Xiangdong Tang

Insomnia With Physiological Hyperarousal Is Associated With Hypertension

Previous studies have suggested that insomnia with objective short sleep duration is associated with a higher risk of hypertension, and it has been speculated that the underlying mechanism is physiological hyperarousal. In this study, we tested whether insomnia with physiological hyperarousal measured by Multiple Sleep Latency Test (MSLT), a standard test of sleepiness/alertness, is associated with increased risk of hypertension. Two hundred nineteen chronic insomniacs and 96 normal sleepers were included in this study. Chronic insomnia was defined based on standard diagnostic criteria with symptoms lasting ≥6 months. All subjects underwent 1 night in laboratory polysomnography followed by a standard MSLT. We used the median mean MSLT value (ie, >14 minutes) and the 75th percentile of mean MSLT value (ie, >17 minutes) to define hyperarousal. Hypertension was defined based either on blood pressure measures or on diagnosis treatment by a physician. After controlling for age, sex, body mass index, apnea–hypopnea index, diabetes mellitus, smoking, alcohol, and caffeine use, insomnia combined with MSLT >14 minutes increased the odds of hypertension by 300% (odds ratio=3.27; 95% confidence interval=1.20–8.96), whereas insomnia combined with MSLT >17 minutes increased even further the odds of hypertension by 400% (odds ratio=4.33; 95% confidence interval=1.48–12.68) compared with normal sleepers with MSLT ⩽14 minutes. Insomnia associated with physiological hyperarousal is associated with a significant risk of hypertension. Long MSLT values may be a reliable index of the physiological hyperarousal and biological severity of chronic insomnia.

Insomnia with Physiological Hyperarousal is Associated with Hypertension.Hypertension.

Previous studies have suggested that insomnia with objective short sleep duration is associated with a higher risk of hypertension, and it has been speculated that the underlying mechanism is physiological hyperarousal. In this study, we tested whether insomnia with physiological hyperarousal measured by Multiple Sleep Latency Test (MSLT), a standard test of sleepiness/alertness, is associated with increased risk of hypertension. Two hundred nineteen chronic insomniacs and 96 normal sleepers were included in this study. Chronic insomnia was defined based on standard diagnostic criteria with symptoms lasting ≥6 months. All subjects underwent 1 night in laboratory polysomnography followed by a standard MSLT. We used the median mean MSLT value (ie, >14 minutes) and the 75th percentile of mean MSLT value (ie, >17 minutes) to define hyperarousal. Hypertension was defined based either on blood pressure measures or on diagnosis treatment by a physician. After controlling for age, sex, body mass index, apnea–hypopnea index, diabetes mellitus, smoking, alcohol, and caffeine use, insomnia combined with MSLT >14 minutes increased the odds of hypertension by 300% (odds ratio=3.27; 95% confidence interval=1.20–8.96), whereas insomnia combined with MSLT >17 minutes increased even further the odds of hypertension by 400% (odds ratio=4.33; 95% confidence interval=1.48–12.68) compared with normal sleepers with MSLT ⩽14 minutes. Insomnia associated with physiological hyperarousal is associated with a significant risk of hypertension. Long MSLT values may be a reliable index of the physiological hyperarousal and biological severity of chronic insomnia.

Effect of conditioned stimulus exposure during slow wave sleep on fear memory extinction in humans.

STUDY OBJECTIVES Repeated exposure to a neutral conditioned stimulus (CS) in the absence of a noxious unconditioned stimulus (US) elicits fear memory extinction. The aim of the current study was to investigate the effects of mild tone exposure (CS) during slow wave sleep (SWS) on fear memory extinction in humans. DESIGN The healthy volunteers underwent an auditory fear conditioning paradigm on the experimental night, during which tones served as the CS, and a mild shock served as the US. They were then randomly assigned to four groups. Three groups were exposed to the CS for 3 or 10 min or an irrelevant tone (control stimulus, CtrS) for 10 min during SWS. The fourth group served as controls and was not subjected to any interventions. All of the subjects completed a memory test 4 h after SWS-rich stage to evaluate the effect on fear extinction. Moreover, we conducted similar experiments using an independent group of subjects during the daytime to test whether the memory extinction effect was specific to the sleep condition. PARTICIPANTS Ninety-six healthy volunteers (44 males) aged 18-28 y. MEASUREMENTS AND RESULTS Participants exhibited undisturbed sleep during 2 consecutive nights, as assessed by sleep variables (all P > 0.05) from polysomnographic recordings and power spectral analysis. Participants who were re-exposed to the 10 min CS either during SWS and wakefulness exhibited attenuated fear responses (wake-10 min CS, P < 0.05; SWS-10 min CS, P < 0.01). CONCLUSIONS Conditioned stimulus re-exposure during SWS promoted fear memory extinction without altering sleep profiles.

A review of neurocognitive function and obstructive sleep apnea with or without daytime sleepiness.

Excessive daytime sleepiness (EDS) and neurocognitive dysfunction are commonly observed in patients with obstructive sleep apnea (OSA), and these daytime functional deficits can be reversed partly or completely with treatment such as continuous positive airway pressure (CPAP). Although daytime sleepiness is a possible etiology for neurocognitive dysfunction in OSA patients, EDS is not universally present in all patients with OSA. The objective of this review is to summarize the relationship between neurocognitive function and EDS in OSA, as well as the difference in cognitive domains, improvement, and application of CPAP therapy between patients with and without EDS. Two authors independently searched PubMED/Medline, The Cochrane Library and Scopus through May 27, 2015. Sixty-five articles were included in this review. The literature demonstrated a wide range of neurocognitive deficits in OSA patients with EDS, but no more extensive and complex cognitive domains (eg, executive function) in patients without EDS. However, the current literature had very few studies with large sample sizes and extended follow-up that evaluated the effect of CPAP for OSA in patients with and without sleepiness. CPAP failed to improve cognitive dysfunction in OSA patients without EDS after short-term therapy. The evidence suggests that daytime sleepiness possibly relates to the domain and extent of cognitive impairments in OSA, and CPAP therapy has little effect on the improvement of cognitive deficits in OSA patients without EDS. We recommend that additional prospective studies be performed to further quantify the relationship between neurocognitive function in OSA patients with and without EDS.

Sleep perception and the multiple sleep latency test in patients with primary insomnia.

The purpose of this study was to examine the relationship between overnight sleep perception and the daytime multiple sleep latency test (MSLT) among individuals who were primary insomnia patients (PIPs) or good sleeper controls (GSCs). We collected overnight sleep data via polysomnography (PSG), subjective sleep data via a morning questionnaire (self‐evaluated) and MSLT data via four 20‐min naps over 8 h. Subjects included 122 PIPs and 48 GSCs. Sleep perception was calculated as subjective sleep time/objective sleep time × 100%. PIPs showed a significant difference (P < 0.001) between sleep time, as determined by PSG (387.8 ± 100 min) and self‐report (226.3 ± 160 min), but no difference was obtained for GSCs (440.6 ± 53 versus 435.4 ± 65 min). The means for sleep perception were 56.4 ± 38.8% for the PIPs and 99.3 ± 13.6% for the GSCs (P < 0.001). In the PIPs group, weak but statistically significant negative correlations (r: −0.20 to −0.25) were found for MSLT versus sleep perception and versus self‐ and PSG‐evaluated sleep time. Compared to PIPs with low scores on the MSLT, those with high scores had less sleep perception (%), less self‐ and PSG‐evaluated sleep time and greater sleep misperception time. GSCs did not show significant correlations between MSLT and sleep measures or differences in comparisons between individuals with high and low scores on the MSLT. These results add novel data to the literature by suggesting that 24‐h hyperarousal potentially plays a key role in the pathophysiological issues of insomnia.

Excessive Daytime Sleepiness Predicts Neurodegeneration in Idiopathic REM Sleep Behavior Disorder

Study Objectives To determine the association of excessive daytime sleepiness (EDS) with the conversion of neurodegenerative diseases in patients with idiopathic REM sleep behavior disorder (iRBD). Methods A total of 179 patients with iRBD (79.1% males, mean age = 66.3 ± 9.8 years) were consecutively recruited. Forty-five patients with Epworth Sleepiness Scale score ≥14 were defined as having EDS. Demographic, clinical, and polysomnographic data were compared between iRBD patients with and without EDS. The risk of developing neurodegenerative diseases was examined using Cox proportional hazards model. Results After a mean follow-up of 5.8 years (SD = 4.3 years), 50 (27.9%) patients developed neurodegenerative diseases. There was a significantly higher proportion of conversion in patients with EDS compared to those without EDS (42.2 % vs. 23.1%, p = .01). EDS significantly predicted an increased risk of developing neurodegenerative diseases (adjusted hazard ratios [HR] = 2.56, 95% confidence interval [CI] 1.37 to 4.77) after adjusting for age, sex, body mass index, current depression, obstructive sleep apnea, and periodic limb movements during sleep. Further analyses demonstrated that EDS predicted the conversion of Parkinsons disease (PD) (adjusted HR = 3.55, 95% CI 1.59 to 7.89) but not dementia (adjusted HR = 1.48, 95% CI 0.44 to 4.97). Conclusions EDS is associated with an increased risk of developing neurodegenerative diseases, especially PD, in patients with iRBD. Our findings suggest that EDS is a potential clinical biomarker of α-synucleinopathies in iRBD.

Characteristics of early- and late-onset rapid eye movement sleep behavior disorder in China: a case-control study

OBJECTIVE To investigate demography and clinic and polysomnographic characteristics in Chinese rapid eye movement (REM) sleep behavior disorder (RBD) patients across onset ages. METHODS Ninety consecutive patients fulfilling the criteria for RBD were recruited for study in our sleep center. Patients were separated into early- and late-onset groups according to age when symptoms began (< or =50 and >50 years, respectively). Ninety age- and gender-matched healthy subjects served as controls. All subjects were interviewed for their clinical history, completed an RBD questionnaire, and underwent an overnight video polysomnography assessment. Demographics, comorbidities, scores on the RBD questionnaire, sleep architecture, and EMG activity were compared between the patients and controls and between the early- and late-onset groups. RESULTS Of all RBD patients, 63 were male, and mean age of RBD onset was 54.3±15.7 years. In 25 patients (28%), RBD was secondary and associated with neurodegenerative disease, narcolepsy or antidepressant use. Twenty-three patients (26%) had early-onset RBD and 67 (74%) were in the late-onset group. RBD patients had significantly more comorbidities, dreams and dream-enacting behaviors, and poorer sleep quality than did controls. The early-onset group had a high proportion of females (48%) and an increased proportion of cases associated with narcolepsy. The early-onset group also had fewer movements, lower EMG activity during REM sleep, and better sleep quality when compared to the late-onset group. EMG activity was positively correlated with age of onset. The mean follow-up time was 1.57±0.82 years, and four patients in the late-onset group were subsequently diagnosed with neurodegenerative diseases. CONCLUSIONS Stratifying patients into early and late-onset RBD revealed different characteristics from those previously described as typical for RBD. EMG activity during REM sleep was positively correlated with age of onset. We suggest that it will be valuable to explore the relationship between age of onset conversion and neurodegenerative diseases.

The acute effects of levetiracetam on nocturnal sleep and daytime sleepiness in patients with partial epilepsy

This study investigated the effect of the novel antiepileptic drug levetiracetam (LEV) on sleep in eleven patients with partial epilepsy. At baseline and one week after therapy with LEV (1000 mg/day), patients underwent polysomnography (PSG) and the Multiple Sleep Latency Test (MSLT). Patients also rated their own degree of sleep disturbance and daytime sleepiness with the Athens Insomnia Scale (AIS) and the Epworth Sleepiness Scale (ESS). A group of 10 age- and gender-matched control participants were also included in the study. Patients had decreased total sleep time and increased daytime sleepiness compared to baseline, as evaluated by AIS subscales. Furthermore, LEV therapy significantly decreased the rapid eye movement sleep time and percentage as measured by PSG. Patients reported a significant increase in ESS score but did not exhibit changes in MSLT performance after LEV treatment. The study demonstrated that short-course LEV treatment can affect subjective sleep time and objective sleep architecture. Furthermore, LEV treatment affected subjective daytime sleepiness but did not influence objective mean daytime sleep latencies in patients with partial epilepsy.

Gender differences in REM sleep behavior disorder: a clinical and polysomnographic study in China

OBJECTIVE Rapid eye movement (REM) sleep behavior disorder (RBD) has been considered a male-predominant parasomnia, and there is little comparative data on potential differences between males and females. Therefore, the aim of our study was to examine and characterize gender difference in RBD. METHODS Ninety patients diagnosed with RBD were consecutively recruited from a sleep medicine clinic. All patients were assessed by a RBD questionnaire and overnight video polysomnography. Demographic, clinical data, presence of dreams and dream-enacting behaviors, sleep parameters and electromyographic (EMG) activity were compared for male and female patients with RBD. RESULTS Females were significantly younger than males, both in the mean age of RBD onset (45.3 ± 19.3 vs. 56.2 ± 14.1; p = 0.027) and the mean age at diagnosis (50.4 ± 18.2 vs. 61.1 ± 14.1; p = 0.022). Secondary RBD was 21% in males and 44% in females (p = 0.021). Antidepressant use was more common among females (22%) than males (2%; p = 0.003). There was no significant gender difference in dream content (eg, violent and frightening dreams) of RBD patients. However, females had less dream-enacting behaviors, especially in movement related dreams and falling out of bed. Interestingly, no significant difference was found in the quantification of EMG activity during REM sleep between male and female patients. CONCLUSIONS We found significant gender differences in demographics, associated comorbidities, and dream-related behaviors in patients with RBD. Female RBD patients reported significantly less behavior during dreams, but there was no significant gender difference in EMG activity during REM sleep.

Altered Sleep Stage Transitions of REM Sleep: A Novel and Stable Biomarker of Narcolepsy.

OBJECTIVES To determine the diagnostic values, longitudinal stability, and HLA association of the sleep stage transitions in narcolepsy. METHODS To compare the baseline differences in the sleep stage transition to REM sleep among 35 patients with type 1 narcolepsy, 39 patients with type 2 narcolepsy, 26 unaffected relatives, and 159 non-narcoleptic sleep patient controls, followed by a reassessment at a mean duration of 37.4 months. RESULTS The highest prevalence of altered transition from stage non-N2/N3 to stage R in multiple sleep latency test (MSLT) and nocturnal polysomnography (NPSG) was found in patients with type 1 narcolepsy (92.0% and 57.1%), followed by patients with type 2 narcolepsy (69.4% and 12.8%), unaffected relatives (46.2% and 0%), and controls (39.3% and 1.3%). Individual sleep variables had varied sensitivity and specificity in diagnosing narcolepsy. By incorporating a combination of sleep variables, the decision tree analysis improved the sensitivity to 94.3% and 82.1% and enhanced specificity to 82.4% and 83% for the diagnosis of type 1 and type 2 narcolepsy, respectively. There was a significant association of DBQ1*0602 with the altered sleep stage transition (OR = 16.0, 95% CI: 1.7-149.8, p = 0.015). The persistence of the altered sleep stage transition in both MSLT and NPSG was high for both type 1 (90.5% and 64.7%) and type 2 narcolepsy (92.3% and 100%), respectively. CONCLUSION Altered sleep stage transition is a significant and stable marker of narcolepsy, which suggests a vulnerable wake-sleep dysregulation trait in narcolepsy. Altered sleep stage transition has a significant diagnostic value in the differential diagnosis of hypersomnias, especially when combined with other diagnostic sleep variables in decision tree analysis.