Walter Moraes

Donepezil improves obstructive sleep apnea in Alzheimer disease - A double-blind, placebo-controlled study

BACKGROUND There is an association between Alzheimer disease and sleep-disordered breathing. Donepezil is the drug most frequently used to treat cognitive symptoms in Alzheimer disease. This study evaluates the effects of donepezil on obstructive sleep apnea in patients with Alzheimer disease. METHODS Randomized, double-blind, placebo-controlled design. Twenty-three patients with mild-to-moderate Alzheimer disease and apnea-hypopnea index (AHI) > 5/h were allocated to two groups: donepezil treated (n = 11) and placebo treated (n = 12). Polysomnography and cognitive evaluation using Alzheimer disease assessment scale-cognitive (ADAS-cog) subscale were performed at baseline and after 3 months. Cognitive and sleep data were analyzed using analysis of variance. RESULTS AHI and oxygen saturation improved significantly after donepezil treatment compared to baseline and placebo (p < 0.05). Rapid eye movement (REM) sleep duration increased after donepezil treatment (p < 0.05). ADAS-cog scores improved after donepezil treatment, although they did not correlate with REM sleep increase and sleep apnea improvement (p < 0.01). CONCLUSIONS Donepezil treatment improved AHI and oxygen saturation in patients with Alzheimer disease. Treatment also increased REM sleep duration and reduced ADAS-cog scores. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT00480870.

Association between body mass index and sleep duration assessed by objective methods in a representative sample of the adult population

INTRODUCTION Sleep duration has been associated with overweight individuals in many epidemiological studies; however, few studies have assessed sleep using objective methods. Our study was designed to evaluate the association between body mass index (BMI) and sleep duration measured by actigraphy (Acti), polysomnography (PSG) and the Pittsburgh sleep quality index questionnaire (PSQIO). Furthermore, we evaluated other biochemical and polysomnographic parameters. METHODS A representative sample of 1042 individuals from Sao Paulo, Brazil, including both genders (20-80 yrs), participated in our protocol. Weight and other anthropometric parameters were measured at the onset of the study. Sleep duration was calculated by Acti, PSG, and the PSQIQ. The population was sorted by sleep duration, body, slow wave sleep (SWS) and REM sleep (REMS) duration subsets. In addition, other biochemical and polysomnographic parameters were analyzed. Differences between population subsets were analyzed by one-way analysis of variance (ANOVA). Linear regression analysis was performed between sleep and anthropometric parameters. RESULTS Shorter sleep duration was associated with higher BMI and waist and neck circumference when measured by Acti and PSG (p<0.05). Lower leptin levels were associated with short sleep in normal-weight (BMI>18 and ⩽25) individuals (p<0.01). The association between short sleep duration Acti and higher BMI was present when apnea-hypopnea index (AHI) was less than 15 (p=0.049). Shorter REMS and SWS also were associated with higher BMI (p<0.01). Normal-weight individuals tended to sleep longer, have higher sleep efficiency and longer SWS and REMS than obese individuals (Acti, PSG; p=0.05). Sleep duration was negatively correlated with BMI (Acti, PSG; p<0.05). Short SWS and REMS were associated with higher cardiovascular risk factors (p<0.05). CONCLUSION Shorter sleep, SWS, and REMS duration were associated with higher BMI, central adiposity measurements, and cardiovascular risk factors when measured by objective methods.

Effects of aging on sleep structure throughout adulthood: a population-based study

OBJECTIVE 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. METHODS 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. RESULTS Total sleep time, sleep efficiency, percentage of rapid eye movement (REM) sleep and slow wave sleep showed a significant age-related decrease (P<0.05). 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 (P<0.05). 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. CONCLUSIONS 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.

Beneficial effect of donepezil on obstructive sleep apnea: A double-blind, placebo-controlled clinical trial

INTRODUCTION/OBJECTIVES Previous publications have shown beneficial effects of cholinergic medication on obstructive sleep apnea (OSA) in Alzheimers disease (AD) patients. We hypothesized that cholinergic medication could also improve OSA in non-AD patients. The present study evaluated the effects of donepezil on OSA in non-AD patients. METHODS A randomized, double-blind, placebo-controlled study was conducted. The final sample consisted of 21 male patients with mild to severe OSA and AHI >10 divided into two groups, a donepezil-treated group (n=11) and a placebo-treated group (n=10). The dosage was one tablet/day (5 mg) for the first two weeks and two tablets/day (10 mg) for the last two weeks. Polysomnography and sleepiness evaluations were performed at baseline and after one month of treatment. Groups were compared using two-way ANOVA for repeated measures with treatment-group and treatment-time as the main factors and time-treatment as an interaction effect. RESULTS Considering the effect of the interaction with time-treatment, there was a significant improvement in the obstructive apnea/hypopnea index, desaturation index, percentage of time with O(2) saturation ≤3% lower than baseline, lowest oxygen saturation, and the Epworth Sleepiness Scale (ESS) scores with donepezil treatment (p<0.05). Sleep efficiency significantly decreased (p<0.01). CONCLUSIONS Donepezil treatment improved obstructive sleep apnea index, oxygen saturation, and sleepiness in parallel with a reduction in sleep efficiency. Our findings support the concept that cholinergic transmission may influence breathing regulation in OSA patients.

O sono em transtornos psiquiátricos

Altered sleep patterns are prominent in the majority of psychiatric disorders. This article examines the psychiatric disorders that are most often associated to sleep dysfunction as it is related in clinical practice and describes the polysomnographic findings. Patients main complaints are related to difficulty in initiating and maintaining sleep (initial or middle insomnia, respectively) and poor quality of sleep. Early awakening or terminal insomnia is most described in the depressive conditions. Hypersomnia may be the main symptom in some depressive disorders, as seasonal depression, depression with atypical features or depressive episodes in bipolar disorder. Polysomnographic evaluation shows, in general, a significative reduction in the efficiency and total time of sleep, in detriment to the amount of slow wave sleep. The reduction of rapid eye movement (REM) sleep latency is mainly described for the depression, but has also been reported in other psychiatric disorders.

Cerebellar volume in patients with dementia

OBJECTIVE The aim of this study was to examine the cerebellar volume of subjects at different stages of Alzheimers disease and to investigate whether volume reductions in this structure are related to cognitive decline. METHOD Ninety-six subjects from an epidemiological study were submitted to a magnetic resonance imaging scan and evaluated using the Mini-Mental State Examination and the Functional Activities Questionnaire. Subjects were divided into five groups according to the Clinical Dementia Rating scale. Twenty-six subjects from the original group who had no dementia diagnosis at baseline were re-evaluated for the onset of dementia after two years. RESULTS The volumes of the cerebellar hemispheres, posterior cerebellar lobe, vermis and temporal lobe were found to be reduced as a function of the severity of the disease. There were significant positive correlations between the volume of the temporal lobe and cerebellum and the language, attention, and total scores in the Mini-Mental State Examination and the Functional Activities Questionnaire. A logistic regression analysis demonstrated that reduced temporal lobe, posterior cerebellar lobe and vermal volume at baseline is a risk factor for the onset of dementia. CONCLUSION This is the first study demonstrating that reduced cerebellar volume is already apparent at the predementia stage. The results of this study support the involvement of the cerebellum in the progression of dementia. Whereas the cerebellum might not be directly associated with the origin of Alzheimers disease, it may provide useful information related to its prognosis.

Human longevity is associated with regular sleep patterns, maintenance of slow wave sleep, and favorable lipid profile

Some individuals are able to successfully reach very old ages, reflecting higher adaptation against age-associated effects. Sleep is one of the processes deeply affected by aging; however few studies evaluating sleep in long-lived individuals (aged over 85) have been reported to date. The aim of this study was to characterize the sleep patterns and biochemical profile of oldest old individuals (N = 10, age 85–105 years old) and compare them to young adults (N = 15, age 20–30 years old) and older adults (N = 13, age 60–70 years old). All subjects underwent full-night polysomnography, 1-week of actigraphic recording and peripheral blood collection. Sleep electroencephalogram spectral analysis was also performed. The oldest old individuals showed lower sleep efficiency and REM sleep when compared to the older adults, while stage N3 percentage and delta power were similar across the groups. Oldest old individuals maintained strictly regular sleep-wake schedules and also presented higher HDL-cholesterol and lower triglyceride levels than older adults. The present study revealed novel data regarding specific sleep patterns and maintenance of slow wave sleep in the oldest old group. Taken together with the favorable lipid profile, these results contribute with evidence to the importance of sleep and lipid metabolism regulation in the maintenance of longevity in humans.

Diretrizes brasileiras para o tratamento da narcolepsia

This manuscript contains the conclusion of the consensus meeting of the Brazilian Sleep Association with Brazilian sleep specialists on the treatment of narcolepsy based on the review of medical literature from 1980 to 2010. The manuscript objectives were to reinforce the use of agents evaluated in randomized placebo-controlled trials and to issue consensus opinions on the use of other available medications as well as to inform about safety and adverse effects of these medications. Management of narcolepsy relies on several classes of drugs, namely, stimulants for excessive sleepiness, antidepressants for cataplexy and hypnotics for disturbed nocturnal sleep. Behavioral measures are likewise valuable and universally recommended. All therapeutic trials were analyzed according to their class of evidence. Recommendations concerning the treatment of each single symptom of narcolepsy as well as general recommendations were made. Modafinil is the first-line pharmacological treatment of excessive sleepiness. Second-line choices for the treatment of excessive sleepiness are slow-release metylphenidate followed by mazindol. The first-line treatments of cataplexy are the antidepressants, reboxetine, clomipramine, venlafaxine, desvenlafaxine or high doses of selective serotonin reuptake inibitors antidepressants. As for disturbed nocturnal sleep the best option is still hypnotics. Antidepressants and hypnotics are used to treat hypnagogic hallucinations and sleep paralysis.

Brazilian guidelines for the diagnosis of narcolepsy

This manuscript contains the conclusion of the consensus meeting on the diagnosis of narcolepsy based on the review of Medline publications between 1980-2010. Narcolepsy is a chronic disorder with age at onset between the first and second decade of life. Essential narcolepsy symptoms are cataplexy and excessive sleepiness. Cataplexy is defined as sudden, recurrent and reversible attacks of muscle weakness triggered by emotions. Accessory narcolepsy symptoms are hypnagogic hallucinations, sleep paralysis and nocturnal fragmented sleep. The clinical diagnosis according to the International Classification of Sleep Disorders is the presence of excessive sleepiness and cataplexy. A full in-lab polysomnography followed by a multiple sleep latency test is recommended for the confirmation of the diagnosis and co-morbidities. The presence of two sleep-onset REM period naps in the multiple sleep latency test is diagnostic for cataplexy-free narcolepsy. A positive HLA-DQB1*0602 with lower than 110pg/mL level of hypocretin-1 in the cerebrospinal fluid is required for the final diagnosis of cataplexy- and sleep-onset REM period -free narcolepsy.

Obesidade e distúrbio respiratório do sono, uma associação de fatores de risco

estar acima do peso sao os principais fatoresde risco para a sindrome da apneia e hipopneia obstrutiva do sono(SAHOS). Entretanto, obesidade e sobrepeso tem sido consideradosagravantes e nao determinantes da sindrome (1). Tendo em vista aepidemia de obesidade em varios paises ocidentais, estima-se que aprevalencia de SAHOS seja maior do que a anteriormente estimada. ASAHOS e conhecida por aumentar o risco cardiovascular e por ser fator derisco independente para hipertensao arterial (2). Recentemente, essasindrome tem sido tambem implicada na patogenese da alteracao dometabolismo da glicose (3). Aumento do esforco respiratorio, hipoxiaintermitente e fragmentacao do sono podem levar a uma cascata de eventosincluindo alteracoes autonomicas, especialmente aumento do tonussimpatico, alteracoes da funcao neuroendocrina e liberacao de potentesagentes inflamatorios como o TNF-alfa e interleucina (1,2). Alem disso,alteracao da leptina tem sido descrita como secundaria a SAHOS, e algunsespeculam que isso poderia, em parte, explicar a dificuldade que essespacientes apresentam em perder peso, antes de serem adequadamentetratados com o CPAP nasal (pressao positiva continua na VAS) (1). Poroutro lado, a obesidade por si so pode determinar o aparecimento dehipertensao, inflamacao, lesao endotelial e dislipidemia, justificando amaior mortalidade e morbidade observada nesse grupo de pacientes (4) econtribuindo para a evolucao desfavoravel dos pacientes com SAHOS.Esses dados reforcam o conceito de que o disturbio respiratorio do sonodeve ser investigado em pacientes obesos. Os sintomas apresentados pelosobesos tem pouca capacidade de prever a SAHOS. O melhor preditorainda e considerado a observacao dos eventos pelos familiares (5). Apolissonografia e o exame de escolha para o diagnostico apropriado. Odiagnostico precoce pode determinar melhor prognostico ao paciente (6).O artigo “Apresentacao Clinica de Pacientes Obesos com DiagnosticoPolissonografico de Apneia Obstrutiva do Sono”, de Gregorio e cols. (7),avaliou todos os pacientes obesos (IMC ≥30 Kg/m