Plasma extracellular vesicle synaptic proteins as biomarkers of clinical progression in patients with Parkinson's disease.

Synaptic dysfunction plays a key role in Parkinson's disease (PD), and plasma extracellular vesicle (EV) synaptic proteins are emerging as biomarkers for neurodegenerative diseases. Assessment of plasma EV synaptic proteins for their efficacy as biomarkers in PD and their relationship with disease progression was conducted. In total, 144 participants were enrolled, including 101 people with PD (PwP) and 43 healthy controls (HCs). The changes in plasma EV synaptic protein levels between baseline and 1-year follow-up did not differ significantly in both PwP and HCs. In PwP, the changes in plasma EV synaptic protein levels were significantly associated with the changes in Unified Parkinson's Disease Rating Scale (UPDRS)-II and III scores. Moreover, PwP with elevated levels (first quartile) of any one plasma EV synaptic proteins (synaptosome-associated protein 25, growth-associated protein 43 or synaptotagmin-1) had significantly greater disease progression in UPDRS-II score and the postural instability and gait disturbance subscore in UPDRS-III than did the other PwP after adjustment for age, sex, and disease duration. The promising potential of plasma EV synaptic proteins as clinical biomarkers of disease progression in PD was suggested. However, a longer follow-up period is warranted to confirm their role as prognostic biomarkers.

Adult-onset hearing loss and incident cognitive impairment and dementia - A systematic review and meta-analysis of cohort studies.

BACKGROUND: We comprehensively summarized the cohort evidence to date on adult-onset hearing loss as risk factor for incident cognitive impairment and dementia, and examined the evidence for dose-response, risk for various dementia subtypes, and other moderators. Previous meta-analyses were less comprehensive. METHODS: We included cohort studies with participants without dementia and with hearing assessments at baseline, minimum 2 years follow-up and incident cognitive outcomes. We used random-effect models and subgroup and meta-regression on moderator analyses. RESULTS: We identified fifty studies (N=1,548,754). Hearing loss (yes/no) was associated with incident dementia risk (HR=1.35 [95% CI = 1.26 - 1.45), mild cognitive impairment (MCI HR=1.29 [95% CI = 1.11 - 1.50]), cognitive decline not specified as MCI or dementia (HR=1.29 [95% CI = 1.17 - 1.42]), and Alzheimer's disease dementia (ADD, HR=1.56 [95% CI = 1.30 - 1.87]), but not with vascular dementia (HR, 1.30 [95% CI = 0.83 - 2.05]). Each 10-decibel worsening of hearing was associated with a 16% increase in dementia risk (95% CI = 1.07 - 1.27). The effect of hearing loss did not vary across potential moderators. CONCLUSIONS: Cohort studies consistently support that adult-onset hearing loss increases the risk of incident cognitive decline, dementia, MCI, and ADD.

Cytokine profiles of plasma extracellular vesicles as progression biomarkers in Parkinson's disease.

BACKGROUND: Inflammation contributes substantially to the pathogenesis of Parkinson's disease (PD). Plasma extracellular vesicle (EV)-derived cytokines are emerging biomarkers of inflammation. We conducted a longitudinal study of the plasma EV-derived cytokine profiles of people with PD (PwP). METHODS: A total of 101 people with mild to moderate PD and 45 healthy controls (HCs) were recruited, and they completed motor assessments (Unified Parkinson Disease Rating Scale [UPDRS]) and cognitive tests at baseline and 1-year follow-up. We isolated the participants' plasma EVs and analyzed their levels of cytokines, including interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-ß. RESULTS: We noted no significant changes in the plasma EV-derived cytokine profiles of the PwPs and HCs between baseline and the 1-year follow-up. Among the PwP, changes in plasma EV-derived IL-1ß, TNF-α and IL-6 levels were significantly associated with changes in the severity of postural instability and gait disturbance (PIGD) and cognition. Baseline plasma EV-derived IL-1ß, TNF-α, IL-6, and IL-10 levels were significantly associated with the severity of PIGD and cognitive symptoms at follow-up, and PwP with elevated IL-1ß and IL-6 levels exhibited significant progression of PIGD over the study period. CONCLUSION: These results suggested the role of inflammation in PD progression. In addition, baseline levels of plasma EV-derived proinflammatory cytokines can be used to predict the progression of PIGD, the most severe motor symptom of PD. Additional studies with longer follow-up periods are necessary, and plasma EV-derived cytokines may serve as effective biomarkers of PD progression.

Systematic Review and Meta-Analysis of Brief Cognitive Instruments to Evaluate Suspected Dementia in Chinese-Speaking Populations.

Background: Chinese is the most commonly spoken world language; however, most cognitive tests were developed and validated in the West. It is essential to find out which tests are valid and practical in Chinese speaking people with suspected dementia. Objective: We therefore conducted a systematic review and meta-analysis of brief cognitive tests adapted for Chinese-speaking populations in people presenting for assessment of suspected dementia. Methods: We searched electronic databases for studies reporting brief (≤20 minutes) cognitive test's sensitivity and specificity as part of dementia diagnosis for Chinese-speaking populations in clinical settings. We assessed quality using Centre for Evidence Based Medicine (CEBM) criteria and translation and cultural adaptation using the Manchester Translation Reporting Questionnaire (MTRQ), and Manchester Cultural Adaptation Reporting Questionnaire (MCAR). We assessed heterogeneity and combined sensitivity in meta-analyses. Results: 38 studies met inclusion criteria and 22 were included in meta-analyses. None met the highest CEBM criteria. Five studies met the highest criteria of MTRQ and MCAR. In meta-analyses of studies with acceptable heterogeneity (I2 <  75%), Addenbrooke's Cognitive Examination Revised &III (ACE-R & ACE-III) had the best sensitivity and specificity; specifically, for dementia (93.5% & 85.6%) and mild cognitive impairment (81.4% & 76.7%). Conclusions: Current evidence is that the ACE-R and ACE-III are the best brief cognitive assessments for dementia and mild cognitive impairment in Chinese-speaking populations. They may improve time taken to diagnosis, allowing people to access interventions and future planning.

Validation of the Taiwanese Version of ACE-III (T-ACE-III) to Detect Dementia in a Memory Clinic.

OBJECTIVE: The Addenbrooke's Cognitive Examination III (ACE-III) is a 100-points cognitive test used in detecting dementia in many countries. There has been no validation study of the ACE-III in patients with suspected dementia in a Taiwanese population, where the language is traditional Chinese. We aimed to culturally adapt and validate the ACE-III as a cognitive assessment tool for differentiating between people with and without dementia presenting to healthcare professionals in Taiwan with possible dementia. METHODS: We culturally adapted the ACE-III for Taiwan (T-ACE-III) and tested it with consenting patients with suspected dementia in northern Taiwan who had been through the diagnostic process. We calculated receiver operating characteristic (ROC) curves to test the ability of the T-ACE-III to differentiate between dementia and non-dementia cases using clinician diagnosis as the gold standard. We generated the Youden Index to determine the best cut-off score. RESULTS: We recruited 90 Taiwanese individuals aged 49-93 years: 24 males and 33 females had dementia and 12 males and 21 females did not. The area under the ROC curve was 0.99 for distinguishing dementia from non-dementia. The T-ACE-III had a sensitivity of 100% and specificity of 78.8% when the cut-off score was 86/87. With a cut-off value of 73/74, the specificity was 100.0%, and sensitivity 89.5%. The highest Youden Index was 0.895, indicating the best overall cut-off point to be 73/74. CONCLUSIONS: The T-ACE-III is an acceptable cognitive test with excellent psychometric properties for discriminating dementia from non-dementia in Taiwanese populations in memory clinic settings.

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.