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Study Objectives: Sleep breathing disorder (SBD) may be an important factor in age-related cognitive decline. In a cohort of healthy elderly subjects, we performed an 8-y longitudinal study to assess whether changes in cognitive function occur in untreated elderly patients with SBD and without dementia and the factors implicated in these changes., Design: A population-based longitudinal study., Setting: Clinical research settings., Participants: A total of 559 participants of the PROOF study aged 67 y at the study entry and free from neurological disorders were examined., Interventions: N/A., Measurements and Results: Abnormal breathing events were defined by an apnea-hypopnea index (AHI) > 15. The raw cognitive data and averaged Z-scores for the attentional, executive, and memory functions were collected at the baseline and follow-up. At baseline, AHI > 15 was found in 54% of subjects with 18% having an AHI > 30. At follow-up, the presence of abnormal breathing events was associated with a slight but significant decline in the attentional domain (P = 0.01), which was more evident in the subjects with an AHI > 30 (P = 0.004). No significant changes over time were observed in the executive and memory functions. Several indices of chronic hypoxemia, defined either as a cumulative peripheral oxygen saturation (SpO2) < 90% or a minimal SpO2, accounted for portions of the variance in the decline in attention. All observed effects were small, accounting for 4-7% of variance in multivariate models., Conclusion: In healthy elderly subjects, various components of sleep breathing disorder at baseline were associated with small changes in selected cognitive functions specific to the attention domain after controlling for multiple comorbidities, such as sleepiness, hypertension, diabetes, anxiety, and depression., Clinical Trial Registration: ClinicalTrials.gov identifiers NCT 00759304 and NCT 00766584., (© 2015 Associated Professional Sleep Societies, LLC.)

Study Objectives: Chronic intermittent hypoxia (IH) acts as a stimulator of mesenchymal stem cell (MSC) mobilization, intensifying osteoblast formation in animal models. The recurrence of apnea and oxygen desaturation in obstructive sleep apnea (OSA) may mimic experimental models of IH. We hypothesized that in elderly with OSA, apnea-related IH may mobilize MSCs and thereby prevent the age-related decline in osteogenesis. This study explored the relationship between OSA and bone mineral density (BMD), and the effect of IH on BMD, in a large sample of elderly subjects., Participants: There were 833 volunteers age 68.6 ± 0.8 y (59% women)., Intervention: Each participant underwent evaluation of BMD at lumbar spine and femoral sites by dual-energy x-ray absorptiometry (DEXA) as well as clinical and polygraphic examinations. OSA was diagnosed on the basis of an apnea-hypopnea index (AHI) ≥ 15., Measurements and Results: There were 55% of the participants who presented with OSA, and these subjects were predominantly male and overweight. Compared with subjects without OSA, those with OSA had a higher femoral and spinal BMD (P < 0.001). Body mass index (BMI), AHI, and oxygen desaturation index (ODI) (P < 0.01) were significantly related to BMD. After adjustment for sex, BMI, metabolic values, and hypertension, multiple regression analysis showed a significant association between femoral and lumbar T scores and both daily energy expenditure (P < 0.001) and ODI (P = 0.007)., Conclusions: In elderly subjects, the presence of obstructive sleep apnea is associated with higher bone mineral density, with oxygen desaturation index being a significant determinant of bone metabolism. These results suggest that apnea-related intermittent hypoxia may stimulate the bone remodeling process in older population., Clinical Trial Registration: NCT 00759304 and NCT 00766584.

Study Objectives: Obesity is a recognized risk factor for obstructive sleep apnea syndrome (OSAS). We evaluated whether total trunk and central fat mass (CFM) is associated with OSAS in elderly subjects., Design: Cross-sectional., Setting: Body composition assessment by dual-energy X-ray absorbsiometry (DEXA)., Participants: 749 volunteers aged 67.2 ± 0.8 years (59.4% women)., Intervention: All participants underwent evaluation of their body composition by DEXA in parallel with clinical and polygraphic assessments. The presence of OSAS was defined by an apnea plus hypopnea index (AHI) ≥ 15., Measurements and Results: A total of 44.8% of the population had an AHI < 15, and 55.2% presented OSAS. OSAS subjects were more frequently overweight and had a higher total trunk fat mass and central fat mass (CFM). Correlation analyses revealed that body mass index (r = 0.27, P < 0.001), neck circumference (r = 0.35, P < 0.001), and CFM (r = 0.23, P < 0.001) were significantly related to AHI. Logistic regression analysis indicated that in mild OSAS cases (> 15AHI < 30), BMI (OR: 1.10; 95% CI: 1.03-1.18; P = 0.008), and male gender (OR: 1.49; 95% CI: 1.05-2.12, P = 0.03) were key factors explaining an AHI between 15 and 30. In severe cases (AHI > 30), male gender (OR: 3.65; 95% CI: 2.40-5.55; P < 0.001) and CFM (OR: 1.10; 95% CI: 1.03-1.19; P = 0.009) were significant independent predictors of OSAS., Clinical Trial Registration: NCT 00759304 and NCT 00766584., Conclusions: Although central fat mass plays a role in the occurrence of severe OSAS in men older than 65 years of age, its low discriminative sensitivity in mild OSAS cases does not warrant systematic use of DEXA for the diagnosis of OSAS.

Study Objectives: Pulse transit time (PPT) has been introduced as a useful screening tool to diagnose sleep disordered breathing (SDB). Since the prevalence of SDB increases with age, the question is whether PTT could be used to diagnose SDB in the elderly. We assess the effectiveness of PTT for SDB screening in a large healthy elderly population., Setting: Community-based sample in home and research clinical settings., Intervention: N/A., Participants: Seven hundred eighty volunteers, free of cardiac and neurologic disease, aged 68.6 ± 1.0 years, underwent ambulatory polygraphy to measure the apnea-hypopnea index (AHI). The presence of SDB was defined as an AHI of 15 or greater. The PTT was continuously monitored during the nocturnal study, and the overall autonomic arousal index (AAI) was calculated., Results: SDB was diagnosed in 447 (57.3%) subjects. In these subjects, the Bland-Altman plot for AAI revealed an underestimation with a bias of -8.04 ± 16.55 events per hour (mean ± 95% confidence interval). Receiver operating characteristic curves constructed for an AHI of 15 or greater defined an area under the curve of 0.67 and a cutoff point to AAI 32.3 events per hour, giving a sensitivity of 70.5% and a specificity of 54.7%. For prediction of an AHI of at least 30, the area under the curve was equal to 0.74 for a cutoff point of 56.3 events per hour, giving a better specificity (94.7%) but a lower sensitivity (32.2%)., Conclusions: In a healthy older population, the AAI showed moderate sensitivity for predicting SDB. This data does not allow us to use PTT as a screening tool for the diagnosis of SDB in the elderly., Clinical Trial Registration: NCT 00759304 and NCT 00766584.

Study Objectives: Sleep related breathing disorders (SRBD) are risk factors for cognitive dysfunction in middle-aged subjects, but this association has not been observed in the elderly. We assess the impact of SRBD on cognitive performance in a large cohort of healthy elderly subjects., Design: Cross-sectional study examining the association between subjective memory test, neuropsychological battery testing and SRBD in the elderly., Setting: Community-based sample in home and research clinical settings., Participants: 827 subjects, 58.5% women, aged 68 y at study entry, participated in the study. All were free of previously diagnosed SRBD, coronary heart disease, and neurological disorders, including stroke and dementia. Clinical interview, neurological assessment, polygraphy, and extensive cognitive testing were conducted for all participants., Intervention: N/A., Measurement and Results: SRBD (apnea-hypopnea index [AHI] > 15 events/h) was diagnosed in 445 (53%) subjects, 167 (37%) of them with AHI > 30. Minimal daytime sleepiness was found in the group; 9.2% of the population had an Epworth Sleepiness Scale score > 10. No significant association was found between AHI, nocturnal hypoxemia, and cognitive scores. Comparison of mild vs severe cases showed a trend toward lower cognitive scores with AHI > 30, affecting delayed recall and Stroop test., Conclusions: The impact of undiagnosed SRBD on cognitive function appeared quite limited in a generally older healthy population, and only slightly affected severe cases. The implication of undiagnosed SRBD on the cognitive impairment in elderly subjects remains hypothetical and needs to be prospectively studied.

Study Objectives: The ratio between the heart-rate increment to total power spectral density (%VLFI) has been introduced as a sensitive measure of sleep-related breathing disorders (SRBD). Since a complex interaction is present between sleep disorders and occurrence of arousals, we hypothesized that %VLFI and other indexes of heart-rate variability (HRV) measures reflect the degree of sleep fragmentation., Methods: The high- and low-frequency peaks from spectral analysis (FFT) of R-R intervals, the HRV changes using wavelet transform (WT), the geometric and time domain HRV, and the %VLFI were measured in 336 sleep studies performed in patients with insomnia, SRBD and restless legs syndrome/periodic limb movement disorder (RLS/PLMD). The ability of HRV measures to assess sleep fragmentation was examined by correlation analysis and from the area under the receiver operating characteristic (ROC) curve., Results: The ratio of low frequency to high frequency (LF/HF ratio) at the FFT and WT and the %VLFI were higher in patients with SRBD and RLS/PLMD, compared with patients with insomnia. These measures were related to the arousal (MA) index as well as to the apnea-hypopnea index, oxygen desaturations, and periodic leg movement index (p < .001). The presence of a sleep fragmentation defined as an MA index > 20 was well detected by the %VLFI (ROC area: 0.66 +/- 0.03) and the LF/HF ratio at WT (ROC area: 0.66 +/- 0.03)., Conclusion: The %VLFI and LF/HF ratio provide indirect measures of sleep fragmentation, suggesting that HRV measures during sleep assess more the associated sleep fragmentation than the presence of a specific sleep disorder.

Study Objectives: The relationship between event-related potentials (ERPs) and sleep alterations in patients with sleep disorders is still controversial. Whether the ERP alterations are affected by sleep loss and sleep discontinuity can be addressed by studying presleep-to-postsleep changes in ERPs. We investigated if presleep-to-postsleep ERP latencies and amplitudes differ in patients with insomnia and sleep-related breathing disorders and whether these changes are affected by the degree of subjective and objective sleep alterations., Methods: Fifteen patients with a diagnosis of insomnia, 45 patients with sleep-related breathing disorders, and 13 healthy controls were examined. Auditory ERPs were measured in the evening before sleep and in the morning after polysomnography. Subjective sleepiness and sleep quality were assessed by the Epworth Sleepiness Scale and the Saint Mary's Hospital Quality of Sleep Questionnaire., Results: Analysis of evening-to-morning ERP variations did not reveal significant between-group differences in N100 latency and amplitude or in P200 and P300 amplitudes. Patients with sleep-related breathing disorders had a significant lengthening of P200 and P300 latencies in the morning, compared with controls and insomniacs. A trend to delayed morning P300 was present in patients with insomnia but did not reach statistical significance. The evening-to-morning ERP differences were not significantly related to subjective sleep quality, indexes of sleep fragmentation, or total sleep time., Conclusions: ERPs are sufficiently sensitive to assess attention dysfunction in patients with sleep disorders when presleep-to-postsleep changes are considered. The lack of relationship between indexes of sleep loss and sleep fragmentation and presleep-to-postsleep ERP changes might suggest that other factors outside sleep alterations affect ERP deterioration in patients with sleep disorders.

Study Objectives: The hierarchical definition of arousals from sleep includes a range of physiologic responses including microarousals, delta and K-complex bursts, and variations in autonomic system. Whether patterns in slow-wave electroencephalographic activity and autonomic activation are primary forms of arousal response can be addressed by studying effects of total sleep deprivation. We therefore examined changes in arousal density during recovery sleep in healthy subjects., Design: Participants spent 6 consecutive 24-hour periods in the laboratory. Nights 1 and 2 were baseline nights followed by 64-hour total sleep deprivation, then 2 consecutive recovery nights., Setting: Sleep-deprivation protocol was conducted under laboratory conditions with continuous behavioral and electrophysiologic monitoring., Participants: Twelve drug-free men aged 27.4 +/- 7.9 years were studied. None reported sleepiness or altered sleep-wake cycle, and none had neurologic, psychiatric or sleep disorders., Intervention: N/A., Measurements and Results: Arousals were classified into 4 levels: microarousals, phases of transitory activation, and delta and K-complex bursts. Sleep deprivation induced changes in the density of considered arousals except phases of transitory activation, with a distinct pattern among the different types. The greatest change was found for microarousals, which showed a significant decrease in the first recovery night (P = .01), with return to baseline thereafter. A fall in K-complex and delta-burst density was noted in the first recovery night, not, however, reaching statistical significance. The phases of transitory activation rate were virtually unaffected throughout the experimental nights., Conclusions: We conclude that homeostatic sleep processes exert an inhibitory effect on arousal response from sleep with a significant effect only on the microarousal density. Decreased delta and K-complex burst rates, though not significant, support the hypothesis that they may be activating processes, probably modulated by factors independent from those implicated in cortical arousal.

It has recently been described that the maximal respiratory effort developed at the end of an apnea (Pesmax)--which is regarded as an index of arousal threshold in patients with obstructive sleep apnea syndrome (OSA)--increases progressively during the night, probably as a consequence of associated sleep fragmentation. In order to find out whether the nocturnal trend of Pesmax may be more influenced by a sleep-dependent circadian rhythm than by sleep fragmentation, we revised the polygraphic recordings of 37 patients in whom obstructive apneas were recorded for at least 7 hours. In 15 of these patients, analysis was made for eight hours of the night. During each hour we analyzed at least 7 obstructive apneas, in which we measured the minimal esophageal pressure at the start of the apnea, the maximum value recorded at the end of the apnea (Pesmax), the difference from the minimum to the maximum (delta Pes), and the rate of increase in esophageal pressure (RPes). As indices of sleep fragmentation, we defined the number of arousals, awakenings and sleep state transitions. In the group of patients as a whole, we found a trend toward a gradual increase for apnea duration (F = 98.8, p < 0.001) and Pesmax F = 31.6, p < 0.001) which was significant from the first to the last hour. The time-dependent evolution of apnea duration and Pesmax showed that the rise in these two variables peaked during the first 3 hours of sleep, followed by a plateau and a decrease in the last hour of the night. This temporal profile was more evident when the analysis was available for 8 hours. No significant changes across the night were found for nocturnal hypoxemia and number of arousals. Considering the slope of Pesmax changes across the night, we saw that neither the apnea+hypopnea index nor the indices of sleep fragmentation affected the nocturnal trend. The present data demonstrate the presence of a nocturnal trend in arousal threshold in OSA patients independent of sleep fragmentation. The biphasic evolution of the arousal threshold may be caused by factors that influence the circadian and homeostatic processes.

A prospective study aimed at objectively evaluating compliance with nasal continuous positive airway pressure (CPAP) treatment was conducted in 728 obstructive sleep apnea [OSA; apnea/hypopnea index (AHI) > 15 events/hour] patients and 98 nonapneic snorers (AHI < or = 15 events/hour). Five-hundred seventy-five OSA patients and 33 nonapneic snorers underwent CPAP therapy and were followed-up for an average of 1,176 +/- 38 days (27 to 4,203 days). Compliance to treatment was measured by the mean rate of use of the CPAP device obtained from a built-in time counter. Acceptance of treatment was measured using Kaplan-Meier's model. The acceptance of CPAP was greater than 90% at 3 years and greater than 85% at 7 years in OSA patients. It was greater than 60% at 3 years in nonapneic snorers. The mean rate of CPAP use was 5.7 +/- 1.8 hours/day in OSA patients and 5.6 +/- 1.4 hours/day in snorers who were still on CPAP on October 1, 1995. It was correlated positively with age, body mass index, and AHI, and it was correlated negatively with daytime partial pressure of oxygen (PaO2), forced expiratory volume in 1 second (FEV1), and vital capacity in the group of OSA patients. This study shows that CPAP therapy is reasonably accepted by OSA patients as well as by nonapneic snorers. Both within and between groups, objective disease severity (as measured by the respiratory event index and daytime and nighttime hypoxemia), rather than patients' symptoms or complaints, seemed to play a role in the quality of compliance to treatment.

A multiple sleep latency test (MSLT) was performed in 30 patients with obstructive sleep apnea syndrome (OSAS) at the time of diagnosis and after 1 year of home therapy with nasal continuous positive airway pressure (nCPAP). The MSLT was administered after two consecutive polysomnographic studies, one with (CPAP) and one without nCPAP (NCPAP) at baseline and at follow-up. After a year of therapy, the MSLT significantly rose from 3.1 +/- 0.3 to 9.8 +/- 1.0 minutes (p = 0.001). The increase in mean sleep latency was significantly correlated with the decrease in the number of arousals during the night (r = -0.48, p = 0.009). On the basis of MSLT value at follow-up, patients were split into two subgroups: the normalized group, in which 15 patients had an MSLT > or = 10 minutes, and the unnormalized group, consisting of 15 patients with an MSLT < 10 minutes. Normalized patients differed for a higher apnea+hypopnea index (AHI) time at baseline, a greater improvement in nocturnal hypoxemia and a greater nCPAP use at follow-up. After 1 night of therapy withdrawal, MSLT fell dramatically to 5.3 +/- 0.6 minutes, even though the subjects said they did not feel sleepy. The changes in MSLT after the night of treatment suspension were not correlated with changes in body mass index (BMI), AHI or nocturnal hypoxemia, whereas they were correlated negatively with changes in AHI time (r = -0.53, p = 0.003) and with the decrease in the number of arousals (r = -0.47, p = 0.009).(ABSTRACT TRUNCATED AT 250 WORDS)

Fatal familial insomnia (FFI) is a disease characterized by loss of sleep activity due to selective thalamic degeneration. To assess the secretory pattern of melatonin (MT) in FFI, we studied two cases of overt disease under standardized conditions and polysomnographic control. Each patient underwent repeated 24-h study sessions, and MT was assayed at 30-min intervals. Six healthy volunteers were used as controls. Slow wave sleep was never recorded, whereas occasional episodes of enacted dreaming accompanied by rapid ocular movements and complex muscular activities were documented, with no detectable rhythm. Plasma MT concentrations gradually decreased as the disease progressed. A significant circadian rhythm was detected in the earlier recordings, with decreasing amplitudes with disease progression. Complete rhythm obliteration was achieved in the most advanced stage. Normally placed nocturnal acrophases were detected in the earlier stages, but then a shift toward the daytime hours was observed. Thalamic lesions of FFI appear to determine a progressive disruption of the sleep/wake cycle accompanied by decreased circulating levels of MT, with progressive alterations in the circadian rhythm of this hormone. On the other hand, decreased secretion of MT may contribute to the sleep disturbances of FFI.

Although ventilation during sleep has been studied in normal young and elderly subjects, little data are available concerning possible quantitative changes in ventilatory parameters in normal middle-aged subjects. We studied the occurrence of respiratory events and the changes in minute ventilation, tidal volume, and respiratory rate during rapid-eye-movement (REM) and non-REM (NREM) sleep in 40 normal (20 men and 20 women) middle-aged subjects, using polysomnography with pneumotachography and oximetry. Apnea indices greater than 5, with apneas predominantly of the obstructive type, were found in 17.5% of the subjects (30% of the men and 5% of the women). These "apneic" subjects differed from the "nonapneic" subjects only in that they had a higher body mass index. Minute ventilation decreased from wakefulness to sleep by 14% to 19%, owing to a decrease in tidal volume without a significant change in respiratory rate. This decrease was not greater in slow wave (stage 3-4 NREM) or in REM sleep than in stage 2 NREM sleep, nor was it greater in men than in women. It correlated with the minute ventilation during wakefulness: the higher the minute ventilation during wakefulness, the greater the decrease during sleep. The occurrence of respiratory events was not related to the degree of the decrease in minute ventilation from wakefulness to apnea-free sleep.