Impact of Sleep Disorders and Disturbed Sleep on Brain Health: A Scientific Statement From the American Heart Association.

Accumulating evidence supports a link between sleep disorders, disturbed sleep, and adverse brain health, ranging from stroke to subclinical cerebrovascular disease to cognitive outcomes, including the development of Alzheimer disease and Alzheimer disease-related dementias. Sleep disorders such as sleep-disordered breathing (eg, obstructive sleep apnea), and other sleep disturbances, as well, some of which are also considered sleep disorders (eg, insomnia, sleep fragmentation, circadian rhythm disorders, and extreme sleep duration), have been associated with adverse brain health. Understanding the causal role of sleep disorders and disturbances in the development of adverse brain health is complicated by the common development of sleep disorders among individuals with neurodegenerative disease. In addition to the role of sleep disorders in stroke and cerebrovascular injury, mechanistic hypotheses linking sleep with brain health and biomarker data (blood-based, cerebrospinal fluid-based, and imaging) suggest direct links to Alzheimer disease-specific pathology. These potential mechanisms and the increasing understanding of the "glymphatic system," and the recognition of the importance of sleep in poststroke recovery, as well, support a biological basis for the indirect (through the worsening of vascular disease) and direct (through specific effects on neuropathology) connections between sleep disorders and brain health. Given promising evidence for the benefits of treatment and prevention, sleep disorders and disturbances represent potential targets for early treatment that may improve brain health more broadly. In this scientific statement, we discuss the evidence supporting an association between sleep disorders and disturbances and poor brain health ranging from stroke to dementia and opportunities for prevention and early treatment.

Role of sleep in neurodegeneration: the consensus report of the 5th Think Tank World Sleep Forum.

Sleep abnormalities may represent an independent risk factor for neurodegeneration. An international expert group convened in 2021 to discuss the state-of-the-science in this domain. The present article summarizes the presentations and discussions concerning the importance of a strategy for studying sleep- and circadian-related interventions for early detection and prevention of neurodegenerative diseases. An international expert group considered the current state of knowledge based on the most relevant publications in the previous 5 years; discussed the current challenges in the field of relationships among sleep, sleep disorders, and neurodegeneration; and identified future priorities. Sleep efficiency and slow wave activity during non-rapid eye movement (NREM) sleep are decreased in cognitively normal middle-aged and older adults with Alzheimer's disease (AD) pathology. Sleep deprivation increases amyloid-ß (Aß) concentrations in the interstitial fluid of experimental animal models and in cerebrospinal fluid in humans, while increased sleep decreases Aß. Obstructive sleep apnea (OSA) is a risk factor for dementia. Studies indicate that positive airway pressure (PAP) treatment should be started in patients with mild cognitive impairment or AD and comorbid OSA. Identification of other measures of nocturnal hypoxia and sleep fragmentation could better clarify the role of OSA as a risk factor for neurodegeneration. Concerning REM sleep behavior disorder (RBD), it will be crucial to identify the subset of RBD patients who will convert to a specific neurodegenerative disorder. Circadian sleep-wake rhythm disorders (CSWRD) are strong predictors of caregiver stress and institutionalization, but the absence of recommendations or consensus statements must be considered. Future priorities include to develop and validate existing and novel comprehensive assessments of CSWRD in patients with/at risk for dementia. Strategies for studying sleep-circadian-related interventions for early detection/prevention of neurodegenerative diseases are required. CSWRD evaluation may help to identify additional biomarkers for phenotyping and personalizing treatment of neurodegeneration.

Associations of Physical Activity and Heart Rate Variability from a Two-Week ECG Monitor with Cognitive Function and Dementia: The ARIC Neurocognitive Study.

Low physical activity (PA) measured by accelerometers and low heart rate variability (HRV) measured from short-term ECG recordings are associated with worse cognitive function. Wearable long-term ECG monitors are now widely used, and some devices also include an accelerometer. The objective of this study was to evaluate whether PA or HRV measured from long-term ECG monitors was associated with cognitive function among older adults. A total of 1590 ARIC participants had free-living PA and HRV measured over 14 days using the Zio® XT Patch [aged 72-94 years, 58% female, 32% Black]. Cognitive function was measured by cognitive factor scores and adjudicated dementia or mild cognitive impairment (MCI) status. Adjusted linear or multinomial regression models examined whether higher PA or higher HRV was cross-sectionally associated with higher factor scores or lower odds of MCI/dementia. Each 1-unit increase in the total amount of PA was associated with higher global cognition (ß = 0.30, 95% CI: 0.16-0.44) and executive function scores (ß = 0.38, 95% CI: 0.22-0.53) and lower odds of MCI (OR = 0.38, 95% CI: 0.22-0.67) or dementia (OR = 0.25, 95% CI: 0.08-0.74). HRV (i.e., SDNN and rMSSD) was not associated with cognitive function. More research is needed to define the role of wearable ECG monitors as a tool for digital phenotyping of dementia.

Sleep Duration Polygenic Risk and Phenotype: Associations with Biomarkers of Accelerated Aging in the Baltimore Longitudinal Study of Aging.

We sought to explore whether genetic risk for, and self-reported, short sleep are associated with biological aging and whether age and sex moderate these associations. Participants were a subset of individuals from the Baltimore Longitudinal Study of Aging who had complete data on self-reported sleep (n = 567) or genotype (n = 367). Outcomes included: Intrinsic Horvath age, Hannum age, PhenoAge, GrimAge, and DNAm-based estimates of plasminogen activator inhibitor-1 (PAI-1) and granulocyte count. Results demonstrated that polygenic risk for short sleep was positively associated with granulocyte count; compared to those reporting <6 hr sleep, those reporting >7 hr demonstrated faster PhenoAge and GrimAge acceleration and higher estimated PAI-1. Polygenic risk for short sleep and self-reported sleep duration interacted with age and sex in their associations with some of the outcomes. Findings highlight that polygenic risk for short sleep and self-reported long sleep is associated with variation in the epigenetic landscape and subsequently aging.

Associations of Vascular Risk and Amyloid Burden with Subsequent Dementia.

OBJECTIVE: Midlife vascular risk factors (MVRFs) are associated with incident dementia, as are amyloid ß (Aß) deposition and neurodegeneration. Whether vascular and Alzheimer disease-associated factors contribute to dementia independently or interact synergistically to reduce cognition is poorly understood. METHODS: Participants in the Atherosclerosis Risk in Communities-Positron Emission Tomography study were followed from 1987-1989 (45-64 years old) through 2016-2017 (74-94 years old), with repeat cognitive assessment and dementia adjudication. In 2011-2013, dementia-free participants underwent brain magnetic resonance imaging (with white matter hyperintensity [WMH] and brain volume measurement) and florbetapir (Aß) positron emission tomography. The relative contributions of vascular risk and injury (MVRFs, WMH volume), elevated Aß standardized uptake value ratio (SUVR), and neurodegeneration (smaller temporoparietal brain regions) to incident dementia were evaluated with adjusted Cox models. RESULTS: In 298 individuals, 36 developed dementia (median follow-up = 4.9 years). Midlife hypertension and Aß each independently predicted dementia risk (hypertension: hazard ratio [HR] = 2.57, 95% confidence interval [CI] = 1.16-5.67; Aß SUVR [per standard deviation (SD)]: HR = 2.57, 95% CI = 1.72-3.84), but did not interact significantly, whereas late life diabetes (HR = 2.50, 95% CI = 1.18-5.28) and Aß independently predicted dementia risk. WMHs (per SD: HR = 1.51, 95% CI = 1.03-2.20) and Aß SUVR (HR = 2.52, 95% CI = 1.83-3.47) independently contributed to incident dementia, but WMHs lost significance when MVRFs were included. Smaller temporoparietal brain regions were associated with incident dementia, independent of Aß and MVRFs (HR = 2.18, 95% CI = 1.18-4.01). INTERPRETATION: Midlife hypertension and late life Aß are independently associated with dementia risk, without evidence for synergy on a multiplicative scale. Given the independent contributions of vascular and amyloid mechanisms, multiple pathways should be considered when evaluating interventions to reduce the burden of dementia. ANN NEUROL 2022;92:607-619.

Association of common infections with cognitive performance in the Baltimore Epidemiologic Catchment Area study follow-up.

INTRODUCTION: Growing evidence suggests that some common infections are causally associated with cognitive impairment; however, less is known about the burden of multiple infections. METHODS: We investigated the cross-sectional association of positive antibody tests for herpes simplex virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), and Toxoplasma gondii (TOX) with Mini-Mental State Examination (MMSE) and delayed verbal recall performance in 575 adults aged 41-97 from the Baltimore Epidemiologic Catchment Area Study. RESULTS: In multivariable-adjusted zero-inflated Poisson (ZIP) regression models, positive antibody tests for CMV (p = .011) and herpes simplex virus (p = .018) were individually associated with poorer MMSE performance (p = .011). A greater number of positive antibody tests among the five tested was associated with worse MMSE performance (p = .001). DISCUSSION: CMV, herpes simplex virus, and the global burden of multiple common infections were independently associated with poorer cognitive performance. Additional research that investigates whether the global burden of infection predicts cognitive decline and Alzheimer's disease biomarker changes is needed to confirm these findings.

Hospital-diagnosed sleep disorders and incident dementia: a nationwide observational cohort study.

BACKGROUND AND PURPOSE: Several smaller, community-based studies have suggested a link between sleep disorders and dementia with a focus on sleep as a modifiable risk factor for dementia. Studies on neurodegenerative diseases are prone to reverse causation, and few studies have examined the association with long follow-up time. Our aim was to explore the possible association between sleep disorders and late-onset dementia in an entire population. METHODS: In a nationwide cohort with 40-year follow-up, associations between hospital-based sleep disorder diagnoses and late-onset dementia were assessed. Incidence rate ratios (IRR) were calculated using Poisson regression. RESULTS: The cohort consisted of 1,491,276 people. Those with any sleep disorder had a 17% higher risk of dementia (IRR 1.17, 95% confidence interval [CI] 1.11-1.24) compared to people with no sleep disorder, adjusted for age, sex, calendar year, highest attained educational level at age 50, and somatic and psychiatric comorbidity. The risk of dementia was significantly increased 0-5 years after sleep disorder diagnosis (IRR 1.35, 95% CI 1.25-1.47), whilst the association after 5 years or more was non-significant (1.05, 95% CI 0.97-1.13). CONCLUSIONS: Our findings show an increased short-term risk of dementia following a hospital-based sleep disorder diagnosis, whilst weaker evidence of a long-term risk was found. This could potentially point towards sleep disorders as an early symptom of dementia. Further research is needed to distinguish sleep disorders as an early symptom of dementia, a risk factor, or both.

Association between walking energy utilisation and longitudinal cognitive performance in older adults.

BACKGROUND: Human motor function is optimised for energetic efficiency, however, age-related neurodegenerative changes affects neuromotor control of walking. Energy utilisation has been associated with motor performance, but its association with cognitive performance is unknown. METHODS: The study population included 979 Baltimore Longitudinal Study of Aging participants aged $\ge$50 years (52% female, mean age: 70$\pm$10.2 years) with a median follow-up time of 4.7 years. Energy utilisation for walking was operationalised as a ratio of the energy cost of slow walking to peak walking energy expenditure during standardised tasks ('cost-ratio'). Cognitive functioning was measured using the Trail Making Tests, California Verbal Learning Test, Wechsler Adult Intelligence Scale (WAIS), letter and category fluency and card rotation tests. Linear mixed models adjusted for demographics, education and co-morbidities assessed the association between baseline cost-ratio and cognitive functioning, cross-sectionally and longitudinally. To investigate the relationship among those with less efficient energy utilisation, subgroup analyses were performed. RESULTS: In fully adjusted models, a higher cost-ratio was cross-sectionally associated with poorer performance on all cognitive tests except WAIS (P < 0.05 for all). Among those with compromised energy utilisation, the baseline cost-ratio was also associated with a faster decline in memory (long-delay free recall: ß = -0.4, 95% confidence interval [CI] = [-0.8, -0.02]; immediate word recall: ß = -1.3, 95% CI = [-2.7, 0.1]). CONCLUSIONS: These findings suggest cross-sectional and longitudinal links between energy utilisation and cognitive performance, highlighting an intriguing link between brain function and the energy needed for ambulation. Future research should examine this association earlier in the life course to gauge the potential for interventive mechanisms.

Effects of Weight Loss on Obstructive Sleep Apnea Severity. Ten-Year Results of the Sleep AHEAD Study.

Rationale: Weight loss is recommended to treat obstructive sleep apnea (OSA).Objectives: To determine whether the initial benefit of intensive lifestyle intervention (ILI) for weight loss on OSA severity is maintained at 10 years.Methods: Ten-year follow-up polysomnograms of 134 of 264 adults in Sleep AHEAD (Action for Health in Diabetes) with overweight/obesity, type 2 diabetes mellitus, and OSA were randomized to ILI for weight loss or diabetes support and education (DSE).Measurements and Main Results: Change in apnea-hypopnea index (AHI) was measured. Mean ± SE weight losses of ILI participants of 10.7 ± 0.7, 7.4 ± 0.7, 5.1 ± 0.7, and 7.1 ± 0.8 kg at 1, 2, 4, and 10 years, respectively, were significantly greater than the 1-kg weight loss at 1, 2, and 4 years and 3.5 ± 0.8 kg weight loss at 10 years for the DSE group (P values ≤ 0.0001). AHI was lower with ILI than DSE by 9.7, 8.0, and 7.9 events/h at 1, 2, and 4 years, respectively (P values ≤ 0.0004), and 4.0 events/h at 10 years (P = 0.109). Change in AHI over time was related to amount of weight loss, baseline AHI, visit year (P values < 0.0001), and intervention independent of weight change (P = 0.01). OSA remission at 10 years was more common with ILI (34.4%) than DSE (22.2%).Conclusions: Participants with OSA and type 2 diabetes mellitus receiving ILI for weight loss had reduced OSA severity at 10 years. No difference in OSA severity was present between ILI and DSE groups at 10 years. Improvement in OSA severity over the 10-year period with ILI was related to change in body weight, baseline AHI, and intervention independent of weight change.

Impacts of depression subcase and case on all-cause mortality in older people: The findings from the multi-centre community-based cohort study in China.

OBJECTIVES: It is unclear whether and to what extent depression subcases and cases in older age were associated with all-cause mortality. Little is known about gender differences in the associations. We assess these in older Chinese. METHODS: We examined a random sample of 6124 participants aged ≥60 years across five provinces in China. They were interviewed using a standard method of the GMS-AGECAT to diagnose depression subcase and case and record sociodemographic and disease risk factors at baseline, and to follow up their vital status. We employed Cox regression models to determine all-cause mortality in relation to depression subcases and cases, with adjustment for important variables, including social support and co-morbidities. RESULTS: Over the 10-year follow-up, 928 deaths occurred. Compared to those without depression at baseline, participants with depression subcase (n = 196) and case (n = 264) had increased risk of mortality; adjusted hazard ratios (HRs) were 1.46 (95% CI 1.07-2.00) and 1.45 (1.10-1.91). The adjusted HRs in men were 1.15 (0.72-1.81) and 1.85 (1.22-2.81), and in women 1.87 (1.22-2.87) and 1.22 (0.83-1.77) respectively. In participants aged ≥65 years, the adjusted HRs were 1.12 (0.68-1.84) and 1.99 (1.28-3.10) in men, and 2.06 (1.32-2.24) and 1.41 (0.94-2.10) in women. Increased HR in depression subcases was higher in women than man (ratio of HRs was 1.84, p = 0.034). CONCLUSIONS: Older people with depression subcase could have increased all-cause mortality to a similar extent to those with depression case. More attention should be paid to subcases of depression in women to tackle gender inequalities and improve survival.

Sleep Duration and Cognition in a Nationally Representative Sample of U.S. Older Adults.

OBJECTIVE: Excessive and insufficient sleep have been associated with cognitive dysfunction in older adults in U.S. and non-U.S. STUDIES: However, the U.S. studies were not in nationally representative samples. The authors investigated the association between sleep duration and cognitive performance in a nationally representative sample of U.S. older adults. PARTICIPANTS: The authors studied 1,496 survey participants aged 60 years or older from the National Health and Nutrition Examination Survey 2013-2014 dataset. MEASUREMENTS: Our primary predictor was weekday (or workday) nighttime sleep duration, categorized as 2-4, 5, 6, 7 (reference), 8, 9, and 10 hours or more. The authors studied five cognitive outcomes: Consortium to Establish a Registry for Alzheimer's Disease Word Learning (CERAD-WL) immediate recall, CERAD-WL delayed recall, Animal Fluency Test (AFT), Digital Symbol Substitution Test (DSST), and subjective cognitive problems (SCP). RESULTS: After adjusting for age, sex, race, education, depressive symptoms, and sedative-hypnotic use, sleep duration of 10 hours or more was significantly associated with lower scores on CERAD-WL immediate recall, CERAD-WL delayed recall, AFT, and DSST, and greater odds of SCP; sleep duration of 8 hours or more was associated with lower CERAD-WL delayed recall scores: 8, 9, and 10 hours or more. After adjustment, there were no significant associations of shorter sleep duration with cognition. CONCLUSION: In U.S. adults aged 60 years or older, long nighttime weekday or workday sleep duration is associated with poorer verbal memory, semantic fluency, working memory, and processing speed in addition to greater odds of self-reported cognitive problems. Long sleep duration may be a marker of fragmented sleep or neurodegeneration in U.S. older adults.

Napping characteristics and cognitive performance in older adults.

OBJECTIVES: To determine the association of napping intention, frequency, and duration with cognition in a nationally-representative sample of US older adults. METHODS: We performed a cross-sectional analysis of community-dwelling Medicare beneficiaries aged ≥65 years from Rounds 3 or 4 (2013-2014) of the National Health and Aging Trends Study (N = 2549). Participants reported past-month napping intention (intentional/unintentional), napping frequency (rarely/never [non-nappers], some days [infrequent nappers], most days/every day [frequent nappers]), and average nap duration (we categorized as ≤30 minutes [short]; 31-60 minutes [moderate]; and > 60 minutes [long]). Cognitive outcomes were performance on immediate and delayed word recall tests (IWR and DWR, respectively), the Clock Drawing Test (CDT), and self-rated memory (score: 1[excellent]-5[very poor]). RESULTS: After adjustment for potential confounders, unintentional nappers had poorer immediate word recall test performance than non-nappers (B = -0.23, P < 0.01) and intentional nappers (B = -0.26, P < 0.01). After further adjustment for daytime sleepiness, frequent nappers reported poorer self-rated memory than non-nappers (B = 0.14, P < 0.05). Compared with short nappers, long nappers had poorer IWR (B = -0.26, P < 0.05) and CDT scores (B = -0.17, P < 0.05). Except for the association of nap duration with IWR and CDT, these associations remained after excluding participants with dementia and/or proxy respondents. Among participants undiagnosed with dementia or proxies, moderate-duration naps were associated with better DWR than short naps (B = 0.24, P < 0.05). Neither napping intentionality nor frequency was associated with CDT performance. CONCLUSIONS: Among older adults, distinct aspects of napping are associated with cognitive performance. Prospective research, with objective measures of napping, is needed to elucidate the link between napping and cognitive trajectories.

Stressful life events and cognitive decline: Sex differences in the Baltimore Epidemiologic Catchment Area Follow-Up Study.

INTRODUCTION: The reasons why women are at higher risk than men for developing dementia are unclear. Although studies implicate sex differences in the effect of stress on cognitive functioning, whether stressful life events are associated with subsequent cognitive decline has received scant research attention. METHODS: In Wave 3 (1993-1996) of the Baltimore Epidemiologic Catchment Area study, 337 men and 572 women (mean age = 47 years) reported recent (within the last year) and remote (from 1981 until 1 year ago) traumatic events (eg, combat) and stressful life events (eg, divorce/separation). At Waves 3 and 4 (2004-2005), they completed the Mini Mental State Examination (MMSE) and a word-list memory test. Multivariable models were used to examine the association between traumatic and stressful life events at Wave 3 and cognitive change by Wave 4. RESULTS: A greater number of recent stressful life events at Wave 3, but not of more remote stressful events, was associated with greater verbal memory decline by Wave 4 in women but not in men. Stressful events were not associated with change in MMSE, and there were no associations between traumatic events occurring at any time and subsequent memory or MMSE decline in either sex. CONCLUSIONS: Unlike men, middle-aged women with a greater number of recent stressful life events demonstrate memory decline over a decade later. Sex differences in cognitive vulnerability to stressful life events may underlie women's increased risk of memory impairment in late life, suggesting that stress reduction interventions may help prevent cognitive decline in women.

E-cigarette use and sleep-related complaints among youth.

INTRODUCTION: E-cigarette use is highly prevalent among adolescents. However, little research has examined the relationship between e-cigarette use and sleep-related complaints in this population. The objective of this study was to assess whether exclusive e-cigarette, exclusive combusted cigarette, and dual-product use are associated with sleep-related complaints among adolescents. METHODS: Participants were 9,588 U.S. adolescents from the Population Assessment of Tobacco and Health Study, a nationally representative cohort, followed from 2013 through 2015. Using logistic regression, we examined the cross-sectional association between past-year e-cigarette, combusted cigarette, or dual-product use and past-year sleep-related complaints (bad dreams, sleeping restlessly, or falling asleep during the day), both measured at Wave 2. We controlled for Wave 1 demographic characteristics, emotional and behavioral health, and prior history of e-cigarette use, combusted cigarette use, and sleep-related complaints. RESULTS: In unadjusted analyses, e-cigarette, combusted cigarette, and dual-product use were significantly associated with greater odds of sleep-related complaints, compared to use of neither product (e-cigarettes: OR = 1.61, 95% CI 1.34-1.94; combusted cigarettes: OR = 1.62, 95% CI 1.26-2.09; dual-product use: OR = 2.00, 95% CI 1.63-2.46). Associations between e-cigarette and dual-product use and sleep-related complaints remained significant in fully adjusted analyses (e-cigarettes: aOR = 1.29, 95% CI 1.05-1.59; dual-product use: aOR = 1.57, 95% CI 1.24-1.99), whereas associations with combusted cigarette use were significant in all models except the fully adjusted model (aOR = 1.30, 95% CI 0.98-1.71). CONCLUSIONS: E-cigarette and dual-product use are significantly associated with greater odds of reporting sleep-related complaints among adolescents. Future research should evaluate whether this association may be causal.

Job strain and cognitive change: the Baltimore Epidemiologic Catchment Area follow-up study.

OBJECTIVES: To investigate the association between job strain and subsequent cognitive change over approximately 11 years, using data from the population-based Baltimore Epidemiologic Catchment Area follow-up study. METHODS: The sample ranged from 555 to 563 participants, depending on the outcome, who reported psychosocial characteristics corresponding to the full-time job they held at baseline (1993-1996). Overall cognitive performance was measured by the Mini-Mental State Examination (MMSE), and verbal memory was measured by the ImmediateWord Recall Task and Delayed Word Recall Task at baseline and follow-up (2004-2005). Multiple linear regression was used to examine the association between job strain and cognitive change, and inverse probability weighting was used to account for differential attrition. RESULTS: Participants with high job demands (psychological or physical demands) and/or low job control had greater decrease in the MMSE and memory scores than those with low job demands and high job control. After adjustment for baseline outcome scores, age and sex, the greatest decrease was observed in participants with high job demands and low job control (MMSE: -0.24, 95% CI -0.36 to -0.11; verbal memory scores: -0.26, 95% CI -0.44 to -0.07). The differences were partially explained by sociodemographic characteristics, occupational prestige and health factors. CONCLUSIONS: Findings from this prospective study suggest that job strain is associated with and may be a potential modifiable risk factor for adverse cognitive outcomes.

Sleep disturbance: an emerging opportunity for Alzheimer's disease prevention?

As the older segment of our population grows, cognitive decline and dementia will increase in prevalence, with Alzheimer's disease (AD) as the cause in most cases. Until a cure exists, prevention through the identification and manipulation of modifiable risk factors for dementia, in general, or AD, in particular, will be our only means of reducing dementia prevalence or delaying its onset. Furthermore, it is likely that eventual treatments for AD, when available, will depend on the ability to identify individuals at greatest risk for developing AD. Sleep disturbances are common in later life - roughly half of older adults experience regular insomnia (Ohayon, 2002) and about as many have some degree of sleep-disordered breathing (SDB) (Ancoli-Israel et al., 1991) - and accumulating evidence suggests they may contribute to cognitive decline, at least in part, by promoting the development of AD pathology (Spira et al., 2014). Because they are treatable, sleep disturbances are an important potential target for ongoing study in AD prevention. Moreover, understanding the mechanisms underlying an effect of sleep on subsequent cognitive decline and AD would allow for better identification of opportunities and optimal timing for treatment of sleep disorders, and ultimately perhaps, AD prevention.

Emergency department visits involving benzodiazepines and non-benzodiazepine receptor agonists.

OBJECTIVE: Sedative-hypnotic medications (e.g., Benzodiazepines [BZDs] and non-benzodiazepine receptor agonists [nBZRAs]) are associated with adverse events, especially in the elderly, that may require emergency department (ED) treatment. This study assessed outcomes from ED visits attributed to BZDs and/or nBZRAs, and variations in these associations by age group. METHODS: Data came from the 2004-2011 waves of the Drug Abuse Warning Network (DAWN). Visits were categorized as involving: (1) BZDs-only, (2) nBZRAs-only, (3) combination of BZDs and nBZRAs, or (4) any other sedative-hypnotic medication. DAWN also recorded the disposition (i.e., outcome) of the visit. Analyses focused on outcomes indicating a serious disposition defined as hospitalization, patient transfer or death. Using logistic regression, the association of BZD and nBZRA use with visit disposition was assessed after applying sample weights so as to be nationally representative of ED visits in the United States involving medications or illicit substances. RESULTS: Nineteen percent of visits involving other sedative-hypnotics, 28% involving BZDs-only, 20% involving nBZRAs-only and 48% involving a combination of BZDs and nBZRAs resulted in a serious disposition. Compared to visits involving other sedative-hypnotics, visits involving BZDs-only had 66% greater odds (Odds Ratio [OR]=1.66, 95% Confidence Interval [CI]=1.37-2.01), and visits involving a combination of BZDs and nBZRAs had almost four times increased odds of a serious disposition (OR=3.91, 95% CI=2.38-6.41). Results were similar across age groups. CONCLUSIONS: Findings highlight the need for clinical and regulatory initiatives to reduce BZD use, especially in combination with nBZRAs, and to promote treatment with safer alternatives to these medications.

Continuing Versus New Prescriptions for Sedative-Hypnotic Medications: United States, 2005-2012.

OBJECTIVES: To assess trends in continuing and new prescriptions for sedative-hypnotic medications, including benzodiazepines (BZDs) and non-BZD receptor agonists (nBZRAs). METHODS: Data came from the National Ambulatory Medical Care Survey and comprised 287 288 randomly sampled patient visits. Physicians reported medications prescribed and whether they were "continuing" or "new" prescriptions. We assessed trends in continuing BZD, new BZD, continuing nBZRA, and new nBZRA prescriptions from 2005 to 2012. RESULTS: Proportions of visits with continuing prescriptions increased from 3.4% in 2005 to 4.7% in 2012 (P < .01) for BZDs, and from 1.0% to 1.7% (P < .01) for nBZRAs. We noted no changes in new prescriptions. We observed the same patterns across patient age and physician specialties, except psychiatry. Despite no growth over time, the prevalence of visits involving continuing and new BZD and nBZRA prescriptions was much higher in psychiatry than in primary care and other specialties. CONCLUSIONS: Increased sedative-hypnotic prescribing in recent years may be attributable to long-term growth in continuing prescriptions, rather than new prescriptions. Public Health Implications. Findings call for renewed efforts to limit continuing prescribing of sedative-hypnotics to reduce their use in the population.

Measures of Sleep-Wake Patterns and Risk of Mild Cognitive Impairment or Dementia in Older Women.

OBJECTIVE: Sleep disturbances are common in older adults. Little is known about the sleep of cognitively intact older adults and its relationship to subsequent cognitive impairment. The objective of this study was to examine the association between objective sleep-wake measures and risk of incident cognitive impairment. METHODS: In this prospective cohort study encompassing four U.S. sites, 1,245 women (mean age: 82.6 years) without dementia participated in the Study of Osteoporotic Fractures and completed actigraphy at the baseline visit and comprehensive cognitive assessment at follow-up. The association between sleep-wake patterns measured by actigraphy and risk of incident mild cognitive impairment (MCI) and dementia was examined. RESULTS: A total of 473 women (38%) developed cognitive impairment during an average (SD) follow-up of 4.9 (0.6) years; 290 (23.3%) developed MCI and 183 (14.7%) developed dementia. After controlling for multiple potential confounders, women in the lowest quartile of average sleep efficiency (<74%) had a 1.5-fold higher odds of developing MCI or dementia compared with women in the highest quartile of sleep efficiency (>86%) (odds ratio: Q1 versus Q4 1.53; 95% CI: 1.07, 2.19; Wald χ(2) [1, N = 1,223] = 5.34 for p for trend = 0.03). Longer average sleep latency, but not total sleep time, was also associated with higher odds of developing cognitive impairment. Greater variability in both sleep efficiency and total sleep time was associated with an increased odds of developing MCI or dementia. CONCLUSION: Lower average sleep efficiency, longer average sleep latency, and greater variability in sleep efficiency and total sleep time are associated with increased odds of developing cognitive impairment. Further research is needed to explore the mechanisms underlying these associations.