Cognitive processes in hypertension.

In 15 normotensive subjects, 17 newly diagnosed, untreated hypertensive patients, and 22 effectively treated hypertensive patients, a battery of neuropsychological tests was given. All subjects were neurologically asymptomatic. The neuropsychological battery included tests evaluating global cognitive functions (Card Sorting Test, Wechsler Memory Scale, Progressive Matrices 1938), as well as specific cognitive functions (Benton Test, subtests of the Wechsler-Bellevue Scale). Normotensive controls obtained better scores in all the tests. Statistical analysis of th scores suggests that hypertension is highly correlated with impairment of memory, logical reasoning, visuospatial organization, and attention. Therapy seems to impair attention, while the duration of disease seems to influence visuospatial performances.

Ambulatory polysomnography of never-depressed borderline subjects: a high-risk approach to rapid eye movement latency.

The sleep parameters of never-depressed borderline subjects and age- and sex-matched normal controls were compared by continuous 48-hr ambulatory electroencephalographic (EEG) monitoring. Borderline subjects had a significantly shorter rapid eye movement latency, normal architecture of rapid eye movements sleep, and had familial risks for mood disorders four times greater than in the families of controls. Reduced latency of rapid eye movement can be a trait indicator of liability to depression, present before the clinical appearance of the disorder, and demonstrable in a putative high-risk population.

Decreased CSF concentrations of homovanillic acid and gamma-aminobutyric acid in Alzheimer's disease. Age- or disease-related modifications?

Fifteen patients, 48 to 72 years old, with Alzheimer's disease were studied. Clinical status was assessed by neurologic and neuropsychologic examinations and psychometric testing. Patients were divided into two groups on the basis of clinical assessment: group 1, little mental deterioration, and group 2, serious mental deterioration. Nineteen subjects, 27 to 72 years old, without neurologic disease served as controls. Levels of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and gamma-aminobutyric acid (GABA) were determined in lumbar CSF by fluorimetric or radioreceptor binding (GABA) methods. The HVA concentrations increased with age in the controls, whereas the GABA levels decreased with age and 5-HIAA levels were not modified. When compared with the age-matched controls, the patients with Alzheimer's disease showed low concentrations of HVA but not of 5-HIAA or GABA. The decrease in HVA level was more pronounced in patients with severe mental deterioration and therefore appeared to be disease related.

Prevalence and pathologic associations of sleep paralysis in the general population.

BACKGROUND: Previous epidemiologic data on sleep paralysis (SP) came from small specific samples. The true prevalence and associated factors of SP in the general population remain unknown. METHOD: A representative sample of the noninstitutionalized general population of Germany and Italy age > or =15 years (n = 8,085) was surveyed by telephone using the Sleep-EVAL questionnaire and the Sleep Questionnaire of Alertness and Wakefulness. RESULTS: Overall, 6.2% (5.7 to 6.7%) of the sample (n = 494) had experienced at least one SP episode in their lifetime. At the time of the interview, severe SP (at least one episode per week) occurred in 0.8% of the sample, moderate SP (at least one episode per month) in 1.4%, and mild SP (less than one episode per month) in 4.0%. Significant predictive variables of SP were anxiolytic medication, automatic behavior, bipolar disorders, physical disease, hypnopompic hallucinations, nonrestorative sleep, and nocturnal leg cramps. CONCLUSIONS: SP is less common in the general population than was previously reported. This study indicates that the disorder is often associated with a mental disorder. Users of anxiolytic medication were nearly five times as likely to report SP, even after we controlled for possible effects of mental and sleep disorders.

Prevalence of narcolepsy symptomatology and diagnosis in the European general population.

OBJECTIVE: To determine the prevalence of narcolepsy in the general population of five European countries (target population 205,890,882 inhabitants). METHODS: Overall, 18,980 randomly selected subjects were interviewed (participation rate 80.4%). These subjects were representative of the general population of the UK, Germany, Italy, Portugal, and Spain. They were interviewed by telephone using the Sleep-EVAL expert system, which provided narcolepsy diagnosis according to the International Classification of Sleep Disorders (ICSD). RESULTS: Excessive daytime sleepiness was reported by 15% of the sample, with a higher prevalence in the UK and Germany. Napping two times or more in the same day was reported by 1.6% of the sample, with a significantly higher rate in Germany. Cataplexy (episodes of loss of muscle function related to a strong emotion), a cardinal symptom of narcolepsy, was found in 1.6% of the sample. An ICSD narcolepsy diagnosis was found in 0.047% of the sample: The narcolepsy was severe for 0.026% of the sample and moderate in 0.021%. CONCLUSION: This is the first epidemiologic study that estimates the prevalence of narcolepsy in the general population of these five European countries. The disorder affects 47 individuals/100,000 inhabitants.

Sleep arousal response to experimental thermal stimulation during sleep in human subjects free of pain and sleep problems.

Although the interaction between sleep and pain is generating considerable interest (NIH Technology Assessment Panel, 1996), it is still unknown if chronic pain is the cause or effect of poor sleep. To further this understanding, subjects free of pain and sleep problems need to be studied in order to assess their response to pain during sleep, defined as a behavioral and a physiological state in which sensory processing is altered. (For example, while auditory perception remains active, other sensory inputs are facilitated, attenuated, or suppressed (Velluti, 199746 degrees C) was statistically greater in the lighter sleep stage 2 (48.3%) than in the deeper stages 3&4 (27.9%). A nocifensive behavioral-motor response was associated with only 2.5% of the 351 heat pain stimuli. Two other markers of sleep quality-sleep stage shift and awakening-were not influenced by the thermal stimuli. None of the subjects demonstrated any burns in the morning following the thermal stimulations applied during sleep. We conclude that the processing of nociceptive inputs is attenuated across sleep stages.

Excessive daytime sleepiness: a 1-year study in an unselected inpatient population.

A prospective epidemiological investigation of excessive daytime sleepiness (EDS) was carried out in an unselected inpatient population admitted to a general hospital during a 1-year period. The study comprised 2518 patients, 1347 female and 1171 male, aged 6-92 years (mean, 55.2). On the basis of histories and clinical and polysomnographic data, EDS was found in 28 cases (1.11%). Of these, 25 (0.99%; 18 female and 7 male; mean age, 61.3) had sleep apnea syndromes (SAS) with predominantly obstructive apnea. Two patients (0.07%; one female and one male; mean age, 65.5) had idiopathic CNS hypersomnia, and one male patient (0.03%) aged 48 years had a combination of narcolepsy and SAS. Differences and agreements of our findings with previous literature data are discussed. The present study shows that in an unselected inpatient population, EDS is a relatively common sleep disorder, usually found in mild to moderate forms. Because it is not severe, it disturbs only relatively domestic activities of elderly retired patients or others who do not work outside the home, and is often masked by other troubles. For these reasons, EDS in the aging population may pass unnoticed in epidemiological studies based only on data from sleep disorder centers.

Cardiac autonomic activity during wakefulness and sleep in REM sleep behavior disorder.

In REM sleep behavior disorder (RBD) it has been reported that tachycardia may not accompany the impressive movements associated with dream mentation. Up to now there are no data concerning the cardiac autonomic activity during wakefulness as well as during sleep out of nocturnal dream-enacting behaviors, in RBD. We evaluated 14 RBD patients. Our study shows that only 36% of patients had normal results in all traditional autonomic tests during wakefulness. Moreover, RBD patients had a reduced tonic and phasic heart rate variability during sleep. Autonomic evaluation during sleep may show impairment earlier than the traditional tests during wakefulness. No difference was found between idiopathic RBD patients and symptomatic ones.

Effect of melatonin on sleep microstructure: preliminary results in healthy subjects.

The ability of melatonin (MLT) to potentiate the effects of gamma-aminobutyric acid and the benzodiazepines has been demonstrated repeatedly in animal models, and recent experimental data favored the hypothesis that MLT, given together with threshold doses of benzodiazepines, could significantly improve the quality of sleep. This preliminary study was designed to compare the effects of MLT (100 mg) with those of a benzodiazepine hypnotic [triazolam (TRI) 0.125 mg] and to explore the effects of a combination of MLT and TRI at a low dose in healthy volunteers. No significant changes in the classical polysomnographic variables were observed following MLT, TRI and MLT + TRI, whereas MLT and especially MLT + TRI resulted in significant modulation of some microstructural parameters. These changes were paralleled by ameliorated subjective sleep quality. A combination of MLT and low benzodiazepine doses could avoid the residual, dose-related benzodiazepine effects.

Slow wave sleep and cyclic alternating pattern (CAP) in HIV-infected asymptomatic men.

Alterations of sleep structure have been reported in asymptomatic human immunodeficiency virus (HIV)-infected subjects. In these patients some authors have found an increased percentage of slow wave sleep (SWS) and a SWS preponderance in the second half of the night, as well as subjective sleep complaints. Other authors have found an increased stage 1 non-rapid eye movement (NREM) and reduced stage 2 NREM percentages in asymptomatic subjects. We evaluated the macrostructure and the microstructure (cyclic alternating pattern, CAP) of sleep in nine HIV-infected asymptomatic men without sleep complaints or psychiatric illness, in comparison with nine age-matched controls. Our study showed a decreased amount of SWS and a significantly higher CAP rate in HIV-subjects, suggesting an altered organization of the sleep process in these patients.

Cardiac autonomic nervous activity in sleep-related painful erections.

Sleep-related painful erections (SRPE) are characterized by penile pain that occurs during erections, typically during REM sleep. Afflicted individuals usually have normal erections during wakefulness. The disorder could be related to an altered autonomic function only during sleep. The aim of this study was to evaluate tonic and phasic heart rate (HR) modifications during sleep in 10 SRPE patients compared to 25 age-matched controls. A reduced cardiac vagal activity during sleep, as well as a trend towards a higher HR acceleration in relation to spontaneous body movements, have been found in SRPE patients. The possible beta-adrenergic hyperactivity during sleep in these patients could explain the reported efficacy of a beta-blocker, such as propranolol, in this disorder.

Snoring & sleep apnea: a population study in Italian women.

The aim of this cross-sectional study was to evaluate the prevalence of sleep-disordered breathing by means of a validated portable instrument (MESAM IV) and to investigate the relationship between snoring and sleep apnea in a sample of Italian middle-aged female population. We randomly chose 750 subjects aged 40 to 65 years and 365 agreed to participate to the study. In this group, 19.7% of subjects were every-night snorers according to the questionnaire; when recorded, 54.2% snored for more than 10% of the night, and 7.1% for more than 50% of the night. Sleep apnea was also common: 10.7% of subjects had a respiratory disturbances per hour (RDI) between 5 and 9, 7.7% an RDI between 10 and 19, and 2.2% had an RDI > or =20. Snoring percentage and RDI were significantly correlated. However, 50% of subjects who snored for more than half the night had no evidence of sleep apnea. Snoring amount >50% resulted influenced by body mass index, while RDI>10 was influenced by neck diameter. We concluded that in middle-aged women, both snoring and sleep apnea are very common. A high percentage of snoring is not essential for the occurrence of sleep apnea, nor it necessarily indicates the presence of sleep apnea.

An international study on sleep disorders in the general population: methodological aspects of the use of the Sleep-EVAL system.

The comparability among epidemiological surveys of sleep disorders has been encumbered because of the array of methodologies used from study to study. The present international initiative addresses this limitation. Many such studies using the exact same methodology are being completed in six European countries (France, the United Kingdom, Germany, Italy, Portugal, and Spain), two Canadian cities (metropolitan areas of Montreal and Toronto), New York State, and the city of San Francisco. These surveys have been undertaken with the aim of documenting the prevalence of sleep disorders in the general population according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) and the International Classification of Sleep Disorders (ICSD-90). Data are gathered over the telephone by lay interviewers using the Sleep-EVAL expert system. This paper describes the methodology involved in the realization of these studies. Sample design and selection procedures are discussed.

Myocardial ischemia during sleep.

The role of sleep in the pathogenesis of coronary ischaemic events such as myocardial infarction, transient myocardial ischaemia, or cardiac sudden death, is unclear. This review will analyse the available data on the subject according to: (i) the autonomic and cardiovascular changes during sleep that may potentially favour myocardial ischaemia; (ii) the evidence of a circadian distribution of coronary events; and (iii) the factors possibly involved in the pathogenesis of nocturnal angina. Available data suggest that myocardial ischaemia may occur by different mechanisms in non-rapid eye movement (NREM) (decreased coronary perfusion pressure) and rapid eye movement (REM) sleep (increased myocardial oxygen demand). Coronary events show a major peak of occurrence between 6.00 a.m. and noon; however, the myocardial ischaemic threshold, defined as the heart rate value at which myocardial ischaemia develops, may be lower at night than during the daytime, suggesting an unexpectedly higher susceptibility to myocardial ischaemia during sleep than during wakefulness. These data warrant further study on the pathophysiology of coronary circulation during sleep. Finally, some evidence is available that sleep disordered breathing may precipitate nocturnal angina especially in REM sleep, through decreased arterial oxygen content secondary to hypoventilation or true apnoeas. More data are needed to better understand the effects of sleep on the coronary circulation, and to improve the therapeutic approach of nocturnal angina.

Structured psychiatric interview and ambulatory sleep monitoring in young psychophysiological insomniacs.

BACKGROUND: The presence of psychiatric disorders (according to DSM-III-R), the discriminating power of a psychiatric structured interview, and sleep monitoring were investigated in psychophysiological insomnia. METHOD: Forty young (20-40 years old) patients, selected for putative psychophysiological insomnia, underwent a psychiatric structured interview and home ambulatory sleep monitoring for 2 nights. The results were compared with those of a group of nine young normal sleepers. RESULTS: 48% of the insomniacs showed some psychiatric disorders, while 52% did not meet DSM-III-R criteria for a psychiatric diagnosis. Both groups, but not the controls, showed a slight first-night effect in the sleep analysis. The sleep structure of all insomniacs was found to be disturbed, mainly in sleep continuity, but essentially the two groups showed no significant differences. When we used a stepwise logistic regression analysis, the number of sleep stage shifts (indicating sleep instability) was the best variable in discriminating the insomniacs from controls, but not the patients with psychiatric disturbances from those without psychopathologies. CONCLUSION: The evaluation of young insomniacs with a structured psychiatric interview rather than with ambulatory sleep monitoring seems to be most useful in discriminating between patients with only psychophysiological insomnia and patients with both insomnia and an associated diagnosis of another mental disorder.

Heart rate variability during sleep in snorers with and without obstructive sleep apnea.

Changes in sympathetic and vagal tone may be the substrate for the development of cardiac arrhythmias in patients with obstructive sleep apnea (OSA). The cardiovascular responses in the traditional autonomic tests show great interindividual and intraindividual variations. During sleep there are repetitive modifications of heart rate (HR) that are not influenced by psychologic factors or the patient's cooperation. For this reason, we evaluated HR modifications in relation to spontaneous body movements (BM) and sleep apneas during nonrapid eye movement (NREM) and rapid eye movement (REM) sleep in habitual snorers with normal and pathologic respiratory disturbance index (RDI). From 132 consecutive patients referred to our sleep center for habitual snoring and/or daytime somnolence, we selected 35 male patients younger than 60 years without clinical evidence of autonomic dysfunction. They were divided into three groups: group A (RDI < 10); group B (RDI > 10 and < 20); and group C (RDI > 20). No significant difference was found among the three groups in the HR variability related to BM. In the evaluation of bradytachyarrhythmias related to apneic events of 20 to 30 s, we found a significant difference between group A and the other two groups. In patients with RDI > 10, a reduced HR variability related to a reduced sympathetic tone in the post-apnea phase was observed. Some authors suggested that an HR increase during the post-apnea period can be used as an index of "brainstem arousal." Our results seem to indicate a reduced apnea-related "arousability" in patients with RDI > 10. This finding might be one of the factors contributing to the worsening of OSA.

Snoring and nocturnal oxygen desaturations in an Italian middle-aged male population. Epidemiologic study with an ambulatory device.

Recent studies have suggested that portable monitoring may be a valid means of finding respiratory disturbances in epidemiologic research on a large scale. The aim of this cross-sectional study was to evaluate by means of an appropriately validated portable instrument (MESAM 4) the nocturnal oxygen desaturations in a representative sample of adult male population in North Italy. We randomly chose 750 subjects: 399 subjects (53.2 percent) agreed to participate and a complete evaluation of nocturnal recording was possible in 349 subjects (87.5 percent). Seventeen percent of subjects were every-night snorers; a number of oxygen desaturations per hour (ODI) > 10 was found in 13.7 percent, and an ODI > 20 resulted in 4.8 percent. Age, neck circumference corrected for height, snoring time (measured by MESAM), and self-reported snoring were the variables best explaining ODI in our multivariate approach. This study reports the highest prevalence, using nocturnal oxygen desaturation indices as marker, of sleep-disordered breathing than any reported until now in a general population.

How age and daytime activities are related to insomnia in the general population: consequences for older people.

OBJECTIVES: To determine the role of activity status and social life satisfaction on the report of insomnia symptoms and sleeping habits. DESIGN: Cross-sectional telephone survey using the Sleep-EVAL knowledge base system. SETTING: Representative samples of three general populations (United Kingdom, Germany, and Italy). PARTICIPANTS: 13,057 subjects age 15 and older: 4,972 in the United Kingdom, 4,115 in Germany, and 3,970 in Italy. These subjects were representative of 160 million inhabitants. MEASUREMENTS: Clinical questionnaire on insomnia and investigation of associated pathologies (psychiatric and neurological disorders). RESULTS: Insomnia symptoms were reported by more than one-third of the population age 65 and older. Multivariate models showed that age was not a predictive factor of insomnia symptoms when controlling for activity status and social life satisfaction. The level of activity and social interactions had no influence on napping, but age was found to have a significant positive effect on napping. CONCLUSIONS: These results indicate that the aging process per se is not responsible for the increase of insomnia often reported in older people. Instead, inactivity, dissatisfaction with social life, and the presence of organic diseases and mental disorders were the best predictors of insomnia, age being insignificant. Healthy older people (i.e., without organic or mental pathologies) have a prevalence of insomnia symptoms similar to that observed in younger people. Moreover, being active and satisfied with social life are protective factors against insomnia at any age.

Impairment of memory and plasma flunitrazepam levels.

Flunitrazepam was administered to volunteers in three different oral doses. The effects on psychomotor sedation, attention, working memory and explicit memory were then assessed at various intervals after dosing and compared with levels of the drug in the plasma. Three groups of 12 healthy males with similar levels of education were given placebo or flunitrazepam (1, 2 or 4 mg) in a double-blind, random-sequence study. Volunteers completed a battery of tests at night, 3.5 h after taking the drug and in the morning, 10 h afterward. Blood samples were collected for drug analysis before and after the nocturnal tests and before morning tests. At night, only the highest dose of flunitrazepam (4 mg) induced significant changes in psychomotor sedation, attention, working memory, and prose immediate recall. Doses of 2 and 4 mg flunitrazepam significantly reduced the mean scores of explicit memory (morning tests). Z-scores, calculated from differences between flunitrazepam and placebo, revealed that 2 mg flunitrazepam impaired memory but not alertness or attention. Linear regression analysis of the relationship between plasma levels of flunitrazepam and its effects (Z-scores) indicated that there was a significant positive correlation between peak levels of flunitrazepam at night and impairment of night attention and explicit memory, i.e. delayed recall of prose (r = 0.59, P < 0.01) and trigrams (r = 0.55, P < 0.01). However, memory and attention Z-scores as a function of plasma levels fitted with nonlinear regression analysis to the Emax model had higher correlation coefficients. To produce an effect equal to 50% of the maximum effect for memory impairment, concentrations (EC50) were 6.1 and 6.4 ng/ml for prose and trigrams delayed recall; but for attention they were much higher, at 13.2 ng/ml. The overall results indicate that higher concentrations were needed to impair attention than were required to impair memory.

Effects of flunitrazepam on cognitive functions.

The effects of various oral doses (1, 2, 4 mg) of flunitrazepam on vigilance, attention, immediate memory, short-term memory, learning, non-consolidated and consolidated long-term memory were determined. Twelve healthy young male volunteers were given placebo or flunitrazepam in a double-blind, random latin-square sequence, crossing over every 2 weeks. Volunteers completed a battery of tests at night, 3.5 h after drug administration, and in the morning, 10 h after drug administration. Flunitrazepam 1 mg did not significantly impair any of the functions tested at night, while 4 mg impaired vigilance, attention, immediate memory, short-term verbal memory and learning. The impairments of immediate and short-term memory seem to be related and proportional to reductions in vigilance and attention. Doses of 2 mg and 4 mg impaired the speed of learning but did not decrease the amount of material learned. Flunitrazepam caused dose-related impairment of long-term memory, both consolidated and not. This reduction of long-term memory does not seem to be related to the impairments of vigilance, attention or learning. The lowest dose did not modify vigilance and learning in any subject, improved attention in half of the subjects but reduced long-term memory in a similar number of subjects. Therefore, our results indicate selective impairment of long-term memory. Since there were no differences between the effects on consolidated and non-consolidated memory, the amnesic effect of flunitrazepam seems to be due to a decrease in the storage of memory traces. There were no clear generalized residual effects in the morning after administration.