Cheng-Hung Yang

Reduced physiologic complexity is associated with poor sleep in patients with major depression and primary insomnia

BACKGROUND Depression is known to be associated with altered cardiovascular variability and increased cardiovascular comorbidity, yet it is unknown whether altered cardiac autonomic function in depression is associated with insomnia, a common symptom comorbid with depression. This study aimed to investigate the long-term diurnal profile of autonomic function as measured by heart rate variability (HRV) in both major depression and primary insomnia patients. METHOD A total of 52 non-medicated patients with major depression, 47 non-medicated patients with primary insomnia, and 88 matched controls without insomnia were recruited. Each subject was assessed by means of sleep and mood questionnaires and underwent twenty-four-hour ambulatory electrocardiogram monitoring. Standard HRV analysis and a well-validated complexity measure, multiscale entropy, were applied to comprehensively assess the diurnal profiles of autonomic function and physiologic complexity in our study sample. RESULTS Compared with the controls, the patients with major depression and those with primary insomnia exhibited significant reductions in parasympathetic-related HRV indices, and this association was mainly driven by the presence of poor sleep. Both groups of patients also exhibited significant reductions in physiologic complexity during the sleep period as compared with the healthy controls. Alterations in HRV indices were correlated with perceived sleep questionnaire scores but not with depression scales. CONCLUSIONS Our findings suggest a pivotal role of sleep disturbance in regulating cardiovascular variability in major depression and primary insomnia patients. These findings could highlight the importance of treating insomnia as an independent disease rather than a symptom.

Cognitive and neuropsychiatric correlates of EEG dynamic complexity in patients with Alzheimer's disease.

This study assessed the utility of multiscale entropy (MSE), a complexity analysis of biological signals, to identify changes in dynamics of surface electroencephalogram (EEG) in patients with Alzheimers disease (AD) that was correlated to cognitive and behavioral dysfunction. A total of 108 AD patients were recruited and their digital EEG recordings were analyzed using MSE methods. We investigate the appropriate parameters and time scale factors for MSE calculation from EEG signals. We then assessed the within-subject consistency of MSE measures in different EEG epochs and correlations of MSE measures to cognitive and neuropsychiatric symptoms of AD patients. Increased severity of AD was associated with decreased MSE complexity as measured by short-time scales, and with increased MSE complexity as measured by long-time scales. MSE complexity in EEGs of the temporal and occipitoparietal electrodes correlated significantly with cognitive function. MSE complexity of EEGs in various brain areas was also correlated to subdomains of neuropsychiatric symptoms. MSE analysis revealed abnormal EEG complexity across short- and long-time scales that were correlated to cognitive and neuropsychiatric assessments. The MSE-based EEG complexity analysis may provide a simple and cost-effective method to quantify the severity of cognitive and neuropsychiatric symptoms in AD patients.

Behavioural disturbances in psychiatric inpatients with dementia of the Alzheimer's type in Taiwan

This report studied behavioural disturbances in psychiatric inpatients with dementia of the Alzheimers type (DAT) in Taiwan. The sample consisted of 75 inpatients with DAT who were consecutively admitted to the geropsychiatric ward. Their behavioural disturbances were obtained from semistructured interviews with families and ward observation. There were eight main behavioural disturbances: getting lost, repetitive phenomena, sleep disturbance, aggression, wandering, hyperphagia, hoarding behaviour, and inappropriate sexual behaviour. Number of behavioural disturbances, wandering, hyperphagia and sleep disturbance were significantly associated with the severity of cognitive impairment.

Sleep state instabilities in major depressive disorder: Detection and quantification with electrocardiogram-based cardiopulmonary coupling analysis.

Sleep disruption is an important aspect of major depressive disorder but lacks an objective and inexpensive means of assessment. We evaluated the utility of electrocardiogram (ECG)-based cardiopulmonary coupling analysis to quantify physiologic sleep stability in patients with major depression. Relative to controls, unmedicated depressed patients had a reduction in high-frequency coupling, an index of stable sleep, an increase in low-frequency coupling, an index of unstable sleep, and an increase in very-low-frequency coupling, an index of wakefulness/REM sleep. The medicated depressed group showed a restoration of stable sleep to a level comparable with that of the control group. ECG-based cardiopulmonary coupling analysis may provide a simple, cost-efficient point-of-care method to quantify sleep quality/stability and to objectively evaluate the severity of insomnia in patients with major depression.

BDNF Val66Met polymorphism alters sympathovagal balance in healthy subjects

A common polymorphism of the brain‐derived neurotrophic factor (BDNF) gene (Val66Met) has been implicated in anxiety, which is associated with lower vagal activity. We hypothesize that the BDNF Val66Met polymorphism may have a modulatory effect on the cardiac sympathovagal balance. A total of 211 healthy Chinese‐Han adults (58 male, 153 female, aged 33.3 ± 10.3 years) were recruited with three BDNF genotypes: Val/Val (47, 22.3%), Val/Met (108, 51.2%), and Met/Met (56, 26.5%). Autonomic function was assessed via an analysis of heart rate variability. Reductions in high‐frequency power, an index for parasympathetic activity, and increases in the low‐frequency/high‐frequency ratio, an index for sympathovagal balance, were found in subjects bearing the Met/Met genotype as compared to the Val/Val group. These results suggest that an altered sympathovagal balance with relatively decreased parasympathetic activity is associated with the Met/Met genotype, suggesting a potential role for the studied BDNF polymorphism in modulating cardiac autonomic functions.

Depression is the Strongest Independent Risk Factor for Poor Social Engagement Among Chinese Elderly Veteran Assisted-living Residents

Background: Social engagement prolongs the lifespan and preserves cognition in the elderly. However, most studies concerning social engagement have been conducted in Western countries; few have been performed in the Chinese population. This study attempted to identify the risk factors for poor social engagement among elderly veterans in Taiwan. Methods: A total of 597 male veterans were enrolled, with a mean age of 80.8 ± 5.0 years. This cross‐sectional study employed the Resident Assessment Instrument (RAI) Minimum Data Set (MDS), the Geriatric Depression Scale–Short Form (GDS‐SF), and the Mini‐Mental State Examination (MMSE). Multivariate logistic regression analysis was done to investigate significant independent risk factors for poor social engagement, which were identified using the MDS Index of Social Engagement (ISE). Results: Mean ISE score was 1.5 ± 1.3 (range, 0–5); 52% of subjects had poor levels of social engagement (ISE < 2; 312/597). Regression analyses suggested that depression (OR, 6.6; 95% CI, 2.7–16.1; p < 0.001), illiteracy (OR, 2.2; 95% CI, 1.3–3.8; p = 0.003), the presence of unsettled relationships (OR, 3.6; 95% CI, 1.5–8.7; p = 0.004), and cognitive impairment (OR, 2.0; 95% CI, 1.1–3.9; p = 0.03) were significant independent risk factors for poor social engagement, after controlling for age, marital status, level of daily living activity and degree of sensory impairment. Conclusion: Poor social engagement is common among Chinese assisted‐living veteran home residents. Depression is the greatest risk factor of poor social engagement in this population.

The efficacy and safety of quetiapine for treatment of geriatric psychosis

Quetiapine, an atypical antipsychotic, is effective for psychosis in younger patients, with limited adverse effects reported. This open-label naturalistic study was conducted to assess the 4-week efficacy and safety of quetiapine for treatment of geriatric psychosis. Clinical efficacy was evaluated using the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Improvement (CGI-I) instruments before and after 4 weeks of quetiapine treatment. The sample population consisted of 100 geropsychiatric inpatients with psychosis, with the therapeutic evaluation completed by 91. Eighty-one of these 91 patients (89.0%) experienced mild-to-substantial improvement, as determined from the CGI-I. Further, a mean reduction in BPRS score of 39.5% (from baseline) was also determined. The mean daily dose of quetiapine for the fourth week was 276.1 177.2mg/day (range 50-800). Higher quetiapine dosages were administered for patients with functional psychoses compared to an analogous group with organic mental disorders. The most common adverse effects were somnolence (30.0%), lower-limb weakness (28.0%) and dizziness (27.0%). Body weight and fasting triglyceride were significantly elevated after quetiapine treatment (2.2% and 8.9% from baseline, respectively). Based on the results of this study, it appears that quetiapine is an efficacious and safe treatment for geriatric inpatients with psychosis, however, there is a wide dosing range and optimal dosage is diagnosis-dependent.

The ADAMTS9 gene is associated with cognitive aging in the elderly in a Taiwanese population

Evidence indicates that the pathophysiologic mechanisms associated with insulin resistance may contribute to cognitive aging and Alzheimer’s diseases. In this study, we hypothesize that single nucleotide polymorphisms (SNPs) within insulin resistance-associated genes, such as the ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9), glucokinase regulator (GCKR), and peroxisome proliferator activated receptor gamma (PPARG) genes, may be linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population. A total of 547 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examinations (MMSE) were administered to all subjects, and MMSE scores were used to measure cognitive functions. Our data showed that four SNPs (rs73832338, rs9985304, rs4317088, and rs9831846) in the ADAMTS9 gene were significantly associated with cognitive aging among the subjects (P = 1.5 x 10−6 ~ 0.0002). This association remained significant after performing Bonferroni correction. Additionally, we found that interactions between the ADAMTS9 rs9985304 and ADAMTS9 rs76346246 SNPs influenced cognitive aging (P < 0.001). However, variants in the GCKR and PPARG genes had no association with cognitive aging in our study. Our study indicates that the ADAMTS9 gene may contribute to susceptibility to cognitive aging independently as well as through SNP-SNP interactions.

The rs1277306 Variant of the REST Gene Confers Susceptibility to Cognitive Aging in an Elderly Taiwanese Population

Background/Aims: There is growing evidence that the RE1-silencing transcription factor (REST) gene may contribute to cognitive aging and Alzheimer diseases. In this replication study, we reassessed whether single nucleotide polymorphisms (SNPs) within the REST gene are linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population. Methods: A total of 634 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examination (MMSE) scores were performed for all subjects to weigh cognitive functions. Results: Our data showed that the REST rs1277306 SNP was significantly associated with cognitive aging among all subjects (p = 0.0052). Furthermore, the association remained significant for individuals without APOE ε4 allele (p = 0.0092), but not for individuals with at least 1 APOE ε4 allele. This association remained significant after Bonferroni correction. Additionally, we found the interactions between the rs1713985 and rs1277306 SNPs on cognitive aging (p = 0.016). However, the 3-marker haplotype derived from the rs1713985, rs3796529, and rs7680734 SNPs in the REST gene demonstrated no association with cognitive aging. Conclusion: Our study indicates that the REST gene may contribute to susceptibility to cognitive aging independently as well as through SNP-SNP and APOE-REST interactions.

Profiling Objective Sleep Quality in a Healthy Taiwanese Sample: Using a Novel Electrocardiogram-based Cardiopulmonary Coupling Analysis

Objectives: Sleep affects the regulation of circulatory and respiratory function. The factors of age and gender are also known to have a significant impact on the cardiac physiology. We investigated the impact of the factors of age and gender on sleep-related cardiovascular and respiratory dynamics with a novel, validated cardiopulmonary coupling analysis based solely on the electrocardiogram (ECG) signal. Methods: We recruited 155 healthy subjects (41 males and 114 females, aged 37.6±13.0 years, range being 19-67 years) to participate in this study. We evaluated their mood and sleep with self-reported questionnaires - the Beck Depression Inventory, the Pittsburgh Sleep Quality Index, and the Epworth Sleepiness Scales. Physiologic sleep measures were quantified by analysis of continuous ECG recordings using the cardiopulmonary coupling analysis. Three sleep states were determined, namely stable, unstable, and rapid eye movement (REM)/wake state, by measuring the degree of association between autonomic and respiratory drives during sleep. Results: The key findings in this study included: (A) Compared to subjects under age 40, subjects over age 40 showed to have significantly decreased very-low-frequency coupling, an index of REM/wake state. (B) Compared to female subjects, male subjects revealed to have lower high-frequency-coupling, an index of stable sleep, and higher low-frequency-coupling, an index of unstable sleep. And (C) ECG-based sleep characteristics were not fount to be correlated with self-reported questionnaires in this healthy adult sample. Conclusions: Our study results showed that aging and gender as factors had significant effects on cardiopulmonary coupling dynamics during sleep. This study also provided a profile of the physiological sleep characteristics of a healthy Taiwanese sample. We suggest that further research may enhance the use of this relatively simple ECG-based method to give a cost-efficient way to objectively evaluate sleep quality.