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Objective: People with Alzheimer’s disease (AD) dementia have impaired sleep. However, the characteristics of sleep in the early stages of AD are not well known, and studies with the aid of biomarkers are lacking. We assessed the subjective sleep characteristics of non-demented older adults and compared their amyloid profiles. Methods: We enrolled 30 participants aged ≥ 60 years, with no dementia or major clinical and psychiatric diseases. They underwent [11C]PiB-PET-CT, neuropsychological evaluations, and completed two standardized sleep assessments (Pittsburgh Sleep Quality Inventory and Epworth Sleep Scale). Results: Comparative analysis of subjective sleep parameters across the two groups showed longer times in bed (p = 0.024) and reduced sleep efficiency (p = 0.05) in individuals with positive amyloid. No differences in other subjective sleep parameters were observed. We also found that people with multiple-domain mild cognitive impairment (MCI) had shorter self-reported total sleep times (p = 0.034) and worse overall sleep quality (p = 0.027) compared to those with single-domain MCI. Conclusions: Older adults testing positive for amyloid had a longer time in bed and lower sleep efficiency, regardless of cognitive status. In parallel, individuals with multiple-domain MCI reported shorter sleep duration and lower overall sleep quality.

Background Dementia is the main cause of disability in older people living in low- and middle-income countries (LMIC). Monitoring mortality rates and mortality risk factors in people with dementia (PwD) may contribute to improving care provision. Objective We aimed to estimate mortality rates and mortality predictors in PwD from eight LMICs. Methods This 3-5-year prospective cohort study involved a sample of 1,488 older people with dementia from eight LMIC. Total, age- and gender-specific mortality rates per 1,000 person-years at risk, as well as the total, age- and gender-adjusted mortality rates were estimated for each country's sub-sample. Cox's regressions were used to establish the predictors of mortality. Results At follow-up, vital status of 1,304 individuals (87.6%) was established, of which 593 (45.5%) were deceased. Mortality rate was higher in China (65.9%) and lower in Mexico (26.9%). Mortality risk was higher in males (HR = 1.57; 95% CI: 1.32,1.87) and increased with age (HR = 1.04; 95% CI: 1.03,1.06). Neuropsychiatric symptoms (HR = 1.03; 95% CI: 1.01,1.05), cognitive decline (HR 1.04; 95% CI: 1.03,1.05), undernutrition (HR = 1.55; 95% CI: 1.19, 2.02), physical impairments (HR = 1.15; 95% CI: 1.03,1.29), and disease severity (HR = 1.43; 95% CI: 1.22,1.63) predicted higher mortality risk. Conclusion Several factors predicted higher mortality risk in PwD in LMICs. Males, those with higher age, higher severity of neuropsychiatric symptoms, higher number of physical impairments, higher disease severity, lower cognitive performance, and undernutrition had higher mortality risk. Addressing these indicators of long-term adverse outcomes may potentially contribute to improved advanced care planning, reducing the burden of disease in low-resourced settings.

Investigate associations of objective and subjective indicators of sleep impairment and disorders with low muscle strength (LMS) in different age groups and genders using data from a population-based cohort study.Polysomnographic and subjective sleep data from participants (aged 40-80 years) of the HypnoLaus study (Lausanne, Switzerland) were cross-sectionally analyzed. Indicators of sleep impairment and disorders were based on pre-defined cutoffs. LMS was defined according to the diagnosis of sarcopenia (grip strength27 kg for men and16 kg for women). Results obtained by multivariate logistic regression were controlled for confounders.1902 participants (mean [SD] age, 57.4 [10.5] years; 968 [50.9 %] female) were enrolled. Objective short (6.2 h) and long sleep durations (8.5 h) were associated with LMS (OR = 1.74, 95 % CI = 1.07-2.82; OR = 6.66, 95 % CI = 3.45-12.87, respectively). Increased nighttime wakefulness90 min and severe obstructive apnea (OSA) (AHI 30) were associated with LMS (OR = 1.60, 95 % CI = 1.01-2.56; OR = 2.36, 95 % CI = 1.29-4.31, respectively). In adults aged over 60 years, these associations persisted, and reduced sleep efficiency was associated with LMS (aOR = 1.81, 95 % CI 1.05-3.13). Objective long sleep duration was associated with LMS in both genders and severe OSA predicted LMS among women (aOR = 2.64, 95 % CI 1.11-6.24).Markers of early sarcopenia are affected by long sleep duration from middle age onwards in both genders. Older adults are more susceptible to the effects of other indicators of inappropriate sleep duration and quality. The findings support a potential role of sarcopenia in age-related OSA. The intricate relationships between sleep and muscle health are potential targets of public health interventions and clinical research on preventive and therapeutic strategies against the increasing morbimortality observed with ageing.

Aging is accompanied by changes in the quantity and quality of sleep. Obstructive sleep apnea (OSA) is also more prevalent in the older population. Although severe OSA has been linked to a higher risk of cardiovascular disease regardless of adult age, clinical consequences of mild-to-moderate OSA in the older adults are still uncertain.ObjectivesTo investigate the relationships between severity and metabolic, cognitive, and functional characteristics in community-dwelling older adults from a representative sample of the city of São Paulo.MethodsIn total, 199 participants of the first follow-up of the São Paulo Epidemiologic Sleep Study (EPISONO, São Paulo, Brazil) >60 years were cross-sectionally assessed through questionnaires, physical evaluations, laboratory tests, and full in-lab polysomnography (PSG). Three groups according to the OSA severity were compared according to sociodemographic characteristics, anthropometric measures, PSG parameters, the frequency of comorbidities, and the use of medications.ResultsParticipants' age ranged from 60 to 87 years with a mean of 70.02 ± 7.31, 59.8% female. In the univariate analysis, body mass index (BMI, kg/m2) (p = 0.049) and waist circumference (p = 0.005) were significantly higher in the participants with moderate OSA, but not among those with severe OSA. Participants with severe OSA had a higher arousal index (p = 0.007). Multivariate analysis showed that severe OSA was significantly associated with hypertension (p = 0.005), heart diseases (p = 0.025), and the use of two or more medications (p = 0.035).ConclusionIn a population-based study, severe, but not mild-to-moderate, OSA in older adults was associated with hypertension and the use of more medications. As age advances, anthropometric indicators of obesity may not increase the risk of severe OSA.

The association between Alzheimer's disease (AD) and sleep disturbances has received increasing scientific attention in the last decades. However, little is known about the impact of sleep and its disturbances on the development of preclinical AD stages, such as mild cognitive impairment. This review describes the evolution of knowledge about the potential bidirectional relationships between AD and sleep disturbances exploring recent large prospective studies and meta-analyses and studies of the possible mechanisms through which sleep and the neurodegenerative process could be associated. The review also makes a comprehensive exploration of the sleep characteristics of older people, ranging from cognitively normal individuals, through patients with mild cognitive impairment, up to the those with dementia with AD. RESUMO A associação entre Doença de Alzheimer (DA) e distúrbios do sono vem recebendo atenção crescente nas últimas décadas. No entanto, pouco se sabe sobre o impacto do sono e suas alterações no desenvolvimento de estágios pré-clínicos da doença, como é o caso do Comprometimento Cognitivo Leve (CCL). Esta revisão descreve a evolução do conhecimento sobre as relações potencialmente bidirecionais entre DA e distúrbios do sono, explorando grandes estudos prospectivos e meta-análises, assim como estudos dos possíveis mecanismos da associação entre o sono e as doenças neurodegenerativas. Também revisamos amplamente as características do sono de pessoas idosas, incluindo indivíduos cognitivamente normais, com CCL e com demência por DA.

Background Evidence suggests anthropometric indicators of obesity are associated with changes in sleep quality and quantity, and the presence of obstructive sleep apnoea (OSA). Investigations including diverse and objective evaluations of sleep and body composition are scarce. We aimed to evaluate the associations between indicators of sleep impairment and body composition states in a sample from a population‐based study. Methods Participants of the first follow‐up of the EPISONO (São Paulo, Brazil) >50 years were cross‐sectionally evaluated. Sleep was assessed through questionnaires, actigraphy, and polysomnography. Body composition was evaluated by bioelectrical impedance analysis. Appendicular skeletal muscle mass adjusted for body mass index defined sarcopenia (men 30% and women >40%). The overlap between both conditions defined sarcopenic obesity (SO). Final results were obtained by multinomial logistic regression analysis. Results Three hundred fifty‐nine adults [mean (standard deviation) age, 61 (8.8) years; 212 (59.1%) female] were enrolled. Obesity was detected in 22.6% of the sample, sarcopenia in 5.6%, and SO in 16.2%. After controlling for covariates, OSA was associated with SO [odds ratio = 3.14, 95% confidence interval (CI) = 1.49–6.61]. Additionally, nocturnal hypoxaemia was associated with both obesity (adjusted odds ratio = 2.59, 95% CI = 1.49–4.49) and SO (odds ratio = 2.92, 95% CI = 1.39–6.13). Other indicators of poor sleep/sleep disorders were not associated with body composition states. Conclusions Sarcopenic obesity but not obesity alone was associated with OSA. Both obesity and SO but not sarcopenia were associated with nocturnal hypoxaemia. The findings suggest a complex pathophysiologic relationship between adverse body composition states and OSA. Upcoming research on risk factors and therapeutic interventions for OSA should target synchronically the lean and adipose body tissues.

Introduction Sarcopenia is a multifactorial condition that, like sleep debt, affects the elderly and is related to metabolic, endocrine, inflammatory alterations and risk to mortality. Resistance training (RT), in turn, can improve both factors. Aim: investigate the effects of 12-week RT on sleep and muscle function in the sarcopenic elderly. Methods 28 sarcopenic elderly were equally distributed in 2 groups at random: CTL: who participated in weekly lifestyle change lectures or; RT: who did the progressive load RT. Sleep was assessed by polysomnography, actigraphy and questionnaires. Isokinetic and isometric of peak torque (PT) of skeletal muscle, anabolic and catabolic hormones, pro and anti-inflammatory cytokines concentrations were also evaluated. For intention to treat analysis (Δ) the generalized linear/non-linear for absolute variables or Wilcoxon rank-sum (Mann-Whitney) test. Data are expressed as mean±standard deviation or median, minimum and maximum values and difference witch p Results The RT reduced the time to sleep onset (16.09±15.21) compared to CTL (29.98±22.57) group after the intervention. The Δ shows that RT had more N3 sleep (median:0.90, min:-13.40, max: 25.00) than CTL (median:-3.35, min:-15.20, max:19.10). The RT increases TTS (median:57.55, min:-204.75, max:220.91 vs median:-9.63, min:-120.98, max:185.57) and improved self-reported sleep quality (median: -1.50, min: -9.00, max: 4.00 vs median: 0.50, min: -3.00, max: 6.00) and sleep efficiency (median: 9.50, min: -15.00, max: 34.00 vs 0.00, min: -28.00, max: 18.00). For all muscle function parameters (extension and flexion knee in isokinetic or isometric PT) RT had higher values compared to CTL group after 12 weeks of intervention (p Conclusion Progressive load resistance training improves sleep parameters associated to muscle recovery in elderly people with sarcopenia, along with positive changes in physical performance. Support Associação Fundo de Incentivo à Pesquisa (AFIP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).

Introduction Residual excessive sleepiness (RES) is presented by 6% of obstructive sleep apnea patients despite effective CPAP therapy. Few interventions have been tested for this condition and are focused on daytime stimulants. Recently, cholinergic activity decline was suggested as a potential mechanism in the pathophysiology of RES. This study aimed to investigate the effects of donepezil, an anticholinesterase inhibitor, in patients with RES. Methods This double-blind, randomized, placebo-controlled crossover study included participants with RES (35-65 years). Neuropsychiatric disorders, alcoholism, smoking, shiftwork, psychoactive drugs, other sleep disorders were exclusion criteria. Participants were assigned to one intervention arm (donepezil 5 mg for 15 days followed by donepezil 10mg for 15 days or placebo in the morning). After a 20-day wash-out, the same procedure was repeated following the crossover design. Somnolence measured by the Epworth sleepiness scale (ESS) and Maintenance of Wakefulness Test (MWT) were the primary endpoints. PSG, cognitive (trail test, continuous performance test) and Beck’s depression scale parameters were secondary endpoints. General Linear Models for repeated measures compared interventions responses. Cohen’s d measured effect sizes. Adverse events (AEs) were assessed by questionnaire. Results The study enrolled eight individuals. ESS was lower in the donepezil arm than in the placebo arm (8.9±4.4 vs 15.7±4.1, p Conclusion Donepezil improved subjective sleepiness in individuals with RES. To our knowledge, this is the first study to report the effects of a cholinergic intervention in patients with RES. Effect size was high for self-reported sleepiness, which may impact on quality of life and risk of disability in people with RES. Agents acting on the cholinergic system are potential targets for treating RES. Support Acknowledgements Brazilian National Council for Scientific and Technological Development (CNPq) This study is supported by AFIP (Associacao Fundo Incentivo a Pesquisa).

Objective To evaluate the association between objective short sleep duration in patients with insomnia and changes in blood parameters related to hypothalamic-pituitary-adrenal (HPA) axis activity.Method A cross-sectional pilot study was conducted in 30 middle-aged adults with chronic insomnia who were divided into 2 groups according to polysomnography (PSG) total sleep time (TST) (TST > 5h and < 5h). All patients underwent subjective analysis of sleep quality, anthropometric measurements, PSG, and determination off asting blood parameters.Results The results revealed lower sleep efficiency and higher sleep latency for those with a TST < 5h. The subjective sleep quality was worse in the TST < 5h. Significantly, higher glucose and cortisol levels were observed with a TST < 5h. Glucose, cortisol and ACTH levels were inversely correlated with the PSG total sleep time.Conclusion Patients with insomnia with objective short sleep duration had HPA-associated endocrine and metabolic imbalances chronically linked to increases in cardiovascular risk observed with this more severe insomnia phenotype. Objetivo Avaliar a associação entre insônia com tempo de sono curto e alterações sanguíneas relacionados com a atividade do eixo hipotálamo-hipófise-adrenal (HPA).Método Estudo piloto transversal, com 30 adultos de meia-idade, distribuídos em 2 grupos de acordo com o tempo total de sono (TTS) pela polisonografia (PSG) (TTS > 5h e < 5h). Os pacientes foram submetidos a análise subjetiva da qualidade do sono, medidas antropométricas, PSG e parâmetros sanguíneos em jejum.Resultados Revelaram baixa eficiência do sono e maior latência do sono para aqueles com TTS < 5h. A qualidade subjetiva do sono foi pior no TTS < 5h. Significativamente, os níveis de glicose e cortisol mais elevados foram observados no grupo com TTS < 5h. Os níveis de glicose, cortisol e ACTH foram inversamente correlacionados com o TTS da PSG.Conclusão Pacientes com insônia com tempo de sono curto apresentaram desequilíbrios endócrinos e metabólicos associados a atividade do eixo HPA, correlacionados ao aumento do risco cardiovascular observado neste fenótipo mais grave de insônia.

Although many studies have shown the evolution of sleep parameters across the lifespan, not many have included a representative sample of the general population. The objective of this study was to describe age-related changes in sleep structure, sleep respiratory parameters and periodic limb movements of the adult population of São Paulo.We selected a representative sample of the city of São Paulo, Brazil that included both genders and an age range of 20-80 years. Pregnant and lactating women, people with physical or mental impairments that prevent self-care and people who work every night were not included. This sample included 1024 individuals who were submitted to polysomnography and structured interviews. We subdivided our sample into five-year age groups. One-way analysis of variance was used to compare age groups. Pearson product-moment was used to evaluate correlation between age and sleep parameters.Total sleep time, sleep efficiency, percentage of rapid eye movement (REM) sleep and slow wave sleep showed a significant age-related decrease (P0.05). WASO (night-time spent awake after sleep onset), arousal index, sleep latency, REM sleep latency, and the percentage of stages 1 and 2 showed a significant increase (P0.05). Furthermore, apnea-hypopnea index increased and oxygen saturation decreased with age. The reduction in the percentage of REM sleep significantly correlated with age in women, whereas the reduction in the percentage of slow wave sleep correlated with age in men. The periodic limb movement (PLM) index increased with age in men and women.Sleep structure and duration underwent significant alterations throughout the aging process in the general population. There was an important correlation between age, sleep respiratory parameters and PLM index. In addition, men and women showed similar trends but with different effect sizes.

A challenging aspect of geriatric practice is that it often requires decision-making under conditions of uncertainty. The Script Concordance Test (SCT) is an assessment tool designed to measure clinical data interpretation, an important element of clinical reasoning under uncertainty. The purpose of this study was to develop and analyze the validity of results of an SCT administered to undergraduate students in geriatric medicine. An SCT consisting of 13 cases and 104 items covering a spectrum of common geriatric problems was designed and administered to 41 undergraduate medical students at a medical school in Sao Paulo, Brazil. A reference panel of 21 practicing geriatricians contributed to the test's score key. The responses were analyzed, and the psychometric properties of the tool were investigated. The test's internal consistency and discriminative capacity to distinguish students from experienced geriatricians supported construct validity. The Cronbach alpha for the test was 0.84, and mean scores for the experts were found to be significantly higher than those of the students (80.0 and 70.7, respectively; P < .001). This study demonstrated robust evidence of reliability and validity of an SCT developed for use in geriatric medicine for assessing clinical reasoning skills under conditions of uncertainty in undergraduate medical students. These findings will be of interest to those involved in assessing clinical competence in geriatrics and will have important potential application in medical school examinations.

Little research has been done in Brazilian medical education on the evaluation of clinical reasoning in situations of uncertainty. The most common tests are still multiple-choice, which are capable of evaluating skills when dealing with well-defined problems. However, in practice the majority of situations involve uncertainties. A method for the evaluation of clinical reasoning in contexts of uncertainty was developed on the basis of the cognitive script theory in relation to professional reasoning. The objectives of the research were to develop, apply, and analyze this methodology in a Brazilian educational setting, based on clinical situations in Geriatrics that involved diagnostic, therapeutic, or ethical dilemmas. A group of specialists in this area and a group of undergraduate students that were completing their training in the Geriatrics internship took the test. Comparison of the results led to evidence of the instrument's validity, capable of distinguishing clinical reasoning according to the participants' level of experience. The mean score for the specialists (80,41) was higher than that of students (70,71) (p < 0,001). In addition, analyses of the internal consistency and a G study design furnished results that are consistent with a scoring system that seeks to evaluate a professional skill. In conclusion, a proposal for a script concordance test in the Portuguese language, applied in a Brazilian teaching institution, may be a viable alternative for evaluating clinical reasoning in contexts of uncertainty.

Studies carried out in several countries and in different ethnic groups have suggested that the hip axis length (HAL) may be a risk factor for hip fractures. To evaluate if the HAL is an independent risk factor for hip fractures in elderly Caucasian Brazilian women, this study includes 112 participants sustaining proximal femur osteoporosis. Through HAL and bone mineral density (BMD) measurements, a statistical analysis using a multivaried regression curve was done. HAL was significantly longer in women sustaining a hip fracture than in the control group (99.24 +/- 5.9 mm vs. 96.95 +/- 5.6 mm, P0.05). After adjusting the standard HAL deviation for neck and trochanter BMD, OR was 1.43 (IC 95% 0.29 - 1.07; P0.08). When HAL was categorized for 97.8 mm (average HAL in all women), OR was 2.24 (IC 95% 1.04 - 4.84; P0.05). In conclusion, HAL may be associated with risk of hip fracture regardless of age, weight or BMD of elderly Brazilian Caucasian women.

Obstructive sleep apnea (OSA) is a prevalent condition characterized by momentary cessations in breathing during sleep due to intermittent obstruction of the upper airway. OSA has been frequently associated with a number of medical comorbidities. CPAP (continuous positive airway pressure) is the gold standard treatment and is known to improve OSA symptoms, including excessive sleepiness. However, 12-14% of CPAP-treated patients continue to complain of sleepiness despite normalization of ventilation during sleep, and 6% after exclusion of other causes of EDS. This is of great concern because EDS is strongly associated with systemic health disorders, lower work performance, and a high risk of accidents. We hypothesized that decreased central cholinergic activity plays a role in the pathophysiology of residual excessive sleepiness in patients with OSA treated with CPAP. Acetylcholine (Ach) plays a large role in wakefulness physiology, and its levels are reduced in sleepiness. Herein, we discuss the potential role of the cholinergic system in this new clinical condition.

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo Background Studies demonstrate an association between vitamin D (25(OH) D) deficiency and sleep disturbances, such as obstructive sleep apnea (OSA) and short sleep duration. However, to date, no studies have concurrently and objectively evaluated the effect of these factors on 25(OH) D. Objectives To evaluate whether OSA and objective short sleep duration are independently associated with reduced 25(OH) D in an adult population sample. Methods A cross-sectional study included 657 individuals from the city of Sao Paulo, Brazil, as part of the ERA project. Participants fulfilled questionnaires and underwent clinical evaluation, polysomnography and blood sample collection for 25(OH) D quantification. OSA was classified into three categories (mild, moderate and severe). The risk of 25(OH) D deficiency was considered as levels= 50 years. Conclusion OSA and short sleep duration are independently associated with the risk of 25(OH) D deficiency in an adult population. Age-related changes in vitamin D metabolism and the frequency of sleep disorders may be involved in these associations. Future studies exploring whether 25(OH) D levels may modulate OSA and sleep curtailment-related outcomes are needed. Univ Fed Sao Paulo, Dept Psychobiol, Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Dept Med, Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Dept Psychobiol, Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Dept Med, Sao Paulo, SP, Brazil FAPESP: 2014/15259-2 FAPESP: 98/14303-3 Web of Science

Sarcopenia is a geriatric condition that comprises declined skeletal muscle mass, strength and function, leading to the risk of multiple adverse outcomes, including death. Its pathophysiology involves neuroendocrine and inflammatory factors, unfavorable nutritional habits and low physical activity. Sleep may play a role in muscle protein metabolism, although this hypothesis has not been studied extensively. Reductions in duration and quality of sleep and increases in prevalence of circadian rhythm and sleep disorders with age favor proteolysis, modify body composition and increase the risk of insulin resistance, all of which have been associated with sarcopenia. Data on the effects of age-related slow-wave sleep decline, circadian rhythm disruptions and obstructive sleep apnea (OSA) on hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG), somatotropic axes, and glucose metabolism indicate that sleep disorder interventions may affect muscle loss. Recent research associating OSA with the risk of conditions closely related to the sarcopenia process, such as frailty and sleep quality impairment, indirectly suggest that sleep can influence skeletal muscle decline in the elderly. Several protein synthesis and degradation pathways are mediated by growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, cortisol and insulin, which act on the cellular and molecular levels to increase or reestablish muscle fiber, strength and function. Age-related sleep problems potentially interfere intracellularly by inhibiting anabolic hormone cascades and enhancing catabolic pathways in the skeletal muscle. Specific physical exercises combined or not with nutritional recommendations are the current treatment options for sarcopenia. Clinical studies testing exogenous administration of anabolic hormones have not yielded adequate safety profiles. Therapeutic approaches targeting sleep disturbances to normalize circadian rhythms and sleep homeostasis may represent a novel strategy to preserve or recover muscle health in older adults. Promising research results regarding the associations between sleep variables and sarcopenia biomarkers and clinical parameters are required to confirm this hypothesis.

The nigrostriatal dopaminergic system seems to be involved in both reserpine-induced orofacial dyskinesia in normal rats and in the pathogenesis of hypertension in spontaneously hypertensive rats. In the present study, repeated reserpine administration (1.0 mg/kg, s.c., every other day, for 3 days) increased tongue protrusion and vacuous chewing frequencies as well as the duration of facial twitching in Wistar normotensive but not in spontaneously hypertensive rats. These results suggest that genetic hypertension and drug-induced orofacial movements may be inversely modulated by similar mechanisms in the nigrostriatal dopaminergic system.