Prevalence Of Parkinson's Disease Research Articles

Long-term exposure to major constituents of fine particulate matter and neurodegenerative diseases: A population-based survey in the Pearl River Delta Region, China

BackgroundExposure to PM2.5 has been linked to neurodegenerative diseases, with limited understanding of constituent-specific contributions. ObjectivesTo explore the associations between long-term exposure to PM2.5 constituents and neurodegenerative diseases. MethodsWe recruited 148,274 individuals aged ≥ 60 from four cities in the Pearl River Delta region, China (2020 to 2021). We calculated twenty-year average air pollutant concentrations (PM2.5 mass, black carbon (BC), organic matter (OM), ammonium (NH4+), nitrate (NO3-) and sulfate (SO42-)) at the individuals' home addresses. Neurodegenerative diseases were determined by self-reported doctor-diagnosed Alzheimer’s disease (AD) and Parkinson’s disease (PD). Generalized linear mixed models were employed to explore associations between pollutants and neurodegenerative disease prevalence. ResultsPM2.5 and all five constituents were significantly associated with a higher prevalence of AD and PD. The observed associations generally exhibited a non-linear pattern. For example, compared with the lowest quartile, higher quartiles of BC were associated with greater odds for AD prevalence (i.e., the adjusted odds ratios were 1.81; 95% CI, 1.45–2.27; 1.78; 95% CI, 1.37–2.32; and 1.99; 95% CI, 1.54–2.57 for the second, third, and fourth quartiles, respectively). ConclusionsLong-term exposure to PM2.5 and its constituents, particularly combustion-related BC, OM, and SO42-, was significantly associated with higher prevalence of AD and PD in Chinese individuals. Environmental implicationPM2.5 is a routinely regulated mixture of multiple hazardous constituents that can lead to diverse adverse health outcomes. However, current evidence on the specific contributions of PM2.5 constituents to health effects is scarce. This study firstly investigated the association between PM2.5 constituents and neurodegenerative diseases in the moderately to highly polluted Pearl River Delta region in China, and identified hazardous constituents within PM2.5 that have significant impacts. This study provides important implications for the development of targeted PM2.5 prevention and control policies to reduce specific hazardous PM2.5 constituents.

Trends in Physiotherapy Interventions and Medical Costs for Parkinson's Disease in South Korea, 2011-2020.

Physiotherapy (PT), which is an effective strategy for managing Parkinson's disease (PD), can influence health care utilization. We analyzed trends in health care utilization, PT interventions, and medical costs among patients with PD. Using data from the Korean National Health Insurance Service from 2011 to 2020, we analyzed the number of patients with PD and their health care utilization and assessed the odds ratio (OR) for receiving regular PTs. Over 10 years, 169,613 patients with PD were included in the analysis. The number of patients with PD increased annually from 49,417 in 2011 to 91,841 in 2020. The number of patients with PD receiving PT increased from 4,847 (9.81%) in 2011 to 13,163 (14.33%) in 2020, and the number of PT prescriptions increased from 81,220 in 2011 to 377,651 in 2019. Medical costs per patient with PD increased from 1,686 United States dollars (USD) in 2011 to 3,202 USD in 2020. The medical expenses for each patient with PD receiving PT increased from 6,582 USD in 2011 to 13,475 USD in 2020. Moreover, regular PTs were administered to 31,782 patients (18.74%) and were administered only through hospitalization. Those patients in their 50s with disabilities demonstrated a high OR for regular PTs, whereas those aged 80 years or older and residing outside of Seoul had a low OR. The PD burden increased in South Korea between 2011 and 2020, as did health care utilization and medical costs. A significant increase in medical expenses can be associated with increased PD incidence and PT interventions. Regular PT applications remain restricted and have barriers to access.

Disparities in the treatment of movement disorders using deep brain stimulation.

Deep brain stimulation (DBS) is a well-established treatment for Parkinson's disease (PD) and essential tremor (ET). Although the prevalence of PD and ET can vary by sex and race, little is known about the accessibility of neurosurgical treatments for these conditions. In this nationwide study, the authors aimed to characterize trends in the use of DBS for the treatment of PD and ET and to identify disparities in the neurosurgical treatment of these diseases based on ethnic, racial, sex, insurance, income, hospital, and geographic factors. Using the dates January 1, 2012, to December 31, 2019, the authors queried the National Inpatient Sample database for all discharges with an ICD-9 or ICD-10 diagnosis of PD or ET. Among these discharges, the DBS rates were reported for each subgroup of race, ethnicity, and sex. To develop national estimates, all analyses were weighted. Among 2,517,639 discharges with PD, 29,820 (1.2%) received DBS, and among 652,935 discharges with ET, 11,885 (1.8%) received DBS. Amid the PD cases, Black patients (n = 405 [0.2%], OR 0.16, 95% CI 0.12-0.20) were less likely than White patients (n = 23,975 [1.2%]) to receive DBS treatment, as were Hispanic patients (n = 1965 [1.1%], OR 0.76, 95% CI 0.65-0.88), whereas Asian/Pacific Islander patients (n = 855 [1.5%]) did not statistically differ from White patients. Amid the ET cases, Black (n = 230 [0.8%], OR 0.39, 95% CI 0.27-0.56), Hispanic (n = 215 [1.0%], OR 0.39, 95% CI 0.28-0.55), and Asian/Pacific Islander (n = 55 [1.0%], OR 0.51, 95% CI 0.28-0.93) patients were less likely than White patients (n = 10,440 [1.9%]) to receive DBS. Females were less likely than males to receive DBS for PD (OR 0.69, p < 0.0001) or ET (OR 0.70, p < 0.0001). The authors describe significant racial and sex-based differences in the utilization of DBS for the treatment of PD and ET. Further research is required to ascertain the causes of these disparities, as well as any differences in access to specialty neurosurgical care and referral for neuromodulation approaches.

Prevalence of Parkinson’s disease in Pakistan – A Systematic Review

Numerous epidemiological investigations pertaining to Parkinson's disease (PD) have been carried out on a global scale during the course of time. While each research documented an increase in the frequency and incidence rate of PD as individuals age, there were variations in the overall estimations seen across various nations. Objective: The purpose of this study is to provide a thorough analysis of PD incidence and prevalence rates in Pakistan. Methods: Google Scholar, Medline, and Embase were used to look for studies which reported the incidence of PD around the world. The searches were limited to English-language studies about people that happened between 1965 to 2023. Results: A total of 7 studies were conducted on Parkinson’s disease in Pakistan. Muhammad Tufail et al. in a cross-sectional study observed a heightened prevalence of Parkinson's disease, with 600 patients identified in Khyber Pakhtunkhwa (KPK). In a cross-sectional study conducted in Lahore, 85 cases of PD were identified within a hospital setting. Fifty cases in a cross-sectional study were conducted at a Hospital in Rawalpindi. Saira et al. performed an observational study at Islamabad Hospital and found the prevalence of We estimated the overall frequency of PD in Pakistan was 1016 cases in this systematic review. Males were more diagnosed with PD as compared to females. Conclusions: The data from the studies reviewed here indicate that PD increased in Pakistan during the last decade. While males were dominant in this study which is not different from across the globe.

Evidence Synthesis on Gait and Balance Training: Meta-Analysis of Physical Therapy Intervention in Parkinson’s Patients

Background: Parkinson Disease is considered to be posing a significant impact worldwide. According to the Global Burden of Disease study (GBD), there has been 1.02 million incident cases recorded in 2017 and 6.1 million cases worldwide in 2016. Between 1990 and 2016, the standardized rate of age among Parkinson's disease prevalence rose by 21.7%. Methods: Studies examining the effects of physiotherapy on balance, gait and other pertinent outcomes among individuals with PD undergoing rehabilitation program were included in the inclusion criteria. Studies performed between 2015 and 2023 were taken into account for inclusion. Studies conducted in languages other than English, or those that did not have readily available open access or for which open access could not receive after contacting corresponding authors were all excluded. Results: The risk of bias assessment was performed based on the guidelines of SYRCLE. The author-The findings of this meta-analysis examining the effectiveness of rehabilitation on balance across different trials. Results of fixed-effects model analysis indicated that physical therapy showed a statistically significant favorable influence on balance among individuals with Parkinson's disease, with an overall affect size (Standardized Mean Difference, SMD) of 0.511 (95% CI: 0.255 to 0.766). A somewhat greater impact size of 0.654 (95% CI: 0.0441 to 1.264) was seen in the model of the random-effects. Noticeable heterogeneity was detected in the test (Q = 32.8633, DF = 6, p &lt; 0.0001), indicating a highest degree of variability among included studies. Conclusion: In conclusion, a thorough meta-analysis of research on the influence of physical therapy treatments on gait, balance among people with Parkinson's disease found positive findings. Keywords: Gait, Risk of Fall, Parkinson Disease, Postural Balance.

Machine Learning-Based Classification of Parkinson's Disease Patients Using Speech Biomarkers.

Parkinson's disease (PD) is the most prevalent neurodegenerative movement disorder and a growing health concern in demographically aging societies. The prevalence of PD among individuals over the age of 60 and 80 years has been reported to range between 1% and 4%. A timely diagnosis of PD is desirable, even though it poses challenges to medical systems. This study aimed to classify PD and healthy controls based on the analysis of voice records at different frequencies using machine learning (ML) algorithms. The voices of 252 individuals aged 33 to 87 years were recorded. Based on the voice record data, ML algorithms can distinguish PD patients and healthy controls. One binary decision variable was associated with 756 instances and 754 attributes. Voice records data were analyzed through supervised ML algorithms and pipelines. A 10-fold cross-validation method was used to validate models. In the classification of PD patients, ML models were performed with 84.21 accuracy, 93 precision, 89 Sensitivity, 89 F1-scores, and 87 AUC. The pipeline performance improved to accuracy: 85.09, precision: 92, Sensitivity:91, F1-score: 89, and AUC: 90. The Pipeline methods improved the performance of classifying PD from voice record. Our study demonstrated that ML classifiers and pipelines can classify PD patients based on speech biomarkers. It was found that pipelines were more effective at selecting the most relevant features from high-dimensional data and at accurately classifying PD patients and healthy controls. This approach can therefore be used for early diagnosis of initial forms of PD.

Young human alpha synuclein transgenic (BAC-SNCA) mice display sex- and gene-dose-dependent phenotypic disturbances

Parkinson's disease (PD) is a common neurodegenerative movement disorder, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta and the accumulation of aggregated alpha synuclein (aSyn). The disease often presents with early prodromal non-motor symptoms and later motor symptoms. Diagnosing PD based purely on motor symptoms is often too late for successful intervention, as a significant neuronal loss has already occurred. Furthermore, the lower prevalence of PD in females is not well understood, highlighting the need for a better understanding of the interaction between sex and aSyn, the crucial protein for PD pathogenesis. Here, we conducted a comprehensive phenotyping study in 1- to 5-month-old mice overexpressing human aSyn gene (SNCA) in a bacterial artificial chromosome (BAC-SNCA). We demonstrate a SNCA gene-dose-dependent increase of human aSyn and phosphorylated aSyn, as well as a decrease in tyrosine hydroxylase expression in BAC-SNCA mice, with more pronounced effects in male mice. Phosphorylated aSyn was already found in the dorsal motor nucleus of the vagus nerve of 2-month-old mice. This was time-wise associated with significant gait altrations in BAC-SNCA mice as early as 1 and 3 months of age using CatWalk gait analysis. Furthermore, anxiety-related behavioral tests revealed an increase in anxiety levels in male BAC-SNCA mice. Finally, 5-month-old male BAC-SNCA mice exhibited a SNCA gene-dose-dependent elevation in energy expenditure in automated home-cage monitoring. For the first time, these findings describe early-onset, sex- and gene-dose-dependent, aSyn-mediated disturbances in BAC-SNCA mice, providing a model for sex-differences, early-onset neuropathology, and prodromal symptoms of PD.

Relationship among α‑synuclein, aging and inflammation in Parkinson's disease (Review).

Parkinson's disease (PD) is a common neurodegenerative pathology whose major clinical symptoms are movement disorders. The main pathological characteristics of PD are the selective death of dopaminergic (DA) neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies containing α-synuclein (α-Syn) within these neurons. PD is associated with numerous risk factors, including environmental factors, genetic mutations and aging. In many cases, the complex interplay of numerous risk factors leads to the onset of PD. The mutated α-Syn gene, which expresses pathologicalα-Syn protein, can cause PD. Another important feature of PD is neuroinflammation, which is conducive to neuronal death. α-Syn is able to interact with certain cell types in the brain, including through phagocytosis and degradation of α-Syn by glial cells, activation of inflammatory pathways by α-Syn in glial cells, transmission of α-Syn between glial cells and neurons, and interactions between peripheral immune cells and α-Syn. In addition to the aforementioned risk factors, PD may also be associated with aging, as the prevalence of PD increases with advancing age. The aging process impairs the cellular clearance mechanism, which leads to chronic inflammation and the accumulation of intracellular α-Syn, which results in DA neuronal death. In the present review, the age-associated α-Syn pathogenicity and the interactions between α-Syn and certain types of cells within the brain are discussed to facilitate understanding of the mechanisms of PD pathogenesis, which may potentially provide insight for the future clinical treatment of PD.

Evaluating Manganese, Zinc, and Copper Metal Toxicity on SH-SY5Y Cells in Establishing an Idiopathic Parkinson's Disease Model.

Parkinson's disease (PD) is a neurodegenerative condition marked by loss of motor coordination and cognitive impairment. According to global estimates, the worldwide prevalence of PD will likely exceed 12 million cases by 2040. PD is primarily associated with genetic factors, while clinically, cases are attributed to idiopathic factors such as environmental or occupational exposure. The heavy metals linked to PD and other neurodegenerative disorders include copper, manganese, and zinc. Chronic exposure to metals induces elevated oxidative stress and disrupts homeostasis, resulting in neuronal death. These metals are suggested to induce idiopathic PD in the literature. This study measures the effects of lethal concentration at 10% cell death (LC10) and lethal concentration at 50% cell death (LC50) concentrations of copper, manganese, and zinc chlorides on SH-SY5Y cells via markers for dopamine, reactive oxygen species (ROS) generation, DNA damage, and mitochondrial dysfunction after a 24 h exposure. These measurements were compared to a known neurotoxin to induce PD, 100 µM 6-hydroxydopamine (6-ODHA). Between the three metal chlorides, zinc was statistically different in all parameters from all other treatments and induced significant dopaminergic loss, DNA damage, and mitochondrial dysfunction. The LC50 of manganese and copper had the most similar response to 6-ODHA in all parameters, while LC10 of manganese and copper responded most like untreated cells. This study suggests that these metal chlorides respond differently from 6-ODHA and each other, suggesting that idiopathic PD utilizes a different mechanism from the classic PD model.

Burden of Parkinsonism and Parkinson's Disease on Health Service Use and Outcomes in Latin America.

Little is known about the burden of parkinsonism and Parkinson's disease (PD) in Latin America. Better understanding of health service use and clinical outcomes in PD is needed to improve its prognosis. The aim of the study was to estimate the burden of parkinsonism and PD in six Latin American countries. 12,865 participants aged 65 years and older from the 10/66 population-based cohort study were analysed. Baseline assessments were conducted in 2003-2007 and followed-up 4 years later. Parkinsonism and PD were defined using current clinical criteria or self-reported diagnosis. Logistic regression models assessed the association between parkinsonism/PD with baseline health service use (community-based care or hospitalisation in the last 3 months) and Cox proportional hazards regression models with incident dependency (subjective assessment by interviewer based on informant interview) and mortality. Separate analyses for each country were combined via fixed effect meta-analysis. At baseline, the prevalence of parkinsonism and PD was 7.9% (n = 934) and 2.6% (n = 317), respectively. Only parkinsonism was associated with hospital admission at baseline (OR 1.89, 95% CI 1.30-2.74). Among 7,296 participants without dependency at baseline, parkinsonism (HR 2.34, 95% CI 1.81-3.03) and PD (2.10, 1.37-3.24) were associated with incident dependency. Among 10,315 participants with vital status, parkinsonism (1.73, 1.50-1.99) and PD (1.38, 1.07-1.78) were associated with mortality. The Higgins I2 tests showed low to moderate levels of heterogeneity across countries. Our findings show that older people with parkinsonism or PD living in Latin America have higher risks of developing dependency and mortality but may have limited access to health services.

Prevalence of Parkinson disease in Korea: a comprehensive analysis and regional comparison

Prevalence of Parkinson disease in Korea: a comprehensive analysis and regional comparison

Association between blood selenium with parkinson's disease in the US (NHANES 2011-2020).

Selenium is an essential trace element for human health, playing a key role in regulating cellular oxidative stress, immune response, and inflammation. In recent years, the association between selenium and Parkinson's disease (PD) has aroused people's attention. The objective of this study is to investigate the relationship between blood selenium concentrations and PD risk in a sample of U.S. adults. A cross-sectional study was conducted using the National Health and Nutrition Examination Survey (NHANES) data from 2011-2020 and included 15,660 adults aged over 40 years old. Univariate logistic regression and multivariate logistic regression models were utilized to analyze the association between blood selenium concentrations and PD prevalence. Additionally, the restricted cubic spline (RCS) model was applied to investigate the dose-response relationships between blood selenium and PD. The findings indicated a link between elevated blood selenium levels and a reduced occurrence of Parkinson's disease (PD). Notably, this association between blood selenium and PD exhibited a non-linear pattern, wherein the decline in PD risk was more pronounced at higher selenium concentrations than at lower levels. An inflection point emerged at approximately 2.4 μmol/L, beyond which the rate of decline in risk significantly diminished with increasing selenium levels. A potential association between blood selenium concentrations and PD has been observed, with PD patients having lower blood selenium levels compared to non-PD patients. Higher levels of blood selenium may have a protective effect against PD. However, further prospective studies are needed to investigate the effect of blood selenium in PD patients and to determine causality.

Correlation between 25-hydroxy-vitamin D and Parkinson's disease

BackgroundPrevious cross-sectional studies have shown that Parkinson’s disease (PD) patients have lower serum 25-hydroxyvitamin D (25(OH)D) concentrations than controls. Other studies have not yet tested whether research findings from other regions are generalizable to Chinese populations. In this case-control study, we examined the correlation between 25-hydroxyvitamin D and Parkinson's disease. MethodsWe established an association between 25-hydroxyvitamin D deficiency and PD in a case-control study of 100 PD patients and 100 control subjects free of neurological disease at the First Affiliated Hospital of Xinjiang Medical University. ResultsTotal 25-hydroxyvitamin D levels were deficient in 21 % of patients with PD compared with 4 % of controls. In univariate analyses, plasma levels of 25-hydroxyvitamin D were associated with PD (p < 0.001). In multivariate analyses, vitamin D deficiency (25(OH)D < 20 ng/mL) was significantly associated with PD (p = 0.008, Odds Ratio =17.13, 95 % CI= 2.082–141.075). Individuals with 25(OH)D levels in the lowest quartile had the highest prevalence of PD (p = 0.026, OR=11.786, 95 % CI =1.342–103.51 compared to individuals with values in the highest quartile). ConclusionsOur study reveals an association between 25-hydroxyvitamin D and PD. Patients with incident PD had significantly lower serum 25(OH)D concentrations than age-matched controls. High-risk PD patients with vitamin D deficiency who have not yet developed exercise impairment should undergo vitamin D measurement and any necessary treatment as soon as possible. Limitations of the study: the study needs further assessment of populations with low vitamin D levels in other regions of China; further assessment of the effect of different sources of vitamin D on PD; further study of longitudinal cohorts at different time points.

New horizons in Parkinson's disease in older populations.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Ageing is considered to be the greatest risk factor for PD, with a complex interplay between genetics and the environment. With population ageing, the prevalence of PD is expected to escalate worldwide; thus, it is of utmost importance to reduce the burden of PD. To date, there are no therapies to cure the disease, and current treatment strategies focus on the management of symptoms. Older adults often have multiple chronic diseases and geriatric syndromes, which further complicates the management of PD. Healthcare systems and care models necessary to address the broad needs of older PD patients are largely unavailable. In this New Horizon article, we discuss various aspects of PD from an ageing perspective, including disease management. We highlight recent advancements in PD therapies and discuss new care models with the potential to improve patient's quality of life.

Pharmacological and toxicological evaluation of methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxoide against haloperidol induced Parkinson like symptoms in animal model: In-vitro and in-vivo studies

In Parkinson's disease (PD), degradation of dopaminergic neurons in substantia nigra causes striatal deficiency of dopamine, which results in tremors, bradykinesia with instability in posture, rigidity and shuffled gait. Prevalence of PD increases with age as from 65 to 85 years. In an attempt to devise targeted safe therapy, nanoparticles of methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (MBD) (MBDN), were prepared and their acute toxicity and safety was evaluated. Thirty-six healthy albino mice were randomly divided into six groups (n = 6): normal control, diseased control, standard (levodopa/carbidopa (100/25 mg/kg) and the remaining three groups were administered 1.25, 2.5 and 5 mg/kg MBDN during 21 days study. Except control, all mice, were injected haloperidol (1 mg/ kg i.p.) 1-h prior to treatment to induce PD. Acute toxicity test showed, no effect of MBDN on lipid profile, brain, renal and liver function and histoarchitecture of kidney, liver and heart, except decreased (p < 0.05) platelet count. Behavioral studies showed significant improvement (p < 0.001) in motor function and reduction of oxidation status in a MBDN in a dose dependent manner. Thus, the study findings revealed significance of MBDN as a selective MAO-B inhibitor for the improvement of Parkinson's symptoms in animal model.

Validation of Administrative Health Data Algorithms for Identifying Persons with Parkinson’s Disease and the 10-Year Prevalence Trend in Bologna, Italy

Introduction: Health administrative databases are widely used for the estimation of the prevalence of Parkinson’s disease (PD). Few in general, and none used in Italy, have been validated by testing their diagnostic accuracy. The primary objective was to validate two algorithms for the identification of persons with PD using clinical diagnosis as the reference standard on an Italian sample of people with PD. The second objective was to estimate 10-year trends in PD prevalence in the Bologna Local Health Trust from 2010 to 2019. Methods: Two algorithms (index tests) applied to health administrative databases (hospital discharge, drug prescriptions, exemptions for medical costs) were validated against clinical diagnosis of PD by an expert neurologist (reference standard) in a cohort of consecutive outpatients. Sensitivity and specificity with relative 95% confidence intervals (CIs) were calculated. The prevalence of PD in a specific year was estimated as the ratio between the number of subjects fulfilling any criteria of the algorithm with better diagnostic accuracy and the total population in the same year (×1,000), stratified by age, sex, and district of residence. Results: The two algorithms showed high accuracy for identifying patients with PD: one with greater sensitivity of 94.2% (CI: 88.4–97.6) and the other with greater specificity of 98.1% (CI: 97.7–98.5). For the estimation of prevalence, we chose the most specific algorithm with the fewest total number of misclassified cases. We identified 3,798 people with PD as of December 31, 2019, corresponding to a prevalence of 4.3 per 1,000 inhabitants (CI: 4.2–4.4). Prevalence was higher in males (4.7, CI: 4.5–5.0) than females (3.8, CI: 3.7–4.0) and increased with age. The crude prevalence over time was slightly elevated as it followed a progressive aging of the population. When stratifying the prevalence for age groups, we did not observe a trend except in the 45–64 year category where we observed an increasing trend over time. Conclusion: Algorithms based on administrative data are accurate when detecting people with PD in the Italian public health system. In a large northern Italian population, increased prevalence of about 10% was observed in the decade 2010–2019 and is explained by increased life expectancy. These data may be useful in planning the allocation of health care resources for people with PD.

Minor Phenomena in Parkinson's Disease-Prevalence, Associations, and Risk of Developing Psychosis.

Minor phenomena, including passage phenomena, feeling of presence, and illusions, are common and may represent a prodromal form of psychosis in Parkinson's disease (PD). We examined the prevalence and clinical correlates of minor phenomena, and their potential role as a risk factor for PD psychosis. A novel questionnaire, the Psychosis and Mild Perceptual Disturbances Questionnaire for PD (PMPDQ), was completed by Fox Insight cohort participants with and without PD. Additional assessments included the Non-Motor Symptoms Questionnaire (NMSQuest), REM Sleep Behavior Disorder Single Question Screen (RBD1Q), Movement Disorder Society-Unified Parkinson Disease Rating Scale Part II, demographic features, and medication usage. For participants with PD, we used regression models to identify clinical associations and predictors of incident psychosis over one year of follow-up. Among participants with PD (n = 5950) and without PD (n = 1879), the prevalence of minor phenomena was 43.1% and 31.7% (P < .001). Of the 3760 participants with PD and no baseline psychosis, independent correlates of minor phenomena included positive responses on the NMSQuest apathy/attention/memory (OR 1.7, 95% CI 1.3-2.1, P < .001) or sexual function domain (OR 1.3, 95% CI 1.1-1.6, P = .01) and positive RBD1Q (OR 1.3, 95% CI 1.05-1.5, P = .01). Independent risk factors for incident PD psychosis included the presence of minor phenomena (HR 3.0, 95% CI 2.4-3.9, P < .001), positive response on the NMSQuest apathy/attention/memory domain (HR 1.8, 95% CI 1.3-2.6, P < .001), and positive RBD1Q (HR 1.5, 95% CI 1.1-1.9, P = .004). Minor phenomena are common, associated with specific non-motor symptoms, and an independent predictor of incident psychosis in PD.

Inhibition of Protein Aggregation and Endoplasmic Reticulum Stress as a Targeted Therapy for α-Synucleinopathy.

α-synuclein (α-syn) is an intrinsically disordered protein abundant in the central nervous system. Physiologically, the protein regulates vesicle trafficking and neurotransmitter release in the presynaptic terminals. Pathologies related to misfolding and aggregation of α-syn are referred to as α-synucleinopathies, and they constitute a frequent cause of neurodegeneration. The most common α-synucleinopathy, Parkinson's disease (PD), is caused by abnormal accumulation of α-syn in the dopaminergic neurons of the midbrain. This results in protein overload, activation of endoplasmic reticulum (ER) stress, and, ultimately, neural cell apoptosis and neurodegeneration. To date, the available treatment options for PD are only symptomatic and rely on dopamine replacement therapy or palliative surgery. As the prevalence of PD has skyrocketed in recent years, there is a pending issue for development of new disease-modifying strategies. These include anti-aggregative agents that target α-syn directly (gene therapy, small molecules and immunization), indirectly (modulators of ER stress, oxidative stress and clearance pathways) or combine both actions (natural compounds). Herein, we provide an overview on the characteristic features of the structure and pathogenic mechanisms of α-syn that could be targeted with novel molecular-based therapies.

Neuroprotective role for RORA in Parkinson’s disease revealed by analysis of post-mortem brain and a dopaminergic cell line

Parkinson’s disease (PD) is almost twice as prevalent in men, which has largely been attributed to neuroprotective effect of oestradiol in women. RORA (retinoic acid receptor-related orphan receptor alpha) regulates the transcription of central aromatase, the enzyme responsible for local oestradiol synthesis, simultaneously, RORA expression is regulated by sex hormones. Moreover, RORA protects neurones against oxidative stress, a key mechanism contributing to the loss of dopaminergic neurones in PD. Therefore, we hypothesized that there would be sex differences in RORA expression in the substantia nigra pars compacta (SNpc), which could contribute to sex differences observed in PD prevalence and pathogenesis. In a case control study, qPCR and western blot analyses were used to quantify gene and protein expression in the SNpc of post-mortem brains (n = 14 late-stage PD and 11 age and sex matched controls). The neuroprotective properties of a RORA agonist were then investigated directly using a cell culture toxin-based model of PD coupled with measures of viability, mitochondrial function and apoptosis. RORA was expressed at significantly higher levels in the SNpc from control females’ brains compared to males. In PD, we found a significant increase in SNpc RORA expression in male PD compared to female PD. Treatment with a RORA agonist showed a significant neuroprotection in our cell culture model of PD and revealed significant effects on intracellular factors involved in neuronal survival and demise. This study is the first to demonstrate a sex specific pattern of RORA protein and gene expression in the SNpc of controls post-mortem human brains, and to show that this is differentially altered in male and female PD subjects, thus supporting a role for RORA in sex-specific aspects of PD. Furthermore, our in vitro PD model indicates mechanisms whereby a RORA agonist exerts its neuroprotective effect, thereby highlighting the translational potential for RORA ligands in PD.

Tabular data augmentation for video-based detection of hypomimia in Parkinson’s disease

Background and Objective: This paper presents a method for the computerized detection of hypomimia in people with Parkinson’s disease (PD). It overcomes the difficulty of the small and unbalanced size of available datasets. Methods: A public dataset consisting of features of the video recordings of people with PD with four facial expressions was used. Synthetic data was generated using a Conditional Generative Adversarial Network (CGAN) for training augmentation. After training the model, Test-Time Augmentation was performed. The classification was conducted using the original test set to prevent bias in the results. Results: The employment of CGAN followed by Test-Time Augmentation led to an accuracy of classification of the videos of 83%, specificity of 82%, and sensitivity of 85% in the test set that the prevalence of PD was around 7% and where real data was used for testing. This is a significant improvement compared with other similar studies. The results show that while the technique was able to detect people with PD, there were a number of false positives. Hence this is suitable for applications such as population screening or assisting clinicians, but at this stage is not suitable for diagnosis. Conclusions: This work has the potential for assisting neurologists to perform online diagnose and monitoring their patients. However, it is essential to test this for different ethnicity and to test its repeatability.