Association Between EEG Power During Sleep and Attention Levels in Patients with Major Depressive Disorder.

Purpose: Major depressive disorder (MDD) is associated with cognitive impairment through unclear mechanisms. We examined the relationship between sleep electroencephalogram (EEG) power and attention level in MDD. Patients and Methods: Forty-seven untreated patients with MDD and forty-seven age- and sex-matched controls were included. We examined relative EEG power during non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep by fast Fourier transform. The Attention Network Test (ANT) was performed to evaluate attention levels. Results: Compared to controls, patients with MDD had lower theta power during NREM (P = 0.018) and REM (P = 0.002) sleep, while higher beta power (P = 0.050) during NREM sleep and delta power (P = 0.018) during REM sleep. Regarding attention level, patients with MDD had lower levels of accuracy (P = 0.021), longer mean reaction time (P < 0.001), poorer manifestations of the alerting effect (P = 0.038) and worse executive control (P = 0.048). Moreover, decreased theta power during NREM sleep was correlated with worsened accuracy (ß = 0.329, P = 0.040), decreased theta power during REM sleep was correlated with worsened alerting effect (ß = 0.355, P = 0.020), and increased delta power during REM sleep was correlated with longer mean reaction time (ß = 0.325, P = 0.022) in patients with MDD. No association between ANT performance and other frequency bands was observed in patients with MDD. Conclusion: Our findings suggest that patients with MDD manifest impaired selective attention function that is associated with decreased theta power during NREM/REM sleep and increased delta power during REM sleep.

The different roles of homocysteine metabolism in hypertension among normal-weight and obese patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with hypertension. However, the differential mechanisms underlying OSA-related hypertension between normal-weight vs. obese patients is limited. METHODS: We studied 92 patients with OSA and 24 patients with continuous positive airway pressure (CPAP) treatment. Blood pressure (BP) was measured twice during awake and continuously monitored during sleep. Obesity was defined as body mass index ≥28 kg/m2. Serum metabolite levels were assessed by metabolomics. RESULTS: Among 59 normal-weight and 33 obese patients, 651 and 167 metabolites showed differences between hypertension and normotension or were associated with systolic and diastolic BP (SBP, DBP) after controlling confounders. These metabolites involved 16 and 12 Kyoto Encyclopedia of Genes and Genomes enrichment pathways in normal-weight and obese patients respectively, whereas 6 pathways overlapped. Among these 6 overlapping pathways, 4 were related to homocysteine metabolism and 2 were non-specific pathways. In homocysteine metabolism pathway, 13 metabolites were identified. Interestingly, the change trends of 7 metabolites associated with SBP (all interaction-p≤0.083) and 8 metabolites associated with DBP (all interaction-p≤0.033) were opposite between normal-weight and obese patients. Specifically, increased BP was associated with down-regulated folate-dependent remethylation and accelerated transsulfuration in normal-weight patients, whereas associated with enhanced betaine-dependent remethylation and reduced transsulfuration in obese patients. Similar findings were observed in ambulatory BP during sleep. After CPAP treatment, baseline low homocysteine levels predicted greater decrease in DBP among normal-weight but not obese patients. CONCLUSIONS: Mechanisms in OSA-related hypertension differ between normal-weight and obese patients, which are explained by different changes in homocysteine metabolism.

A meta-analysis of the association between insomnia with objective short sleep duration and risk of hypertension.

The aim of this meta-analysis was to examine the association between insomnia with objective short sleep duration (ISSD) with prevalent and incident hypertension in cross-sectional and longitudinal studies, respectively. Data were collected from 6 cross-sectional studies with 5914 participants and 2 longitudinal studies with 1963 participants. Odds ratios (ORs) for prevalent and risk ratios (RRs) for incident hypertension were calculated through meta-analyses of adjusted data from individual studies. Compared to normal sleepers with objective normal sleep duration (NNSD), ISSD was significantly associated with higher pooled OR for prevalent hypertension (pooled OR = 2.67, 95%CI = 1.45-4.90) and pooled RR for incident hypertension (pooled RR = 1.95, 95%CI = 1.19-3.20), respectively. Compared to insomnia with objective normal sleep duration, ISSD was associated with significantly higher pooled OR of prevalent hypertension (pooled OR = 1.94, 95%CI = 1.29-2.92) and pooled RR for incident hypertension (pooled RR = 2.07, 95%CI = 1.47-2.90), respectively. Furthermore, normal sleepers with objective short sleep duration were not associated with either prevalent (pooled OR = 1.21, 95%CI = 0.84-1.75) or incident (pooled RR = 0.97, 95%CI = 0.81-1.17) hypertension compared to NNSD. Our findings suggest that ISSD is a more severe phenotype of the disorder associated with a higher risk of hypertension. Objective short sleep duration might be a valid and clinically useful index of insomnia's impact on cardiovascular health.

Insomnia with objective, but not subjective, short sleep duration is associated with increased risk of incident hypertension: the Sleep Heart Health Study.

STUDY OBJECTIVES: Insomnia with objective short sleep duration has been associated with higher risk of cardiometabolic morbidity. In this study, we examined the association between insomnia with objective short sleep duration, also based on subjective sleep duration, with incident hypertension in the Sleep Heart Health Study. METHODS: We analyzed data from 1,413 participants free of hypertension or sleep apnea at baseline from the Sleep Heart Health Study, with a median follow-up duration of 5.1 years. Insomnia symptoms were defined based on difficulty falling asleep, difficulty returning to sleep, early morning awakening, or sleeping pill use more than half the days in a month. Objective short sleep duration was defined as polysomnography-measured total sleep time < 6 hours. Incident hypertension was defined based on blood pressure measures and/or use of antihypertensive medications at follow-up. RESULTS: Individuals with insomnia who slept objectively < 6 hours had significantly higher odds of incident hypertension compared to normal sleepers who slept ≥ 6 hours (odds ratio = 2.00, 95% confidence interval = 1.09-3.65) or < 6 hours (odds ratio = 2.00, 95% confidence interval = 1.06-3.79) or individuals with insomnia who slept ≥ 6 hours (odds ratio = 2.79, 95% confidence interval = 1.24-6.30). Individuals with insomnia who slept ≥ 6 hours or normal sleepers who slept < 6 hours were not associated with increased risk of incident hypertension compared to normal sleepers who slept ≥ 6 hours. Finally, individuals with insomnia who self-reported sleeping < 6 hours were not associated with significantly increased odds of incident hypertension. CONCLUSIONS: These data further support that the insomnia with objective short sleep duration phenotype based on objective, but not subjective measures, is associated with increased risk of developing hypertension in adults. CITATION: Dai Y, Chen B, Chen L, et al. Insomnia with objective, but not subjective, short sleep duration is associated with increased risk of incident hypertension: the Sleep Heart Health Study. J Clin Sleep Med. 2023;19(8):1421-1428.

Insomnia with objective short sleep duration is associated with hypertension.

Insomnia with objective short sleep duration has been proposed as the most biologically severe phenotype of the disorder associated with cardiometabolic morbidity in population-based samples. In this study, we investigated the association between insomnia with objective short sleep duration and hypertension in a large clinical sample. We studied 348 patients diagnosed with chronic insomnia disorder based on International Classification of Sleep Disorders Third Edition criteria and 150 normal sleepers. Objective short sleep duration was defined by the median total sleep time of the sample (< 7 hr) measured with 1-night polysomnography. Hypertension was defined based on blood pressure levels, antihypertensive medication use and/or a physician diagnosis. After adjusting for potential confounders, patients with chronic insomnia disorder who slept < 7 hr were associated with 2.8-fold increased odds of hypertension compared with normal sleepers who slept ≥ 7 hr (odds ratio = 2.81, 95% confidence interval = 1.068-7.411) or < 7 hr (odds ratio = 2.75, 95% confidence interval = 1.005-7.542), whereas patients with chronic insomnia disorder who slept ≥ 7 hr (odds ratio = 1.52, 95% confidence interval = 0.537-4.285) or normal sleepers who slept < 7 hr (odds ratio = 1.07, 95% confidence interval = 0.294-3.904) were not significantly associated with increased odds of hypertension compared with normal sleepers who slept ≥ 7 hr. Linear regression analyses showed that, for every hour decrease in total sleep time, systolic and diastolic blood pressure increased by 1.014 mmHg (p = 0.045) and 0.923 mmHg (p = 0.015), respectively, in patients with chronic insomnia disorder but not in normal sleepers. Our findings further support that insomnia with objective short sleep duration is a risk factor for hypertension, and objective short sleep duration may be a useful marker of the biological severity of chronic insomnia disorder in clinical practice.

The underestimation of sleep duration phenotype is associated with better treatment response to cognitive behavior therapy for insomnia in patients with chronic insomnia: a preliminary study.

STUDY OBJECTIVES: To examine treatment response to cognitive behavior therapy for insomnia (CBT-I) in patients with chronic insomnia with and without underestimation of sleep duration. METHODS: We studied 41 patients with chronic insomnia who had received 5-week CBT-I. Self-reported and objective sleep were assessed with sleep diary and actigraphy, respectively. Sleep perception was calculated as self-reported total sleep time/objective total sleep time. The underestimation of sleep duration group was defined based on sleep perception less than the median of the overall sample (85%). Insomnia Severity Index was used to assess the severity of insomnia. RESULTS: The total scores of Insomnia Severity Index decreased significantly after CBT-I in both groups with and without underestimation of sleep duration. Compared to pretreatment, self-reported sleep efficiency increased and total wake time decreased after CBT-I, while the magnitude of changes in sleep efficiency (d = 1.40 vs d=0.81, interaction P = .016) and total wake time (d = -1.82 vs d = -0.85, interaction P < .001) were larger in the underestimation of sleep duration group . Furthermore, self-reported sleep onset latency (interaction P = .520) and wake after sleep onset (interaction P = .052) decreased in the underestimation of sleep duration group (all P < .05), but not in patients without underestimation of sleep duration. Linear regressions showed that lower sleep perception at baseline predicted greater increase in self-reported sleep efficiency (ß = -0.99, P < .001) and total sleep time (ß = -0.51, P = .006) and greater decrease in self-reported total wake time (ß=1.22, P = .023) after CBT-I after adjusting for confounders. CONCLUSIONS: The current preliminary study suggests that sleep perception moderates the self-reported CBT-I effects on chronic insomnia: the phenotype of underestimation of sleep duration is associated with a better response to CBT-I, especially in self-reported sleep parameters. CITATION: Sun Q, Dai Y, Chen B, et al. The underestimation of sleep duration phenotype is associated with better treatment response to cognitive behavior therapy for insomnia in patients with chronic insomnia: a preliminary study. J Clin Sleep Med. 2022;18(10):2443-2450.

Implications of sympathetic activation for objective versus self-reported daytime sleepiness in obstructive sleep apnea.

STUDY OBJECTIVES: Objective excessive daytime sleepiness (EDS) is associated with systemic inflammation and a higher risk of cardiometabolic morbidity in obstructive sleep apnea (OSA). We hypothesized that OSA with objective EDS is associated with higher levels of sympathetic nerve activity (SNA) when compared with self-reported EDS. We, therefore, examined the associations between objective and self-reported EDS with SNA in patients with OSA. METHODS: We studied 147 consecutive male patients with OSA from the institutional sleep clinic. Objective EDS and self-reported EDS were defined based on Multiple Sleep Latency Test (MSLT) latency ≤ 8 minutes and Epworth Sleepiness Scale (ESS) > 10, respectively. Twenty-four-hour urinary norepinephrine was used for assessing SNA. Blood pressure (BP) was measured both in the evening and in the morning. RESULTS: Twenty-four-hour urinary norepinephrine was significantly higher in patients with OSA with objective EDS compared with those without objective EDS (p = 0.034), whereas it was lower in patients with OSA with self-reported EDS compared with those without self-reported EDS (p = 0.038) after adjusting for confounders. Differences in the sympathetic drive were most striking in those with an objective but not self-reported EDS versus those with self-reported but not objective EDS (p = 0.002). Moreover, shorter MSLT latency was significantly associated with higher diastolic BP (ß = -0.156, p = 0.049) but not systolic BP. No significant association between ESS scores and BP was observed. CONCLUSIONS: Objective, but not self-reported EDS, is associated with increased SNA and diastolic BP among males with OSA, suggesting that objective EDS is a more severe phenotype of OSA that is accompanied by higher sympathetic drive, higher BP, and possibly greater cardiovascular morbidity and mortality.

A meta-analysis of the first-night effect in healthy individuals for the full age spectrum.

OBJECTIVES: The first-night effect (FNE) affects the accuracy of polysomnography (PSG) findings. However, the levels of FNE in different ages are unclear. METHODS: We searched PubMed, Cochrane Library, Embase and Web of Science. The studies that reported sleep parameters by PSG for at least 2 consecutive nights from healthy individuals were included. The weighted mean differences were used to assess the effect size of differences in each sleep parameters between the first and second nights, as well as between the second and the third. RESULTS: A total of 53 studies from 1422 subjects with mean age of 9.2-85.5 years were included. Meta-analyses showed that prolonged sleep onset latency, wake time after sleep onset and rapid eye movement sleep (REM) latency, accompanied by decreased total sleep time, sleep efficiency, and REM and increased non-rapid eye movement sleep stage 1 (N1) during the first night compared to the second (all P-value ≤ 0.001). No significant differences were observed in N2 and slow wave sleep, apnea-hypopnea index or periodic limb movement index (all P-value > 0.5). A non-linear association between FNE and age was observed: young adults (age 20-29 years) had the lowest level of FNE compared to other age ranges. Moreover, no significant differences were observed in most sleep parameters between the second and third night except more N2 and less REM in the second night (both P-value < 0.05). CONCLUSIONS: The FNE exists in most cases but only in the first night of PSG recording and is less pronounced among young adults.

Insomnia symptoms during the early and late stages of the COVID-19 pandemic in China: a systematic review and meta-analysis.

BACKGROUND: Evidence suggests that the outbreak of the coronavirus disease 2019 (COVID-19) and the prevention/control measures for COVID-19 may cause insomnia during the acute phase of COVID-19 pandemic in China. However, it is unclear whether insomnia sustains during the later phases of the pandemic. METHODS: We searched PubMed/Medline, EMBASE, PsycINFO and China National Knowledge Infrastructure from the 27th December 2019 to the 2nd February 2021. As early stage studies on COVID-19 pandemic in China were defined as those conducted prior to April 1st, 2020, while late stage studies were those conducted after April 1st, 2020. RESULTS: A total of 98 studies with 193,889 participants were included. The pooled prevalence of insomnia symptoms among all populations was 39.1% (95% CI 36.2-42.0%); the pooled prevalence of insomnia symptoms during the early and late stages of COVID-19 in China were 37.0% (95% CI 34.1-39.9%) and 41.8% (95% CI 33.6-50.0%), respectively. Importantly, there was no significant difference regarding the prevalence of insomnia symptoms between the early and late stages of COVID-19. Meta-regression showed that healthcare workers, COVID-19 patients, patients with chronic medical conditions and patients with mental disorders had a higher prevalence of insomnia symptoms compared to the general population. This association remained significant in healthcare workers and patients with chronic medical conditions after adjusting for age, gender, areas of high or low prevalence of COVID-19 cases, anxiety and depression. CONCLUSIONS: Over one third of our sample present insomnia symptoms during the early stage of COVID-19 pandemic in China. Interestingly, prevalence of insomnia symptoms sustains high during the late stage of the pandemic despite the control of the disease and the amelioration of its adverse effects. Our findings suggest that insomnia symptoms related to COVID-19 appear to persist of over time.

Effects of electrostatic therapy on nighttime sleep and daytime symptoms in patients with chronic insomnia: Evidences from an open label study.

Introduction: Transcranial electric stimulation (TES) is a neuromodulation approach that applies low-intensity electrical current to the brain and has been proposed as a treatment for insomnia. Electrostatic therapy is a kind of TES and people do not have a feeling of electrical stimuli when the voltage of static electricity is lower than 2,000 volts. However, no studies have examined the effects of electrostatic therapy on objective sleep and daytime symptoms in patients with insomnia. Materials and methods: Thirty chronic insomnia patients were included. All patients received a 6 week electrostatic therapy and three comprehensive assessments including two consecutive polysomnography (PSG) and daytime symptoms assessments, at pre-treatment, 3 week and 6 week of treatment. Insomnia Severity Index (ISI) was used to assess the severity of insomnia. Multiple sleep latency test (MSLT), Epworth Sleepiness Scale (ESS), and Flinders Fatigue Scale (FFS) were used to assess objective and self-reported daytime sleepiness and fatigue, respectively. Attention network test (ANT) was used to assess attention levels. Results: Total ISI scores decreased significantly at 3 weeks (p < 0.001) and 6 weeks (p < 0.001) after initiation of treatment. Furthermore, objective total sleep time (TST, p = 0.020) and sleep efficiency (SE, p = 0.009) increased and wake time after sleep onset (p = 0.012) decreased significantly after 6 weeks electrostatic therapy. Regarding daytime symptoms, ESS and FFS scores decreased significantly at 3 weeks (ESS, p = 0.047; FFS, p = 0.017) and 6 weeks (ESS, p = 0.008; FFS, p = 0.003) after initiation of treatment. Moreover, executive control improved significantly from pre-treatment to 3 weeks (p = 0.006) and 6 weeks (p = 0.013) and altering network improved significantly at 6 weeks (p = 0.003) after initiation of treatment. Secondary analyses showed that TST and SE improved significantly after electrostatic therapy in insomnia patients who slept < 390 min (all p-value < 0.05). However, no significant changes regarding TST and SE were observed in insomnia patients who slept ≥ 390 min. Conclusion: Electrostatic therapy improves both nighttime sleep and daytime symptoms in patients with chronic insomnia. The effect on objective sleep appears to be stronger in patient with objective short sleep duration. Electrostatic therapy might be a therapeutic choice for insomnia patients with difficulty maintaining sleep and not responding to behavioral treatments. Clinical trial registration: [www.clinicaltrials.gov], identifier [ChiCTR2100051590].

Clinical manifestations and polysomnography-based analysis in nine cases of probable sporadic Creutzfeldt-Jakob disease.

PURPOSE: To summarize the clinical characteristics of patients with sporadic Creutzfeldt-Jakob disease (sCJD), analyze its sleep disorder characteristics using polysomnography (PSG), and compare sleep disturbances with those of fatal familial insomnia (FFI). PATIENTS AND METHODS: We retrospectively reviewed the sleep disturbances; cerebrospinal fluid (CSF) protein 14-3-3 (CSF-14-3-3 protein); prion protein gene, PRNP; magnetic resonance imaging; and electroencephalogram (EEG) of nine sCJD patients RESULTS: Of the nine sCJD patients, six were positive for CSF-14-3-3 protein. In the eight patients who completed diffusion-weighted imaging, seven showed cortical "ribbons sign" and two showed high signal in the basal ganglia. All nine patients had an EEG, which showed an increase in background slow waves; moreover, four showed typical periodic sharp wave complexes. The codon diversity at position 129, 219 of nine patients were MM, EE. Almost all nine patients had sleep disturbances such as insomnia, hypersomnia, and periodic limb movement disorder (PLMD). Five patients completed PSG, which demonstrated severe sleep structure disorder, prolonged total waking time, significantly reduced sleep efficiency, and absent rapid eye movement in some severe patients. CONCLUSION: Sleep disturbances are common in sCJD patients, manifested as insomnia, lethargy, and PLMD. The sCJD patients often demonstrate severe sleep structure disorder through PSG, which is similar to patients with FFI.

Expression and functions of cellular prion proteins in immunocytes.

Prion diseases are fatal neurodegenerative processes caused by the accumulation of the pathological prion protein, PrPSc . While pathological lesions are limited to the central nervous system (CNS), disease-specific proteins accumulate and replicate in secondary lymphoid organs prior to neuroinvasion, and their replication there depends on the abundance of cellular prion protein (PrPC ). PrPC is expressed in both central and peripheral lymphoid tissues, and up- or downregulates innate and adaptive immune responses. In addition to prion diseases, PrPC is also immunologically involved in other neurological disorders and infectious diseases, including Alzheimer's disease and human immunodeficiency virus infection. Herein, we summarize the expression and functions of PrPC in various immunocytes, as well as its immunological and pathological roles in neurodegeneration and infection.

Rare genetic Creutzfeldt-Jakob disease with E196A mutation: a case report.

Genetic Creutzfeldt-Jakob disease (gCJD) accounts for approximately 10-15% of human prion diseases. It is an autosomal dominant disease caused by missense or insertion mutations of the gene that encodes prion protein (PRNP). In general, the manifestations and neuropathological changes of gCJD are similar to those of sporadic CJD (sCJD), and the diagnostic sensitivities of cerebrospinal fluid (CSF) markers, electroencephalography (EEG), and magnetic resonance imaging (MRI) are generally lower in gCJD than sCJD. Here we report on a 56-year-old Chinese woman who was diagnosed with gCJD and suspected to have thyroid cancer. The patient carried the glutamate to alanine substitution at codon 196 (E196A) of PRNP, which is quite a rare mutation and has only been reported in China. To our knowledge, this is the fourth case of E196A gCJD in the world. Here, we compared the manifestations and assistant examinations of the current patient with those of three previously reported Chinese patients with E196A gCJD in order to illustrate the common features of E196A gCJD.