Chung-Hsing Chou

Potential of Neural Stem Cell-Based Therapy for Parkinson's Disease.

Neural stem cell (NSC) transplantation is an emerging strategy for restoring neuronal function in neurological disorders, such as Parkinsons disease (PD), which is characterized by a profound and selective loss of nigrostriatal dopaminergic (DA) neurons. Adult neurogenesis generates newborn neurons that can be observed at specialized niches where endothelial cells (ECs) play a significant role in regulating the behavior of NSCs, including self-renewal and differentiating into all neural lineage cells. In this minireview, we highlight the importance of establishing an appropriate microenvironment at the target site of NSC transplantation, where grafted cells integrate into the surroundings in order to enhance DA neurotransmission. Using a novel model of NSC-EC coculture, it is possible to combine ECs with NSCs, to generate such a neurovascular microenvironment. With appropriate NSCs selected, the composition of the transplant can be investigated through paracrine and juxtacrine signaling within the neurovascular unit (NVU). With target site cellular and acellular compartments of the microenvironment recognized, guided DA differentiation of NSCs can be achieved. As differentiated DA neurons integrate into the existing nigrostriatal DA pathway, the symptoms of PD can potentially be alleviated by reversing characteristic neurodegeneration.

Associations between serum total bilirubin levels and functional dependence in the elderly.

Many studies support the role of bilirubin as a cytoprotector in chronic inflammatory diseases, such as stroke and atherosclerosis.

Association Between Tuberculosis and Parkinson Disease: A Nationwide, Population-Based Cohort Study

AbstractFew studies have investigated the association between tuberculosis (TB) and Parkinson disease (PD). This nationwide, population-based, retrospective cohort study investigated the risk of PD in patients with TB.We selected patients newly diagnosed with TB (International Classification of Diseases, Ninth Revision, Clinical Modification: 011) from 2000 to 2009 in the Taiwan National Health Insurance Database as the TB cohort. The comparison cohort (the non-TB cohort) was frequency matched to the TB cohort at a ratio of 4:1 by sex, age, and the index date. We analyzed the risks of PD by using Cox proportional hazard regression models.A total of 121,951 patients with TB and 487,800 non-TB controls were enrolled in this study. The TB cohort had a 1.38-fold risk of PD compared with the non-TB cohort after adjustment for age, sex, and comorbidities (aHR, 95% CI: 1.30–1.46). The adjusted risk of PD in the TB and non-TB cohorts increased in subgroups regardless of age, sex, and comorbidities. Combined effect of TB and comorbidities on the risk of PD were significant in patients with TB who had diabetes (aHR: 2.26, 95% CI: 2.02–2.52), hypertension (aHR: 2.23, 95% CI: 2.04–2.44), head injury (aHR: 2.32, 95% CI: 1.95–2.77), chronic kidney disease (aHR: 2.02, 95% CI: 1.49–2.72), chronic obstructive pulmonary disease (aHR: 1.84, 95% CI: 1.66–2.05), depression (aHR: 4.66, 95% CI: 3.59–6.05), dementia (aHR: 3.70, 95% CI: 2.99–4.59), and stroke (aHR: 2.56, 95% CI: 2.28–2.87). The risk of PD was higher in a follow-up within 1 year (aHR: 1.78, 95% CI: 1.58–2.00) and decreased with the follow-up period in the TB cohort.Patients with TB have an independently 1.38-fold risk of PD. The risk of PD decreased with the follow-up period in the TB cohort. Physicians should be aware of the risk of PD in patients with TB when treating such patients.

Increased Risk of Dementia Among Sleep-Related Movement Disorders: A Population-Based Longitudinal Study in Taiwan.

AbstractSleep-related movement disorders (SRMD) are sleep disorders. As poor sleep quality is associated with cognitive impairment, we hypothesized that SRMD patients were exposed to a great risk for developing dementia.The present study was aimed to retrospectively examine the association of SRMD and dementia risk.A retrospective longitudinal study was conducted using the data obtained from the Longitudinal Health Insurance Database (LHID) in Taiwan. The study cohort enrolled 604 patients with SRMD who were initially diagnosed and 2416 patients who were randomly selected and age/gender matched with the study group. SRMD, dementia, and other confounding factors were defined according to International Classification of Diseases Clinical Modification Codes. Cox proportional-hazards regressions were employed to examine adjusted hazard ratios (HR) after adjusting with confounding factors.Our data revealed that patients with SRMD had a 3.952 times (95% CI = 1.124–4.767) higher risk to develop all-cause dementia compared with individuals without SRMD. The results showed that SRMD patients aged 45 to 64 exhibited highest risk of developing all-cause dementia (HR: 5.320, 95% CI = 1.770–5.991), followed by patients age ≥65 (HR: 4.123, 95% CI = 2.066–6.972) and <45 (HR: 3.170, 95% CI = 1.050–4.128), respectively. Females with SRMD were at greater risk to develop all-cause dementia (HR: 4.372, 95% CI = 1.175–5.624). The impact of SRMD on dementia risk was progressively increased by various follow-up time intervals (<1 year, 1–2 years, and ≥2 years).The results suggest that SRMD is linked to an increased risk for dementia with gender-dependent and time-dependent characteristics.

The potential impact of primary headache disorders on stroke risk

BackgroundHeadache such as migraine is associated with stroke. Studies focused on primary headache disorders (PHDs) as a risk factor for stroke are limited. The purpose of this population-based cohort study was to explore whether patients with PHDs were at a high risk for developing stroke.MethodsA total of 1346 patients with PHDs were enrolled and compared with 5384 age-, gender- and co-morbidity-matched control cohorts. International Classification of Diseases, Clinical Modification codes were administered for the definition of PHDs, stroke, and stroke risk factors. Cox proportional-hazards regressions were performed for investigating hazard ratios (HR).ResultsPHDs patients exhibited a 1.49 times (95% CI :1.15–1.98, p < 0.01) higher risk for developing ischaemic stroke compared with that of control cohorts. Both migraine (HR = 1.22, 95% CI :1.13–1.97, p < 0.05) and tension-type headache (HR = 2.29, 95% CI :1.22–2.80, p < 0.01) were associated with an increased risk of ischemic stroke. Females with PHDs were at greater risk of developing ischaemic stroke (HR = 1.49, 95% CI :1.13–1.90, p < 0.01) than those without PHDs. PHDs patient aged 45 to 64 years displayed significantly higher risk to develop ischaemic stroke (HR = 1.50, 95% CI: 1.11–2.10, p < 0.05) than the matched controls. The impact of PHDs on ischaemic stroke risk became gradually apparent by different following time intervals beyond 2 years after first diagnosis.ConclusionPHDs is suggestive of an incremental risk for ischaemic stroke with gender-dependent, age-specific and time-dependent characteristics.

Increased risk of stroke in patients with atopic dermatitis: A population-based, longitudinal study in Taiwan

Background: Chronic inflammation has been linked to stroke, but it is not known whether atopic dermatitis (AD), a chronically inflammatory skin disease, is related to stroke. The aim of this study was to investigate the association of AD and stroke. Materials and Methods: In this population-based, cohort study, data were collected from a Longitudinal Health Insurance Database released from the National Health Research Institute in Taiwan in 2011. All patients with AD between 2000 and 2006 without prior stroke were included and an age- and gender-matched cohort without prior stroke, 4-fold of the AD sample size, was served as the control group. The two cohorts were followed until the end of 2010 for stroke incidence. Coxs proportional hazards regressions were used to assess the difference in stroke risk between groups. Results: During the follow-up period of 4–11 years, 471 (incidence: 4.46/1,000 person-years) and 1497 (incidence: 3.56/1,000 person-years) stroke incidents were noted in the study and control cohort, respectively. The patients with AD had an increased incidence of ischemic stroke (adjusted hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.08–1.36) but not hemorrhagic stroke (adjusted HR: 0.97; 95% CI: 0.74–1.29). The severity of AD was significantly correlated with the risk of ischemic stroke. Conclusions: These results suggest that AD is independently associated with ischemic stroke but not with hemorrhagic stroke. The risk of ischemic stroke is correlated significantly with the severity of AD. Further research is necessary to explore the underlying mechanism.

Septicemia is associated with increased risk for dementia: a population-based longitudinal study

Background Systemic infection has been linked to cognitive impairment. We hypothesized that patients with septicemia are predisposed to increased risks for developing dementia in a long-term setting. Methods This observational, retrospective, longitudinal, nation-wide population-based study was conducted using the data deduced from Longitudinal Health Insurance Database (LHID) in Taiwan. All patients with septicemia hospitalized for the first time from 2001 to 2011 without prior dementia were included. The development of Alzheimers disease (AD) or non-Alzheimer dementias (NAD) in relation to the development of septicemia for each patient was recorded. An age- and sex-matched cohort without septicemia and without prior dementia served as the control. Septicemia, dementia, and other confounding factors were defined according to International Classification of Diseases Clinical Modification Codes. Cox proportional-hazards regressions were utilized to analyze adjusted hazard ratios. Results Patients with septicemia had a higher risk for developing dementia based on hazard ratios (HRs) (p<0.001). Patients with septicemia in the younger age groups had a greater dementia risk (p<0.01). Septicemia was associated with subsequent NAD (p<0.001), whereas the increased risk of AD was statistically insignificant (p>0.05). Furthermore, higher severity of septicemia was associated with increased risk of developing dementia. Conclusions Our findings suggest that septicemia is associated with an increased risk in developing NAD but not AD. A likely causal role of septicemia in increasing the risk of NAD is suggested, according to the findings that patients with higher severity of septicemia carried greater risk of sustaining dementia.

Global-cognitive health metrics: A novel approach for assessing cognition impairment in adult population

Dementia is the supreme worldwide burden for welfare and the health care system in the 21st century. The early identification and control of the modifiable risk factors of dementia are important. Global-cognitive health (GCH) metrics, encompassing controllable cardiovascular health (CVH) and non-CVH risk factors of dementia, is a newly developed approach to assess the risk of cognitive impairment. The components of ideal GCH metrics includes better education, non-obesity, normal blood pressure, no smoking, no depression, ideal physical activity, good social integration, normal glycated hemoglobin (HbA1c), and normal hearing. This study focuses on the association between ideal GCH metrics and the cognitive function in young adults by investigating the Third Health and Nutrition Examination Survey (NHANES III) database, which has not been reported previously. A total of 1243 participants aged 17 to 39 years were recruited in this study. Cognitive functioning was evaluated by the simple reaction time test (SRTT), symbol-digit substitution test (SDST), and serial digit learning test (SDLT). Participants with significantly higher scores of GCH metrics had better cognitive performance (p for trend <0.01 in three cognitive tests). Moreover, better education, ideal physical activity, good social integration and normal glycated hemoglobin were the optimistic components of ideal GCH metrics associated with better cognitive performance after adjusting for covariates (p < 0.05 in three cognitive tests). These findings emphasize the importance of a preventive strategy for modifiable dementia risk factors to enhance cognitive functioning during adulthood.

The association between vertebrobasilar insufficiency and the risk of dementia: a nationwide register-based retrospective cohort study in Taiwan

Objectives Neurodegenerative disorders are reportedly characterised by decreased regional cerebral blood flow. However, the association between vertebrobasilar insufficiency (VBI) and dementia remains unclear. In this nationwide, population-based, retrospective cohort study, we explored the potential association between VBI and dementia. Design Nationwide population-based cohort study. Setting Patients with VBI were newly diagnosed between 2000 and 2005 from the Taiwan National Health Insurance Research Database. Participants We included 3642 subjects as the VBI group. The control cohort included 14 568 randomly selected age-matched and sex-matched VBI-free individuals. Outcome measures All subjects were followed until the diagnosis of dementia, death or the end of 2010. Patients with VBI, dementia (viz, vascular and non-vascular, including Alzheimer’s) subtypes and other confounding factors were identified according to the International Classification of Diseases Clinical Modification Codes. Cox proportional hazards regression analysis was employed to examine adjusted HRs after adjusting for confounding factors. Results Patients with VBI had a 1.807-fold (95% CI 1.643 to 1.988, p<0.001) higher risk to develop all-cause dementia than individuals without VBI. The risk was significantly higher in the VBI group than in the non-VBI group regardless of age (<65 years: HR: 2.997, 95% CI 1.451 to 6.454, p<0.001; ≥65 years: HR: 1.752, 95% CI 1.584 to 1.937, p<0.001). The VBI group had a higher risk of all-cause dementia than the non-VBI group regardless of sex and follow-up time intervals (<1 year, 1–2 years and≥2 years). Conclusion Patients with VBI appear to have an increased risk of developing dementia. Further research is needed to investigate the underlying pathophysiology.

Cell division cycle-associated 7-like gene: A novel biomarker for adverse survival in human high-grade gliomas

Background: High-grade primary gliomas are aggressively growing and have an unfavorable prognosis. The utility of prognostic biomarkers of outcome in glioma patients is important for medical practice. Cell division cycle-associated 7-like (CDCA7L) protein modifies cancer progression and metastasis. Nevertheless, its character in defining the clinical prognosis of human gliomas has not been illuminated. Subjects and Methods: The hypothesis of this study was that CDCA7L is upregulated in human gliomas. We studied two de-linked data from Gene Expression Omnibus (GEO) profile. The first dataset (GDS1816/225081_s_at/CDCA7L) in primary high-grade glioma included age, gender, and survival time. Another dataset (GDS1962/225081_s_at/CDCA7L) was also encompassed to estimate CDCA7L gene expression in each pathological grading. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) was used to survey the protein-protein interaction (PPI) network of CDCA7L-regulated oncogenesis. Results: Statistical analysis of the GEO profile revealed that the World Health Organization (WHO) Grade IV (n = 81) gliomas had higher CDCA7L mRNA expression level than in Grade II (n = 7, P = 2.15 × 10 −14) gliomas and nontumor controls (n = 23, P = 2.87 × 10 − 18). Kaplan-Meier analysis reported that patients with high CDCA7L mRNA levels (n = 49) had adverse survival than those with low CDCA7L expression (n = 28). The PPI analysis of CDCA7L-regulated oncogenesis showed CDCA7L as a potential hub protein. Conclusions: The expression of CDCA7L has a positive correlation with the WHO pathological grading and shorter survival. This finding suggests that CDCA7L may be a potential biomarker of prognosis in human gliomas.