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Background: The effect of sleep medications on cognition in older adults is controversial, possibly dependent upon sleep quality, and may differ by race. Objective: To determine the longitudinal association between sleep medication use and incident dementia over 15 years, and to explore whether the association is independent of nighttime sleep disturbances and if it differs by race. Methods: We examined 3,068 community-dwelling older adults (aged 74.1±2.9 years, 41.7% Black, 51.5% female) without dementia. Sleep medication use was recorded three times by asking “Do you take sleeping pills or other medications to help you sleep?” with the response options: “Never (0)”, “Rarely (≤1/month)”, “Sometimes (2–4/month)”, “Often (5–15/month)”, or “Almost Always (16–30/month)”. Incident dementia was defined using hospitalization records, dementia medication prescription or clinically significant decline in global cognition. Results: 138 (7.71%) of Whites and 34 (2.66%) of Blacks reported taking sleep medications “often or almost always”. Whites were almost twice as likely to take all prescription hypnotics. 617 participants developed dementia over the follow-up. After adjustment for all covariates, participants who reported taking sleep medications ≥ 5/month versus ≤1/month were significantly more likely to develop dementia, and the association was only observed among Whites (HR = 1.79,1.21–2.66) but not Blacks (HR = 0.84,0.38–1.83); p for interaction = 0.048. Further adjustment for nighttime sleep did not appreciably alter the results. The association was similar for the cumulative frequency of sleep medication use and remained after introducing a time lag of 3 years. Conclusion: Frequent sleep medication use was associated with an increased risk of dementia in White older adults. Further research is needed to determine underlying mechanisms.

Background Sleep-disordered breathing is a common disorder associated with significant morbidity. The genetic architecture of sleep-disordered breathing remains poorly understood. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we performed the first whole-genome sequence analysis of sleep-disordered breathing. Methods The study sample was comprised of 7988 individuals of diverse ancestry. Common-variant and pathway analyses included an additional 13,257 individuals. We examined five complementary traits describing different aspects of sleep-disordered breathing: the apnea-hypopnea index, average oxyhemoglobin desaturation per event, average and minimum oxyhemoglobin saturation across the sleep episode, and the percentage of sleep with oxyhemoglobin saturation Results We identified a multi-ethnic set-based rare-variant association (p = 3.48 × 10−8) on chromosome X with ARMCX3. Additional rare-variant associations include ARMCX3-AS1, MRPS33, and C16orf90. Novel common-variant loci were identified in the NRG1 and SLC45A2 regions, and previously associated loci in the IL18RAP and ATP2B4 regions were associated with novel phenotypes. Transcription factor binding site enrichment identified associations with genes implicated with respiratory and craniofacial traits. Additional analyses identified significantly associated pathways. Conclusions We have identified the first gene-based rare-variant associations with objectively measured sleep-disordered breathing traits. Our results increase the understanding of the genetic architecture of sleep-disordered breathing and highlight associations in genes that modulate lung development, inflammation, respiratory rhythmogenesis, and HIF1A-mediated hypoxic response.

Importance The burden of fractures among postmenopausal women is high. Although nontraumatic fractures are strong risk factors for future fracture, current clinical guidelines do not address traumatic fractures. Objective To determine how future fracture risk varies according to whether an initial fracture is traumatic or nontraumatic. Design, Setting, and Participants We conducted a prospective observational study using data from the Women’s Health Initiative Study (WHI) (enrollment, September 1994-December 1998; data analysis, September 2020 to March 2021), which enrolled postmenopausal women aged 50 to 79 years at baseline at 40 US clinical centers. The WHI Clinical Trials and WHI Bone Density Substudy, conducted at 3 of the clinical centers, asked participants to report the mechanism of incident fractures. Of 75 335 participants, information regarding incident fracture and covariates was available for 66 874 participants (88.8%), who comprised the analytic sample of this study. Mean (SD) follow-up was 8.1 (1.6) years. Interventions None. Main Outcomes and Measures Incident clinical fractures were self-reported at least annually and confirmed using medical records. Participants reported the mechanism of incident fracture as traumatic or nontraumatic. Results Among the 66 874 participants in the analytic sample (mean [SD] age, 63.1 [7.0] years and 65.3 [7.2] years among women without and with clinical fracture, respectively), 7142 participants (10.7%) experienced incident fracture during the study follow-up period. The adjusted hazard ratio (aHR) of subsequent fracture after initial fracture was 1.49 (95% CI, 1.38-1.61). Among women whose initial fracture was traumatic, the association between initial fracture and subsequent fracture was significantly increased (aHR, 1.25; 95% CI, 1.06-1.48). Among women whose initial fracture was nontraumatic, the association between initial fracture and subsequent fracture was also increased (aHR, 1.52; 95% CI, 1.37-1.68). Confidence intervals for associations between initial fracture and subsequent fracture were overlapping for traumatic and nontraumatic initial fracture strata. Conclusions and Relevance In this cohort study, among postmenopausal women older than 50 years, fracture was associated with a greater risk of subsequent fracture regardless of whether the fracture was traumatic or nontraumatic. These findings suggest that clinical osteoporosis assessment should include high-trauma as well as low-trauma fractures.

Background The locations of subsequent fractures after initial fracture in postmenopausal women are poorly characterized. Methods We conducted a prospective analysis of subsequent fractures after initial fracture in Women's Health Initiative (1993–2018) participants who provided follow-up (mean 15.4 years, SD 6.2 years) data (n = 157,282 participants; baseline age 50–79; 47,458 participants with incident fracture). Cox proportional hazards models were adjusted for age, race/ethnicity, body mass index, and other covariates. Findings The risk of each type of subsequent fracture was increased after each type of initial fracture. Incident lower arm/wrist fracture was associated with significantly elevated risks of subsequent fractures at the upper arm/shoulder, upper leg, knee, lower leg/ankle, hip/pelvis, and spine (adjusted hazard ratios [aHRs] ranging 2·63–5·68). The risk of hip fracture was increased after initial lower arm or wrist fracture (aHR 4·80, 95% CI 4·29–5·36), initial upper arm or shoulder fracture (aHR 5·06, 95% CI 4·39–5·82), initial upper leg fracture (aHR 5·11, 95% CI 3·91–6·67), initial knee fracture (aHR 5·03, 95% CI 4·20–6·03), initial lower leg/ankle fracture (aHR 4·10, 95% CI 3·58–4·68), and initial spine fracture (aHR 6·69, 95% CI 5·95–7·53). Associations were significant in all age groups, even women aged 50–59 years. Risks of subsequent fracture were more pronounced among non-Hispanic Black, Hispanic/Latina, and Asian/Pacific Islander than among non-Hispanic White women. Interpretation Increased risk of subsequent fracture is observed for all fracture types across all ages. Women who experience any of these fractures should be targeted for interventions to prevent subsequent fractures. Funding National Institutes of Health HHSN268201600018C,HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C.

BACKGROUND: The effects on patient safety of eliminating extended-duration work shifts for resident physicians remain controversial. METHODS: We conducted a multicenter, cluster-randomized, crossover trial comparing two schedules for pediatric resident physicians during their intensive care unit (ICU) rotations: extended-duration work schedules that included shifts of 24 hours or more (control schedules) and schedules that eliminated extended shifts and cycled resident physicians through day and night shifts of 16 hours or less (intervention schedules). The primary outcome was serious medical errors made by resident physicians, assessed by intensive surveillance, including direct observation and chart review. RESULTS: The characteristics of ICU patients during the two work schedules were similar, but resident physician workload, described as the mean (±SD) number of ICU patients per resident physician, was higher during the intervention schedules than during the control schedules (8.8±2.8 vs. 6.7±2.2). Resident physicians made more serious errors during the intervention schedules than during the control schedules (97.1 vs. 79.0 per 1000 patient-days; relative risk, 1.53; 95% confidence interval [CI], 1.37 to 1.72; P

Author(s): Lee, Soomi; Stone, Katie L; Engeland, Christopher G; Lane, Nancy E; Buxton, Orfeu M | Abstract: ObjectiveTo examine the associations of prevalent arthritis with systemic inflammation in older men and to test whether sleep health mediates the associations.MethodsCross-sectional data came from 2,562 community-dwelling older men (all were age 65 years or older; mean age 76 years) in the Osteoporotic Fractures in Men Study who participated in a sleep ancillary study in 2003-2005. Participants were classified as having osteoarthritis (OA) (24%) or rheumatoid arthritis (RA) (0.7%) based on self-reported diagnoses and medication use. We constructed a composite score of multidimensional sleep health (i.e., perceived sleep quality, sleepiness, frequency of daytime napping, wake after sleep onset, and sleep duration) measured by both self-report and actigraphy. We also created binary indicators of elevated inflammation using C-reactive protein (CRP) (g3 mg/liter) and interleukin-6 (IL-6) (g1.08 pg/ml) levels. Analyses controlled for age, diagnosed sleep disorders, body mass index, smoking status, relevant medication use, and comorbidities.ResultsOlder men with OA did not have higher risk of elevated CRP or IL-6 levels. However, indirect associations of OA through sleep health were found. OA was associated with poorer sleep health, which was further associated with 16% higher odds of elevated CRP (P l 0.001) and 12% higher odds of elevated IL-6 (P l 0.01) levels after controlling for OA. Older men with RA had higher odds of elevated CRP and IL-6 levels, but the associations were not mediated by sleep health.ConclusionFindings suggest that promoting sleep health may help reduce the risk of systemic inflammation in older men with OA.

Study Objectives To estimate the association of self-reported poor sleep in multiple dimensions with health care costs in older men. Methods Participants were 1,413 men (mean [SD] age 76.5 [5.7] years) enrolled in both the Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study and Medicare Fee-for-Service. Poor sleep was characterized at the baseline MrOS Sleep visit on five dimensions (satisfaction, daytime sleepiness, timing, latency, and duration). Health care costs and utilization were ascertained over 3 years of follow-up using Medicare Claims. Results Median (interquartile range [IQR]) annualized total health care costs (2018 US dollars) rose from $3,616 (IQR 1,523–7,875) for those with no impaired sleep dimensions to $4,416 (IQR 1,854–11,343) for men with two impaired sleep dimensions and $5,819 (IQR 1,936–15,569) for those with at least three impaired sleep dimensions. After multivariable adjustment, the ratio of total health care costs (CR) was significantly higher for men with two (1.24, 95% confidence interval [CI] 1.03– to 1.48) and men with at least three impaired sleep dimensions (1.78, 95% CI 1.42 to 2.23) vs. those with no impaired sleep dimensions. After excluding 101 men who died during the 3-year follow-up period, these associations were attenuated and not significant (CR 1.22, 95% CI 0.98 to 1.53 for men ≥3 impaired sleep dimensions vs. none). Conclusions Self-reported poor sleep on multiple dimensions is associated with higher subsequent total health care costs in older men, but this may be due to higher mortality and increased health care costs toward the end of life among those with poor sleep health.

Genetic association studies of many heritable traits resulting from physiological testing often have modest sample sizes due to the cost and burden of the required phenotyping. This reduces statistical power and limits discovery of multiple genetic associations. We present a strategy to leverage pleiotropy between traits to both discover new loci and to provide mechanistic hypotheses of the underlying pathophysiology. Specifically, we combine a colocalization test with a locus-level test of pleiotropy. In simulations, we show that this approach is highly selective for identifying true pleiotropy driven by the same causative variant, thereby improves the chance to replicate the associations in underpowered validation cohorts and leads to higher interpretability. Here, as an exemplar, we use Obstructive Sleep Apnea (OSA), a common disorder diagnosed using overnight multi-channel physiological testing. We leverage pleiotropy with relevant cellular and cardio-metabolic phenotypes and gene expression traits to map new risk loci in an underpowered OSA GWAS. We identify several pleiotropic loci harboring suggestive associations to OSA and genome-wide significant associations to other traits, and show that their OSA association replicates in independent cohorts of diverse ancestries. By investigating pleiotropic loci, our strategy allows proposing new hypotheses about OSA pathobiology across many physiological layers. For example, we identify and replicate the pleiotropy across the plateletcrit, OSA and an eQTL of DNA primase subunit 1 (PRIM1) in immune cells. We find suggestive links between OSA, a measure of lung function (FEV1/FVC), and an eQTL of matrix metallopeptidase 15 (MMP15) in lung tissue. We also link a previously known genome-wide significant peak for OSA in the hexokinase 1 (HK1) locus to hematocrit and other red blood cell related traits. Thus, the analysis of pleiotropic associations has the potential to assemble diverse phenotypes into a chain of mechanistic hypotheses that provide insight into the pathogenesis of complex human diseases.Author SummaryLarge genetic studies with hundreds of thousands of patients have been successful at finding genetic variants that associate with disease traits in humans. However, smaller-scale studies can often have inadequate power to discover new genetic associations. Here, we use a small genetic study of Obstructive Sleep Apnea (OSA), to introduce a strategy that both helps find genetic associations and proposes biological hypotheses for the mechanisms behind those associations. To achieve this, we use large genetic studies carried out on traits that are related to OSA, and look for genetic variants that affect both OSA in our small study and the trait in question in the large study. By linking two or more traits at select loci, we were able to, among other results, find a locus that affects the expression of a gene in immune cells (DNA primase subunit 1), a marker of thrombotic and inflammatory processes (plateletcrit) and OSA. This results in a novel genetic association to OSA and a corresponding biological hypothesis behind its effect on OSA.

Short sleep duration, recognized as a public health epidemic, is associated with adverse health conditions, yet little is known about the association between sleep and bone health. We tested the associations of usual sleep behavior and bone mineral density (BMD) and osteoporosis. In a sample of 11,084 postmenopausal women from the Women's Health Initiative (WHI; mean age 63.3 years, SD = 7.4), we performed a cross-sectional study of the association of self-reported usual hours of sleep and sleep quality (WHI Insomnia Rating Score) with whole body, total hip, femoral neck, and spine BMD using linear regression models. We also studied the association of sleep duration and quality with dual-energy X-ray absorptiometry (DXA)-defined low bone mass (T-score

Objectives To reveal sleep health phenotypes in older adults and examine their associations with time to 5-year all-cause and cardiovascular mortality. Design Prospective longitudinal cohorts. Setting The Study of Osteoporotic Fractures and Outcomes of Sleep Disorders in Older Men Study. Participants N = 1722 men and women aged ≥65 years matched 1:1 on sociodemographic and clinical measures. Measurements Self-reported habitual sleep health characteristics (satisfaction, daytime sleepiness, timing, efficiency, and duration) measured at an initial visit and longitudinal follow-up for mortality. Results Latent class analysis revealed 3 sleep health phenotypes: (1) heightened sleep propensity (HSP; medium to long duration, high sleepiness, high efficiency/satisfaction; n = 322), (2) average sleep (AS; medium duration, average efficiency, high satisfaction, low sleepiness; n = 1,109), and (3) insomnia with short sleep (ISS; short to medium duration, low efficiency/satisfaction, moderate sleepiness; n = 291). Phenotype predicted time to all-cause mortality (χ2 = 9.4, P = .01), with HSP conferring greater risk than AS (hazard ratio [95% confidence interval] = 1.48 [1.15-1.92]) or ISS (1.52 [1.07-2.17]), despite ISS reporting the poorest mental and physical health. Although sex did not formally moderate the relationship between phenotype and mortality, subgroup analyses indicated that these findings were driven primarily by women. Phenotype did not predict cardiovascular mortality. Conclusions These analyses support the utility of examining multidimensional sleep health profiles by suggesting that the combination of long sleep, high efficiency/satisfaction, and daytime sleepiness—previously identified as independent risk factors—may be components of a single high-risk sleep phenotype, HSP. Further investigation of sex differences and the mechanisms underlying mortality risk associated with HSP is warranted.

Study Objectives To determine the associations of sleep-disordered breathing (SDB) with subsequent healthcare costs and utilization including inpatient and post-acute care facility stays among community-dwelling older men. Methods Participants were 1,316 men (mean age 76.1 [SD = 5.7] years) in the Outcomes of Sleep Disorders in Older Men (MrOS sleep) study (from December 2003 to March 2005), who were enrolled in a Medicare Fee-For-Service plan. Primary SDB measures including apnea hypopnea index (AHI) and oxygen desaturation index (ODI) were collected using in-home level 2 polysomnography. Incident healthcare costs and utilization were determined from claims data in the subsequent 3-year period post-MrOS sleep visit. Results Five hundred and twenty-nine (40.2%) men had at least one hospitalization in the 3-year period. Compared with those without sleep apnea (AHI < 5/hour), men with moderate to severe sleep apnea (AHI ≥ 15/hour) had a higher odds of all-cause hospitalization (odds ratio [OR] adjusted for age and site 1.43, 95% confidence interval [CI]: 1.07–1.90). This association was slightly attenuated after further adjustment for traditional prognostic factors including education, body mass index, comorbid medical conditions, and health status (OR = 1.36; 95% CI: 1.01–1.83). Similar associations were observed for ODI. However, measures of SDB were not related to subsequent healthcare costs (total or outpatient) or odds of post-acute skilled nursing facility stay. Conclusions Older men with SDB have an increased risk of hospitalization, not entirely explained by the greater prevalence of comorbid conditions, but not higher subsequent total healthcare costs. These findings indicate a need to evaluate the impact of SDB treatment on subsequent healthcare utilization.

Background Evidence suggests that short and long sleep durations are potential lifestyle factors associated with cardiovascular disease (CVD). Research on sleep duration and CVD risk is limited by use of self-report sleep measures, homogeneous populations, and studies on individual CVD risk factors. For women, risk of CVD and inadequate sleep duration increases with age. We hypothesized that accelerometer-measured sleep duration was associated with 10-year predicted probability of future CVD risk in a cohort of aging women. Methods This cross-sectional analysis included 3,367 older women (mean age 78.9 years; 53.3% White), from the Objective Physical Activity and Cardiovascular Health Study, ancillary study to the Women’s Health Initiative. Women wore ActiGraph GT3X+ accelerometers on the hip for 24 hours/7 days. A 10-year predicted probability of future CVD risk, the Reynolds Risk Score (RRS), was computed using age, systolic blood pressure, high-sensitivity C-reactive protein (CRP), total and HDL cholesterol, diabetes mellitus status, smoking status, and family history of CVD. Average nightly sleep duration was derived from accelerometer data. Adjusted linear regression models investigated the association between sleep duration and RRS. Results Results suggested a U-shaped relationship between sleep duration and RRS, with both short and long sleep associated with higher RRS (p < .001). The association remained significant after adjustments for race/ethnicity, education, lifestyle factors, and health status indicators. Conclusion In older women, actigraphy-ascertained sleep duration was associated with a 10-year predicted probability of future CVD risk. This study supports sleep duration as a modifiable risk factor for CVD in older women.

IntroductionLittle is known about the longitudinal association between napping and cognitive impairment in older adults.MethodsWe used wrist actigraphy to measure naps in 2751 community-dwelling older men. Cognition was assessed repeatedly over 12years, and clinically significant cognitive impairment was determined by physician diagnosis, Alzheimer's medication use or a significant cognitive decline.ResultsAfter adjustment for all covariates, men with longer napping duration had greater cognitive decline and higher risk of cognitive impairment. Men who napped for ≥120min/day (vs.

Introduction: While the Accreditation Council for Graduate Medical Education limited first year resident-physicians to 16 consecutive work hours from 2011 to 2017, resident-physicians in their second year or higher were permitted to work up to 28 h consecutively. This paper describes the Randomized Order Safety Trial Evaluating Resident-physician Schedules (ROSTERS) study, a clustered-randomized crossover clinical trial designed to evaluate the effectiveness of eliminating traditional shifts of 24 h or longer for second year or higher resident-physicians in pediatric intensive care units (PICUs). Methods: ROSTERS was a multi-center non-blinded trial in 6 PICUs at US academic medical centers. The primary aim was to compare patient safety between the extended duration work roster (EDWR), which included shifts �24 h, and a rapidly cycling work roster (RCWR), where shifts were limited to a maximum of 16 h. Information on potential medical errors was gathered and used for classification by centrally trained physician reviewers who were blinded to the study arm. Secondary aims were to assess the relationship of the study arm to resident-physician sleep duration, work hours and neurobehavioral performance. Results: The study involved 6577 patients with a total of 38,821 patient days (n = 18,749 EDWR, n = 20,072 RCWR). There were 413 resident-physician rotations included in the study (n = 203 EDWR, n = 210 RCWR). Resident-physician questionnaire data were over 95% complete. Conclusions: Results from data collected in the ROSTERS study will be evaluated for the impact of resident-physician schedule roster on patient safety outcomes in PICUs, and will allow for examination of a number of secondary outcome measures. ClinicalTrials.gov Identifier: NCT02134847 © 2019 Elsevier Inc.

Castleman disease (CD) describes a spectrum of heterogeneous disorders defined by characteristic lymph node histopathology. Enlarged lymph nodes demonstrating CD histopathology can occur in isolation (unicentric CD; UCD) sometimes accompanied by mild symptoms, or at multiple sites (multicentric CD, MCD) with systemic inflammation and cytokine-driven multi-organ dysfunction. The discovery that Kaposi sarcoma herpesvirus/human herpesvirus (HHV)-8 drives MCD in a subset of patients has led to the hypotheses that UCD and MCD patients with negative HHV-8 testing by conventional methods may represent false negatives, or that these cases are driven by another virus, known or unknown. To investigate these hypotheses, the virome capture sequencing for vertebrate viruses (VirCapSeq-VERT) platform was employed to detect RNA transcripts from known and novel viruses in fresh frozen lymph node tissue from CD patients (12 UCD, 11 HHV-8-negative MCD [idiopathic MCD; iMCD], and two HHV-8-positive MCD) and related diseases (three T cell lymphoma and three Hodgkin lymphoma). This assay detected HHV-8 in both HHV-8-positive cases; however, HHV-8 was not found in clinically HHV-8-negative iMCD or UCD cases. Additionally, no novel viruses were discovered, and no single known virus was detected with apparent association to HHV-8-negative CD cases. Herpesviridae family members, notably including Epstein-Barr virus (EBV), were detected in 7 out of 12 UCD and 5 of 11 iMCD cases with apparent correlations with markers of disease severity in iMCD. Analysis of a separate cohort of archival formalin-fixed, paraffin-embedded lymph node tissue by In situ hybridization revealed significantly fewer EBV-positive cells in UCD and iMCD compared to tissue from HHV-8-positive MCD and EBV-associated lymphoproliferative disorder. In an additional cohort, quantitative testing for EBV by PCR in peripheral blood during disease flare did not detect systemic EBV viremia, suggesting detection lymph node tissue is due to occult, local reactivation in UCD and iMCD. This study confirms that HHV-8 is not present in UCD and iMCD patients. Further, it fails to establish a clear association between any single virus, novel or known, and CD in HHV-8-negative cases. Given that distinct forms of CD exist with viral and non-viral etiological drivers, CD should be considered a group of distinct and separate diseases with heterogeneous causes worthy of further study.

Castleman disease (CD) describes a group of heterogeneous hematologic disorders with characteristic histopathological features. CD can present with unicentric or multicentric (MCD) regions of lymph node enlargement. Some cases of MCD are caused by human herpesvirus-8 (HHV-8), whereas others are HHV-8–negative/idiopathic (iMCD). Treatment of iMCD is challenging, and outcomes can be poor because no uniform treatment guidelines exist, few systematic studies have been conducted, and no agreed upon response criteria have been described. The purpose of this paper is to establish consensus, evidence-based treatment guidelines based on the severity of iMCD to improve outcomes. An international Working Group of 42 experts from 10 countries was convened by the Castleman Disease Collaborative Network to establish consensus guidelines for the management of iMCD based on published literature, review of treatment effectiveness for 344 cases, and expert opinion. The anti–interleukin-6 monoclonal antibody siltuximab (or tocilizumab, if siltuximab is not available) with or without corticosteroids is the preferred first-line therapy for iMCD. In the most severe cases, adjuvant combination chemotherapy is recommended. Additional agents are recommended, tailored by disease severity, as second- and third-line therapies for treatment failures. Response criteria were formulated to facilitate the evaluation of treatment failure or success. These guidelines should help treating physicians to stratify patients based on disease severity in order to select the best available therapeutic option. An international registry for patients with CD (ACCELERATE, #NCT02817997) was established in October 2016 to collect patient outcomes to increase the evidence base for selection of therapies in the future.

Falls occur in 25% of adults aged ≥65 years. The number of fall-related injuries is increasing, highlighting the need to identify modifiable risk factors. We examined the role of perceived physical and mental fatigability on prospective fall risk in 2,113 men aged 77–101 years (mean=84.6 ± 4.3) in MrOS. The Pittsburgh Fatigability Scale (0–50 score) was completed in 2014–16; established cutpoints classified higher physical (≥15, 57%) and higher mental (≥13, 26.1%) fatigability. Prospective falls were captured by triannual questionnaire post-fatigability assessment. After 12 months, 25.3% with higher vs. 16.7% with lower physical fatigability had a fall; 29.1% with higher vs. 19% with lower mental fatigability had a fall. Using GEE, higher physical fatigability increased prospective fall risk by 20% (RR: 1.20, 95%CI: 1.01,1.44) independent of mental fatigability, and adjusted for demographics, medical history, medications, depression, and physical and cognitive function. Higher physical fatigability may indicate a high-risk group for fall risk interventions.

We examined the association of arthritis with sleep health in older men, and whether sleep health mediates the associations of arthritis with systemic inflammation. Data came from 2,560 community-dwelling older men. Participants reported whether they had osteoarthritis (OA) or rheumatoid arthritis (RA). We constructed sleep health index (self-reported sleep quality, sleepiness; actigraphy-assessed wake-after-sleep-onset, sleep duration, and napping, Range=0–5) and binary indicators of elevated inflammation using C-reactive protein (CRP) and interleukin-6 (IL-6). Analyses adjusted for age, sleep disorders, comorbidities, BMI, smoking status, and relevant medication use. Older men with OA or RA had poorer sleep health. Poorer sleep health was associated with 16%-15% higher risk of elevated CRP and 12%-11% higher risk of elevated IL-6, respectively, after controlling separately for OA or RA. The associations of OA or RA with inflammation were mediated by poorer sleep health. Promoting sleep health may reduce associations between older men’s arthritis and high systemic inflammation.

Sleep is a significant contributor to health and wellbeing across the lifespan, especially in later life. Poor sleep is common among older adults and can be both a risk factor for and consequence of numerous physical and mental health-related outcomes. In this symposium, we will present novel results from four studies that will advance understanding of the biological, psychological, and social factors that may contribute to or result from poor sleep in older adults. Specifically, Study 1 will present findings tying objectively measured sleep to performance on cognitive tasks administered using ecological momentary assessment (EMA) in the day-to-day lives of older adults with or without mild cognitive impairment (MCI). Study 2 will examine associations of personality dimensions and facets with insomnia symptoms in well-functioning older adults. Study 3 will examine psychological pathways linking parent-child relationships to subjective and objective sleep characteristics among older parents. Finally, study 4 will examine use patterns of cannabis for the treatment of sleep problems in older adults, and the ways in which this might differ from patients using cannabis for other reasons (e.g., pain). Together, this symposium will highlight novel links of an array of factors with sleep health in the aging population and their implications for prevention. Sleep, Circadian Rhythms and Aging Interest Group Sponsored Symposium.

BACKGROUND: It is unknown whether subjective daytime sleepiness or objective napping could precede the risk of Parkinson’s disease (PD) in the long term. METHODS: We studied 2920 men (mean age 76 years) without a history of PD and followed them for 11 years. Excessive daytime sleepiness (EDS) was defined as having an Epworth Sleepiness Scale score >10. Objective naps were defined as ≥5 consecutive minutes of inactivity as measured by actigraphy, and napping duration was the accumulated time of naps outside the main sleep period. We used logistic regression to compare PD risk across four groups: no EDS& napping

Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10 -8 ) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.

Slow wave (or stage N3) sleep has been linked to a variety of cognitive processes. However, the role of stage N3 in the elderly is debated. The link between stage N3 and episodic memory may be weakened or changed in the older adult population, possibly due to several altered mechanisms impacting the cellular structure of the brain. The bases for the age-related dissociation between stage N3 and cognition are not understood. Since APOEε4 status is the strongest genetic risk factor for cognitive decline, we assessed whether the ε4 allele is associated with stage N3 sleep. Participants were from the population-based Osteoporotic Fractures in Men (MrOS) cohort with polysomnography and APOEε4 genotype data (n = 2,302, 100% male, mean age 76.6 years). Sleep stages were objectively measured using overnight in-home polysomnography and central electroencephalogram data were used to score stage N3 sleep. Cognitive function was assessed using the Modified Mini Mental State Exam (3MS). The APOE rs429358 single nucleotide polymorphism, which defines the APOEε4 allele, was genotyped using a custom genotyping array. Total time in stage N3 sleep was significantly higher (p

STUDY OBJECTIVES:To examine whether change in caregiving status and intensity among community-dwelling older women was associated with sleep characteristics at follow-up, and whether perceived stress modified these associations. METHODS:The sample included 800 women aged 65 years or older who completed baseline and second follow-up interviews in the Caregiver-Study of Osteoporotic Fractures (Caregiver-SOF). Respondents were categorized into four groups based on change in caregiving status and intensity between the two time points: continuous noncaregivers, ceased caregivers, low-intensity caregivers (continuous caregivers with low/decreased intensity), and high-intensity caregivers (continuous caregivers with high/increased intensity or new caregivers). Perceived Stress Scale scores at the second follow-up were dichotomized into high versus low stress. Sleep outcomes at SOF Visit 8 (which overlapped with Caregiver-SOF second follow-up) included the Pittsburgh Sleep Quality Index total score; and actigraphy-measured total sleep time, sleep efficiency, wake after sleep onset, and sleep latency. RESULTS:Multivariate-adjusted sleep characteristics did not differ significantly across caregiving groups. Among high-intensity caregivers, however, those with high stress levels had significantly longer wake after sleep onset (mean 82.3 minutes, 95% confidence interval = 70.9-93.7) than those with low stress levels (mean 65.4 minutes, 95% confidence interval = 55.2-75.7). No other sleep outcomes were modified by stress levels. Further, higher stress was significantly associated with worse Pittsburgh Sleep Quality Index scores, regardless of the caregiving group. CONCLUSIONS:Overall, sleep characteristics did not differ among noncaregivers, ceased caregivers, or those with high-/low-intensity caregiving among older women. However, subgroups of caregivers may be vulnerable to developing sleep problems, particularly those with high stress levels.

Despite the widespread belief that napping is common among older adults, little is known about the correlates of napping. We examined the prevalence and correlates of self-reported and objectively measured napping among very old women.We studied 2,675 community-dwelling women (mean age 84.5 ± 3.7 years; range 79-96). Self-reported napping was defined as a report of regular napping for ≥1 hour per day. Individual objective naps were defined as ≥5 consecutive minutes of inactivity as measured by actigraphy and women were characterized as "objective nappers" if they had at least 60 minutes of naps per day.Seven percent of the women only had self-reported napping, 29% only had objective napping, and 14% met the criteria for both. Multinomial logistic regression showed that the independent correlates of "both subjective and objective napping" were age (per 5 year odds ratio [OR] = 1.59; 95% CI: 1.31-1.93), depressive symptoms (per SD of score, OR = 1.53; 1.32-1.77), obesity (OR =1.93; 1.42-2.61), current smoking (OR = 3.37; 1.56-7.30), heavier alcohol drinking (OR = 0.49; 0.34-0.71), history of stroke (OR = 1.56; 1.08-2.26), diabetes (OR = 2.40; 1.61-3.57), dementia (OR = 3.31; 1.27-8.62), and Parkinson's disease (OR = 7.43; 1.87-29.50). Besides, having objective napping alone was associated with age and diabetes, whereas subjective napping was associated with stroke and myocardial infarction. These associations were independent of nighttime sleep duration and fragmentation.Daytime napping is very common in women living in their ninth decade and both subjective and objective napping were significantly related to age and comorbidities. Future studies are needed to better understand napping and its health implications.

BACKGROUND: There is growing interest in the area of “wearable tech” and its relationship to health. A common element of many of these devices is a triaxial accelerometer that can yield continuous information on gross motor activity levels; how such data might predict changes in health is less clear. METHODS: We examined accelerometry data from 2,976 older men who were part of the Osteoporotic Fractures in Men (MrOS) study. Using a shape-naive technique, functional principal component analysis, we examined the patterns of motor activity over the course of 4–7 days and determined whether these patterns were associated with changes in polysomnographic-determined sleep and cognitive function (Trail Making Test—Part B [Trails B], Modified Mini-Mental State Examination [3MS]), as well as mortality over 6.5–8 years of follow-up. RESULTS: In comparing baseline to 6.5 years later, multivariate modeling indicated that low daytime activity at baseline was associated with worsening of sleep efficiency (p < .05), more wake after sleep onset (p < .05), and a decrease in cognition (Trails B; p < .001), as well as a 1.6-fold higher rate of all-cause mortality (hazard ratio = 1.64 [1.34–2.00]). Earlier wake and bed times were associated with a decrease in cognition (3MS; p < .05). Having a late afternoon peak in activity was associated with a 1.4-fold higher rate of all-cause mortality (hazard ratio = 1.46 [1.21–1.77]). Those having a longer duration of their daytime activity with a bimodal activity pattern also had over a 1.4-fold higher rate of cardiovascular-related mortality (hazard ratio = 1.42 [1.02–1.98]). CONCLUSIONS: Patterns of daily activity may be useful as predictive biomarkers for changes in clinically relevant outcomes, including mortality and changes in sleep and cognition in older men.

© 2016, International Osteoporosis Foundation and National Osteoporosis Foundation. Summary: Dysregulated rest-activity rhythm (RAR) patterns have been associated with several health conditions in older adults. This study showed that later acrophase was associated with a modestly greater risk of falls but not fractures in elderly men. Associations between dysregulated RAR patterns and osteoporosis risk warrant further investigation. Purpose: The purpose of this study was to investigate the relationship between rest-activity rhythm (RAR) patterns and risk of falls/fractures in older men. We hypothesized that dysregulated RAR would be associated with incident falls/fractures. Methods: We used wrist-worn actigraphy to measure RAR over 4.8 ± 0.8 24-h periods in men (≥67 years) enrolled in the multicenter Outcomes of Sleep Disorders in Men (MrOS Sleep) Study (n = 3001). Men were contacted every 4 months to report occurrence of falls/fractures. RAR parameters included amplitude (difference between peak and nadir activity in counts/minute), mesor (activity counts/minute), acrophase (time of day of peak activity), and pseudo-F statistic (rhythm robustness) and were evaluated as continuous variables with associations reported per SD increase/decrease in models adjusted for confounders. Logistic regression was used to estimate the likelihood (odds ratio, OR) of recurrent falls in the year after the visit. Proportional hazards models were used to estimate the risk (hazard ratio, HR) of fractures. Results: One year after the visit, 417 men (14%) had recurrent (≥2) falls. Later acrophase (OR 1.18, 95% CI 1.06–1.32) was associated with a modestly greater likelihood of falls. In 8.6 years (SD 2.6 years) of >97% complete follow-up, 256 men (8.53%) had a major osteoporotic fracture, 85 (2.8%) had a clinical spine fracture, and 110 (3.7%) had a hip fracture. No consistent, significant associations were observed between RAR patterns and fractures. Conclusions: Later acrophase was associated with a modestly greater risk of falls; this association did not translate into a higher fracture risk in this cohort of elderly men.

The "first-night effect" of polysomnography (PSG) has been previously studied; however, the ability to quantify the sleep disruption level has been confounded with the use of PSG on all nights. We used actigraphy to quantify disruption level and examined characteristics associated with disruption.Totally, 778 older men (76.2 ± 5.4 years) from a population-based study at six US centers underwent one night of in-home PSG. Actigraphy was performed on the PSG night and three subsequent nights. Actigraphically measured total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), and sleep onset latency (SOL) from the PSG night and subsequent nights were compared. Linear regression models were used to examine the association of characteristics and sleep disruption.On average, sleep on the PSG night was worse than the following night (p 0.05, TST 21 ± 85 min less, SE 2.3 ± 11.3% less, WASO 4.9 ± 51.8 min more, SOL 6.6 ± 56.2 min more). Sleep on the PSG night was significantly worse than that two and three nights later. Characteristics associated with greater sleep disruption on the PSG night included older age, higher apnea-hypopnea index, worse neuromuscular function, and more depressive symptoms. Minorities and men with excessive daytime sleepiness slept somewhat better on the PSG night.Among older men, there was sleep disruption on the PSG night, which may lead to sleep time underestimation. The increase of sleep on the night after the PSG suggests that data from the second monitoring may overestimate sleep.

Time to fall asleep (sleep latency) is a major determinant of sleep quality. Chronic, long sleep latency is a major characteristic of sleep-onset insomnia and/or delayed sleep phase syndrome. In this study we aimed to discover common polymorphisms that contribute to the genetics of sleep latency. We performed a meta-analysis of genome-wide association studies (GWAS) including 2 572 737 single nucleotide polymorphisms (SNPs) established in seven European cohorts including 4242 individuals. We found a cluster of three highly correlated variants (rs9900428, rs9907432 and rs7211029) in the RNA-binding protein fox-1 homolog 3 gene (RBFOX3) associated with sleep latency (P-values=5.77 × 10(-08), 6.59 × 10(-)(08) and 9.17 × 10(-)(08)). These SNPs were replicated in up to 12 independent populations including 30 377 individuals (P-values=1.5 × 10(-)(02), 7.0 × 10(-)(03) and 2.5 × 10(-)(03); combined meta-analysis P-values=5.5 × 10(-07), 5.4 × 10(-07) and 1.0 × 10(-07)). A functional prediction of RBFOX3 based on co-expression with other genes shows that this gene is predominantly expressed in brain (P-value=1.4 × 10(-316)) and the central nervous system (P-value=7.5 × 10(-)(321)). The predicted function of RBFOX3 based on co-expression analysis with other genes shows that this gene is significantly involved in the release cycle of neurotransmitters including gamma-aminobutyric acid and various monoamines (P-values

STUDY OBJECTIVES To examine the association between periodic limb movements in sleep (PLMS) and change in selected aspects of cognition in community-dwelling older men. METHODS We studied 2,636 older men without dementia who underwent in-home polysomnography with measurement of the periodic limb movement index (PLMI) and periodic limb movement arousal index (PLMAI) using piezoelectric sensors. Random-effects models and logistic regression were used to examine the association between PLMI, PLMAI, and 3- to 4-y change in cognition. RESULTS After multivariable adjustment, men with a high PLMI had greater decline on the Trail Making Test - Part B (P trend = 0.02); those with a PLMI ≥ 30 were 48% more likely (odds ratio = 1.48, 95% confidence interval = 1.05-2.07) to experience the development of significant cognitive impairment (≥ 1 SD above mean change). Further adjustment for sleep efficiency, nocturnal hypoxemia, or dopaminergic medication use and analysis among men without Parkinson disease (n = 2,607) showed similar findings. No significant association was found for PLMAI or for Modified Mini-Mental State Examination scores. CONCLUSIONS Among older men without dementia, higher PLMS frequency was associated with greater decline in cognition, particularly in executive function.

Background: Recently, the first estimated glomerular filtration rate (eGFR) formula specifically developed for community-dwelling older adults, the Berlin Initiative Study Equation 2 (BIS2), was reported. To date, however, no study has examined the performance of the BIS2 to predict death in older adults as compared to equations used clinically and in research. Methods: We prospectively followed 2,994 community-dwelling men (age 76.4 ± 5.6) enrolled in the MrOS Sleep Study. We calculated baseline eGFR from serum creatinine and cystatin-C using the BIS2, Chronic Kidney Disease Epidemiology (CKD-EPIcr,cysc), CKD-EPIcysc and CKD-EPIcr equations. Analyses included Cox-proportional hazards regression and net reclassification improvement (NRI) for the outcomes of all-cause and cardiovascular death. Results: Follow-up time was 7.3 ± 1.9 years. By BIS2, 42 and 11% had eGFR cr (23 and 6%), CKD-EPIcysc (36 and 13%) and CKD-EPIcr,cysc (28 and 8%). BIS2 eGFR cr,cysc cysc cr cr,cysc, both BIS2 and CKD-EPIcr equations more often misclassified participants with respect to mortality. We found similar results for cardiovascular death. Conclusion: The BIS2 did not outperform and the CKD-EPIcr was inferior to the cystatin C-based CKD-EPI equations to predict death in this cohort of older men. Thus, the cystatin C-based CKD-EPI equations are the formulae of choice to predict death in community-dwelling older men.

Sleep duration is implicated in the etiologies of chronic diseases and premature mortality. However, the genetic basis for sleep duration is poorly defined. We sought to identify novel genetic components influencing sleep duration in a multi-ethnic sample. Meta-analyses were conducted of genetic associations with self-reported, habitual sleep duration from seven Candidate Gene Association Resource (CARe) cohorts of over 25 000 individuals of African, Asian, European and Hispanic American ancestry. All individuals were genotyped for ∼50 000 SNPs from 2000 candidate heart, lung, blood and sleep genes. African-Americans had additional genome-wide genotypes. Four cohorts provided replication. A SNP (rs17601612) in the dopamine D2 receptor gene (DRD2) was significantly associated with sleep duration (P = 9.8 × 10(-7)). Conditional analysis identified a second DRD2 signal with opposite effects on sleep duration. In exploratory analysis, suggestive association was observed for rs17601612 with polysomnographically determined sleep latency (P = 0.002). The lead DRD2 signal was recently identified in a schizophrenia GWAS, and a genetic risk score of 11 additional schizophrenia GWAS loci genotyped on the IBC array was also associated with longer sleep duration (P = 0.03). These findings support a role for DRD2 in influencing sleep duration. Our work motivates future pharmocogenetics research on alerting agents such as caffeine and modafinil that interact with the dopaminergic pathway and further investigation of genetic overlap between sleep and neuro-psychiatric traits.

Objective The objective of this study was to assess the relationship between single-nucleotide polymorphisms associated with restless legs syndrome and periodic limb movements of sleep in a population cohort of elderly individuals. Methods Single-nucleotide polymorphisms previously associated with periodic limb movements of sleep or restless legs syndrome were analyzed in 2356 white male participants in the Osteoporotic Fractures in Men Sleep Study cohort. The associations between single-nucleotide polymorphisms and polysomnographically measured periodic limb movement index ≥15 were examined with logistic regression adjusted for age, ancestry markers, and periodic limb movements of sleep risk factors. Results Of the men in this cohort, 61% had a periodic limb movement index ≥15. Significant associations were observed between a periodic limb movement index ≥15 and the number of risk alleles for the two BTBD9 single-nucleotide polymorphisms (rs9357271[T], odds ratio [OR] = 1.38, 95% confidence interval [CI] 1.20–1.58; and rs3923809[A], OR = 1.43, 95% CI 1.26–1.63), one of the MEIS1 single-nucleotide polymorphisms (rs2300478[G], OR = 1.31, 95% CI 1.14–1.51) and the mitogen-activated protein kinase kinase 5 (MAP2K5)/Ski family transcriptional corepressor 1 (SKOR1) single-nucleotide polymorphism (rs1026732[G], OR = 1.16, 95% CI 1.02–1.31). In a multivariable model controlling for each of the two MEIS1 single-nucleotide polymorphisms, the rs6710341[A] single-nucleotide polymorphism became a significant risk allele (OR = 1.59, 95% CI 1.26–2.00). Conclusions Our findings confirm an association between the BTBD9, MEIS1, and MAP2K5/SKOR1 single-nucleotide polymorphisms and periodic limb movements of sleep in an elderly cohort not selected for the presence of restless legs syndrome.

© 2015 Taylor & Francis Group, LLC. Activity rhythm disturbances and depression often co-occur among older adults. However, little is known about how activity rhythm disturbances themselves co-occur, or how disturbances to multiple aspects of the activity rhythm relate to depression over time. In this study, we performed a Latent Class Analysis to derive sub-groups of older men [total n = 2933, mean age = 76.28, standard deviation (SD) = 5.48] who shared similar patterns of activity rhythm disturbances (defined as extreme values of modeled activity rhythm parameters). We found eight sub-groups with distinct combinations of activity rhythm disturbances: one had all normative activity rhythm parameters (32.09%), one had only lower activity (10.06%), three had earlier activity (totaling 26.96%) and three had later activity (totaling 30.89%). Groups with similar timing were distinguished depending on whether the relative length of the active period was shorter and/or if the activity rhythm had lesser amplitude/robustness. We next examined whether the derived activity rhythm sub-groups were associated with different rates of change in depression symptom levels over an average of 5.5 (0.52 SD) follow-up years. The sub-group with lower activity only had faster increases in depressive symptoms over time (compared with the group with normative rhythm parameters), but this association was accounted for by adjustments for concurrently assessed health status covariates. Independent of these covariates, we found that four activity rhythm disturbance sub-groups experienced faster depressive symptom increases (compared with the normative sub-group): These included all three sub-groups that had later activity timing and one sub-group that had earlier activity timing plus a shorter active period and a dampened rhythm. Low activity rhythm height/robustness with normal timing therefore may mark depression risk that is attributable to co-occurring disease processes; in contrast, having late or combined early/compressed/dampened activity rhythms may independently contribute to depression symptom development. Our findings suggest that activity rhythm-related depression risk is heterogeneous, and may be detected when multiple aspects of rhythm timing are delayed or when early timing is accompanied by compressed/dampened activity rhythms. Future studies should consider how distinct combinations of altered activity rhythm timing and height/robustness develop and conjointly determine health risks. Further research is also needed to determine whether/how activity rhythms can be modified to improve depression outcomes.

Highly activated/expanded natural killer (NK) cells can be generated by stimulation with the human leukocyte antigen-deficient cell line K562, genetically modified to express 41BB-ligand and membrane-bound interleukin (IL)15. We tested the safety, persistence, and activity of expanded NK cells generated from myeloma patients (auto-NK) or haploidentical family donors (allo-NK) in heavily pretreated patients with high-risk relapsing myeloma. The preparative regimen comprised bortezomib only or bortezomib and immunosuppression with cyclophosphamide, dexamethasone, and fludarabine. NK cells were shipped overnight either cryopreserved or fresh. In 8 patients, up to 1×10⁸ NK cells/kg were infused on day 0 and followed by daily administrations of IL2. Significant in vivo expansion was observed only in the 5 patients receiving fresh products, peaking at or near day 7, with the highest NK-cell counts in 2 subjects who received cells produced in a high concentration of IL2 (500 U/mL). Seven days after infusion, donor NK cells comprised90% of circulating leukocytes in fresh allo-NK cell recipients, and cytolytic activity against allogeneic myeloma targets was retained in vitro. Among the 7 evaluable patients, there were no serious adverse events that could be related to NK-cell infusion. One patient had a partial response and in another the tempo of disease progression decreased; neither patient required further therapy for 6 months. In the 5 remaining patients, disease progression was not affected by NK-cell infusion. In conclusion, infusion of large numbers of expanded NK cells was feasible and safe; infusing fresh cells was critical to their expansion in vivo.

STUDY OBJECTIVES To examine associations of objectively and subjectively measured sleep with subsequent cognitive decline. DESIGN A population-based longitudinal study. SETTING Six centers in the United States. PARTICIPANTS Participants were 2,822 cognitively intact community-dwelling older men (mean age 76.0 ± 5.3 y) followed over 3.4 ± 0.5 y. INTERVENTIONS None. MEASUREMENTS AND RESULTS OBJECTIVELY MEASURED SLEEP PREDICTORS FROM WRIST ACTIGRAPHY: total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), number of long wake episodes (LWEP). Self-reported sleep predictors: sleep quality (Pittsburgh Sleep Quality Index [PSQI]), daytime sleepiness (Epworth Sleepiness Scale [ESS]), TST. Clinically significant cognitive decline: five-point decline on the Modified Mini-Mental State examination (3MS), change score for the Trails B test time in the worse decile. Associations of sleep predictors and cognitive decline were examined with logistic regression and linear mixed models. After multivariable adjustment, higher levels of WASO and LWEP and lower SE were associated with an 1.4 to 1.5-fold increase in odds of clinically significant decline (odds ratio 95% confidence interval) Trails B test: SE < 70% versus SE ≥ 70%: 1.53 (1.07, 2.18); WASO ≥ 90 min versus WASO < 90 min: 1.47 (1.09, 1.98); eight or more LWEP versus fewer than eight: 1.38 (1.02, 1.86). 3MS: eight or more LWEP versus fewer than eight: 1.36 (1.09, 1.71), with modest relationships to linear change in cognition over time. PSQI was related to decline in Trails B performance (3 sec/y per standard deviation increase). CONCLUSIONS Among older community-dwelling men, reduced sleep efficiency, greater nighttime wakefulness, greater number of long wake episodes, and poor self-reported sleep quality were associated with subsequent cognitive decline.

Objectives: To determine the association between interleukin-6 (IL-6), IL-6 soluble receptor (sR), and soluble tumor necrosis factor receptor-1 (sTNF-R1) and cognitive status in the oldest-old women. Design: Twenty-year longitudinal cohort study. Setting: Four clinical sites in the United States. Participants: Women from the Study of Osteoporotic Fractures (N = 905; mean age 88.3 ± 2.8 at cognitive status adjudication). Measurements: At Year 20, cognitive status was adjudicated as normal, mild cognitive impairment (MCI), or dementia. Inflammatory markers were measured from blood serum at Years 10 and 16 in a random sample of women. Results: Over 10 years, 199 (22.0%) women developed MCI and 145 (16.0%) dementia. There were no significant associations between IL-6 or sTNF-R1 and cognitive status. High IL-6-sR (?37,401.36 pg/mL, highest tertile) at Year 16 was significantly associated with lower risk of dementia (odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.30�0.97) than in women with lower levels (

To test the hypothesis that subjective and objective sleep disturbances are associated with risk of incident falls in older men.The prospective observational MrOS Sleep Study.Six academic clinical centers in the United States.Community-dwelling men aged 67 and older (mean 76) (n = 3,101).Subjective sleep measurements included daytime sleepiness (Epworth Sleepiness Scale (ESS)), sleep quality (Pittsburgh Sleep Quality Index (PSQI)), and total sleep time (TST). Objective sleep measurements included actigraphic TST and sleep efficiency (an index of fragmentation) and sleep disordered breathing (measured using in-home polysomnography). Fall frequency during the subsequent year was ascertained three times per year using questionnaires. Recurrent falling was defined as having two or more falls in the subsequent year.In multivariable-adjusted models, participants with excessive daytime sleepiness (ESS10) but not poor subjective sleep quality (PSQI5) had greater odds of experiencing two or more falls in the subsequent year (odds ratio (OR) = 1.52 95% confidence interval (CI) = 1.14-2.03). Based on actigraphic recordings, the odds of having recurrent falls was higher for men who slept 5 hours or less (OR = 1.79, 95% CI = 1.22-2.60) than for those who slept 7 to 8 hours. Actigraphically measured sleep efficiency was also associated with greater risk of falls, as was nocturnal hypoxemia (≥ 10% of sleep time with arterial oxygen saturation90%; OR = 1.62, 95% CI = 1.17-2.24) but not apnea hypopnea index.Subjective and objective sleep disturbances were associated with risk of falls in older men, independent of confounders.

Introduction Self-reported sleep disturbances are associated with an increased risk of depression in younger and older adults, but associations between objective assessments of sleep/wake disturbances via wrist actigraphy and risk of depression are unknown. Methods Depressive symptoms (Geriatric Depression Scale [GDS]), self-reported (questionnaires), and objective (actigraphy) sleep parameters were measured at baseline in 2,510 nondepressed men 67 y or older. Depressive symptoms were reassessed an average of 3.4 ± 0.5 y later. Results Of the 2,510 men without evidence of depression at baseline, 116 (4.6%) were depressed (GDS ≥ 6) at the follow-up examination. After adjusting for multiple potential confounders, including baseline depressive symptoms (GDS 0-5), there was evidence of an association between poor self-reported sleep quality and higher odds of being depressed at follow-up (multivariable odds ratio [MOR] = 1.53, 95% confidence interval (CI) 1.00-2.33). In age- and site-adjusted models, objectively measured reduced sleep efficiency (odds ratio [OR] = 1.88, 95% CI 1.13-3.13), prolonged sleep latency (OR = 1.77, 95% CI 1.04-3.00), greater nighttime wakefulness (OR = 1.48, 95% CI 1.01-2.18) and multiple long-wake episodes (OR = 1.69, 95% CI 1.15-2.47) were associated with increased odds of depression at follow-up, but these associations were attenuated and no longer significant after further adjustment for number of depressive symptoms at baseline. Self-reported excessive daytime sleepiness and objectively measured total sleep time were not associated with depression status at follow-up. Excluding baseline antidepressant users from the analyses did not alter the results. Conclusions Among nondepressed older men, poor self-reported sleep quality was associated with increased odds of depression several years later. Associations between objectively measured sleep disturbances (e.g., reduced sleep efficiency, prolonged sleep latency, greater nighttime wakefulness, and greater long-wake episodes) and depression several years later were largely explained by a greater burden of depressive symptoms at baseline. Citation Paudel M; Taylor BC; Ancoli-Israel S; Blackwell T; Maglione JE; Stone K; Redline S; Ensrud KE; for the Osteoporotic Fractures in Men Study Group. Sleep disturbances and risk of depression in older men. SLEEP 2013;36(7):1033-1040.