A multi-omics study of the association between insomnia with objective short sleep duration phenotype and high blood pressureDai, Yanyuan; Vgontzas, Alexandros N; Chen, Le; Zheng, Dandan; Chen, Baixin; Wu, Jun; Shao, Ruifan; Li, Yun
doi: 10.1093/sleep/zsaf030pmid: 39888642
Study ObjectivesInsomnia with objective short sleep duration is associated with increased hypertension risk. We aimed to explore the mechanism underlying the association between objective short sleep duration and hypertension in patients with chronic insomnia disorder (CID) by multi-omics.MethodsCID was defined according to International Classification of Sleep Disorders-3, and objective short sleep duration was based on the median value of total sleep time of the overall subjects during an overnight polysomnography. We used the mean values of measured nighttime and morning systolic (SBP) and diastolic blood pressure (DBP) for analysis. Serum metabolomics and fecal 16S rDNA amplicon sequencing were used to explore characteristic metabolites and analyze gut microbiota distribution, respectively.ResultsOne hundred and three patients with CID and 70 normal sleepers were included. We found 52 objective short sleep duration insomnia phenotype (ISSD)-related serum metabolites. Among the 52 ISSD-related serum metabolites, indoxyl sulfate was positively correlated with BP after adjusting for confounding factors (SBP: β = 0.250, p = .028; DBP: β = 0.256, p = .030) in ISSD. In addition, the level of serum indoxyl sulfate was significantly correlated with the genera Prevotella 9 (r = .378, p = .027), CAG-56 (r = −.359, p = .037), Ruminiclostridium 9 (r = −.340, p = .049), and Ruminococcus 2 (r = −.356, p = .039) in ISSD.ConclusionsOur study suggests that the ISSD phenotype is associated with significant changes in serum metabolic profile, including high levels of indoxyl sulfate. The latter molecule correlates both with BP and gut microbiota in patients with the ISSD phenotype, suggesting that indoxyl sulfate may be the molecular path resulting in increased hypertension risk in this phenotype.
Transcriptional regulation of daily sleep amount by TCF4–HDAC4–CREB complex in miceZhou, Rui; Zhang, Chaodong; Gan, Rui; Yin, Xin; Wang, Meng; Shi, Bihan; Chen, Lin; Wu, Chongyang; Li, Qi; Liu, Qinghua
doi: 10.1093/sleep/zsae313pmid: 39745887
Histone deacetylase HDAC4/5 cooperates with cAMP response element-binding protein (CREB) in the transcriptional regulation of daily sleep amount downstream of LKB1-SIK3 kinase cascade in mice. Here, we report a significant enrichment of the E-box motifs for the basic loop–helix–loop (bHLH) proteins near the CREB- and HDAC4-binding sites in the mouse genome. Adeno-associated virus-mediated expression of class I bHLH transcription factors, such as TCF4, TCF3, or TCF12, across the mouse brain neurons reduces the duration of rapid eye movement sleep (REMS) and non-REMS (NREMS). TCF4 requires its bHLH domain to regulate REMS or NREMS amount, of which the latter is mostly independent of the E-box-binding activity. Consistent with that TCF4 interacts with CREB and HDAC4 via the bHLH domain, TCF4 relies on CREB and partly on HDAC4 to regulate NREMS/REMS amount. Conversely, the ability of CREB to regulate sleep duration also requires its binding to TCF4 and HDAC4. Together, these results indicate that TCF4, HDAC4, and CREB could function cooperatively in the transcriptional regulation of daily sleep amount in mice.
Rest-activity rhythm fragmentation and synchronization are linked with reduced cortical thickness in older adults “at risk” for dementiaEspinosa, Nicole; Hoyos, Camilla M; McKinnon, Andrew C; Almgren, Hannes; Duffy, Shantel L; Naismith, Sharon L
doi: 10.1093/sleep/zsaf017pmid: 40052961
Study ObjectivesWhile alterations in rest-activity rhythms are common in older adults “at risk” for dementia, it is unclear how rest-activity rhythms relate to underlying brain integrity.MethodsOlder adults aged ≥50 years (n = 143, mean age = 67) with subjective and/or objective cognitive impairment underwent magnetic resonance imaging scanning and 14 days of actigraphy. The following nonparametric measures were computed: intra-daily variability (IV), inter-daily stability (IS), relative amplitude (RA), and average activity during the least active 5-h period (L5). A vertex-wise analysis correcting for age, sex, and clinical variables examined the association between nonparametric actigraphy measures and cortical thickness.ResultsWhen controlling for age, sex, and body mass index (BMI), lower IV was associated with greater cortical thickness in the right cuneus (cluster-wise p-values [CWP] < 0.001), left middle frontal gyrus (CWP < 0.001), and lateral orbital frontal cortex (CWP = 0.004). When controlling for age, sex, medical burden (CIRS-G), BMI, and antidepressant use, lower IS was associated with lower cortical thickness in the left (CWP = 0.002) and right superior frontal gyrus (CWP < 0.001), left superior temporal gyrus (CWP = 0.043), and left post-central gyrus (CWP = 0.033). There were no significant associations between RA or L5 and cortical thickness.ConclusionsIn older adults “at risk” for dementia, variability and stability of rest-activity rhythms were associated with reduced cortical thickness in frontal, temporal, parietal, and occipital regions. Further studies could focus on determining the prognostic utility of such markers longitudinally.
Polysomnographic endotypes of successful multilevel upper airway surgery for obstructive sleep apneaWang, Xiaoting; Zhang, Jingyu; Zou, Jianyin; Zhou, Tianjiao; Zhou, Enhui; Shen, Li; Yang, Siyu; Huang, Weijun; Zhu, Huaming; Guan, Jian; Yi, Hongliang; Yin, Shankai
doi: 10.1093/sleep/zsaf012pmid: 39821631
ABSTRACTStudy ObjectivesMultilevel upper airway surgery is effective for some patients with obstructive sleep apnea (OSA), but predicting the response to surgery remains a challenge. The underlying endotypes of OSA include upper airway collapsibility, muscle compensation, loop gain, and the arousal threshold. This study aimed to explore the effect of surgery on polysomnography (PSG)-derived OSA endotypes and establish a surgical response prediction model.MethodsOur study included 54 Chinese patients with OSA who underwent multilevel upper airway surgery. Participants underwent PSG before and after surgery with a median follow-up time of 6.5 months. Using AHIBaseline/AHIpost-surgery ≥ 2 and AHIpost-surgery < 10 events/h as criteria, participants were classified as surgery responders and non-responders. The surgical success rate was 26%. These endotypic traits were derived from a standard PSG data by validated methods.ResultsThe surgery altered both anatomical and non-anatomical endotypic traits, including increased Vpassive (baseline vs post-surgery: 51.5 [18.7–84.2] vs 86.8 [67.4–93.7] %Veupnea, p < .001), decreased loop gain (baseline vs post-surgery: 0.7 [0.7–0.8] vs 0.6 [0.5–0.6]; p < .001), and a higher arousal threshold (baseline vs post-surgery: 202.9 [183.7–222.0] vs 160.7 [143.9–177.4] %Veupnea; p < .001). However, it did not significantly affect muscle compensation. Fully adjusted logistic regression analyses indicated that a favorable response to surgery was independently associated with a lower LG (OR [CI 95%], 0.1 [0.0–0.5], p = .032). In patients with improved muscle compensation or a more collapsible airway (lower Vpassive), a lower loop gain was more strongly indicative of success. However, when muscle compensation was lower or collapsibility was less severe (higher Vpassive), a lower loop gain was less predictive of success.ConclusionsThis study demonstrated that multilevel upper airway surgery altered both anatomical and non-anatomical endotypes in Chinese patients with OSA. An endotype based regression model may meaningfully predict surgical success.
Sleep trajectory of hospitalized medically ill older adults: do sleep medications make a difference?Smichenko, Juliana; Shochat, Tamar; Zisberg, Anna
doi: 10.1093/sleep/zsaf013pmid: 39820479
Study ObjectivesSleep disturbances are prevalent during acute hospitalization in medically ill older patients, with undesirable outcomes. Sleep medication use is common, but its effectiveness is questionable. This study explored the trajectory of sleep parameters from home to hospital and assessed the impact of sleep medication use, considering covariates such as physical symptom burden.MethodsA prospective multicenter study was conducted in four Israeli hospitals. Cognitively intact older patients (n = 683), with an admission interview and at least one follow-up, were recruited. Total sleep time (TST), sleep efficiency (SE), sleep quality (SQ), number of awakenings (NOAs), sleep medication use, sleep medication burden (quantity and dosage), and physical symptom burden were recorded daily. Personal and illness-related covariates were included in a repeated measures mixed models design.ResultsParticipants (male: 54%, aged 77.31 ± 6.60) showed shorter TST (329.73 ± 111.94 vs. 377.03 ± 101.06 min), lower SE (71.49 ± 19.28% vs. 76.14 ± 15.53%), and higher probability for lower SQ, in the hospital compared to home. Sleep medication use was not correlated with any sleep parameters; sleep medication burden was associated with NOA. Physical symptom burden showed significant main effects on SE, SQ, and NOA, and a significant interaction was found with time points on TST, such that higher burden was more strongly associated with shorter TST at first in-hospital follow-up than at admission, with no differences between all subsequent in-hospital time points.ConclusionsSleep declined during acute hospitalization compared to the home, with sleep medications showing minimal effect. Managing symptom burden should be prioritized when addressing sleep disturbances in older patients during hospitalization.