitlement. Regardless of entitlement, TMBs have more chronic conditions than CMBs, and more TMBs have been diagnosed with asthma, autism spectrum disorder, chronic obstructive pulmonary disease, depression, hepatitis, HIV, schizophrenia, and substance use disorders. TMBs also have higher observed rates of potentially disabling mental health and neurological/chronic pain conditions, as well as obesity and other liver conditions (nonhepatitis), compared to CMBs. Conclusion: This is the first systematic look at chronic disease burden in the transgender population using Medicare FFS claims data. We found that TMBs experience multiple chronic conditions at higher rates than CMBs, regardless of Medicare entitlement. TMBs under age 65 show an already heavy chronic disease burden which will only be exacerbated with age.