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.

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)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β1, were evaluated. Patients with PD had significantly increased plasma EV pro-IL-1β 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-1β, 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.

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.

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.

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. 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. 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). 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.

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.