Role of vitamin B12 and folic acid in treatment of Alzheimer's disease: a meta-analysis of randomized control trials.

Vitamin B12 and folic acid could reduce blood homocysteine levels, which was thought to slow down the progression of Alzheimer's disease (AD), but previous studies regarding the effect of vitamin B12 and folic acid in treatment of AD have not reached conclusive results. We searched PubMed and Embase until January 12, 2023. Only randomized control trials involving participants clearly diagnosed with AD and who received vitamin B12 and folic acid were enrolled. Five studies that met the criteria were selected for inclusion in the meta-analysis. Changes in cognitive function were measured based on either the Mini-Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Changes in daily life function and the level of blood homocysteine were also investigated. After a 6-month treatment, administration of vitamin B12 and folic acid improved the MMSE scores more than placebo did (SMD = 0.21, 95% CI = 0.01 to 0.32, p = 0.04) but did not significantly affect ADAS-Cog scores (SMD = 0.06, 95% CI = -0.22 to 0.33, p = 0.68) or measures of daily life function. Blood homocysteine levels were significantly decreased after vitamin B12 and folic acid treatment. Participants with AD who received 6 months of vitamin B12 and folic acid supplementation had better MMSE scores but had no difference in ADAS-Cog scores. Daily life function did not improve after treatment.

Brain Age Is Associated with Cognitive Outcomes of Cholinesterase Inhibitor Treatment in Patients with Mild Cognitive Impairment.

Background: The effect of cholinesterase inhibitor (ChEI) on mild cognitive impairment (MCI) is controversial. Brain age has been shown to predict Alzheimer's disease conversion from MCI. Objective: The study aimed to show that brain age is related to cognitive outcomes of ChEI treatment in MCI. Methods: Brain MRI, the Clinical Dementia Rating (CDR) and Mini-Mental State Exam (MMSE) scores were retrospectively retrieved from a ChEI treatment database. Patients who presented baseline CDR of 0.5 and received ChEI treatment for at least 2 years were selected. Patients with stationary or improved cognition as verified by the CDR and MMSE were categorized to the ChEI-responsive group, and those with worsened cognition were assigned to the ChEI-unresponsive group. A gray matter brain age model was built with a machine learning algorithm by training T1-weighted MRI data of 362 healthy participants. The model was applied to each patient to compute predicted age difference (PAD), i.e. the difference between brain age and chronological age. The PADs were compared between the two groups. Results: 58 patients were found to fit the ChEI-responsive criteria in the patient data, and 58 matched patients that fit the ChEI-unresponsive criteria were compared. ChEI-unresponsive patients showed significantly larger PAD than ChEI-responsive patients (8.44±8.78 years versus 3.87±9.02 years, p = 0.0067). Conclusions: Gray matter brain age is associated with cognitive outcomes after 2 years of ChEI treatment in patients with the CDR of 0.5. It might facilitate the clinical trials of novel therapeutics for MCI.

Cilostazol plus Aspirin vs. Clopidogrel plus Aspirin in Acute Minor Stroke or Transient Ischemic Attack.

AIM: This study compared the effectiveness, safety, and mortality risks between cilostazol plus aspirin and clopidogrel plus aspirin treatment for patients with acute minor ischemic stroke or transient ischemic attack (TIA). METHODS: This retrospective cohort study employed a new-user design and utilized data from the nationwide Health and Welfare Database in Taiwan. Patients were included if they were discharged with newly initiated cilostazol plus aspirin or clopidogrel plus aspirin after primary acute minor ischemic stroke or TIA hospitalization between 2009 and 2018. Inverse probability of treatment weighting was applied to balance covariates between study groups. Effectiveness outcomes were the risks of acute ischemic stroke, acute myocardial infarction (AMI), TIA, and composite cardiovascular events; Safety outcomes were the risks of intracranial hemorrhage (ICH), gastrointestinal bleeding, and composite bleeding events; Mortality outcomes were the risks of fatal stroke, cardiovascular mortality, and all-cause mortality. RESULTS: A total of 3,403 patients were included, of which 578 were treated with cilostazol plus aspirin and 2,825 were treated with clopidogrel plus aspirin. Cilostazol plus aspirin was associated with a higher risk of ICH (HR: 1.82; 95% CI: 1.16-2.84) compared to clopidogrel plus aspirin. No significant differences in the risks of effectiveness or mortality outcomes between the two groups were found. CONCLUSIONS: The effectiveness and mortality of the two groups were similar for patients with acute minor ischemic stroke or TIA. However, cilostazol plus aspirin was associated with a higher risk of ICH compared to clopidogrel plus aspirin. Patients treated with cilostazol plus aspirin among this population should be monitored carefully to ensure their safety.

Outcomes of Endovascular Treatment versus Standard Medical Treatment for Acute Ischemic Stroke with Basilar Artery Occlusion: A Systematic Review and Meta-Analysis.

BACKGROUND: Although endovascular treatment (EVT) is beneficial for large vessel occlusion in anterior circulation stroke, whether these benefits exist for basilar artery occlusion (BAO) remains unclear. This systematic review and meta-analysis compared the outcomes of patients with BAO undergoing EVT and standard medical treatment (SMT). METHODS: The PubMed, Embase, and Cochrane Library databases were searched for eligible randomized control trials (RCTs) and non-RCTs involving patients with acute ischemic stroke and BAO undergoing EVT or SMT. The following outcomes were assessed: 90-day functional outcomes (favorable outcome and functional independence: modified Rankin scale [mRS] score of 0-3 or 0-2, respectively), mortality, and symptomatic intracranial hemorrhage (sICH) incidence. The summary effect sizes were determined as risk ratios (RRs) through the Mantel-Haenszel method with a random-effects model. RESULTS: Four RCTs and four non-RCTs were included. Compared with SMT, EVT resulted in a higher proportion of patients with 90-day mRS scores of 0-3 (RR: 1.54 [1.16-2.06] in RCTs and 1.88 [1.11-3.19] in non-RCTs), a higher proportion of patients achieving functional independence (90-day mRS score of 0-2; RR: 1.83 [1.07-3.12] and 1.84 [0.97-3.48], respectively), a lower risk of mortality (RR: 0.76 [0.65-0.89] and 0.72 [0.62-0.83], respectively), and a higher sICH risk (RR: 5.98 [2.11-16.97] and 4.95 [2.40-10.23], respectively). Severe neurological deficits, intravenous thrombolysis, and higher posterior circulation Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS) were associated with EVT benefits. CONCLUSION: In patients with BAO, EVT results in superior functional outcomes, lower mortality risk, and higher sICH risk than does SMT, independent of age and sex. Higher National Institutes of Health Stroke Scale scores, intravenous thrombolysis, and higher pc-ASPECTSs before treatment are associated with greater benefits from EVT.

XGBoost-Based Simple Three-Item Model Accurately Predicts Outcomes of Acute Ischemic Stroke.

An all-inclusive and accurate prediction of outcomes for patients with acute ischemic stroke (AIS) is crucial for clinical decision-making. This study developed extreme gradient boosting (XGBoost)-based models using three simple factors-age, fasting glucose, and National Institutes of Health Stroke Scale (NIHSS) scores-to predict the three-month functional outcomes after AIS. We retrieved the medical records of 1848 patients diagnosed with AIS and managed at a single medical center between 2016 and 2020. We developed and validated the predictions and ranked the importance of each variable. The XGBoost model achieved notable performance, with an area under the curve of 0.8595. As predicted by the model, the patients with initial NIHSS score > 5, aged over 64 years, and fasting blood glucose > 86 mg/dL were associated with unfavorable prognoses. For patients receiving endovascular therapy, fasting glucose was the most important predictor. The NIHSS score at admission was the most significant predictor for those who received other treatments. Our proposed XGBoost model showed a reliable predictive power of AIS outcomes using readily available and simple predictors and also demonstrated the validity of the model for application in patients receiving different AIS treatments, providing clinical evidence for future optimization of AIS treatment strategies.

Risk factor identification and prediction models for prolonged length of stay in hospital after acute ischemic stroke using artificial neural networks.

Background: Accurate estimation of prolonged length of hospital stay after acute ischemic stroke provides crucial information on medical expenditure and subsequent disposition. This study used artificial neural networks to identify risk factors and build prediction models for a prolonged length of stay based on parameters at the time of hospitalization. Methods: We retrieved the medical records of patients who received acute ischemic stroke diagnoses and were treated at a stroke center between January 2016 and June 2020, and a retrospective analysis of these data was performed. Prolonged length of stay was defined as a hospital stay longer than the median number of days. We applied artificial neural networks to derive prediction models using parameters associated with the length of stay that was collected at admission, and a sensitivity analysis was performed to assess the effect of each predictor. We applied 5-fold cross-validation and used the validation set to evaluate the classification performance of the artificial neural network models. Results: Overall, 2,240 patients were enrolled in this study. The median length of hospital stay was 9 days. A total of 1,101 patients (49.2%) had a prolonged hospital stay. A prolonged length of stay is associated with worse neurological outcomes at discharge. Univariate analysis identified 14 baseline parameters associated with prolonged length of stay, and with these parameters as input, the artificial neural network model achieved training and validation areas under the curve of 0.808 and 0.788, respectively. The mean accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of prediction models were 74.5, 74.9, 74.2, 75.2, and 73.9%, respectively. The key factors associated with prolonged length of stay were National Institutes of Health Stroke Scale scores at admission, atrial fibrillation, receiving thrombolytic therapy, history of hypertension, diabetes, and previous stroke. Conclusion: The artificial neural network model achieved adequate discriminative power for predicting prolonged length of stay after acute ischemic stroke and identified crucial factors associated with a prolonged hospital stay. The proposed model can assist in clinically assessing the risk of prolonged hospitalization, informing decision-making, and developing individualized medical care plans for patients with acute ischemic stroke.

Probiotics treatment for Parkinson disease: a systematic review and meta-analysis of clinical trials.

BACKGROUND AND AIMS: People with Parkinson disease (PwP) exhibit gut dysbiosis and considerable gastrointestinal (GI) symptoms. Probiotics, beneficial strains of microorganisms, supplement and optimize the intestinal environment and alleviate GI symptoms among elderly people. We conducted a systematic review and meta-analysis of clinical trials to investigate the effects of probiotics on PwP. METHODS: We searched the PubMed, Embase, and Cochrane Library databases. Major outcomes were the effects on GI symptoms, including bowel movement and stool characteristics. This study was registered with PROSPERO (CRD42021262036). RESULTS: Six randomized controlled trials (RCTs) and two open-label studies were included. Most of the probiotic regimens were based on Lactobacillus and Bifidobacterium. Six studies investigated the benefit of probiotics for GI symptoms, especially for PwP with functional constipation, and two RCTs assessed probiotics' effect on systematic metabolism and inflammation. In the meta-analysis, probiotic treatment significantly increased the frequency of bowel movements among PwP (mean difference [MD]: 1.06 /week, 95% confidence interval [CI]: 0.61 to 1.51, p < 0.001, I2 = 40%). Additionally, probiotic treatment significantly normalized stool consistency (standard MD: 0.61, 95% CI = 0.31 to 0.91, p < 0.001, I2 = 0%). CONCLUSIONS: Although the probiotic compositions varied, probiotic treatment significantly attenuated constipation for PwP and exhibited possible systematic effects on inflammation and metabolism. Given the tolerability of probiotics, the present meta-analysis may provide more consolidated evidence of the benefit of probiotics on constipation in PwP and a possible new therapeutic approach for disease modification.

Safety and efficacy of endovascular thrombectomy in acute ischemic stroke treated with anticoagulants: a systematic review and meta-analysis.

BACKGROUND: Endovascular thrombectomy (EVT) is an effective therapy in acute ischemic stroke (AIS) with large vessel occlusion, especially for those who are unsuitable for intravenous thrombolysis. However, the safety and efficacy of EVT in AIS patients who receiving oral anticoagulants (OACs) is unclear, especially for the risk of symptomatic intracranial hemorrhage (sICH).  METHODS: Database of PubMed, Embase, and Cochrane Library were searched from Jan 1, 2000, through the final search date of Jun 2, 2021. Eligible studies for enrollment required outcomes reported for events of sICH, mortality, functional status, and successful reperfusion. Meta-analysis was conducted to compare the outcomes difference after EVT between AIS patients with or without OACs use. The primary safety outcome was sICH after EVT, and the primary efficacy outcome was functional status at 3 months.  RESULTS: One thousand nine hundred forty studies were screened for eligibility and 15 of them were included in the meta-analysis. Compared the OACs group to control arm, vitamin K antagonists (VKAs) was associated with higher risk of sICH (OR 1.49, 95% CI 1.10-2.02) and mortality (OR 1.67, 95% CI 1.35-2.06). Poor functional outcomes were noted both in the VKAs and direct oral anticoagulants (DOACs) groups (OR 0.62, 95% CI 0.54-0.71 and OR 0.61, 95% CI 0.53-0.71, respectively). No differences in successful reperfusion were observed. CONCLUSIONS: Comparing with DOACs, VKAs use was associated with a higher risk of sICH and mortality after EVT. Patients who did not receive OACs exhibited more favorable outcomes. The successful reperfusion did not differ between groups. However, results for mortality and functional outcomes have to be interpreted with caution since they are based on non-randomized data and unadjusted proportions.

Advantages of DES over BMS in Preventing the Risk of Myocardial Infarction, Ischemic Stroke, and Mortality in Various Populations.

Backgrounds: Previous studies have demonstrated that drug-eluting stents (DESs) are more effective than bare metal stents (BMSs) in reducing the risk of myocardial infarction in the short term, but the long-term preventive benefits for myocardial infarction, ischemic stroke, and mortality are not clear. Objective: This study deeply analyzed the long-term (within 3 years) advantages of the use of DESs in preventing the risk of myocardial infarction, ischemic stroke, and mortality in various populations compared with those of using BMSs. Methods: This was a retrospective observational cohort study. We used the 2015-2019 claims data from Taiwan's National Health Insurance Research Database. Patients over the age of 18 who underwent coronary stent placement (both DESs and BMSs) for the first time in 2016 were included in the study population. Propensity-score matching was applied to increase the comparability of the DES and BMS groups. We used a Cox proportional hazard regression analysis to compare the effectiveness of DESs and BMSs in preventing myocardial infarction, ischemic stroke, and all-cause mortality. A subgroup analysis was also performed. Results: In total, 21,608 cases were included in this study. Overall, the risk of myocardial infarction (aHR = 0.82; 95% CI: 0.78-0.85), ischemic stroke (aHR = 0.88; 95% CI: 0.81-0.95), and mortality (aHR = 0.61; 95% CI: 0.57-0.65) in the DES group were significantly lower than those in the BMS group. However, in some special cases, the results were not statistically significant. In particular, in patients with obesity (aHR = 2.61; 95% CI: 1.20-5.69), the DES group appeared to have a significantly higher long-term intermediate ischemic risk than the BMS group. Conclusions and Relevance: In conclusion, although DESs were more effective than BMSs in reducing the risk of long-term myocardial infarction, ischemic stroke, and mortality, this study also found that, in some cases, the advantages of DESs over BMSs were not clearly observed.

Cholinesterase inhibitors for gait, balance, and fall in Parkinson disease: a meta-analysis.

Gait disturbance and imbalance are the major symptoms of Parkinson disease (PD), with fall being the most undesirable consequence. However, few effective evidence-based treatments are available for alleviating these symptoms and preventing falls. Cholinesterase inhibitors (ChEIs) are a well-established treatment for PD dementia with possible impacts on gait, balance, and fall reduction. The present study involved a meta-analysis of randomized controlled trials (RCTs) to investigate the effects of ChEIs on gait, balance, and fall in patients with PD. We searched for studies using the PubMed, Embase, and Web of Science databases. The major outcomes were effects on gait parameters, balance, and fall. This study was registered with PROSPERO (CRD42021254733). Five RCTs were included in the present meta-analysis. ChEIs did not significantly increase gait speed in PD patients (mean difference [MD]: 0.03 m/s, 95% confidence interval [CI]: -0.02 to 0.07, p = 0.29). However, ChEI treatment significantly decreased step or stride variability during the single task (standard MD: -0.43, 95% CI = -0.79 to -0.06, p = 0.02). Regarding fall and balance, trending but nonsignificant beneficial effects were observed with ChEI treatment. In conclusion, although ChEI treatment did not significantly improve gait speed and reduce fall, it can significantly reduce step or stride variability. Considering that gait disorder is a challenging issue in patients with PD and that ChEIs are generally tolerable, the present meta-analysis may provide more evidence for the benefit of ChEIs on PD gait disturbance as an alternative treatment consideration.

Blood Neurofilament Light Chain in Parkinson's Disease: Comparability between Parkinson's Progression Markers Initiative (PPMI) and Asian Cohorts.

Elevated blood neurofilament light chain (NfL), which indicates the loss of neuronal integrity, is increasingly implicated as a diagnostic and outcome-predicting biomarker for neurological diseases. However, its diagnostic implication for Parkinson's disease (PD) remains unclear, with conflicting data reported by several studies. This may result from the demographic heterogeneity of the studied cohorts. The present study investigated the comparability of blood NfL between a domestic, single-centered PD cohort from Shuang Ho Hospital (SHH) in Taiwan, with the large international, multi-center cohort, Parkinson's Progression Markers Initiative (PPMI). In the SHH PD cohort, with 61 people with PD (PwP) and 25 healthy non-PD controls, plasma NfL unexpectedly was significantly higher in the control group than PwP (14.42 ± 13.84 vs. 9.39 ± 6.91 pg/mL, p = 0.05). Interestingly, subgroup analysis revealed a non-significant difference of plasma NfL levels in male PwP compared with controls (8.58 ± 6.21 vs. 7.25 ± 4.43 pg/mL, p =0.575), whereas NfL levels were significantly lower in the female PwP group than in their healthy control peers (10.29 ± 7.62 vs. 17.79 ± 15.52 pg/mL, p = 0.033). Comparative analysis of the SHH and PPMI cohorts revealed a comparable gender-stratified distribution of blood NfL based on approximate theoretical quantiles. After adjusting for age and gender, no apparent difference in NfL value distribution was observed between the SHH and PPMI cohorts' control or PD groups. Significant downregulation of blood NfL levels were positively correlated with a reduced probability of having a PD diagnosis in both cohorts. These results demonstrated that the adjustment for demographic background enhances comparability between cohorts, and may be required to eliminate covariate/confounder-associated conflict in blood NfL results between different PD studies. This experience may be beneficial to other researchers around the world who are saddled with limited study participants, especially as data from small cohort sizes are often at greater risk of being skewed by specific variables.

Plasma extracellular vesicles tau and ß-amyloid as biomarkers of cognitive dysfunction of Parkinson's disease.

The contribution of circulatory tau and ß-amyloid in Parkinson's disease (PD), especially the cognitive function, remains inconclusive. Extracellular vesicles (EVs) cargo these proteins throughout the bloodstream after they are directly secreted from many cells, including neurons. The present study aims to investigate the role of the plasma EV-borne tau and ß-amyloid as biomarkers for cognitive dysfunction in PD by investigating subjects with mild to moderate stage of PD (n = 116) and non-PD controls (n = 46). Plasma EVs were isolated, and immunomagnetic reduction-based immunoassay was used to assess the levels of α-synuclein, tau, and ß-amyloid 1-42 (Aß1-42) within the EVs. Artificial neural network (ANN) models were then applied to predict cognitive dysfunction. We observed no significant difference in plasma EV tau and Aß1-42 between PD patients and controls. Plasma EV tau was significantly associated with cognitive function. Moreover, plasma EV tau and Aß1-42 were significantly elevated in PD patients with cognitive impairment when compared to PD patients with optimal cognition. The ANN model used the plasma EV α-synuclein, tau, and Aß1-42, as well as the patient's age and gender, as predicting factors. The model achieved an accuracy of 91.3% in identifying cognitive dysfunction in PD patients, and plasma EV tau and Aß1-42 are the most valuable factors. In conclusion, plasma EV tau and Aß1-42 are significant markers of cognitive function in PD patients. Combining with the plasma EV α-synuclein, age, and sex, plasma EV tau and Aß1-42 can identify cognitive dysfunction in PD patients. This study corroborates the prognostic roles of plasma EV tau and Aß1-42 in PD.

Plasma Extracellular Vesicle α-Synuclein Level in Patients with Parkinson's Disease.

BACKGROUND: The most established pathognomonic protein of Parkinson's disease (PD), α-synuclein, is extensively investigated for disease diagnosis and prognosis; however, investigations into whether the free form of α-synuclein in the blood functions as a PD biomarker have not been fruitful. Extracellular vesicles (EVs) secreted from cells and present in blood transport molecules are novel platforms for biomarker identification. In blood EVs, α-synuclein originates predominantly from the brain without the interference of the blood-brain barrier. The present study investigated the role of plasma EV-borne α-synuclein as a biomarker of PD. METHODS: Patients with mild to moderate stages of PD (n = 116) and individuals without PD (n = 46) were recruited to serve as the PD study group and the control group, respectively. Plasma EVs were isolated, and immunomagnetic reduction-based immunoassay was used to assess EV α-synuclein levels. Conventional statistical analysis was performed using SPSS 25.0, and p < 0.05 was considered significant. RESULTS: Compared with controls, we observed significantly lower plasma EV α-synuclein levels in the patients with PD (PD: 56.0 ± 3.7 fg/mL vs. control: 74.5 ± 4.3 fg/mL, p = 0.009), and the significance remained after adjustment for age and sex. Plasma EV α-synuclein levels in the patients with PD did not correlate with age, disease duration, Part I and II scores of the Unified Parkinson's Disease Rating Scale (UPDRS), or the Mini-Mental State Examination scores. However, such levels were significantly correlated with UPDRS Part III score, which assesses motor dysfunction. Furthermore, the severity of akinetic-rigidity symptoms, but not tremor, was inversely associated with plasma EV α-synuclein level. CONCLUSION: Plasma EV α-synuclein was significantly different between the control and PD group and was associated with akinetic-rigidity symptom severity in patients with PD. This study corroborates the possible diagnostic and subtyping roles of plasma EV α-synuclein in patients with PD, and it further provides a basis for this protein's clinical relevance and feasibility as a PD biomarker.

Cytokine Profile in Plasma Extracellular Vesicles of Parkinson's Disease and the Association with Cognitive Function.

Plasma extracellular vesicles (EVs) containing various molecules, including cytokines, can reflect the intracellular condition and participate in cell-to-cell signaling, thus emerging as biomarkers for Parkinson's disease (PD). Inflammation may be a crucial risk factor for PD development and progression. The present study investigated the role of plasma EV cytokines as the biomarkers of PD. This cross-sectional study recruited 113 patients with PD, with mild to moderate stage disease, and 48 controls. Plasma EVs were isolated, and the levels of cytokines, including pro-interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-ß1, were evaluated. Patients with PD had significantly increased plasma EV pro-IL-1ß and TNF-α levels compared with controls after adjustment for age and sex. Despite the lack of a significant association between plasma EV cytokines and motor symptom severity in patients with PD, cognitive dysfunction severity, assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment, was significantly associated with plasma EV pro-IL-1ß, IL-6, IL-10, and TNF-α levels. This association was PD specific and not found in controls. Furthermore, patients with PD cognitive deficit (MMSE < 26) exhibited a distinguished EV cytokine profile compared to those without cognitive deficit. The findings support the concept of inflammatory pathogenesis in the development and progression of PD and indicate that plasma EV cytokines may serve as PD biomarkers in future.

The effect of monoamine oxidase-B inhibitors on the alleviation of depressive symptoms in Parkinson's disease: meta-analysis of randomized controlled trials.

BACKGROUND: Depression is a major nonmotor symptom of Parkinson's disease (PD). However, few treatments exist for PD depression. Monoamine oxidase-B inhibitors (MAOB-Is) provide symptomatic relief for the motor symptoms of PD and exert antidepressive effects. The present meta-analysis of randomized controlled trials (RCTs) investigated the effects of MAOB-Is on depressive symptoms in patients with PD. METHODS: Articles on PD-management-related RCTs using one of three MAOB-Is approved by the US Food and Drug Administration, that is, selegiline, rasagiline, and safinamide, were identified. The primary outcomes were the benefits of MAOB-Is for depressive symptoms. Subgroup analysis included the effects of MAOB-Is on patients in the early versus middle-to-late stages of PD and the effect of short-term versus long-term treatment. RESULTS: Overall, six studies were included, four of which were conducted on patients with early stage PD. Overall, MAOB-Is significantly reduced the severity of depressive symptoms [standardized mean difference (SMD): -0.14, 95% confidence interval (CI): -0.21 to -0.06, p < 0.001]. Subgroup analysis indicated that the positive effect of MAOB-Is was significant in patients with early stage PD (SMD: -0.20, 95% CI: -0.31 to -0.09, p < 0.001), but not in those with middle-to-late-stage PD (SMD: -0.07, 95% CI: -0.17 to 0.03, p = 0.18). The antidepressive effect was significant for short-term treatment, that is, 90-120 days (SMD: -0.23, 95% CI: -0.35 to -0.10, p < 0.001), but not long-term treatment, that is, 24 weeks to 18 months (SMD: -0.08, 95% CI: -0.18 to 0.01, p = 0.09). CONCLUSION: In addition to the treatment of PD motor symptoms, MAOB-Is may help reduce the severity of depressive symptoms in PD, especially in patients with early stage PD. Considering the tolerability and simultaneous benefits of MAOB-Is, further RCTs are warranted to confirm their therapeutic effects in moderate-to-severe PD depression.

A real-world observational study of drug utilization and clinical outcomes of direct-acting antivirals and interferon therapy for hepatitis C treatment in Taiwan.

OBJECTIVE: In this study, we investigated the use of direct-acting antivirals (DAAs), medical expenses and clinical outcomes since the initiation of national health insurance coverage in Taiwan. METHODS: This was a retrospective observational study. We obtained claims data from Taiwan's National Health Insurance Research Database in 2017. Patients diagnosed with hepatitis C with at least two physician visits or one hospitalization were included in the study. Cases were divided into three groups based on the treatment type: traditional treatment (interferon, INF), new drug treatment (DAA) and INF-experienced (INF followed by DAA). We compared the distributions of various cases based on individual demographic variables, hospital type and comorbidities. Trends in medical expenses by treatment type were estimated. We also analyzed clinical outcomes, including rehospitalization and liver function disorders, using a survival analysis method. RESULTS: Among patients with hepatitis C, the DAA group had a significantly higher proportion of females, a higher mean age and greater disease severity than the INF group. The growth rate of medical expenses was significantly lower in the DAA group. In addition, compared to the INF group, the DAA group and INF-experienced group had significantly lower rehospitalization rates, and the DAA group had a significantly lower risk of liver function disorders. Furthermore, the longer a patient received any form of treatment, the lower was their chance of rehospitalization and liver function disorders. CONCLUSIONS: In conclusion, our results confirmed that insurance coverage of DAAs led to better clinical outcomes than INF, and this may reduce increases in medical expenses and the risks of rehospitalization and liver function disorders. WHAT IS KNOWN ON THIS TOPIC: Interferon for hepatitis C has low efficacy with serious side effects, while the efficacy of new oral drugs (direct-acting antivirals, DAAs) is high. DAAs were approved for listing in Taiwan in December 2013, and they have been covered by National Health Insurance since January 2017. Little is known about DAA-related real-world evidence following the coverage of DAAs in Taiwan, including drug utilization, expenditures and safety. WHAT THIS STUDY ADDS: This study explored three important issues related to DAAs: drug utilization, medical expenses and clinical outcomes following the insurance coverage by using the National Health Insurance Database. Cases were divided into three groups based on the treatment type: traditional treatment (interferon, INF), new drug treatment (DAA) and INF-experienced (INF followed by DAA). After the adjustment of various personal and hospital factors, the DAA group and INF-experienced group had significantly lower rehospitalization rates, and the DAA group had a significantly lower risk of liver function disorders, compared to the interferon group. There was a lower chance of rehospitalization and lower liver function disorder rates with longer treatment.

Neurofilament light chain level in plasma extracellular vesicles and Parkinson's disease.

BACKGROUND: Neurofilament light chain (NfL) is essential for axonal maintenance and reflects neuronal damage. Extracellular vesicles (EVs), especially exosomes, secreted by cells into the blood, are emerging as novel biomedical research platforms of physiological and pathological processes. The present study investigated the possible association between plasma EV NfL and Parkinson's disease (PD). METHODS: One hundred and sixteen patients with mild to moderate PD and 46 non-PD, neurological controls were recruited, and their clinical motor symptoms and cognitive function were evaluated. Plasma EVs were isolated using an exoEasy kit, and immunomagnetic reduction assay was used to assess EV NfL level. Statistical analysis was performed using SPSS 25.0, and p < 0.05 was considered significant. RESULTS: The isolated plasma EVs were validated according to size and the presence of specific surface markers. Compared with the neurological control group, the levels of plasma EV NfL in patients with PD were not significantly different (PD: 9.42 ± 3.89, control: 9.53 ± 3.62 pg/mL plasma, p = 0.71). On the other hand, plasma EV NfL in patients with PD trendwise correlated with the severity of akinetic rigidity (p = 0.05). PD patients with optimal EV NfL (lowest quartile) had 6.66 ± 2.08 lower Unified Parkinson's Disease Rating Scale-III score after adjustment for age, sex, and disease duration. CONCLUSION: Plasma EV NfL levels did not distinguish patients with PD from the neurological control group. The possible correlation between plasma EV NfL with the severity of motor symptoms within the PD patients, especially with akinetic rigidity, was noted. Further clinical validation of the blood EV NfL by a longitudinal follow-up study of PD patients is warranted.

Plasma Exosomal Brain-Derived Neurotrophic Factor Correlated with the Postural Instability and Gait Disturbance-Related Motor Symptoms in Patients with Parkinson's Disease.

Brain-derived neurotrophic factor (BDNF) is an essential neurotrophin, responsible for neuronal development, function, and survival. Assessments of peripheral blood BDNF in patients with Parkinson's disease (PD) previously yielded inconsistent results. Plasma exosomes can carry BDNF, so this study investigated the role of plasma exosomal BDNF level as a biomarker of PD. A total of 114 patients with mild to moderate PD and 42 non-PD controls were recruited, and their clinical presentations were evaluated. Plasma exosomes were isolated with exoEasy Maxi Kits, and enzyme-linked immunosorbent assay was used to assess plasma exosomal BDNF levels. Statistical analysis was performed using SPSS version 19.0, and findings were considered significant at p < 0.05. The analysis revealed no significant differences in plasma exosomal BDNF levels between patients with PD and controls. Patients with PD with low plasma exosomal BDNF levels (in the lowest quartile) exhibited a significant association with daily activity dysfunction but not with cognition/mood or overall motor symptoms as assessed using the Unified Parkinson's Disease Rating Scale (UPDRS). Investigation of UPDRS part III subitems revealed that low plasma exosomal BDNF level was significantly associated with increased motor severity of postural instability and gait disturbance (PIGD)-associated symptoms (rising from a chair, gait, and postural stability) after adjustment for age and sex. In conclusion, although plasma exosomal BDNF level could not distinguish patients with PD from controls, the association with PIGD symptoms in patients with PD may indicate its potential role as a biomarker. Follow-up studies should investigate the association between plasma exosomal BDNF levels and changes in clinical symptoms.

Hand fine motor skill disability correlates with dementia severity.

BACKGROUND: The progression of dementia, which impairs motor skills and cognitive function, is a warning of greater disability. The present study investigated the association between hand fine motor skills, assessed according to the Functioning Disability Evaluation Scale - Adult Version (FUNDES-Adult), and dementia severity. METHODS: People with mild and moderate to severe dementia were identified from the Taiwan Data Bank of Persons with Disability. The FUNDES-Adult was assessed for all enrollees, and the following hand fine motor skills were evaluated: pen-holding, buttoning, and knotting. Statistical analysis was performed using SAS, and P values < 0.05 were considered significant. RESULTS: Disability in all the 3 fin. motor skills was significantly greater in patients with moderate to severe dementia than in those with mild dementia. Disability in any of the skills was sensitive to distinguish mild from moderate to severe dementia (sensitivity: 78.1 %, specificity: 55.2 %, area under the curve: 0.739, 95 % confidence interval [CI]: 0.734-0.745). Those with fine motor skill disability were at a significantly higher risk of moderate to severe dementia (odds ratio: 3.71, 95 % CI: 3.53-3.90, P <  .001). CONCLUSION: Hand fine motor skill disability was more prevalent in patients with moderate to severe dementia than in patients with mild dementia. A straightforward motor skill assessment can serve as a screening tool in the community to detect the progression of dementia.

Hand Fine Motor Skill Disability Correlates with Cognition in Patients with Moderate-to-Advanced Parkinson's Disease.

In older individuals, hand fine motor skill disability is associated with cognitive levels. Similarly, patients with moderate-to-advanced Parkinson's disease (PD) often have cognitive dysfunction. Here, we investigated the association between hand fine motor skill and cognitive dysfunction in patients with moderate-to-advanced PD. Moderate and advanced PD patients with and without dementia were identified from the Taiwan Data Bank of Persons with Disability. Hand fine motor capacities, namely pen holding, buttoning, and knotting, were assessed with the World Health Organization Disability Assessment Schedule 2.0. Statistical analyses were performed on Statistical Analysis System (SAS) and a p value of <0.05 was considered significant. In total, 3440 patients with PD were enrolled, of which 612 had dementia, exhibiting significant disability in all three tasks. After adjustments for age, sex, and PD severity, pen holding and knotting were significantly associated with PD dementia. The presence of any disability in either task was not only sensitive to the presence of dementia but also associated with cognitive disability in moderate and advanced PD patients without dementia. In conclusion, hand fine motor skill disability was associated with cognitive disability in patients with moderate-to-advanced PD. These simple hand fine motor skills may thus be applicable in screening tests for the early identification of cognitive dysfunction in patients with moderate-to-advanced PD.