Comparative analysis of machine learning algorithms for Alzheimer's disease classification using EEG signals and genetic information.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairments, and behavioral changes. The presence of abnormal beta-amyloid plaques and tau protein tangles in the brain is known to be associated with AD. However, current limitations of imaging technology hinder the direct detection of these substances. Consequently, researchers are exploring alternative approaches, such as indirect assessments involving monitoring brain signals, cognitive decline levels, and blood biomarkers. Recent studies have highlighted the potential of integrating genetic information into these approaches to enhance early detection and diagnosis, offering a more comprehensive understanding of AD pathology beyond the constraints of existing imaging methods. Our study utilized electroencephalography (EEG) signals, genotypes, and polygenic risk scores (PRSs) as features for machine learning models. We compared the performance of gradient boosting (XGB), random forest (RF), and support vector machine (SVM) to determine the optimal model. Statistical analysis revealed significant correlations between EEG signals and clinical manifestations, demonstrating the ability to distinguish the complexity of AD from other diseases by using genetic information. By integrating EEG with genetic data in an SVM model, we achieved exceptional classification performance, with an accuracy of 0.920 and an area under the curve of 0.916. This study presents a novel approach of utilizing real-time EEG data and genetic background information for multimodal machine learning. The experimental results validate the effectiveness of this concept, providing deeper insights into the actual condition of patients with AD and overcoming the limitations associated with single-oriented data.

Emergency department visits and associated factors among people with dementia residing in nursing homes in Taiwan: a one-year cohort study.

BACKGROUND: Residing in a nursing home (NH) may increase emergency department (ED) utilization in patients with dementia; however, evidence regarding the status of and predictors for ED utilization of NH residents with dementia remains unclear, especially in Asia. This study aimed to assess the incidence density of ED visits and associated factors for the risk of ED utilization among NH residents with dementia. METHODS: This one-year cohort study followed 6595 NH residents with dementia aged ≧ 40 years from Taiwan's National Health Insurance Research Database between 2012 and 2014. The Andersen-Gill extension of Cox regression analysis with death as a competing risk was applied to investigate the association of the risk of all causes and the most common causes of ED utilization with the predisposing, enabling, and need factors as defined by the Andersen model. RESULTS: All participants encountered 9254 emergency visits in the 5371.49 person-years observed, representing incidence densities of ED visits of 1722.80 per 1000 person-years. Among them, respiratory disease was the most common cause of ED visits. The significant predictors for the risk of all-cause and respiratory-cause ED visits included: (1) predisposing factors (i.e., age and gender); (2) enabling factors (i.e., regional variables); and (3) need factors (i.e., prolonged ventilator dependence and comorbidity status). CONCLUSIONS: Predisposing, enabling, and need factors could influence ED visits among studies patients. NH providers should consider these factors to develop strategies for reducing ED utilization.

The Rehabilitative Effect of Archery Exercise Intervention in Patients with Parkinson's Disease.

Background: Archery exercise exerts a rehabilitative effect on patients with paraplegia and might potentially serve as complementary physiotherapy for patients with Parkinson's disease. Objective: This study aimed to examine the rehabilitative effects of an archery intervention. Methods: A randomized controlled trial of a 12-week intervention was performed in patients with idiopathic Parkinson's disease. Thirty-one of the 39 eligible patients recruited from a medical center in Taiwan participated in the trial, of whom 16 were in the experimental group practicing archery exercises and 15 were in the control group at the beginning; twenty-nine completed the whole process. The Purdue pegboard test (PPT), the Unified Parkinson's Disease Rating Scale I to III (UPDRS I to III), physical fitness test, and timed up and go test (TUG) were used to assess the intervention effects of archery exercise. Results: Compared to the control group, the outcome differences between the posthoc and baseline tests in PPT, UPDRS I to III, lower extremity muscular strength, and TUG in the experimental group (between-group difference in difference's mean: 2.07, 1.59, 1.36, -2.25, -3.81, -9.10, 3.57, and -1.51, respectively) did show positive changes and their effect sizes examined from Mann-Whitney U tests (η: 0.631, 0.544, 0.555, 0.372, 0.411, 0.470, 0.601, and 0.381, respectively; Ps < 0.05) were medium to large, indicating that the archery intervention exerted promising effects on improving hand flexibility and finger dexterity, activity functions in motor movement, lower extremity muscular strength, and gait and balance ability. Conclusions: Traditional archery exercise was suggested to have a rehabilitative effect for mild to moderate Parkinson's disease and could be a form of physiotherapy. Nevertheless, studies with larger sample sizes and extended intervention periods are needed to ascertain the long-term effects of archery exercise.

APOE-ε4 Alleles Modify the Decline of MMSE Scores Associated With Time-Dependent PM2.5 Exposure: Findings From a Community-Based Longitudinal Cohort Study.

OBJECTIVE: Limited research has explored the long-term effect of reduced PM2.5 exposure on cognitive function. This study aimed to investigate the effects of time-dependent PM2.5 exposure and the interactions of PM2.5 and aging on declines in Mini-Mental State Examination (MMSE) scores, in carriers and non-carriers of the APOE-ε4 allele. METHODS: Participants aged over 60 were recruited for this cohort study, undergoing MMSE tests twice from the Taiwan Biobank Program from 2008 to 2020. Participants with dementia or baseline MMSE scores <24 were excluded. Annual PM2.5 levels were estimated using a hybrid kriging/land use regression model with extreme gradient boosting, treated as a time-dependent variable. Generalized estimating equations were used to assess the impacts of repeated PM2.5 on MMSE decline, further stratified by the presence of APOE-ε4 alleles. RESULTS: After follow-up, 290 participants out of the overall 7,000 community residents in the Biobank dataset demonstrated incidences of MMSE declines (<24), with an average MMSE score decline of 1.11 per year. Participants with ε4/ε4 alleles in the APOE gene had significantly 3.68-fold risks of MMSE decline. High levels of PM2.5 across all visits were significantly associated with worsening of scores on the overall MMSE. As annual levels of PM2.5 decreased over time, the impact of PM2.5 on MMSE decline also slowly diminished. CONCLUSION: Long-term PM2.5 exposure may be associated with increased risk of MMSE decline, despite improvements in ambient PM2.5 levels over time. Validation of these results necessitates a large-scale prospective cohort study with more concise cognitive screening tools.

Sum of boxes of the clinical dementia rating scale highly predicts conversion or reversion in predementia stages.

Background: The clinical dementia rating (CDR) scale is commonly used to diagnose dementia due to Alzheimer's disease (AD). The sum of boxes of the CDR (CDR-SB) has recently been emphasized and applied to interventional trials for tracing the progression of cognitive impairment (CI) in the early stages of AD. We aimed to study the influence of baseline CDR-SB on disease progression to dementia or reversion to normal cognition (NC). Materials and methods: The baseline CDR < 1 cohort registered from September 2015 to August 2020 with longitudinal follow-up in the History-based Artificial Intelligence Clinical Dementia Diagnostic System (HAICDDS) database was retrospectively analyzed for the rates of conversion to CDR ≥ 1. A Cox regression model was applied to study the influence of CDR-SB levels on progression, adjusting for age, education, sex, neuropsychological tests, neuropsychiatric symptoms, parkinsonism, and multiple vascular risk factors. Results: A total of 1,827 participants were analyzed, including 1,258 (68.9%) non-converters, and 569 (31.1%) converters with mean follow-up of 2.1 (range 0.4-5.5) and 1.8 (range 0.3-5.0) years, respectively. Conversion rates increased with increasing CDR-SB scores. Compared to a CDR-SB score of 0, the hazard ratios (HR) for conversion to dementia were 1.51, 1.91, 2.58, 2.13, 3.46, 3.85, 3.19, 5.12, and 5.22 for CDR-SB scores of 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, and ≥4.5, respectively (all p < 0.05 except for CDR-SB score = 0.5). In addition, older age, lower education, lower cognitive performance, and a history of diabetes also increased conversion rates. Furthermore, reversions to NC were 12.5, 5.6, 0.9, and 0% for CDR-SB scores of 0.5, 1.0-2.0, 2.5-3.5 and ≥4.0, respectively (p < 0.001). Conclusion: CDR-SB in predementia or very mild dementia (VMD) stages highly predicts progression to dementia or reversion to NC. Therefore, CDR-SB could be a good candidate for tracing the effectiveness of pharmacological and non-pharmacological interventions in populations without dementia.

Operational Determination of Subjective Cognitive Decline, Mild Cognitive Impairment, and Dementia Using Sum of Boxes of the Clinical Dementia Rating Scale.

Objectives: The Clinical Dementia Rating (CDR) Scale is the gold standard for the staging of dementia due to Alzheimer's disease (AD). However, the application of CDR for the staging of subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in AD remains controversial. This study aimed to use the sum of boxes of the CDR (CDR-SB) plus an SCD single questionnaire to operationally determine the different stages of cognitive impairment (CI) due to AD and non-AD. Methods: This was a two-phase study, and we retrospectively analyzed the Show Chwan Dementia registry database using the data selected from 2015 to 2020. Individuals with normal cognition (NC), SCD, MCI, and mild dementia (MD) due to AD or non-AD with a CDR < 2 were included in the analysis. Results: A total of 6,946 individuals were studied, including 875, 1,009, 1,585, and 3,447 with NC, SCD, MCI, and MD, respectively. The cutoff scores of CDR-SB for NC/SCD, SCD/MCI, and MCI/dementia were 0/0.5, 0.5/1.0, and 2.5/3.0, respectively. The receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) values of the test groups were 0.85, 0.90, and 0.92 for discriminating NC from SCD, SCD from MCI, and MCI from dementia, respectively. Compared with the Cognitive Abilities Screening Instrument or the Montreal Cognitive Assessment, the use of CDR-SB is less influenced by age and education. Conclusion: Our study showed that the operational determination of SCD, MCI, and dementia using the CDR-SB is practical and can be applied in clinical settings and research on CI or dementia.

Effectiveness of the 10 cm2 Rivastigmine Patch in Taiwanese Patients with Mild-to-Moderate Alzheimer's Dementia: A 48-Week Real-World Observational Study.

INTRODUCTION: The current study aimed to provide data on the effectiveness of the 10 cm2 rivastigmine patch in patients with Alzheimer's disease (AD) in a real-world setting in Taiwan. METHODS: This was a 48-week, single-arm, open-label, observational, and post-marketing study conducted across seven centers in Taiwan between May 5, 2016 and July 10, 2017. Eligible patients (aged 55-95 years) treated with the 10 cm2rivastigmine patch were enrolled based on physicians' judgment and according to the Taiwan reimbursement criteria of the drug. Data were prospectively collected at Week 0 (baseline), Week 24, and Week 48. The primary endpoint was the change in the cognitive assessment screening instrument (CASI) scores at Week 48 versus baseline. The changes from baseline in clinical dementia rating (CDR), mini-mental state examination (MMSE), and neuropsychiatric inventory (NPI) scores were evaluated, as were treatment persistence and the safety profile. RESULTS: Of the 285 eligible patients [full analysis set (FAS)], 216 (75.8%) completed the study protocol while 180 (63.2%) persisted on the 10 cm2 rivastigmine patch for the full 48 weeks. At baseline, 89.8% of patients had a CDR score of 0.5 or 1, while the change in CDR score at Week 48 was not significant. In the FAS, both the CASI and MMSE scores had numerical improvement at Week 24 but declined by 2.1 and 0.4 points, respectively, at Week 48 (p = 0.005 and p = 0.022). The increment in NPI scores was not significant. The most common drug-related adverse events (AEs) were pruritus (11.2%), nausea (3.5%), rash (3.2%), and vomiting (2.8%). CONCLUSIONS: The use of the 10 cm2 rivastigmine patch in the mild stage of AD maintained cognitive function at Week 24 and neuropsychiatric function at Week 48. The treatment persistency and safety profile support the clinical tolerability of the rivastigmine patch in the management of mild-to-moderate AD in Taiwan.

Transient receptor potential V1 modulates neuroinflammation in Parkinson's disease dementia: Molecular implications for electroacupuncture and rivastigmine.

OBJECTIVES: Parkinson's disease (PD) is a common progressive neurodegeneration disease. Its incidence increases with age and affects about 1% of people over 60. Incidentally, transient receptor potential V1 (TRPV1) and its relation with neuroinflammation in mouse brain has been widely reported. MATERIALS AND METHODS: We used 6-hydroxydopamine (6-OHDA) to induce PDD in mice. We then used the Morris water maze and Bio-Plex to test learning and inflammatory mediators in mouse plasma. Western blotting and immunostaining were used to examine TRPV1 pathway in the hippocampus and medial prefrontal cortex (mPFC). RESULTS: On acquisition days 3 (Control = 4.40 ± 0.8 sec, PDD = 9.82 ± 1.52 sec, EA = 5.04 ± 0.58 sec, Riva = 4.75 ± 0.87 sec; P=0.001) and 4, reversal learning days 1, 2, 3 (Control = 2.86 ± 0.46 sec, PDD = 9.80 ± 1.83 sec, EA = 4.6 ± 0.82 sec, Riva = 4.6 ± 1.03 sec; P=0.001) and 4, PDD mice showed significantly longer escape latency than the other three groups. Results showed that several cytokines were up-regulated in PDD mice and reversed by EA and rivastigmine. TRPV1 and downstream molecules were up-regulated in PDD mice and further reversed by EA and rivastigmine. Interestingly, α7 nicotinic receptors and parvalbumin levels in both the hippocampus and prefrontal cortex increased in EA-treated mice, but not in rivastigmine-treated mice. CONCLUSION: Our results showed that TRPV1 played a role in the modulation of neuroinflammation of PDD, and could potentially be a new target for treatment.

Risk of Alzheimer's disease with metal concentrations in whole blood and urine: A case-control study using propensity score matching.

Environmental exposure to heavy metals is suspected to result in neuropathology damage and cognitive impairment. We aimed to explore the association of Alzheimer's disease (AD) risk with the internal dose of heavy metals by constructing a hospital-based case-control study and using propensity-score-matching methods. We investigated 170 patients with AD and 264 controls from the Department of Neurology and Family Medicine, China Medical University Hospital in Taiwan. All patients with AD received clinical neuropsychological examination and cognitive-function assessments, including the mini-mental status examination and clinical dementia rating scale. We also constructed a propensity-score-matched population of 82 patients with AD and 82 controls by matching age, gender, education, and AD-related comorbidity. Blood levels with cadmium, lead, mercury, selenium, and urinary arsenic profile were measured. Logistic regression models and 95% confidence intervals (CIs) were applied to estimate AD risk. After stratification by respective quartile cutoffs of heavy metals, the AD risk of study participants with high urinary inorganic arsenic (InAs%) or low dimethylarsinic acid (DMA%) significantly increased (p < 0.05), as similarly found in the propensity-score-matched population. In addition, people with a low median level of selenium and high median level of InAs%, or/and a low median level of DMA% had approximately two- to threefold significant AD risk. Urinary arsenic profiles may be associated with increased AD risk. Repeat measurements of heavy metals with large sample size and the surveying of potential exposure sources are recommended in future studies.

Association between different anticholinergic drugs and subsequent dementia risk in patients with diabetes mellitus.

BACKGROUND: The effects of oxybutynin, solifenacin and tolterodine on dementia risk in patients with diabetes mellitus (DM) remain unknown. We investigated the effects of oxybutynin, solifenacin and tolterodine on dementia risk in patients with DM. METHODS: We conducted a cohort study by using the diabetes dataset of the Taiwan National Health Insurance Research Database from 1 January, 2002 to 31 December, 2013. We included 10,938 patients received one type of oxybutynin, solifenacin, or tolterodine, while 564,733 had not. We included a comparable number of patients not receiving oxybutynin, solifenacin, or tolterodine as controls through systematic random sampling matching by age, gender, and the year of the index date with 1 to 1 ratio. The dementia risk was estimated through multivariate Cox proportional hazard regression after adjustment for several confounding factors. RESULTS: The dementia event rates were 3.9% in the oxybutynin group, 4.3% in the solifenacin group, 2.2% in the tolterodine group and 1.2% in the control group (P<0.001). The adjusted HRs compared to nonusers of anticholinergic drugs were 2.35 (95% CI, 1.96 to 2.81), 2.16 (95% CI, 1.81 to 2.58), and 2.24 (95% CI, 1.85 to 2.73), respectively, for patients receiving oxybutynin, solifenacin, or tolterodine. CONCLUSION: Our study indicates an association between taking oxybutynin, solifenacin and tolterodine and the subsequent diagnosis of dementia in DM patients. Moreover, the patients using oxybutynin had highest risk. The impact of these three drugs on risk of dementia in non-diabetic populations is warrant.

Increased risk of Parkinson disease with diabetes mellitus in a population-based study.

This nationwide population-based study investigated the risk of Parkinson disease (PD) in relation to diabetes mellitus (DM) through the National Health Insurance Research Database in Taiwan.A retrospective study was conducted, consisting of 36,294 patients who were newly diagnosed with DM between January 1, 2000 and December 31, 2006 and 108,882 individuals without DM as healthy controls from insurance claims data from Taiwan's National Health Research Institutes Dataset. The subjects were followed up until December 31, 2011 or until the first manifestation of PD. The hazard ratio (HR) of DM for PD incidence was estimated by Cox proportional hazard regression model.Compared with the non-DM cohort, the incidence density rate of PD was 1.36-fold higher in the DM cohort (1.53 vs 2.08 per 1000 person-years) with an adjusted HR of 1.19 (95% confidence interval = 1.08-1.32) after adjusting for age, sex, comorbidities, and medication use. The adjusted HR of PD for DM with a larger magnitude was observed in females (1.29, 1.12-1.49); individuals age 65 years and older (1.20, 1.06-1.35); those without schizophrenia (1.20, 1.08-1.33), bipolar disorder (1.20, 1.08-1.33), hypertension (1.18, 1.06-1.32), hyperlipidemia (1.21, 1.09-1.34), chronic obstructive pulmonary disease (1.19, 1.06-1.32), coronary artery disease (1.22, 1.09-1.36), stroke (1.23, 1.10-1.37), asthma (1.20, 1.08-1.34), flunarizine use (1.21, 1.08-1.35), zolpidem use (1.16, 1.04-1.30), Charlson comorbidity index score of 0 (1.23, 1.08-1.40), and those using metoclopramide (1.35, 1.14-1.60) and zolpidem (1.46, 1.12-1.90).DM increased the risk of PD during a mean follow-up of 7.3 years. Further mechanistic research on the effect of DM on PD is needed.

Effects of the traditional Chinese herb Astragalus membranaceus in patients with poststroke fatigue: A double-blind, randomized, controlled preliminary study.

BACKGROUND AND PURPOSE: Astragalus membranaceus (AM) is the first-choice herb for fatigue treatment in traditional Chinese medicine and the main herb used for stroke treatment in China and Taiwan. The purpose of this study was to evaluate the effect of AM on poststroke fatigue (PSF). MATERIALS AND METHODS: This study was designed as a double-blind, randomized, controlled preliminary study. Sixty-four patients with PSF were assigned to treatment group (TG; 31 patients), which received oral administration of AM (2.8g three times per day) for 28 days, and a control group (CG; 33 patients), which received a placebo. The primary outcome measures were the changes in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Brief Fatigue Index (BFI) scores RESULTS: A total of 61 patients (29 patients in the TG and 32 patients in the CG) completed the trial. The difference in BFI scores between Visit 2 and Visit 1 was -17.83±17.70 in the TG, which was greater than that in the CG (-8.03±9.95; p=0.01); additionally, the difference in BFI scores between Visit 3 and Visit 1 was -16.48±16.41 in the TG, which was also greater than that in the CG (-9.47±13.39; p=0.05). In the EORTC QLQ-C30, the difference in cognitive functioning scores between Visit 2 and Visit 1 was 14.37±13.89 in the TG, which was greater than that in the CG (3.65±19.74; p=0.02); additionally, the difference in these scores between Visit 3 and Visit 1 was 14.37±16.50 in the TG, which again was greater than that in the CG (6.25±19.74; p=0.04). The difference in social functioning scores between Visit 3 and Visit 1 was 9.77±15.12 in the TG, which was greater than that in the CG (-1.56±20.46; p=0.01). The difference in global quality of life (QOL) scores between Visit 2 and Visit 1 was 14.08±18.78 in the TG, which was also greater than that in the CG (1.56±18.14; p=0.003); moreover, the difference in these scores between Visit 3 and Visit 1 was 10.92±17.55 in the TG, and this was greater than that in the CG (1.82±15.8; p=0.05). CONCLUSION: AM can improve BFI scores; cognitive functioning, social functioning, and global QOL scores in the EORTC QLQ-C30. Our results suggest that physicians should pay close attention to the unmet medical needs of patients with PSF. AM is helpful for treating patients with PSF; however, additional studies with a larger sample and a longer period of investigation are required.

Real-world evaluation of compliance and preference in Alzheimer's disease treatment: an observational study in Taiwan.

PURPOSE: Among the medications approved for Alzheimer's disease (AD), rivastigmine is the only one available as transdermal patch. The aim of this study was to evaluate compliance and caregivers' preference with oral and transdermal (rivastigmine) monotherapy in patients with mild-to-moderate AD from Taiwan. METHODS: Real-world Evaluation of Compliance And Preference in Alzheimer's disease treatment (RECAP) in Taiwan was a prospective, noninterventional, observational study with a 24-week (±8 weeks) observational period for each participant. Eligible patients were grouped into one of the two treatment cohorts based on the baseline AD therapy: oral (donepezil, galantamine, rivastigmine, or memantine) or transdermal (rivastigmine patch). The primary end points were caregiver preference and caregiver assessment of patients' compliance to the current medication (oral or transdermal medication) at Week 24 (end of the study). Safety was assessed by recording any adverse events. RESULTS: A total of 301 patients (age: 77.6±7.19 years) were enrolled from nine centers in Taiwan, of whom 138 (45.8%) patients were in the transdermal monotherapy cohort. Caregivers of patients who were exposed to both forms of therapies demonstrated a higher preference for transdermal rivastigmine monotherapy than the oral monotherapy (82.4% [n=61] versus 17.6% [n=13], P<0.0001); for patients treated with only one therapy, the caregivers' preference was significantly in favor of the treatment to which the patient was exposed (both P<0.0001). In both cohorts, patients showed good compliance, with an overall score of 8.65±1.38 on an 11-point scale. Of 301 enrolled patients, 102 (33.9%) reported at least one adverse event during the study (51 patients each in the two cohorts). CONCLUSION: With the higher caregiver preference and a good patient compliance, the trans-dermal rivastigmine patch is a suitable treatment choice for patients with mild-to-moderate AD, especially for patients intolerant to oral therapies.

5-alpha-reductase inhibitors and the risk of diabetes mellitus: A nationwide population-based study.

BACKGROUND: This nationwide population-based study investigated the risk of type 2 diabetes mellitus (DM) after 5-alpha-reductase inhibitor (5ARI) therapy for benign prostate hyperplasia (BPH) using the National Health Insurance Research Database (NHIRD) in Taiwan. METHODS: In total, 1,298 adult patients newly diagnosed with BPH and who used more than 28 cumulative defined daily doses (cDDD) of 5ARI were recruited as the therapy group cohort, along with 1,2887 subjects who did not use more than 28 cDDD of 5ARI as a control group from 2002 to 2009. Each patient was monitored for 5 years (from 2003 to 2008) to identify those who subsequently developed type 2 DM. A Cox proportional hazards model was used to compare the risk of type 2 DM between the study and comparison cohorts after adjusting for possible confounding risk factors. RESULTS: Patients who received 5ARI therapy had a lower cumulative rate of type 2 DM than those who did not receive 5ARI during the five-year follow-up period (3.5% vs. 5.3%, P = 0.003). In sub-group analysis, among the BPH patients aged <65 years, the five-year type 2 DM events hazard ratio (HR) of 5ARI users was lower than that of nonusers (HR: 0.47, 95% confidence interval (CI): 0.24-0.91; P = 0.026). CONCLUSIONS: Therapy with 5ARI may decrease the five-year risk of type 2 DM in the BPH patients younger than 65 years. Further mechanistic research is warranted to validate the results.

CHADS2 scores as a predictor of ischemic stroke after radical prostatectomy.

Patients with prostate cancer have an increased risk of stroke, but their absolute rate of stroke depends on age and comorbid conditions. The Charlson Comorbidity Index Score (CCIS) is a widely accepted measure for risk adjustment in administrative claims data sets. This study assesses the predictive value of CHADS2 scores and CCIS for stroke among patients with prostate cancer. The study was conducted based on data taken from Taiwan's National Health Insurance Research Database (NHIRD). We identified a total of 5414 participants with nonatrial fibrillation (AF) prostate cancer diagnoses who underwent radical prostatectomy between 1997 and 2011. CHADS2 scores and CCIS were used to stratify the 5-year ischemic stroke risk. All participants were followed from the date of enrollment until ischemic stroke, death, or the end of the 5-year follow-up period. The 5-year risk of ischemic stroke in the present study was 1.7%. Ischemic stroke has a better correlation with CHADS2 (CHADS2 score = 0 to 1: 0.02%, CHADS2 score = 2 to 3: 13.9%, CHADS2 score ≥ 4: 44.4%; AUC = 0.978) than CCIS (CCIS = 0 to 1: 1.6%, CCIS = 2 to 3: 1.7%, CCIS ≥ 4: 3.8%; AUC = 0.520). Our results show that patients with prostate cancer who underwent radical prostatectomy show significantly higher risk of ischemic stroke in high CHADS2 score patients, and the CHADS2 score could be applied for ischemic stroke prediction. Cardiovascular risks evaluation and management are suggested for prostate cancer patients with higher CHADS2 score.

CHADS2 Scores as a Predictor of Ischemic Stroke in Patients With Peripheral Artery Disease.

OBJECTIVE: To assess the predictive value of CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke) scores for stroke risk in patients with peripheral artery disease (PAD). PATIENTS AND METHODS: From Taiwan's National Health Insurance Research Database, we identified a total of 479 participants with non-atrial fibrillation PAD diagnoses recorded from January 1, 2002, through December 31, 2009. The CHADS2 score was used to stratify 5-year ischemic stroke risk. All participants were followed up from the date of enrollment until ischemic stroke event, death, or the end of 2009. RESULTS: The 5-year risk of ischemic stroke in the present study was 9.4%. A strong correlation was found between the PAD and CHADS2 score (CHADS2 score of 0-1, 0.4%; CHADS2 score of 2-3, 12.3%; CHADS2 score ≥4, 84.0%; area under the curve = 0.920). After adjustment, CHADS2 score was found to be positively correlated with increased risk of ischemic stroke. CONCLUSIONS: Our results indicate that patients with PAD have a significantly higher risk of ischemic stroke and that the CHADS2 score can be used as an indicator of risk for ischemic stroke. Cardiovascular risk evaluation and management are suggested for patients with PAD and higher CHADS2 scores.

Maslinic Acid Protected PC12 Cells Differentiated by Nerve Growth Factor against ß-Amyloid-Induced Apoptosis.

ß-Amyloid peptide (Abeta) was used to induce apoptosis in PC12 cells differentiated by nerve growth factor, and the protective activities of maslinic acid (MA) at 2-16 µM were examined. Abeta treatment lowered Bcl-2 expression, raised Bax expression, and decreased cell viability. MA pretreatments decreased Bax expression, raised the Bcl-2/Bax ratio, and increased cell viability. MA pretreatments retained glutathione content and decreased subsequent Abeta-induced release of reactive oxygen species, tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6. Abeta treatment up-regulated protein expression of p47(phox), gp91(phox), mitogen-activated protein kinase, advanced glycation end product receptor (RAGE), and nuclear factor-κ B (NF-κB). MA pretreatments at 2-16 µM suppressed the expression of proteins including gp91(phox), p47(phox), p-p38, and NF-κB p65, at 4-16 µM down-regulated RAGE and NF-κB p50 expression, and at 8 and 16 µM reduced p-ERK1/2 expression. These novel findings suggest that maslinic acid is a potent compound against Abeta-induced cytotoxicity.

Use of 5-alpha-reductase inhibitors did not increase the risk of cardiovascular diseases in patients with benign prostate hyperplasia: a five-year follow-up study.

BACKGROUND: This nationwide population-based study investigated the risk of cardiovascular diseases after 5-alpha-reductase inhibitor therapy for benign prostate hyperplasia (BPH) using the National Health Insurance Research Database (NHIRD) in Taiwan. METHODS: In total, 1,486 adult patients newly diagnosed with BPH and who used 5-alpha-reductase inhibitors were recruited as the study cohort, along with 9,995 subjects who did not use 5-alpha-reductase inhibitors as a comparison cohort from 2003 to 2008. Each patient was monitored for 5 years, and those who subsequently had cardiovascular diseases were identified. A Cox proportional hazards model was used to compare the risk of cardiovascular diseases between the study and comparison cohorts after adjusting for possible confounding risk factors. RESULTS: The patients who received 5-alpha-reductase inhibitor therapy had a lower cumulative rate of cardiovascular diseases than those who did not receive 5-alpha-reductase inhibitor therapy during the 5-year follow-up period (8.4% vs. 11.2%, P=0.003). In subgroup analysis, the 5-year cardiovascular event hazard ratio (HR) was lower among the patients older than 65 years with 91 to 365 cumulative defined daily dose (cDDD) 5-alpha-reductase inhibitor use (HR=0.63, 95% confidence interval (CI) 0.42 to 0.92; P=0.018), however there was no difference among the patients with 28 to 90 and more than 365 cDDD 5-alpha-reductase inhibitor use (HR=1.14, 95% CI 0.77 to 1.68; P=0.518 and HR=0.83, 95% CI 0.57 to 1.20; P=0.310, respectively). CONCLUSIONS: 5-alpha-reductase inhibitor therapy did not increase the risk of cardiovascular events in the BPH patients in 5 years of follow-up. Further mechanistic research is needed.

Resetting tremor by single and paired transcranial magnetic stimulation in Parkinson's disease and essential tremor.

OBJECTIVE: The pathogenesis of tremor in Parkinson's disease (PD) and essential tremor (ET) is not fully understood. This study tested the role of primary motor cortex (M1), supplementary motor area (SMA) and cerebellar cortex on PD and ET tremor by single- and paired-pulse transcranial magnetic stimulation (TMS). METHODS: Ten PD patients with resting tremor, six of them also with postural tremor, and ten ET patients with postural tremor were studied. Randomized single- and paired-pulse TMS with an interstimulus interval of 100 ms were delivered over M1, SMA and cerebellum. TMS effects were evaluated by calculating a tremor-resetting index (RI). RESULTS: Single- vs. paired-pulse TMS showed no difference. M1-TMS and SMA-TMS but not by cerebellar TMS induced a significant RI in PD and ET. M1-TMS resulted in a significantly higher RI in PD than ET. Furthermore, M1-TMS in PD but not in ET resulted in a significantly higher RI than SMA-TMS. CONCLUSIONS: Findings suggest a stronger involvement of M1 in resting and postural tremor in PD than postural tremor in ET. SIGNIFICANCE: RI provides a useful marker to explore the differential functional role of M1, SMA and cerebellum in PD vs. ET tremor.