An Exploratory Study of Sleep-Wake Differences of Autonomic Activity in Patients with Mild Cognitive Impairment: The Role of Melatonin as a Modulating Factor.

Purpose: The objective of the present study was to assess sleep-wake differences of autonomic activity in patients with mild cognitive impairment (MCI) compared to control subjects. As a post-hoc objective, we sought to evaluate the mediating effect of melatonin on this association. Patients and Methods: A total of 22 MCI patients (13 under melatonin treatment) and 12 control subjects were included in this study. Sleep-wake periods were identified by actigraphy and 24hr-heart rate variability measures were obtained to study sleep-wake autonomic activity. Results: MCI patients did not show any significant differences in sleep-wake autonomic activity when compared to control subjects. Post-hoc analyses revealed that MCI patients not taking melatonin displayed lower parasympathetic sleep-wake amplitude than controls not taking melatonin (RMSSD -7 ± 1 vs 4 ± 4, p = 0.004). In addition, we observed that melatonin treatment was associated with greater parasympathetic activity during sleep (VLF 15.5 ± 0.1 vs 15.1 ± 0.1, p = 0.010) and in sleep-wake differences in MCI patients (VLF 0.5 ± 0.1 vs 0.2 ± 0.0, p = 0.004). Conclusion: These preliminary findings hint at a possible sleep-related parasympathetic vulnerability in patients at prodromal stages of dementia as well as a potential protective effect of exogenous melatonin in this population.

Heart rate variability and falls in Huntington's disease.

PURPOSE: Persons with Huntington's disease (HD) have a high incidence of falls. Autonomic nervous system dysfunction has been reported even in early stages of this disease. To date, there has been no analysis of the relationship between heart rate variability (HRV) and falls in this patient population. The aim of the study reported here was to evaluate the relationship between HRV and falls in persons with HD. METHODS: Huntington's disease patients enrolled in a prospective study on fear of falling and falls were assessed using short-term HRV analyses and blood pressure measures in both the resting and standing states. Time-frequency domains and nonlinear parameters were calculated. Data on falls, the risk of falling (RoF) and disease-specific scales were collected at baseline and at the end of the 6-month follow-up. RESULTS: Of the 24 HD patients who were invited to participate in the study, 20 completed the baseline analysis and 18 completed the 6-month follow-up. At baseline, seven (35%) HD patients reported at least one fall (single fallers) and 13 (65%) reported ≥ 2 falls (recurrent fallers) in the previous 12 months. At baseline, recurrent fallers had lower RMSSD (root mean square of successive RR interval differences) in the resting state (RMSSD-resting), higher LF/HF (low/high frequency) ratio in both states and higher DFA-α1 parameter (detrended fluctuation analyses over the short term) in both states. This association was similar at the 6-month follow-up for recurrent fallers, who showed lower RMSSD-resting and higher LF/HF ratio in the standing state (LF/HF-standing) than single fallers. Significant correlations were found between the number of falls, RMSSD-resting and LF/HF-standing. No differences were found between recurrent and single fallers for any blood pressure measures. CONCLUSIONS: The observed HRV pattern is consistent with a higher sympathetic prevalence associated with a higher RoF. Reduced parasympathetic HRV values in this patient population predict being a recurrent faller at 6 months of follow-up, independently of orthostatic phenomena.

Sleep disruption in medicine students and its relationship with impaired academic performance: A systematic review and meta-analysis.

Sleep disruption severely impairs learning ability, affecting academic performance in students. This systematic review and meta-analysis aimed at assessing the prevalence of sleep disruption in medical students and its relationship with academic performance. PubMed, Web of Sciences, EBSCO and SciELO databases searches allowed to retrieve 41 papers with data about the prevalence of sleep deprivation, 20 of which also contained data on its association with academic performance. Poor sleep quality was reported by 5646 out of 14,170 students in 29 studies (39.8%, 95% confidence interval = 39.0-40.6%), insufficient sleep duration by 3762/12,906 students in 28 studies (29.1%, 23.3-29.9%) and excessive diurnal sleepiness by 1324/3688 students in 13 studies (35.9%, 34.3-37.4). Academic grades correlated significantly with sleep quality scores (r, 95% CI = 0.15, 0.05-0.26, random-effects model; p = 0.002, n = 10,420 subjects, k = 15 studies) and diurnal sleepiness (r = -0.12, -0.19/-0.06 under the fixed effects model, p < 0.001, n = 1539, k = 6), but not with sleep duration (r = 0.03, -0.12/0.17 under the random-effects model, p = 0.132, n = 2469, k = 9). These findings advocate for an urgent intervention aiming at improving sleep quality among medical students as a way of increasing academic achievements and, ultimately, the quality of health care.

Subjective time estimation in Antarctica: The impact of extreme environments and isolation on a time production task.

Interval timing measures time estimation in the seconds-to-minutes range. Antarctica provides a real-world context to study the effect of extreme photoperiods and isolation on time perception. The aim of this study was to explore interval timing as a cognitive measure in the crew of Belgrano II Argentine Antarctic Station. A total of 13 subjects were assessed for interval timing in short (3 s), intermediate (6 s) and long (12 s) duration stimuli. Measures were taken during the morning and evening, five times along the year. Significant variations were found for 3 s and 6 s during the morning and 6 s during the evening. Results suggest an impact of isolation on morning performances and an effect of the polar night on evening measures. These findings shed some light on the use of interval timing as a cognitive test to assess performance in extreme environments.

Sleep misalignment and circadian rhythm impairment in long-haul bus drivers under a two-up operations system.

OBJECTIVES: The objective of the study was to describe working and sleep conditions and to assess how sleep opportunities are associated with obtained sleep and alertness, in a sample of long-haul bus drivers working with a two-up operations system. METHODS: Measures of subjective sleep and sleepiness, actigraphy, circadian temperature rhythm, and psychomotor vigilance tasks were obtained from a sample of 122 drivers from Argentina. Variables were compared between high and low fatigue risk groups, which were formed using a median split of a fatigue risk score. The score was calculated based on drivers' total working hours, maximum shift duration, minimum short break duration, maximum night work per seven days, and long break frequencies. RESULTS: Considering a standardized one-day period, sleep in the bus accounted for 1.9±0.1 h of total sleep (57±1% efficiency), sleep at destination for 1.6±0.2 h of total sleep (90±1% efficiency), and sleep at home for 3.8±0.2 h of total sleep (89±1% nap efficiency and 90±1% anchor sleep efficiency). In drivers exposed to high-risk working schedules, the circadian temperature rhythm was weaker (lower % of variance explained by the model) (22.0±1.7% vs. 27.6±2.0%, p <0.05) and without a significant acrophase. CONCLUSIONS: Drivers obtained a total amount of weekly sleep similar to the recommended levels for adults, but distributed at different locations and at different times during the day. High-risk working schedules were associated with disruption of circadian temperature rhythms. These results point out to the need of the implementation of shift-work scheduling strategies to minimize sleep misalignment and circadian desynchronization in long-haul bus drivers.

Sleep, napping and alertness during an overwintering mission at Belgrano II Argentine Antarctic station.

During Antarctic isolation personnel are exposed to extreme photoperiods. A frequent observation is a sleep onset phase delay during winter. It is not known if, as a result, daytime sleeping in the form of naps increases. We sought to assess sleep patterns - with focus on daytime sleeping - and alertness in a Latin American crew overwintering in Argentine Antarctic station Belgrano II. Measurements were collected in 13 males during March, May, July, September and November, and included actigraphy and psychomotor vigilance tasks. Sleep duration significantly decreased during winter. A total of eight participants took at least one weekly nap across all measurement points. During winter, the nap onset was delayed, its duration increased and its efficiency improved. We observed a significant effect of seasonality in the association of evening alertness with sleep onset. Our results replicate previous findings regarding sleep during overwintering in Antarctica, adding the description of the role of napping and the report of a possible modulatory effect of seasonality in the relation between sleep and alertness. Napping should be considered as an important factor in the scheduling of activities of multicultural crews that participate in Antarctica.

Executive functioning in cognitively normal middle-aged offspring of late-onset Alzheimer's disease patients.

Episodic memory deficits are traditionally seen as the hallmark cognitive impairment during the prodromal continuum of late-onset Alzheimer's disease (LOAD). Previous studies identified early brain alterations in regions subserving executive functions in asymptomatic, middle-aged offspring of patients with LOAD (O-LOAD), suggesting that premature episodic memory deficits could be associated to executive dysfunction in this model. We hypothesized that O-LOAD would exhibit reduced executive performance evidenced by increased errors and decreased strategy use on an episodic memory task. We assessed 32 asymptomatic middle-aged O-LOAD and 28 age-equivalent control subjects (CS) with several tests that measure executive functions and the Rey Auditory Verbal Learning Test (RAVLT) to measure memory performance. All tests were scored using both traditional and process scores (quantification of errors and strategies underlying overall performance). T-tests were used to compare performance between both groups and Spearman correlations were implemented to measure associations between variables. O-LOAD participants exhibited decreased executive performance compared to CS as it relates to initiation time (Tower of London), mental switching (Trail Making Test B), and interference effects (Stroop Word-Color condition). Traditional RAVLT measures showed a poorer performance by O-LOAD and RAVLT process scores revealed increased interference effects on this group. Positive correlations (rs) were found between the executive measures and several RAVLT measures for O-LOAD but not for CS. In conclusion, O-LOAD participants exhibited early subtle cognitive changes in executive processing. Observed memory difficulties may be associated in part to executive deficits suggesting an interplay between memory and executive functions. Process score impairments were observed earlier than clinical decline on neuropsychological scores in this at-risk cohort and might be useful cognitive markers of preclinical LOAD.

Brain Structural and Amyloid Correlates of Recovery From Semantic Interference in Cognitively Normal Individuals With or Without Family History of Late-Onset Alzheimer's Disease.

Failure to recover from proactive semantic interference (frPSI) has been shown to be more sensitive than traditional cognitive measures in different populations with preclinical Alzheimer's disease. The authors sought to characterize the structural and amyloid in vivo correlates of frPSI in cognitively normal offspring of patients with late-onset Alzheimer's disease (O-LOAD), compared with individuals without a family history of neurodegenerative disorders (CS). The authors evaluated the LASSI-L, a test tapping frPSI and other types of semantic interference and delayed recall on the RAVLT, along with 3-T MRI volumetry and positron emission tomography Pittsburgh compound B, in 27 O-LOAD and 18 CS with equivalent age, sex, years of education, ethnicity, premorbid intelligence, and mood symptoms. Recovery from proactive semantic interference (frPSI) and RAVLT delayed recall were lower in O-LOAD cases. Structural correlates of both cognitive dimensions were different in CS and O-LOAD, involving brain regions concerned with autonomic, motor, and motivational control in the former, and regions traditionally implicated in Alzheimer's disease in the latter. Better recovery from retroactive semantic interference was associated with less amyloid load in the left temporal lobe in O-LOAD but not CS. In middle-aged cognitively normal individuals with one parent affected with LOAD, frPSI was impaired compared with persons without a family history of LOAD. The neuroimaging correlates of such cognitive measure in those with one parent with LOAD involve Alzheimer's-relevant brain regions even at a relatively young age.

Cortical thickness, brain metabolic activity, and in vivo amyloid deposition in asymptomatic, middle-aged offspring of patients with late-onset Alzheimer's disease.

The natural history of preclinical late-onset Alzheimer's disease (LOAD) remains obscure and has received less attention than that of early-onset AD (EOAD), in spite of accounting for more than 99% of cases of AD. With the purpose of detecting early structural and functional traits associated with the disorder, we sought to characterize cortical thickness and subcortical grey matter volume, cerebral metabolism, and amyloid deposition in persons at risk for LOAD in comparison with a similar group without family history of AD. We obtained 3T T1 images for gray matter volume, FDG-PET to evaluate regional cerebral metabolism, and PET-PiB to detect fibrillar amyloid deposition in 30 middle-aged, asymptomatic, cognitively normal individuals with one parent diagnosed with LOAD (O-LOAD), and 25 comparable controls (CS) without family history of neurodegenerative disorders (CS). We observed isocortical thinning in AD-relevant areas including posterior cingulate, precuneus, and areas of the prefrontal and temporoparietal cortex in O-LOAD. Unexpectedly, this group displayed increased cerebral metabolism, in some cases overlapping with the areas of cortical thinning, and no differences in bilateral hippocampal volume and hippocampal metabolism. Given the importance of age in this sample of individuals potentially developing early AD-related changes, we controlled results for age and observed that most differences in cortical thickness and metabolism became nonsignificant; however, greater deposition of ß-amyloid was observed in the right hemisphere including temporoparietal cortex, postcentral gyrus, fusiform inferior and middle temporal and lingual gyri. If replicated, the present observations of morphological, metabolic, and amyloid changes in cognitively normal persons with family history of LOAD may bear important implications for the definition of very early phenotypes of this disorder.

Hours of service regulations for professional drivers in continental Latin America.

OBJECTIVES: To describe the hours of service provisions in continental Latin America. DESIGN: Information on regulations of service hours was extracted from either the national transportation authorities or ministries of transportation (or the equivalent institution) from each country. SETTING: Seventeen sovereign countries in continental Latin America (Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Uruguay, Venezuela). PARTICIPANTS: N/A INTERVENTION (IF ANY): N/A MEASUREMENT: Data on (a) limit on work hours, (b) mandatory daily time off (or rest), (c) overall schedule (mandatory weekly time off), and (d) daily breaks were extracted and summarized. RESULTS: Of the 17 countries surveyed, 9 countries have provisions limiting the daily amount of hours of service for professional drivers. Ten have provisions for mandatory daily rest, but only 5 have explicit provisions limiting the number of continuous working days, with mandatory uninterrupted time off >35 hours. Eight countries have provisions for mandatory breaks that limit the hours of continuous driving (ranging from 3 to 5:30 hours). CONCLUSION: Regulations that govern a population with 6 million injuries and over 100,000 deaths per year due to motor vehicle accidents leave important gaps. A minority, 6, of the countries regulated all 3 aspects; daily hours, breaks, and time off, and 3 regulate none of these. The regulations are less precise and restrictive than those in high-income countries, despite the doubled road injury mortality, and likely expose professional drivers and other road users to an increased risk of fatigue-related accidents.

La actigrafía como herramienta diagnóstica / ROLE OF ACTIGRAPHY IN THE STUDY OF SLEEP AND CIRCADIAN RHYTHMS : ACCURACY, SENSITIVITY AND SPECIFICITY OF ACTIGRAPHY FOR THE ASSESSMENT OF SLEEP DISORDERS

El diagnóstico y tratamiento de los trastornos de sueño, especialmente los asociados al Ritmo Circadiano, utilizan métodos costosos, invasivos e incómodos tanto para los pacientes como para los médicos, quienes deben realizar un seguimiento de los hábitos de sueño. La actigrafía ha sido aceptada como una herramienta válida para el estudio y diagnóstico de trastornos circadianos. Más de 300 dispositivos se comercializan actualmente para el uso personal, pero pocos de estos han sido probados para un uso diagnóstico. En este estudio comparativo compuesto por 21 sujetos, se informa acerca de los patrones de sueño y actividad registrados por algunos dispositivos, como Micro-Mini Motionlogger Watch, Condor Act Trust, MisFit Flash y Fitbit Flex. No se observan diferencias significativas en el análisis del patrón de actividad de descanso entre dispositivos. Tampoco se observan para el sueño Onset (inicio), el Tiempo Total de Sueño y la Eficiencia del Sueño. Según el tipo de estudio y análisis deseado, éstos dispositivos pueden resultar alternativos para los registros de actividad y sueño.

This is a comparative analysis of actigraphy performance in comparison with different sleep Parameters. Actigraphy is a non-invasive and valid method of monitoring human rest activity cycles. The report describes the role of actigraphy to assess the study of sleep-wake patterns and circadian rhythms, evaluating its development as a diagnostic tool, with a comparative analysis of actigraphy performance in comparison with different sleep parameters. The diagnosis and treatment of sleep disorders, especially those associated with the cicardian rhythm, employ very expensive costs, invasives or unconfortable for the patients the same as for physicians, who must perform a demand of the sleeping habits. The International Classification of Sleep Disorders has identified more than 80 sleep disorders, all of them have associated treatments. Actinography has been accepted as a valid tool for the study and diagnosis of circadian disorders. All these aspects are discussed in the article

Failure to Recover from Proactive Semantic Interference and Abnormal Limbic Connectivity in Asymptomatic, Middle-Aged Offspring of Patients with Late-Onset Alzheimer's Disease.

BACKGROUND: We have obtained previous evidence of limbic dysfunction in middle-aged, asymptomatic offspring of late-onset Alzheimer's disease (LOAD) patients, and failure to recover from proactive semantic interference has been shown to be a sensitive cognitive test in other groups at risk for LOAD. OBJECTIVE: To assess the effects of specific proactive semantic interference deficits as they relate to functional magnetic resonance imaging (fMRI) neocortical and limbic functional connectivity in middle aged offspring of individuals with LOAD (O-LOAD) and age-equivalent controls. METHODS: We examined 21 O-LOAD and 20 controls without family history of neurodegenerative disorders (CS) on traditional measures of cognitive functioning and the LASSI-L, a novel semantic interference test uniquely sensitive to the failure to recover from proactive interference (frPSI). Cognitive tests then were correlated to fMRI connectivity of seeds located in entorhinal cortex and anterodorsal thalamic nuclei among O-LOAD and CS participants. RESULTS: Relative to CS, O-LOAD participants evidenced lower connectivity between entorhinal cortex and orbitofrontal, anterior cingulate, and anterior temporal cortex. In the offspring of LOAD patients, LASSI-L measures of frPSI were inversely associated with connectivity between anterodorsal thalamus and contralateral posterior cingulate. Intrusions on the task related to frPSI were inversely correlated with a widespread connectivity network involving hippocampal, insular, posterior cingulate, and dorsolateral prefrontal cortices, along with precunei and anterior thalamus in this group. Different patterns of connectivity associated with frPSI were observed among controls. CONCLUSION: The present results suggest that both semantic interference deficits and connectivity abnormalities might reflect limbic circuit dysfunction as a very early clinical signature of LOAD pathology, as previously demonstrated for other limbic phenotypes, such as sleep and circadian alterations.

Melatonin, mitochondria, and the metabolic syndrome.

A number of risk factors for cardiovascular disease including hyperinsulinemia, glucose intolerance, dyslipidemia, obesity, and elevated blood pressure are collectively known as metabolic syndrome (MS). Since mitochondrial activity is modulated by the availability of energy in cells, the disruption of key regulators of metabolism in MS not only affects the activity of mitochondria but also their dynamics and turnover. Therefore, a link of MS with mitochondrial dysfunction has been suspected since long. As a chronobiotic/cytoprotective agent, melatonin has a special place in prevention and treatment of MS. Melatonin levels are reduced in diseases associated with insulin resistance like MS. Melatonin improves sleep efficiency and has antioxidant and anti-inflammatory properties, partly for its role as a metabolic regulator and mitochondrial protector. We discuss in the present review the several cytoprotective melatonin actions that attenuate inflammatory responses in MS. The clinical data that support the potential therapeutical value of melatonin in human MS are reviewed.

Relationship between Cognitive and Sleep-wake Variables in Asymptomatic Offspring of Patients with Late-onset Alzheimer's Disease.

Early neuropathological changes characteristic of late-onset Alzheimer's disease (LOAD) involve brain stem and limbic structures that regulate neurovegetative functions, including sleep-wake rhythm. Indeed, sleep pattern is an emerging biomarker and a potential pathophysiological mechanism in LOAD. We hypothesized that cognitively asymptomatic, middle-aged offspring of patients with LOAD (O-LOAD) would display a series of circadian rhythm abnormalities prior to the onset of objective cognitive alterations. We tested 31 children of patients with LOAD (O-LOAD) and 19 healthy individuals without family history of Alzheimer's disease (control subjects, CS) with basic tests of cognitive function, as well as actigraphy measures of sleep-wake rhythm, cardiac autonomic function, and bodily temperature. Unexpectedly, O-LOAD displayed subtle but significant deficits in verbal episodic memory (Rey Auditory Verbal Learning Test delayed recall 10.6 ± 0.4 vs. 8.6 ± 0.6, t = 4.97, df = 49, p < 0.01) and language (Weschler's vocabulary 51.4 ± 1.3 vs. 44.3 ± 1.5, t = 2.49, df = 49, p < 0.001) compared to CS, even though all participants had results within the clinically normal range. O-LOAD showed a phase-delayed rhythm of body temperature (2.56 ± 0.47 h vs. 3.8 ± 0.26 h, t = 2.48, df = 40, p = 0.031). Cognitive performance in O-LOAD was associated with a series of cardiac autonomic sleep-wake variables; specifically indicators of greater sympathetic activity at night were related to poorer cognition. The present results suggest sleep pattern deserves further study as a potential neurobiological signature in LOAD, even in middle-aged, at risk individuals.

Changing dynamics: Time-varying autoregressive models using generalized additive modeling.

In psychology, the use of intensive longitudinal data has steeply increased during the past decade. As a result, studying temporal dependencies in such data with autoregressive modeling is becoming common practice. However, standard autoregressive models are often suboptimal as they assume that parameters are time-invariant. This is problematic if changing dynamics (e.g., changes in the temporal dependency of a process) govern the time series. Often a change in the process, such as emotional well-being during therapy, is the very reason why it is interesting and important to study psychological dynamics. As a result, there is a need for an easily applicable method for studying such nonstationary processes that result from changing dynamics. In this article we present such a tool: the semiparametric TV-AR model. We show with a simulation study and an empirical application that the TV-AR model can approximate nonstationary processes well if there are at least 100 time points available and no unknown abrupt changes in the data. Notably, no prior knowledge of the processes that drive change in the dynamic structure is necessary. We conclude that the TV-AR model has significant potential for studying changing dynamics in psychology. (PsycINFO Database Record

Comparative analysis of actigraphy performance in healthy young subjects.

Sleep-related health disorders are increasing worldwide; diagnosis and treatment of such sleep diseases are commonly invasive and sometimes unpractical or expensive. Actigraphy has been recently introduced as a tool for the study of sleep and circadian disorders; however, there are several devices that claim to be useful for research and have not been thoroughly tested. This comparative study provides activity, sleep and temperature information regarding several of the most commonly used actigraphers: Micro-Mini Motion Logger; Act Trust; Misfit Flash; Fitbit Flex & Thermochron. Twenty-two healthy young subjects were assessed with five different commercial actigraphs (Micro-Mini Motionlogger Watch, Condor Act Trust, MisFit Flash and Fitbit Flex) and a temperature recorder (Thermochron), and also completed a sleep diary for a week. There were not significant differences in the analysis of rest-activity pattern between devices. Temperature rhythm comparison between the Act Trust and the Thermochron showed significant differences in rhythm percentage (p<0.05) and mesor (p<0.0563) but not in amplitude or acrophase. Although data accessibility and ease of use was very different for the diverse devices, there were no significant differences for sleep onset, total sleep time and sleep efficiency recordings, where applicable. In conclusion, depending on the type of study and analysis desired (as well as cost and compliance of use), we propose some relative advantages for the different actigraphy/temperature recording devices.

Assessing the efficacy of melatonin to curtail benzodiazepine/Z drug abuse.

The abuse of benzodiazepine (BZP) and Z drugs has become, due to the tolerance and dependence they produce, a serious public health problem. Thirty years ago, we demonstrated in experimental animals the interaction of melatonin with central BZD receptors, and in 1997 we published the first series of elderly patients who reduced BZP consumption after melatonin treatment. Almost every single neuron in the hypothalamic suprachiasmatic nuclei (SCN), the central pacemaker of the circadian system, contains γ-aminobutyric acid (GABA) and many results in animals point out to a melatonin interaction with GABA-containing neurons. In addition, central-type BZD antagonism, that obliterates GABAA receptor function, blunted most behavioral effects of melatonin including sleep. Melatonin is involved in the regulation of human sleep. This is supported by the temporal relationship between the rise of plasma melatonin levels and sleep propensity as well as by the sleep-promoting effects of exogenously administered melatonin. Both meta-analyses and consensus agreements give support to the therapeutic use of melatonin in sleep disorders. This action is attributed to MT1 and MT2 melatoninergic receptors localized in the SCN, as well as in other brain areas. This review discusses available data on the efficacy of melatonin to curtail chronic BZD/Z drug use in insomnia patients. A major advantage is that melatonin has a very safe profile, it is usually remarkably well tolerated and, in some studies, it has been administered to patients at very large doses and for long periods of time, without any potentiality of abuse. Further studies on this application of melatonin are warranted.

The impact of home safety on sleep in a Latin American country.

OBJECTIVES: We sought to assess the impact of feelings of safety in one's neighborhood and home on sleep quality and sleep duration. DESIGN: The design is a cross-sectional survey using face-to-face interviews, as part of the Argentine Social Debt Observatory assessment. SETTING: The setting is a nationwide data from Argentina. PARTICIPANTS: There are 5636 participants aged 18 years and older. INTERVENTION (IF ANY): N/A. MEASUREMENTS: The relationships between both subjective sleep quality and self-reported sleep duration, categorized as short (<7 hours), normal (7-8 hours), and long (>8 hours) with safety in one's neighborhood and one's home, were analyzed. Age, sex, obesity, neighborhood socioeconomic status, and education were included as covariates. RESULTS: Feeling unsafe in one's home was strongly associated with poorer sleep quality and with short sleep duration. Feeling unsafe in one's neighborhood was initially associated with reduced sleep quality but was no longer significant after controlling for home safety. In contrast, we found no correlation between safety measures and long sleep. In analyses stratified by sex, feeling unsafe in one's home was associated with poor sleep quality in women but not in men. CONCLUSIONS: Our findings suggest that safety in the home has an important effect on both sleep quality and duration, particularly among women. In contrast, after accounting for safety in the home, neighborhood safety does not impact sleep. Further research is warranted to identify mechanisms underlying the sex differences in susceptibility to poor sleep quality and shorter sleep duration, as well as to assess whether interventions addressing safety in the home can be used to improve sleep and overall health.

Melatonin Therapy in Patients with Alzheimer's Disease.

Alzheimer's disease (AD) is a major health problem and a growing recognition exists that efforts to prevent it must be undertaken by both governmental and non-governmental organizations. In this context, the pineal product, melatonin, has a promising significance because of its chronobiotic/cytoprotective properties potentially useful for a number of aspects of AD. One of the features of advancing age is the gradual decrease in circulating melatonin levels. A limited number of therapeutic trials have indicated that melatonin has a therapeutic value as a neuroprotective drug in the treatment of AD and minimal cognitive impairment (which may evolve to AD). Both in vitro and in vivo, melatonin prevented the neurodegeneration seen in experimental models of AD. For these effects to occur, doses of melatonin about two orders of magnitude higher than those required to affect sleep and circadian rhythmicity are needed. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects, which were employed in clinical trials in sleep-disturbed or depressed patients in doses considerably higher than those employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin in the range of 50-100 mg/day are urgently needed to assess its therapeutic validity in neurodegenerative disorders such as AD.