Prediction of Future Parkinson Disease Using Plasma Proteins Combined With Clinical-Demographic Measures.

BACKGROUND AND OBJECTIVES: Identification of individuals at high risk of developing Parkinson disease (PD) several years before diagnosis is crucial for developing treatments to prevent or delay neurodegeneration. This study aimed to develop predictive models for PD risk that combine plasma proteins and easily accessible clinical-demographic variables. METHODS: Using data from the UK Biobank (UKB), which recruited participants across the United Kingdom, we conducted a longitudinal study to identify predictors for incident PD. Participants with baseline plasma proteins and no PD were included. Through machine learning, we narrowed down predictors from a pool of 1,463 plasma proteins and 93 clinical-demographic. These predictors were then externally validated using the Parkinson's Progression Marker Initiative (PPMI) cohort. To further investigate the temporal trends of predictors, a nested case-control study was conducted within the UKB. RESULTS: A total of 52,503 participants without PD (median age 58, 54% female) were included. Over a median follow-up duration of 14.0 years, 751 individuals were diagnosed with PD (median age 65, 37% female). Using a forward selection approach, we selected a panel of 22 plasma proteins for optimal prediction. Using an ensemble tree-based Light Gradient Boosting Machine (LightGBM) algorithm, the model achieved an area under the receiver operating characteristic curve (AUC) of 0.800 (95% CI 0.785-0.815). The LightGBM prediction model integrating both plasma proteins and clinical-demographic variables demonstrated enhanced predictive accuracy, with an AUC of 0.832 (95% CI 0.815-0.849). Key predictors identified included age, years of education, history of traumatic brain injury, and serum creatinine. The incorporation of 11 plasma proteins (neurofilament light, integrin subunit alpha V, hematopoietic PGD synthase, histamine N-methyltransferase, tubulin polymerization promoting protein family member 3, ectodysplasin A2 receptor, Latexin, interleukin-13 receptor subunit alpha-1, BAG family molecular chaperone regulator 3, tryptophanyl-TRNA synthetase, and secretogranin-2) augmented the model's predictive accuracy. External validation in the PPMI cohort confirmed the model's reliability, producing an AUC of 0.810 (95% CI 0.740-0.873). Notably, alterations in these predictors were detectable several years before the diagnosis of PD. DISCUSSION: Our findings support the potential utility of a machine learning-based model integrating clinical-demographic variables with plasma proteins to identify individuals at high risk for PD within the general population. Although these predictors have been validated by PPMI, additional validation in a more diverse population reflective of the general community is essential.

Association between Parkinson's disease and cardiovascular disease mortality: a prospective population-based study from NHANES.

BACKGROUND AND AIM: Conflicting results have been reported on the association between Parkinson's disease (PD) and cardiovascular disease (CVD) mortality in different populations. Therefore, studying the relationship between PD and CVD mortality is crucial to reduce mortality caused by the former. METHODS: In this cohort investigation, we enrolled 28,242 participants from the National Health and Nutrition Examination Survey spanning from 2003 to 2018. The 380 cases of PD in the cohort were identified by documenting 'ANTIPARKINSON AGENTS' in their reported prescription medications. Mortality outcomes were ascertained by cross-referencing the cohort database with the National Death Index, which was last updated on 31 December 2019. Cardiovascular disease mortality was categorised according to the 10th revision of the International Classification of Diseases by using a spectrum of diagnostic codes. Weighted multivariable Cox regression analysis was used to examine the association between PD and the risk of CVD mortality. RESULTS: A total of 28,242 adults were included in the study [mean age, 60.156 (12.55) years, 13,766 men (48.74%)], and the median follow-up period was 89 months. Individuals with PD had an adjusted HR of 1.82 (95% CI, 1.24-2.69; p = 0.002) for CVD mortality and 1.84 (95% CI, 1.44-2.33; p < 0.001) for all-cause mortality compared with those without PD. The association between PD and CVD mortality was robust in sensitivity analyses, after excluding participants who died within 2 years of follow-up and those with a history of cancer at baseline [HR,1.82 (95% CI, 1.20-2.75; p = 0.005)]. CONCLUSIONS: PD was associated with a high long-term CVD mortality rate in the US population.

Nonmotor Symptoms and Impulse Control Disorders in Parkinson's Disease Patients in India: A Cross-sectional Study.

INTRODUCTION: Parkinson's disease (PD) is a prevalent neurodegenerative disorder with significant nonmotor symptom (NMS) burden, including impulse control disorders. This study aimed to comprehensively evaluate NMS and impulse control disorders in PD patients under primary care. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted on 32 PD patients and evaluated using standardized assessment tools. Demographics, comorbidities, and symptom burdens were recorded. Evaluation tools included the Hoehn and Yahr Scale, REM Sleep Behavior Disorder assessment, Geriatric Depression Scale, Montreal Cognitive Assessment scale for cognitive impairment, NMS scale, and identification of impulse control disorders. RESULTS: In PD, comorbidities were prevalent (84%), and most were at Hoehn and Yahr Stages 2 and 3. REM Sleep Behavior Disorder was present in 28.12%, with 5 receiving clonazepam treatment. Depression affected 28.12%, with 5 receiving pharmacological treatment. Cognitive impairment was notable in 9 patients. NMS burden was high, with varying severity. Impulse control disorders were limited, whereas one case of dopamine dysregulation syndrome was identified. DISCUSSION: This primary care-based study in India assessed NMS and impulse control disorders in PD patients, highlighting comorbidities and management opportunities. The study's strength lies in evaluating an unselected primary care population, whereas limitations include small sample size. CONCLUSION: This study emphasizes the importance of primary care physicians in monitoring and managing NMS in PD patients. Impulse control disorders and cognitive impairment are critical aspects that need attention. The findings support an integrated approach involving health-care professionals across various disciplines to provide holistic care for PD patients.

Résumé Introduction:La maladie de Parkinson (PD) est un trouble neurodégénératif prévalent avec un fardeau significatif de symptômes non moteurs (NMS), y compris les troubles du contrôle des impulsions. Cette étude visait à évaluer de manière exhaustive les NMS et les troubles du contrôle des impulsions chez les patients atteints de la maladie de Parkinson pris en charge en soins primaires.Matériaux et méthodes:Une étude transversale descriptive a été menée sur 32 patients atteints de la maladie de Parkinson et évaluée à l'aide d'outils d'évaluation standardisés. Les données démographiques, les comorbidités et le fardeau des symptômes ont été enregistrés. Les outils d'évaluation comprenaient l'échelle de Hoehn et Yahr, l'évaluation du trouble du comportement en sommeil paradoxal (RBD), l'échelle de dépression gériatrique, l'échelle d'évaluation cognitive de Montréal pour les troubles cognitifs, l'échelle NMS et l'identification des troubles du contrôle des impulsions.Résultats:Chez les patients atteints de la maladie de Parkinson, les comorbidités étaient prévalentes (84 %), et la plupart étaient aux stades 2 et 3 de l'échelle de Hoehn et Yahr. Le trouble du comportement en sommeil paradoxal était présent chez 28,12 % des patients, dont 5 recevaient un traitement au clonazépam. La dépression affectait 28,12 % des patients, dont 5 recevaient un traitement pharmacologique. Une altération cognitive était notable chez 9 patients. Le fardeau des NMS était élevé, avec une gravité variable. Les troubles du contrôle des impulsions étaient limités, tandis qu'un cas de syndrome de dysrégulation dopaminergique a été identifié.Discussion:Cette étude menée en soins primaires en Inde a évalué les NMS et les troubles du contrôle des impulsions chez les patients atteints de la maladie de Parkinson, mettant en évidence les comorbidités et les opportunités de prise en charge. La force de l'étude réside dans l'évaluation d'une population de soins primaires non sélectionnée, tandis que les limites comprennent une petite taille d'échantillon.Conclusion:Cette étude souligne l'importance des médecins de soins primaires dans la surveillance et la prise en charge des NMS chez les patients atteints de la maladie de Parkinson. Les troubles du contrôle des impulsions et l'altération cognitive sont des aspects critiques qui nécessitent une attention particulière. Les résultats soutiennent une approche intégrée impliquant des professionnels de la santé de différentes disciplines pour fournir des soins holistiques aux patients atteints de la maladie de Parkinson.

Association of Body Mass Index and Parkinson Disease: A Bidirectional Mendelian Randomization Study.

BACKGROUND AND OBJECTIVES: The role of body mass index (BMI) in Parkinson disease (PD) is unclear. Based on the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in PD (Courage-PD) consortium, we used 2-sample Mendelian randomization (MR) to replicate a previously reported inverse association of genetically predicted BMI with PD and investigated whether findings were robust in analyses addressing the potential for survival and incidence-prevalence biases. We also examined whether the BMI-PD relation is bidirectional by performing a reverse MR. METHODS: We used summary statistics from a genome-wide association study (GWAS) to extract the association of 501 single-nucleotide polymorphisms (SNPs) with BMI and from the Courage-PD and international Parkinson Disease Genomics Consortium (iPDGC) to estimate their association with PD. Analyses are based on participants of European ancestry. We used the inverse-weighted method to compute odds ratios (ORIVW per 4.8 kg/m2 [95% CI]) of PD and additional pleiotropy robust methods. We performed analyses stratified by age, disease duration, and sex. For reverse MR, we used SNPs associated with PD from 2 iPDGC GWAS to assess the effect of genetic liability toward PD on BMI. RESULTS: Summary statistics for BMI are based on 806,834 participants (54% women). Summary statistics for PD are based on 8,919 (40% women) cases and 7,600 (55% women) controls from Courage-PD, and 19,438 (38% women) cases and 24,388 (51% women) controls from iPDGC. In Courage-PD, we found an inverse association between genetically predicted BMI and PD (ORIVW 0.82 [0.70-0.97], p = 0.012) without evidence for pleiotropy. This association tended to be stronger in younger participants (≤67 years, ORIVW 0.71 [0.55-0.92]) and cases with shorter disease duration (≤7 years, ORIVW 0.75 [0.62-0.91]). In pooled Courage-PD + iPDGC analyses, the association was stronger in women (ORIVW 0.85 [0.74-0.99], p = 0.032) than men (ORIVW 0.92 [0.80-1.04], p = 0.18), but the interaction was not statistically significant (p-interaction = 0.48). In reverse MR, there was evidence for pleiotropy, but pleiotropy robust methods showed a significant inverse association. DISCUSSION: Using an independent data set (Courage-PD), we replicate an inverse association of genetically predicted BMI with PD, not explained by survival or incidence-prevalence biases. Moreover, reverse MR analyses support an inverse association between genetic liability toward PD and BMI, in favor of a bidirectional relation.

Cardiovascular history and risk of idiopathic Parkinson's disease: a cross-sectional observational study.

BACKGROUND: Parkinson's disease (PD), while often associated with its distinctive motor symptoms, can also exert a notable impact on the cardiovascular system due to the development of severe autonomic dysfunction. One of the initial indicators of PD is the appearance of cardiovascular dysautonomia. As such, it is vital to monitor and manage cardiovascular health of individuals with PD, as it may have clinical implications in the development of commonly recognized motor and non-motor aspects of the disease. To study the association of history of cardiovascular disease (CVD) with occurrence and severity of PD, here, we lend data on the association of CVD history with the frequency and the occurrence of idiopathic PD (iPD) using data from the Luxembourg Parkinson's study (iPD n = 676 patients and non-PD n = 874 controls). RESULTS: We report that patients with a history of CVD are at high risk of developing iPD (odds ratio; OR = 1.56, 95% confidence interval; CI 1.09-2.08). This risk is stronger in males and remains significant after adjustment with confounders (OR 1.55, 95% CI 1.05-2.30). This increased susceptibility to iPD is linked to the severity of iPD symptoms mainly the non-motor symptoms of daily living (MDS-UPDRS I) and motor complications (MDS-UPDRS IV) in the affected individuals. CONCLUSION: Individuals with history of CVD have a high risk of developing severe forms of iPD. This observation suggests that careful monitoring and management of patients with a history of cardiac problems may reduce the burden of iPD.

COVID-19 and Parkinson's disease: a single-center study and Mendelian randomization study.

To investigate the association between COVID-19 and Parkinson's disease (PD) via a single-center study and a Mendelian randomization (MR) study. A questionnaire-based survey was conducted among PD patients at a single center from December 7, 2022, to March 10, 2023. Logistic regression analysis was performed to identify the infection-related risk factors. Subsequently, bidirectional two-sample Mendelian randomization was employed to explore the association between COVID-19 and PD. In the cross-sectional analysis, it was found that the prevalence of COVID-19 infection in PD patients was 65.7%. Forty-eight (35.3%) PD patients experienced exacerbation of motor symptoms following COVID-19 infection. Long PD disease duration (≥ 10 years) (OR: 3.327, P = 0.045) and long time since last vaccination (> 12 m) (OR: 4.916, P = 0.035) were identified as significant risk factors related to infection. The MR analysis results supported that PD increases the COVID-19 susceptibility (ß = 0.081, OR = 1.084, P = 0.006). However, the MR analysis showed that PD did not increases the COVID-19 severity and hospitalization, and no significant association of COVID-19 on PD was observed. The findings from this cross-sectional study suggest that individuals with PD may experience worsened motor symptoms following COVID-19 infection. Long disease duration (≥10 years) and long time since last vaccination (> 12 m) are identified as important risk factors for infection in these patients. Furthermore, our MR study provides evidence supporting an association between PD and COVID-19 susceptibility.

Stress perception and associated factors among patients with Parkinson's disease: a cross-sectional study after the COVID-19 pandemic.

BACKGROUND: Parkinson's disease (PD) is a serious neurodegenerative disease that brings great stress to the physical and mental health of patients. At the same time, long-term treatment will also bring great economic losses and social burden to the family and society, especially after COVID-19 pandemic. The aim of this study is to analyze the current status of stress perception and anxiety in patients with PD and explore the influencing factors after the COVID-19 pandemic. METHODS: This study used the convenient sampling method to select the research objects of patients with PD who were outpatients or inpatients in a general public hospital in Hangzhou, Zhejiang Province, and the survey time was from February 2023 to March 2023. The measurements included the General information questionnaire, The Perceived Stress Scale (PSS) and The Self Rating Anxiety Scale (SAS). SPSS 21.0 software was used for data statistical analysis. RESULT: 394 out of 420 patients with PD completed the questionnaire. The stress perception score of PD was (16.41 ± 6.435) and the anxiety score was (54.77 ± 10.477). The stress perception scores of patients with PD were significantly different in gender, age, educational, occupation, nature of costs, time of sleep, quality of sleep, duration of disease, way of medical treatment and anxiety level (p < 0.05). Among them, age, duration of disease, public expenses, online remote therapy and anxiety level were the main influencing factors of stress perception in patients with PD (p < 0.05). Besides, there were significant differences in gender, educational, nature of costs, time of sleep, quality of sleep and duration of disease in anxiety among patients with PD (p < 0.05). CONCLUSION: After the COVID-19 pandemic, the level of stress perception and anxiety in patients with PD is high, and the influencing factors are complex.

The combined effect of lifestyle factors and polygenic scores on age at onset in Parkinson's disease.

The objective of this study was to investigate the association between a Parkinson's disease (PD)-specific polygenic score (PGS) and protective lifestyle factors on age at onset (AAO) in PD. We included data from 4367 patients with idiopathic PD, 159 patients with GBA1-PD, and 3090 healthy controls of European ancestry from AMP-PD, PPMI, and Fox Insight cohorts. The association between PGS and lifestyle factors on AAO was assessed with linear and Cox proportional hazards models. The PGS showed a negative association with AAO (ß = - 1.07, p = 6 × 10-7) in patients with idiopathic PD. The use of one, two, or three of the protective lifestyle factors showed a reduction in the hazard ratio by 21% (p = 0.0001), 44% (p < 2 × 10-16), and 55% (p < 2 × 10-16), compared to no use. An additive effect of aspirin (ß = 7.62, p = 9 × 10-7) and PGS (ß = - 1.58, p = 0.0149) was found for AAO without an interaction (p = 0.9993) in the linear regressions, and similar effects were seen for tobacco. In contrast, no association between aspirin intake and AAO was found in GBA1-PD (p > 0.05). In our cohort, coffee, tobacco, aspirin, and PGS are independent predictors of PD AAO. Additionally, lifestyle factors seem to have a greater influence on AAO than common genetic risk variants with aspirin presenting the largest effect.

Prevalence of Thai patients with advanced Parkinson's disease and external validation of the 5-2-1 Criteria and the CDEPA Questionnaire: A single-centered, cross-sectional study.

BACKGROUND: Advanced stage of Parkinson's disease (APD) diagnosis is challenging for general neurologists. The 5-2-1 Criteria and the Cuestionario De Enfermedad de Parkinson Avanzada (CDEPA) have been validated for screening for APD. OBJECTIVE: This article reports the period-prevalence of APD defined by a movement disorder expert, the 5-2-1 Criteria, and CDEPA and to improve the screening performance of the 5-2-1 Criteria METHODS: A cross-sectional retrospective study at the Parkinson's disease (PD) clinic of a tertiary hospital in Bangkok, Thailand amongst all PD patients aged ≥ 18 years was performed from January 2016 to January 2020. We compared the characteristics of APD and non-APD patients. We externally validated the 5-2-1 Criteria and CDEPA. We explored improving the 5-2-1 Criteria. RESULTS: Of 480 PD patients with complete data, the period-prevalence of APD by the movement disorder expert, the 5-2-1 Criteria and CDEPA were 37.1 %, 48.5 %, and 27.5 %, respectively. Adding requiring help with an activity of daily living and freezing of gait to the original 5-2-1 Criteria enhanced the sensitivity from 86.5 % (95 %CI 80.6, 91.2) to 94.9 % (95 %CI 90.6, 97.7) and negative predictive value (NPV) from 90.3 % (95 %CI 85.9, 93.7) to 96 % (95 %CI 92.6, 98.2). However, the CDEPA had a sensitivity of 62.9 % (95 %CI 55.4, 70) and NPV of 81.0 (95 %CI 76.5, 85). CONCLUSION: The 5-2-1 Criteria had a good screening tool performance for general neurologists to refer APD patients for optimal treatments. The modified 5-2-1 Criteria had better performance than the original one. External validation is needed.

Temporal trends in the prevalence of Parkinson's disease from 1980 to 2023: a systematic review and meta-analysis.

BACKGROUND: Parkinson's disease is the second most common neurodegenerative disorder, exhibiting an upward trend in prevalence. We aimed to investigate the prevalence of Parkinson's disease, temporal trends between 1980 and 2023, and variations in prevalence by location, age, sex, survey period, sociodemographic index (SDI), human development index (HDI), and study characteristics (sample size, diagnostic criteria, and data source). METHODS: In this systematic review and meta-analysis we searched PubMed, Cochrane, Web of Science, Embase, Scopus, and Global Health for observational studies that reported Parkinson's disease prevalence in the general population from database inception to Nov 1, 2023. We included studies if they were original observational investigations, had participants from the general population or community-based datasets, and provided numerical data on the prevalence of Parkinson's disease either with 95% CIs or with sufficient information to calculate 95% CIs. Studies were excluded if they were conducted in a specific population, had a sample size smaller than 1000, or were review articles, case reports, protocols, meeting abstracts, letters, comments, short communications, posters, and reports. The publication characteristics (first author and publication year), study location (countries, WHO regions, SDI, and HDI), survey period, study design, diagnostic criteria, data source, participant information, and prevalence data were extracted from articles using a standard form. Two authors independently evaluated eligibility, and discrepancies were resolved through discussion with the third author. We used random effect models to pool estimates with 95% CIs. Estimated annual percentage change (EAPC) was calculated to assess the temporal trend in prevalence of Parkinson's disease. The study was registered with PROSPERO, CRD42022364417. FINDINGS: 83 studies from 37 countries were eligible for analysis, with 56 studies providing all-age prevalence, 53 studies reporting age-specific prevalence, and 26 studies providing both all-age and age-specific prevalence. Global pooled prevalence of Parkinson's disease was 1·51 cases per 1000 (95% CI 1·19-1·88), which was higher in males (1·54 cases per 1000 [1·17-1·96]) than in females (1·49 cases per 1000 [1·12-1·92], p=0·030). During different survey periods, the prevalence of Parkinson's disease was 0·90 cases per 1000 (0·48-1·44; 1980-89), 1·38 cases per 1000 (1·17-1·61; 1990-99), 1·18 cases per 1000 (0·77-1·67; 2000-09), and 3·81 cases per 1000 (2·67-5·14; 2010-23). The EAPC of Parkinson's disease prevalence was significantly higher in the period of 2004-23 (EAPC 16·32% [95% CI 6·07-26·58], p=0·0040) than in the period of 1980-2003 (5·30% [0·82-9·79], p=0·022). Statistically significant disparities in prevalence were observed across six WHO regions. Prevalence increased with HDI or SDI. Considerable variations were observed in the pooled prevalence of Parkinson's disease based on different sample sizes or diagnostic criteria. Prevalence also increased with age, reaching 9·34 cases per 1000 (7·26-11·67) among individuals older than 60 years. INTERPRETATION: The global prevalence of Parkinson's disease has been increasing since the 1980s, with a more pronounced rise in the past two decades. The prevalence of Parkinson's disease is higher in countries with higher HDI or SDI. It is necessary to conduct more high-quality epidemiological studies on Parkinson's disease, especially in low SDI countries. FUNDING: National Nature Science Foundation of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

21st century accelerating neurological deaths in UK and major Western countries: - Demographic and/or multiple-interactive-environmental causes?

OBJECTIVE: We examine whether the rise in neurological death rates over the 21st century are solely explained by the Gompertzian hypothesis. STUDY DESIGN: We examine two data-sets. First, Office of National Statistics (ONS, 2022) for nineteen mortality categories in England/Wales, including Alzheimer's, Dementias and Parkinson's Disease. Secondly, WHO (2020) Combined Neurological Mortality (CNM), from WHO Global mortality categories, Nervous Disease Deaths, and Alzheimer's & Other Dementias. METHODS: Based on ONS data we investigate trends in Age-Standardised Mortality Rates (ASMR) of CNM 2000-2022. Based on WHO data we examine rates of Early Deaths (55-74) and ASMR, for CNM between 2000 and 2015 in the ten Major 'Western' economies: Australia, Canada, France, Germany, Italy, Japan, Netherlands, Spain, UK, and the USA. RESULTS: In England & Wales death rates have increased 348% for Alzheimer's, 235% for Dementias, and 105% for Parkinson's Disease in contrast with falls in most other cause mortality. Early Adults Deaths CNM rates increased in eight countries, an average of 19%. Neurological ASMR rose in every country, averaging 43%, the highest was the UK 95%. CONCLUSION: We reject the Gompertzian hypothesis as an all-encompassing explanation for these marked increases in ASMR. Increases in early adult neurological deaths suggests this cannot be solely explained by an aging population. Furthermore, increases in mortality could be related to an increased prevalence of neurological conditions in this age group. Action is urgently needed to investigate factors - whether environmental, lifestyle or health systems - that could explain these findings.

Global, regional, and national health inequalities of Alzheimer's disease and Parkinson's disease in 204 countries, 1990-2019.

BACKGROUND: Alzheimer's disease and related dementias (ADRD) and Parkinson's disease (PD), pose growing global health challenges. Socio-demographic and economic development acts paradoxically, complicating the process that determines how governments worldwide designate policies and allocate resources for healthcare. METHODS: We extracted data on ADRD and PD in 204 countries from the Global Burden of Disease 2019 database. Health disparities were estimated using the slope index of inequality (SII), and concentration index (CIX) based on the socio-demographic index. Estimated annual percentage changes (EAPCs) were employed to evaluate temporal trends. RESULTS: Globally, the SII increased from 255.4 [95% confidence interval (CI), 215.2 to 295.5)] in 1990 to 559.3 (95% CI, 497.2 to 621.3) in 2019 for ADRD, and grew from 66.0 (95% CI, 54.9 to 77.2) in 1990 to 132.5 (95% CI, 118.1 to 147.0) in 2019 for PD; CIX rose from 33.7 (95% CI, 25.8 to 41.6) in 1990 to 36.9 (95% CI, 27.8 to 46.1) in 2019 for ADRD, and expanded from 22.2 (95% CI, 21.3 to 23.0) in 1990 to 29.0 (95% CI, 27.8 to 30.3) in 2019 for PD. Age-standardized disability-adjusted life years displayed considerable upward trends for ADRD [EAPC = 0.43 (95% CI, 0.27 to 0.59)] and PD [0.34 (95% CI, 0.29 to 0.38)]. CONCLUSIONS: Globally, the burden of ADRD and PD continues to increase with growing health disparities. Variations in health inequalities and the impact of socioeconomic development on disease trends underscored the need for targeted policies and strategies, with heightened awareness, preventive measures, and active management of risk factors.

Patterns and determinants of health care utilization among people with Parkinson's disease: A population-based analysis in Ontario, Canada.

In Ontario, despite the increasing prevalence of Parkinson's disease (PD), barriers to access-to-care for people with Parkinson's disease (PwP) and their caregivers are not well understood. The objective of this study is to examine spatial patterns of health care utilization among PwP and identify factors associated with PD-related health care utilization of individuals in Ontario. We employed a retrospective, population-based study design involving administrative health data to identify PwP as of March 31, 2018 (N = 35,482) using a previously validated case definition. An enhanced 2-step floating catchment area method was used to measure spatial accessibility to PD care and a descriptive spatial analysis was conducted to describe health service utilization by geographic area and specialty type. Negative binomial regression models were then conducted to identify associated geographic, socioeconomic, comorbidity and demographic factors. There was marked spatial variability in PD-related service utilization, with neurology and all provider visits being significantly higher in urban areas (CMF>1.20; p<0.05) and family physician visits being significantly higher (CMF >1.20; p<0.05) in more rural areas and remote areas. More frequent visits to family physicians were associated with living in rural areas, while less frequent visitation was associated with living in areas of low spatial accessibility with high ethnic concentration. Visits to neurologists were positively associated with living in areas of high spatial accessibility and with high ethnic concentration. Visits to all providers were also positively associated with areas of high spatial accessibility. For all outcomes, less frequent visits were found in women, older people, and those living in more deprived areas as years living with PD increased. This study demonstrates the importance of geographic, socioeconomic and individual factors in determining PwP's likelihood of accessing care and type of care provided. Our results can be expected to inform the development of policies and patient care models aimed at improving accessibility among diverse populations of PwP.

Association of metabolic syndrome and its components with Parkinson's disease: a cross-sectional study.

BACKGROUND: The interrelation between metabolic syndrome (MetS) and Parkinson's disease (PD) likely arises from shared pathological mechanisms. This study thus aims to examine the impact of MetS and its components on PD. METHODS: This study utilized data extracted from the National Health and Nutrition Examination Survey database spanning 1999 to 2020. The random forest algorithm was applied to fill in the missing data. Propensity score optimal full matching was conducted. The data were adjusted by total weights derived from both sampling and matching weights. The weighted data were utilized to create multifactor logistic regression models. Odds ratios (ORs) and average marginal effects, along with their corresponding 95% confidence intervals (CIs), were calculated. RESULTS: MetS did not significantly affect the risk of PD (OR: 1.01; 95% CI: 0.77, 1.34; P = 0.92). Hypertension elevated the risk of PD (OR: 1.33; 95% CI: 1.01, 1.76; P = 0.045), accompanied by a 0.26% increased probability of PD occurrence (95% CI: 0.01%, 0.52%; P = 0.04). Diabetes mellitus (DM) had a 1.38 times greater likelihood of developing PD (OR:1.38; 95% CI: 1.004, 1.89; P = 0.046), corresponding to a 0.32% increased probability of PD occurrence (95% CI: -0.03%, 0.67%; P = 0.07). Nevertheless, no correlation was observed between hyperlipidemia, waist circumference and PD. CONCLUSION: MetS does not affect PD; however, hypertension and DM significantly increase the risk of PD.

Incidence of Parkinson's disease in Germany based on prevalence data from 70 million patients of the statutory health insurance.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and nonmotor system manifestations and psychiatric symptoms. The aim of this study was to estimate the age- and sex-specific incidence of PD in Germany using an illness-death model and a corresponding partial differential equation (PDE) based on prevalence and mortality data. METHODS: Based on a PDE that describes the dynamics in an illness-death model, the age- and sex-specific incidence of PD in Germany was estimated using published prevalence and mortality rates. Prevalence rates were provided by the Central Institute for Statutory Health Insurance (Zi) for the period from 2010 to 2019. Parkinson's related mortality was estimated based on comparable population data from Norway. Bootstrapping was used for incidence estimation (median of 5000 samples) and to obtain 95% confidence intervals to interpret the accuracy of the incidence estimation. RESULTS: Men had higher incidences of PD than women at all ages. The highest incidences (median of 5000 bootstrap samples) for both groups were estimated for the age of 85 years with an incidence of 538.49 per 100,000 person-years (py) in men and 284.09 per 100,000 py in women, with an increasing width of bootstrapping 95% CIs showing greater uncertainty in the estimation at older ages. CONCLUSION: The illness-death model and the corresponding PDE, which describes changes in prevalence as a function of mortality and incidence, can be used to estimate the incidence of PD as a chronic disease. As overestimation of incidence is less likely with this method, we found incidence rates of Parkinson's disease that are suitable for further analyses with a lower risk of bias.

Unraveling sex differences in Parkinson's disease through explainable machine learning.

Sex differences affect Parkinson's disease (PD) development and manifestation. Yet, current PD identification and treatments underuse these distinctions. Sex-focused PD literature often prioritizes prevalence rates over feature importance analysis. However, underlying aspects could make a feature significant for predicting PD, despite its score. Interactions between features require consideration, as do distinctions between scoring disparities and actual feature importance. For instance, a higher score in males for a certain feature doesn't necessarily mean it's less important for characterizing PD in females. This article proposes an explainable Machine Learning (ML) model to elucidate these underlying factors, emphasizing the importance of features. This insight could be critical for personalized medicine, suggesting the need to tailor data collection and analysis for males and females. The model identifies sex-specific differences in PD, aiding in predicting outcomes as "Healthy" or "Pathological". It adopts a system-level approach, integrating heterogeneous data - clinical, imaging, genetics, and demographics - to study new biomarkers for diagnosis. The explainable ML approach aids non-ML experts in understanding model decisions, fostering trust and facilitating interpretation of complex ML outcomes, thus enhancing usability and translational research. The ML model identifies muscle rigidity, autonomic and cognitive assessments, and family history as key contributors to PD diagnosis, with sex differences noted. The genetic variant SNCA-rs356181 may be more significant in characterizing PD in males. Interaction analysis reveals a greater occurrence of feature interplay among males compared to females. These disparities offer insights into PD pathophysiology and could guide the development of sex-specific diagnostic and therapeutic approaches.

Hospital-treated infectious diseases, infection burden and risk of Parkinson disease: An observational and Mendelian randomization study.

BACKGROUND: Experimental and cross-sectional evidence has suggested a potential role of infection in the ethology of Parkinson's disease (PD). We aim to examine the longitudinal association of infections with the incidence of PD and to explore whether the increased risk is limited to specific infection type rather than infection burden. METHODS: Based on the UK Biobank, hospital-treated infectious diseases and incident PD were ascertained through record linkage to national hospital inpatient registers. Infection burden was defined as the sum of the number of infection episodes over time and the number of co-occurring infections. The polygenic risk score (PRS) for PD was calculated. The genome-wide association studies (GWAS) used in two-sample Mendelian Randomization (MR) were obtained from observational cohort participants of mostly European ancestry. RESULTS: Hospital-treated infectious diseases were associated with an increased risk of PD (adjusted HR [aHR] 1.35 [95 % CI 1.20-1.52]). This relationship persisted when analyzing new PD cases occurring more than 10 years post-infection (aHR 1.22 [95 % CI 1.04-1.43]). The greatest PD risk was observed in neurological/eye infection (aHR 1.72 [95 % CI 1.32-2.34]), with lower respiratory tract infection (aHR 1.43 [95 % CI 1.02-1.99]) ranked the second. A dose-response association was observed between infection burden and PD risk within each PD-PRS tertile (p-trend < 0.001). Multivariable MR showed that bacterial and viral infections increase the PD risk. CONCLUSIONS: Both observational and genetic analysis suggested a causal association between infections and the risk of developing PD. A dose-response relationship between infection burden and incident PD was revealed.

Prevalence of radicular neuropathic pain in idiopathic Parkinson's disease: A systematic review and meta-analysis.

Parkinson's disease (PD) is estimated to impact up to 1 % of the global population aged 60 years and older. Among the non-motor manifestations of idiopathic PD, radicular neuropathic pain emerges as a noteworthy concern due to its potential for debility in affected individuals. In, this systematic review and meta-analysis we aimed to evaluate the prevalence of radicular neuropathic pain and thus provide evidence of how this painful symptom affects the lives of patients with idiopathic PD. We registered the research protocol for this study in PROSPERO (CRD42022327220). We searched the Embase, Scopus, and PubMed platforms for studies on PD and neuropathic pain until April 2023. The search yielded 36 articles considered to have a low risk of bias. The prevalence of radicular neuropathic pain in patients with PD was 12.7 %, without a difference when we consider the duration of diagnosis (cut-off < 7 years) or levodopa dosage (cut-off <600 mg/dL). Moreover, there was no variation in the prevalence of radicular neuropathic pain regarding a Hoehn and Yahr stage cut-off of <2.5 or >2.5. Of note, a limited number of patients received pain treatment (21.5 %). We also found that the source of publication bias is the use of the Ford criteria (FC), suggesting that this type of diagnostic criteria may contribute to an underdiagnosis of radicular neuropathic pain in patients with PD. This study underlines the necessity for a more discerning and comprehensive approach to the diagnosis and management of radicular neuropathic pain in patients with idiopathic PD.

Osteoporosis in Parkinson's disease and the role of lean body mass: a cross-sectional study in a Brazilian tertiary center.

Background: Parkinson's disease (PD) is the second most common neurodegenerative illness and has the highest increase rate in recent years. There is growing evidence to suggest that PD is linked to higher osteoporosis rates and risk of fractures. Objective: This study aims to estimate the prevalence and factors associated with osteoporosis as defined by the National Osteoporosis Foundation (NOF) and World Health Organization in patients with mild to moderate PD. Methods: We performed a cross-sectional study at a tertiary public hospital in Fortaleza, Brazil, dating from May 2021 until April 2022. The study sample was comprised of patients with mild to moderate PD who were at least 40 years old and who had the ability to walk and stand unassisted. Bone Mineral Density (BMD) of both the hip (neck of the femur) and the lumbar spine were obtained via properly calibrated Dual Energy X-ray Absorptiometry (DXA) scanning. The FRAX (Fracture Risk Assessment Tool) score was used to determine a person's 10-year risk of major osteoporotic fracture. The Revised European Working Group on Sarcopenia in Older People (EWGSOP 2) was used as a basis to confirm a sarcopenia diagnosis with the following parameters: low muscle strength gauged by handgrip strength and low muscle quantity by DXA. Physical performance was carefully evaluated by using the Short Physical Performance Battery test. Osteoporosis and osteopenia were diagnosed following the NOF guidelines and WHO recommendations. Results: We evaluated 107 patients in total, of whom 45 (42%) were women. The group's mean age was 68 ± 9 years, and the mean disease time span was 9.9 ± 6.0 years and mean motor UPDRS was 43 ± 15. We found that 42.1% and 34.6% of the sample had osteopenia and osteoporosis following NOF criteria, respectively, and 43% and 33.6% following the WHO recommendations. Lower lean appendicular mass was associated to osteopenia and osteoporosis in multinomial logistic regression analysis in both diagnostic criteria. Conclusion: Our findings provide additional evidence for the protective role of lean mass against osteoporosis in patients with PD.

Enhancing recruitment of individuals living with frailty, multimorbidity and cognitive impairment to Parkinson's research: experiences from the PRIME-UK cross-sectional study.

BACKGROUND AND OBJECTIVES: People with parkinsonism who are older, living in a care home, with frailty, multimorbidity or impaired capacity to consent are under-represented in research, limiting its generalisability. We aimed to evaluate more inclusive recruitment strategies. METHODS: From one UK centre, we invited people with parkinsonism to participate in a cross-sectional study. Postal invitations were followed by telephone reminders and additional support to facilitate participation. Personal consultees provided information on the views regarding research participation of adults with impaired capacity. These approaches were evaluated: (i) using external data from the Parkinson's Real World Impact assesSMent (PRISM) study and Clinical Practice Research Datalink (CPRD), a sample of all cases in UK primary care, and (ii) comparing those recruited with or without intensive engagement. RESULTS: We approached 1,032 eligible patients, of whom 542 (53%) consented and 477 (46%) returned questionnaires. The gender ratio in PRIME-UK (65% male) closely matched CPRD (61% male), unlike in the PRISM sample (46%). Mean age of PRIME participants was 75.9 (SD 8.5) years, compared to 75.3 (9.5) and 65.4 (8.9) years for CPRD and PRISM, respectively. More intensive engagement enhanced recruitment of women (13.3%; 95% CI 3.8, 22.9%; P = 0.005), care home residents (6.2%; 1.1, 11.2%; P = 0.004), patients diagnosed with atypical parkinsonism (13.7%; 5.4, 19.9%; P < 0.001), and those with a higher frailty score (mean score 0.2, 0.1, 0.2; P < 0.001). CONCLUSIONS: These recruitment strategies resulted in a less biased and more representative sample, with greater inclusion of older people with more complex parkinsonism.