Sex difference in the association between excessive daytime sleepiness and health-related quality of life in community-dwelling older adults: The Yilan study, Taiwan.

OBJECTIVES: The association between excessive daytime sleepiness and health-related quality of life among older adults and at-risk individuals remains unclear. This study examined relationships between excessive daytime sleepiness and unfavorable health-related quality of life and explored the moderating effect of sex. STUDY DESIGN: This was a community-based study of adults aged 65 years or more. Excessive daytime sleepiness was defined as a score exceeding 10 on the Epworth Sleepiness Scale. Multiple logistic regression analyses were used to examine the relationships between excessive daytime sleepiness and health-related quality of life. The moderating effect of sex was examined by testing interaction terms. MAIN OUTCOME MEASURES: Health-related quality of life was measured using the Short Form 12 Health Survey, which includes a physical component summary and a mental component summary. Unfavorable health-related quality of life was defined as the lowest tertile of the scores for both components. RESULTS: In total, 3788 individuals participated. After controlling for covariates, older adults with excessive daytime sleepiness did not have an unfavorable physical component summary but were more likely to have an unfavorable mental component summary (odds ratio 1.96; 95 % confidence interval 1.47-2.61). When stratified by sex, excessive daytime sleepiness was associated with a poor physical component summary in men (odds ratio 1.77, 95 % confidence interval 1.00-3.13) but not in women. CONCLUSIONS: Excessive daytime sleepiness was associated with a poor mental component summary in both sexes; however, the association with a poor physical component summary was specific to men.

Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study.

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.

Alternation of social behaviors for zebrafish (Danio rerio) in response to acute cold stress.

Low temperature is one of the most common abiotic stresses for aquatic ectotherms. Ambient low temperatures reduce the metabolic rate of teleosts, therefore, teleosts have developed strategies to modulate their physiological status for energy saving in response to cold stress, including behaviors, circulatory system, respiratory function, and metabolic adjustments. Many teleosts are social animals and they can live in large schools to serve a variety of functions, including predator avoidance, foraging efficiency, and reproduction. However, the impacts of acute cold stress on social behaviors of fish remain unclear. In the present study, we test the hypothesis that zebrafish alter their social behaviors for energy saving as a strategy in response to acute cold stress. We found that acute cold stress increased shoaling behavior that reflected a save-energy strategy for fish to forage and escape from the predators under cold stress. The aggressive levels measured by fighting behavior tests and mirror fighting tests were reduced by cold treatment. In addition, we also found that acute cold stress impaired the learning ability but did not affect memory. Our findings provided evidence that acute cold stress alters the social behaviors of aquatic ectotherms for energy saving; knowledge of their responses to cold is essential for their conservation and management.

Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference.

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.

Different dimensions of daytime sleepiness predicted mortality in older adults: Sex and muscle power-specific risk in Yilan Study, Taiwan.

OBJECTIVES: This study aimed to investigate the relationship between daytime sleepiness and mortality risk among older adults. The moderating effects of sex and physical function were examined. METHODS: This 9-year follow-up study was conducted with community-dwelling individuals aged ≥65 years. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS). Exploratory factor analysis (EFA) was used to examine the ESS factors. Handgrip strength was measured to assess physical function, and the highest quartile was defined as good muscle power. Cox regression analysis was used to estimate the 9-year all-cause mortality risk. The interaction terms were examined to evaluate their moderating effect. RESULTS: In total, 2588 individuals participated in the study. The EFA explored two factors: the passive factor (PF) and the active factor (AF). After controlling for various covariates, the cutoff-defined daytime sleepiness (ESS≥11), total raw scores, and factor scores of the ESS all failed to predict mortality risk. The 3-way interaction terms showed statistical significance in terms of [sex × PF × muscle power (p = 0.03)] but not for [sex × AF × muscle power (p = 0.11)]. Specifically, PF predicted mortality risk in women with good muscle power (hazard ratio (HR): 1.48; 95 % confidence interval (CI): 1.04-2.10), which is female-specific. In contrast, AF predicted mortality risk only in men with good muscle power (HR: 1.35; 95 % CI: 1.02-1.78). CONCLUSIONS: The ESS-measured daytime sleepiness in older adults is multidimensional. The mortality risk for each dimension was determined based on sex and physical function.

A predictive survival model for patients with stage IV oropharyngeal squamous cell carcinoma treated with chemoradiation.

PURPOSE: To evaluate the pre-treatment and post-treatment clinical factors associated with rate of survival at 1, 3, and 5 years in stage IV oropharyngeal cancer patients treated with concurrent chemoradiation with/without neoadjuvant chemotherapy. METHODS: This retrospective cohort study involved 128 Stage IV oropharyngeal cancer patients that were treated at our tertiary referral center between 2008 and 2020. The pre-treatment and post-treatment clinical parameters including nutritional status and inflammatory markers were retrospectively reviewed. RESULTS: The 5-year overall survival rate for all patients was 36.72%. The disease-specific survival (DSS) at 1-year and 3-year were 80% and 63%, whereas the disease-free survival (DFS) at 1-year and 3-year were 49% and 40%, respectively. In multivariate analyses, pretreatment hemoglobin (Hb) < 12 g/dL (hazard ratio [HR] 2.551, 95% confidence interval [CI] 1.366-4.762, p = 0.003), pretreatment systemic immune inflammation (SII) ≥ 1751 (HR 2.173, 95% CI 1.015-4.652, p = 0.046), and posttreatment systemic inflammation response index (SIRI) ≥ 261 (HR 2.074, 95% CI 1.045-4.115, p = 0.037) were independent indicators for worsened DSS. Pretreatment Hb < 12 g/dl (HR 1.692, 95% CI 1.019-2.809, p = 0.032), pretreatment SII ≥ 1751 (HR 1.968, 95% CI 1.061-3.650, p = 0.032), and posttreatment SII ≥ 1690 (HR 1.922, 95% CI 1.105-3.345, p = 0.021) were independent indicators for worsened DFS. A nomogram was developed using pretreatment Hb, pretreatment SII, and posttreatment SIRI to forecast DSS. CONCLUSIONS: The pretreatment Hb, pretreatment SII, posttreatment SII, and posttreatment SIRI are associated with survival in patients with stage IV oropharyngeal cancers. The developed nomogram aids in survival prediction and treatment adjustment.

The differential pattern of associations between nighttime sleep disturbances with dimensions of daytime sleepiness in community-dwelling older adults, the Yilan study, Taiwan.

BACKGROUND: The association between nighttime sleep disturbance and daytime sleepiness remains unclear. This study aimed to examine the relationships between various domains of nighttime sleep disturbance, daytime sleepiness, and their specific dimensions. METHODS: This was a community-based cross-sectional study. The participants were adults aged 65 years and older from Yilan City, Taiwan. Daytime sleepiness (DS) was defined using the Epworth Sleepiness Scale (ESS) with scores ≥ 11. The ESS dimensions were further examined using exploratory factor analysis. The highest 15% factor scores for each factor were defined as factor-specific DS. Various domains of nighttime sleep disturbance were assessed using the Pittsburgh Sleep Quality Index. Logistic regression analysis was used to examine the independent relationships among various nighttime sleep disturbances, ESS, and its dimensions. RESULTS: Of the 2585 participants, a total of 59.0% were women. Two factors were identified by exploratory factor analysis and were designated as 'passive factor' and 'active factor'. Multiple logistic regression analyses elucidated that short sleep duration was a common risk indicator for ESS-defined (odds ratio (OR): 2.01; 95% confidence interval (CI): 1.43-2.83), passive factor-defined (OR: 2.23, 95% CI: 1.65-3.00), and active factor-defined DS (OR: 1.47, 95% CI: 1.07-2.00). Hypnotic use was associated with a lower risk of both ESS-defined (OR: 0.66, 95% CI: 0.47-0.92) and passive factor-defined DS (OR:0.69, 95% CI: 0.52-0.92). Bathroom use (OR: 1.41, 95% CI: 1.04-1.91), coughing or snoring (OR: 2.14, 95% CI: 1.01-4.56), and sleep efficiency (OR: 0.42; 95% CI: 0.31-0.57) were uniquely associated with active factor-defined DS. CONCLUSION: Two factors were identified in the ESS, revealing factor-specific correlates of DS. Specifically, ESS- and passive factor-defined DS shared similar correlates. In contrast, some correlates seem unique to active-factor-defined DS.

Perivascular adipose tissue and adipocyte-derived exosomal miRNAs maintain vascular homeostasis.

Perivascular adipose tissue (PVAT), a fat layer that provides structural support to the blood vessels, is a cushion protecting the vessel wall from neighbouring tissues during contraction and relaxation. PVAT actively regulates vascular tone by secreting vasoactive (vasodilatory and vasoconstrictive) factors (e.g., adipokines, batokines, and lipokines) or microRNA (miRNA)-containing exosomes to reduce the hyperreactivity induced by obesity. Of particular interest are adipocyte-derived exosomal miRNAs, which act as crucial regulators, counteracting the detrimental effects of obesity on cardiovascular well-being. These exosomes serve as potent messengers, facilitating the transport of miRNAs and other bioactive molecules involved in intercellular communication. Undoubtedly, the unique function of exosomal miRNAs promotes vascular homeostasis by fine-tuning endothelial function, vascular remodelling, and inflammatory environment, thereby preventing cardiovascular disease. The collective findings comprehensively explain their protective functions by exploring the intricate mechanisms through which PVAT and adipocyte-derived exosomal miRNAs collaboratively orchestrate vascular health. Taken together, this review strategically focuses on PVAT, exosomes, and adipocyte-derived miRNAs, offering valuable insights that can potentially inform the development of targeted interventions for cardiovascular diseases.

Exploring the genetics of lithium response in bipolar disorders.

Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.

Factors Associated With Levels of Public Engagement in Protective Behaviors During the Early COVID-19 Pandemic: Causal-Comparative Study Based on the Health Belief Model.

BACKGROUND: While the challenges of COVID-19 are still unfolding, the enhancement of protective behavior remains a top priority in global health care. However, current behavior-promoting strategies may be inefficient without first identifying the individuals with lower engagement in protective behavior and the associating factors. OBJECTIVE: This study aimed to identify individuals with and potential contributing factors to low engagement in protective behavior during the COVID-19 pandemic. METHODS: This is a causal-comparative study. A theory-based web-based survey was used to investigate individuals' protective behavior and potential associating factors. During June 2020, the distribution of the survey was targeted to 3 areas: Taiwan, Japan, and North America. Based on the theory of the health belief model (HBM), the survey collected participants' various perceptions toward COVID-19 and a collection of protective behaviors. In addition to the descriptive analysis, cluster analysis, ANOVA, and Fisher exact and chi-square tests were used. RESULTS: A total of 384 responses were analyzed. More than half of the respondents lived in Taiwan, followed by Japan, then North America. The respondents were grouped into 3 clusters according to their engagement level in all protective behaviors. These 3 clusters were significantly different from each other in terms of the participants' sex, residency, perceived barriers, self-efficacy, and cues of action. CONCLUSIONS: This study used an HBM-based questionnaire to assess protective behaviors against COVID-19 and the associated factors across multiple countries. The findings indicate significant differences in various HBM concepts among individuals with varying levels of behavioral engagement.

Handgrip strength is associated with mortality in community-dwelling older adults: the Yilan cohort study, Taiwan.

INTRODUCTION: Hand grip strength (HGS) is one of the methods to help early identification of physical frailty and sarcopenia, the major concerns in the aging societies. It is also crucial to evaluate its impact on mortality. However, the available evidence regarding such impact among specific age cohorts (65 to 74 years and above) is limited. This study tried to investigate the relationship between HGS and mortality among specific cohorts of the community-dwelling older individuals in Yilan, Taiwan. METHODS: A seven-year longitudinal follow-up study was conducted involving 2,468 community-dwelling older individuals in Yilan. The participants were divided into two groups based on their quartiles of hand grip strength: with poor HGS and with good HGS. The association between HGS and mortality was examined using Cox proportional hazards models. RESULTS: The analysis revealed that age, HGS, gender, medical history of cardiovascular diseases, body mass index, and wrist-hip ratio had significant impacts on seven-year survival. Specifically, individuals with poor HGS exhibited increased mortality, with an adjusted hazard ratio (HR) of 1.87 (95% CI: 1.52-2.30). Furthermore, the adverse effect of poor HGS on mortality was more pronounced in males aged 65-74 years (adjusted HR 4.12, 95% CI: 2.16-7.84), females aged 75 years or older (2.09, 1.43-3.04) and males aged 75 years or older (1.49, 1.07-2.07). CONCLUSION: Poor hand grip strength is an independent risk factor for mid-term mortality among community-dwelling older individuals in Yilan. The assessment of HGS can serve as a valuable tool in identifying older individuals at higher risk of death.

Impact of Varying Chest Wall Target Volume Delineation on Postmastectomy Radiation Therapy Outcomes in Breast Cancer Patients with Implant-Based Reconstruction.

BACKGROUND: The target volume for post-mastectomy radiation therapy (PMRT) in breast cancer patients with reconstruction has been a subject of debate. Traditionally, the RT chest wall (CW) volume encompasses the entire implant. For patients with retropectoral implants, the deep lymphatic plexus dorsal part of the implant is no longer considered high risk and can be omitted. This study aimed to assess the radiation dose distribution and treatment outcomes associated with different CW delineation according to ESTRO ACROP guideline for patients who have undergone implant-based reconstruction. METHODS: We conducted a retrospective review of breast cancer patients who underwent a mastectomy followed by two-stage implant-based breast reconstruction and adjuvant radiation therapy (RT) between 2007 and 2022. The expanders/implants were positioned retropectorally. The chest wall target volumes were categorized into two groups: the prepectoral group, which excluded the deep lymphatic plexus, and the whole expander group. RESULTS: The study included 26 patients, with 15 in the prepectoral group and 11 in the whole expander group. No significant differences were observed in normal organ exposure between the two groups. There was a trend toward a lower ipsilateral lung mean dose in the prepectoral group (10.2 vs. 11.1 Gy, p = 0.06). Both groups exhibited limited instances of reconstruction failure and local recurrence. CONCLUSIONS: For patients undergoing two-stage expander/implant retropectoral breast reconstruction and PMRT, our data provided comparable outcomes and normal organ exposure for those omitting the deep lymphatic plexus.

Design and synthesis of pyrazole derivatives against neutrophilic inflammation.

Neutrophils are the most abundant immune cells. However, neutrophil dysregulation leads to acute and chronic inflammation and is involved in various diseases. The aim of this study was to develop anti-inflammatory agents in human neutrophils. A drug screening was conducted on in-house compounds with the potential to inhibit the respiratory burst, which involves the generation of superoxide anions in human neutrophils. Bioisosteric replacement was then applied to design more active derivatives. The most potent inhibitors of superoxide anion generation activity were compounds 58 and 59, which had IC50 values of 13.30 and 9.06 nM, respectively. The inhibitory effects of 58 and 59 were reversed by H89, a PKA inhibitor. PDE selective screening indicated that the best inhibitory effects were PDE4B1 and PDE4D2, and the inhibitory activities were 83% and 85%, respectively, at a 10 µM concentration of 59. The final molecular simulation experiment highlighted the slightly different binding poses of 58 and 59 in the PDE4 active site. An in vivo pharmacokinetic study revealed that the half-life of 59 was approximately 79 min when using intravenous bolus administration. This work introduced a new class structure of PDE4 inhibitors resulting in potent neutrophil inactivation activity, with the aim of contributing to new anti-inflammatory drug discovery.

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. CONCLUSIONS: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.

Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study.

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2,039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.

Longitudinal Outcomes of Resilience, Quality of Life, and Community Integration in Treatment-Resistant Depression: A Two-Group Matched Controlled Trial.

BACKGROUND: Current evidence of nonpharmacological intervention for patients with treatment-resistant depression (TRD) is lacking. AIMS: To examine whether an 8-week nurse-led cognitive-behavioral based group intervention would enhance resilient coping and life quality among community-based patients with TRD. METHOD: The participants were randomly sampled from a cohort of TRD recruited from two general teaching hospitals. The two groups were assessed with multiple outcome measures at baseline (T0); 8-week post-baseline (T1); and at 3, 6, and 9 months after T1 (T2-4). Psychoeducation was nested in the cognitive behavioral group intervention to facilitate discussion. RESULTS: Of the 23 participants (mean age 56 years, 69.6% female) in the experimental group, higher resilient coping and lower mental distress levels at T1 as well as later improved quality of life and community integration at T2-4 were observed compared to the controls across COVID-19 (T3). Overall, the scores of resilience and community integration were higher throughout the four follow-up points of observations for the experimental group. CONCLUSION: The findings indicated that an 8-week nurse-led cognitive-behavioral based group intervention may enhance the TRD patients' resilient coping and mental distress levels while providing the potentials for community reintegration after mental health psychoeducation engagement. It is imperative for the nurses caring for patients with TRD to extend from clinical-based intervention to community-based self-care approach, with the importance of short-term stress management and healthy lifestyle development highlighted during the community reintegration trajectory.

Peptide immunization against the C-terminal of alpha-synuclein reduces locomotor activity in mice overexpressing alpha-synuclein.

Abnormal accumulation of alpha-synuclein (αSyn) in the remaining nigra dopaminergic neurons is a common neuropathological feature found in patients with Parkinson's disease (PD). Antibody-based immunotherapy has been considered a potential approach for PD treatment. This study aims to investigate the effectiveness of active immunization against αSyn in a mouse model of PD. Adult mice were immunized with or without a synthetic peptide containing the C-terminal residues of human αSyn and activation epitopes, followed by an intranigral injection of adeno-associated virus vectors for overexpressing human αSyn. Upon the peptide injection, αSyn-specific antibodies were raised, accompanied by degeneration of dopaminergic neurons and motor deficits. Furthermore, the induction of neuroinflammation was postulated by the elevation of astroglial and microglial markers in the immunized mice. Instead of lessening αSyn toxicity, this peptide vaccine caused an increase in the pathogenic species of αSyn. Our data demonstrated the potential adverse effects of active immunization to raise antibodies against the C-terminal fragment of αSyn. This drawback highlights the need for further investigation to weigh the pros and cons of immunotherapy in PD. Applying the αSyn C-terminal peptide vaccine for PD treatment should be cautiously exercised. This study provides valuable insights into the intricate interplay among immune intervention, αSyn accumulation, and neurodegeneration.

Concurrence of Insomnia and Daytime Sleepiness Predicted 9-Year Mortality Risk in Community-Dwelling Older Adults: The Yilan Study, Taiwan.

BACKGROUND: Co-occurring insomnia and daytime sleepiness has an undetermined clinical significance in older adults. We aimed to investigate the relationship between various combinations of insomnia and daytime sleepiness with mortality risk in community-dwelling older adults. The moderation effect of sex was also assessed. METHODS: We conducted this follow-up study including community-dwelling adults aged ≥65 in Yilan City, Taiwan. Daytime sleepiness was defined as scoring ≥11 on the Epworth Sleepiness Scale. Insomnia was defined as scores ≥5 on the Athens Insomnia Scale-5. Four phenotypes were defined based on the presence of insomnia or daytime sleepiness. The 9-year mortality risks for various phenotypic combinations were estimated using Cox regression analysis. Sex-specific risks were examined using an interaction term. RESULTS: In total, 2 702 older adults participated in the study, and 59.1% were women. The total 9-year mortality rate was 27.5%. After adjusting for all covariates, compared with those without insomnia or daytime sleepiness, the phenotype of co-occurring insomnia with daytime sleepiness predicted higher mortality risk (hazard ratio [HR]: 1.76, confidence interval [CI]: 1.20-2.58). In contrast, insomnia and daytime sleepiness alone did not correlate with higher mortality. The interaction between sex with co-occurring insomnia and daytime sleepiness was significant (p = .01). When stratifying by sex, the association between co-occurring insomnia and daytime sleepiness with higher mortality risk was male-specific (HR: 3.07, CI: 1.87-5.04). CONCLUSIONS: Concurrence of insomnia and daytime sleepiness indicates a toxic phenotypic combination in older adults, particularly in men. Precise public health and preventive medicine can be implemented through geriatric sleep medicine.