Incidence Of Parkinson's Disease Research Articles

Genetic analysis and natural history of Parkinson's disease due to the LRRK2 G2019S variant.

The LRRK2 G2019S variant is the most common cause of monogenic Parkinson's disease (PD); however, questions remain regarding the penetrance, clinical phenotype and natural history of carriers. We performed a 3.5-year prospective longitudinal online study in a large number of 1286 genotyped LRRK2 G2019S carriers and 109 154 controls, with and without PD, recruited from the 23andMe Research Cohort. We collected self-reported motor and non-motor symptoms every 6 months, as well as demographics, family histories and environmental risk factors. Incident cases of PD (phenoconverters) were identified at follow-up. We determined lifetime risk of PD using accelerated failure time modelling and explored the impact of polygenic risk on penetrance. We also computed the genetic ancestry of all LRRK2 G2019S carriers in the 23andMe database and identified regions of the world where carrier frequencies are highest. We observed that despite a 1 year longer disease duration (P = 0.016), LRRK2 G2019S carriers with PD had similar burden of motor symptoms, yet significantly fewer non-motor symptoms including cognitive difficulties, REM sleep behaviour disorder (RBD) and hyposmia (all P-values ≤ 0.0002). The cumulative incidence of PD in G2019S carriers by age 80 was 49%. G2019S carriers had a 10-fold risk of developing PD versus non-carriers. This rose to a 27-fold risk in G2019S carriers with a PD polygenic risk score in the top 25% versus non-carriers in the bottom 25%. In addition to identifying ancient founding events in people of North African and Ashkenazi descent, our genetic ancestry analyses infer that the G2019S variant was later introduced to Spanish colonial territories in the Americas. Our results suggest LRRK2 G2019S PD appears to be a slowly progressive predominantly motor subtype of PD with a lower prevalence of hyposmia, RBD and cognitive impairment. This suggests that the current prodromal criteria, which are based on idiopathic PD, may lack sensitivity to detect the early phases of LRRK2 PD in G2019S carriers. We show that polygenic burden may contribute to the development of PD in the LRRK2 G2019S carrier population. Collectively, the results should help support screening programmes and candidate enrichment strategies for upcoming trials of LRRK2 inhibitors in early-stage disease.

Clarifying the association between Parkinson’s disease and vitiligo: a population-based large-scale study

ObjectiveOur knowledge about the association between vitiligo and Parkinson’s disease (PD) is sparse. We sought to investigate the bidirectional epidemiological association between vitiligo and PD.MethodsA population-based study was conducted using Clalit Health Services (CHS) database (2002–2019) using both a cohort study and a case–control study design. Adjusted hazard ratio (HR) and odds ratio (OR) were calculated by multivariate Cox and logistic regressions, respectively.ResultsOverall, 20,851 vitiligo patients and 102,475 controls were included. The incidence of new-onset PD was 2.9 (95% CI, 2.1–4.1) and 4.3 (95% CI, 3.8–4.9) cases per 10,000 person-years among patients with vitiligo and controls, respectively. Patients with vitiligo had a significantly decreased risk of developing new-onset PD [adjusted HR, 0.62; 95% confidence interval (CI), 0.43–0.89, p = 0.009]. On the other hand, the likelihood of having vitiligo after a preexisting diagnosis of PD was not statistically different (adjusted OR, 0.80; 95% CI, 0.61–1.06; p = 0.117). Relative to the remaining patients with vitiligo, those with vitiligo and comorbid PD experienced an elevated risk of all-cause mortality (adjusted HR, 2.63; 95% CI, 1.82–3.80; p < 0.001) and higher prevalence of cardiometabolic comorbidities.ConclusionVitiligo is associated with a lower risk of developing PD. The presence of comorbid PD predisposes patients with vitiligo to elevated mortality and cardiometabolic outcomes.

Use of antiviral drugs and incidence of Parkinson's disease in Taiwan.

Patients infected with herpes zoster might be at risk for Parkinson's disease (PD). However, antiviral drugs may impede viral deoxyribonucleic acid (DNA) synthesis. This study aimed to determine whether the currently observed association between herpes zoster and PD is consistent with previous findings, and whether antiviral drug use is associated with PD. This retrospective cohort study used the Longitudinal Generation Tracking Database. We included patients aged 40 years and above and applied propensity score matching at 1:1 ratio for study comparability. PD risk was evaluated using Cox proportional hazards regression methods. A total of 234,730 people were analyzed. The adjusted hazard ratio (aHR) for PD in patients with herpes zoster was 1.05. Furthermore, the overall incidence of PD was lower in those treated with antiviral drugs than in the untreated ones (3.17 vs. 3.76 per 1,000 person-years); the aHR was 0.84. After stratifying for sex or age, a similar result was observed. In conclusion, herpes zoster may increase the risk of PD, particularly among females, but receiving antiviral treatment reduces the risk by 16%. Therefore, using antiviral drugs may help prevent PD. However, additional research is required to determine the underlying mechanism(s).

Risk of Parkinson’s disease among users of alpha-adrenergic receptor antagonists: a systematic review and meta-analysis

Background: Recent studies have tried to establish an association between the use of alpha-1-adrenergic receptor antagonists (A1ARAs) used in benign prostatic hyperplasia (BPH) and the risk of PD. The objective of the study is to compare the risk of Parkinson’s disease (PD) between terazosin/alfuzosin/doxazosin (TZ/AZ/DZ) users and tamsulosin users. Methods: PubMed, Google Scholar, and Embase were systematically searched from inception to April 2023. Observational studies comparing the risk of PD among patients using different types of A1ARAs were included in the meta-analysis. The primary outcome was the hazard ratio (HR) with a 95% CI for the risk of occurrence of PD among A1ARAs users of two different classes. Results: This study was based on a total of 678 433 BPH patients, out of which 287 080 patients belonged to the TZ/AZ/DZ cohort and 391 353 patients belonged to the tamsulosin cohort. The pooled incidence of PD was higher in tamsulosin users (1.28%, 95% CI: 1.04–1.55%) than in TZ/AZ/DZ drug users (1.11%, 95% CI: 0.83–1.42%). The risk of occurrence of PD was significantly lower in patients taking TZ/AZ/DZ than tamsulosin (n= 610,363, HR = 0.82, 95% CI = 0.71–0.94, P = 0.01; I2 = 87.4%). Conclusion: This meta-analysis demonstrated that patients with BPH who take TZ/AZ/DZ have a lower risk for developing PD than those who take tamsulosin.

Disease burden of Parkinson's disease in China and its provinces from 1990 to 2021: findings from the global burden of disease study 2021

Parkinson's disease (PD) has become a public health concern with global ageing. However, comprehensive assessments of the temporal and geographical trend of PD disease burden in China remain insufficient. This study aimed to examine the burden of PD by age, gender, and geographical region in China during 1990-2021. Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, we analysed the incidence, prevalence, mortality, and DALY burden of PD in 33 Chinese provinces/regions. We compared the national figure with the global average and the corresponding estimates from the G20 countries. The estimated annual percentage change (EAPC) was used to quantify the temporal trends of PD burden during 1990-2021. We further assessed the PD burden by age and gender during 1990-2021. We used a decomposition analysis to investigate the changes in the number of new cases, patients, and deaths of PD during 1990-2021. In 2021, China recorded the highest age-standardised incidence and prevalence of PD among the G20 countries, at 24.3 per 100,000 and 245.7 per 100,000, respectively, figures that were much higher than the global average. During 1990-2021, the age-standardised incidence of PD in China increased by 89.7%, and the age-standardised prevalence by 167.8%, both marking the largest increases among the G20 countries. In contrast, the age-standardised mortality for PD has significantly decreased since 1990, whereas the age-standardised DALY rate for PD has remained relatively unchanged since 1990. The PD burden gradually increased with age, especially in the elderly population aged ≥65 years. During 1990-2021, the burden in males consistently surpassed that in females, with the gender difference widening over time. The increase in new cases and patients of PD was primarily driven by changes in age-specific rates, while the rise in PD-related deaths was largely attributable to population ageing. The disease burden of PD varied considerably across the Chinese provinces. In 2021, age-standardised incidence and prevalence of PD were generally higher in China's southeastern coastal regions than in the western regions, and age-standardised DALY rates were higher in the northern regions than in other regions. The disease burden of PD in China has consistently risen over the past three decades, particularly among elderly men. The increasing causative factors and population aging highlight the need for enhancing public health intervention and resource allocation, especially in etiological research, early diagnosis, preventive strategies, and region-specific management for PD. Ministry of Science and Technology of the People's Republic of China (2022YFC2304900, 2022YFC2505100); National Key R&D Program of China (2022YFC2505100, 2022YFC2505103, 2018YFC1315300); Outstanding Young Scholars Support Program (grant number: 3111500001); Epidemiology modeling and risk assessment (grant number: 20200344), and Xi'an Jiaotong University Young Scholar Support Grant (grant number: YX6J004).

Renin-angiotensin system inhibitor use and risk of Parkinson's disease: a meta-analysis.

Hypertension is a recognized risk factor for Parkinson's disease (PD). The renin-angiotensin system (RAS) inhibitors are widely used to treat hypertension. However, the association of RAS inhibitor use with PD has still been an area of controversy. Thus, we conducted a meta-analysis to investigate the relationship between RAS inhibitor use and PD. PUBMEDand EMBASE databases were searched for articles published up to Oct 2023. All studies that examined the relationship between RAS inhibitor use and the incidence of PD were included. Seven studies with total 3,495,218 individuals met our inclusion criteria for this meta-analysis. Overall, RAS inhibitor use was associated with a reduction in PD risk (OR = 0.88, 95%CI = 0.79-0.98) compared with the controls. When restricted the analysis to individuals with RAS inhibitor use indication, RAS inhibitor exposure was also associated with a decreased risk of PD (OR = 0.76, 95%CI = 0.62-0.92). Pooled results of cohort studies also did support a protective role of angiotensin converting enzyme inhibitors (ACEIs) (OR = 0.97, 95%CI = 0.89-1.07) users and angiotensin II receptor blockers (ARBs) (OR = 0.8, 95%CI = 0.63-1.02) in PD. Overall, RAS inhibitor use as a class is associated with a reduction in PD risk. However, the findings of ACEIs and ARBs may be limited by small sample size. Future well-designed studies considering the classification by inhibitor type, duration, dose, or property of BBB penetration of RAS inhibitors are needed to clarify the contribution of these exposure parameters on the risk of PD.

Association of Coffee Consumption and Prediagnostic Caffeine Metabolites With Incident Parkinson Disease in a Population-Based Cohort.

Inverse associations between caffeine intake and Parkinson disease (PD) have been frequently implicated in human studies. However, no studies have quantified biomarkers of caffeine intake years before PD onset and investigated whether and which caffeine metabolites are related to PD. Associations between self-reported total coffee consumption and future PD risk were examined in the EPIC4PD study, a prospective population-based cohort including 6 European countries. Cases with PD were identified through medical records and reviewed by expert neurologists. Hazard ratios (HRs) and 95% CIs for coffee consumption and PD incidence were estimated using Cox proportional hazards models. A case-control study nested within the EPIC4PD was conducted, recruiting cases with incident PD and matching each case with a control by age, sex, study center, and fasting status at blood collection. Caffeine metabolites were quantified by high-resolution mass spectrometry in baseline collected plasma samples. Using conditional logistic regression models, odds ratios (ORs) and 95% CIs were estimated for caffeine metabolites and PD risk. In the EPIC4PD cohort (comprising 184,024 individuals), the multivariable-adjusted HR comparing the highest coffee intake with nonconsumers was 0.63 (95% CI 0.46-0.88, p = 0.006). In the nested case-control study, which included 351 cases with incident PD and 351 matched controls, prediagnostic caffeine and its primary metabolites, paraxanthine and theophylline, were inversely associated with PD risk. The ORs were 0.80 (95% CI 0.67-0.95, p = 0.009), 0.82 (95% CI 0.69-0.96, p = 0.015), and 0.78 (95% CI 0.65-0.93, p = 0.005), respectively. Adjusting for smoking and alcohol consumption did not substantially change these results. This study demonstrates that the neuroprotection of coffee on PD is attributed to caffeine and its metabolites by detailed quantification of plasma caffeine and its metabolites years before diagnosis.

Longitudinal cognitive decline characterizes the profile of non-PD-manifest GBA1 mutation carriers

With disease-modifying treatment for Parkinson’s disease (PD) associated with variants in the glucocerebrosidase gene (GBA1) under way, the challenge to design clinical trials with non-PD-manifest GBA mutation carriers (GBA1NMC) comes within close reach. To delineate trajectories of motor and non-motor markers as well as serum neurofilament light (sNfL) levels and to evaluate clinical endpoints as outcomes for clinical trials in GBA1NMC, longitudinal data of 56 GBA1NMC carriers and 112 age- and sex-matched GBA1 wildtype participants (GBA1wildtype) with up to 9 years of follow-up was analyzed using linear mixed-effects models (LMEM) and Kaplan–Meier survival analysis of clinical endpoints for motor and cognitive function. GBA1NMC showed worse performance in Pegboard, 20 m fast walking, global cognition as well as in executive and memory function at baseline. Longitudinally, LMEM revealed a higher annual increase of the MDS-UPDRS III bradykinesia subscore in GBA1NMC compared to GBA1wildtype, but comparable trajectories of all other motor and non-motor markers as well as sNfL. Kaplan–Meier survival analysis showed a significantly earlier progression to clinical endpoints of cognitive decline in GBA1NMC. Incidence of PD was significantly higher in GBA1NMC. In conclusion, our study extends data on GBA1NMC indicating early cognitive decline as a potentially characteristic feature. Comprehensive longitudinal assessments of cognitive function are crucial to delineate the evolution of early changes in GBA1NMC enabling a more accurate stratification and allow for a more precise definition of trial design and sample size.

Risk of Parkinson's disease in people with New Onset Anxiety over 50 years - Incidence and Associated Features.

Anxiety has been identified as a prodromal feature of Parkinson's disease (PD). The prospective risk of PD in those newly presenting with anxiety and factors that increase the risk of PD in patients with anxiety have not been investigated. To investigate the incidence of PD in people with anxiety above the age 50 years and clinical features associated with later diagnosis of PD in people with anxiety. Retrospective cohort study using UK primary care data of people between 2008 and 2018 who had new onset anxiety over the age of 50 years. We fitted Weibull survival regression models and estimated hazard ratios (HR) for modelling time-to-PD in those with and without anxiety and when determining the risk of developing PD in those with anxiety. Results were adjusted for sociodemographic and lifestyle factors and relevant physical and mental health conditions. The risk of PD was increased 2-fold compared to the non-anxiety group after adjustment for age, sex, social deprivation, lifestyle factors, severe mental illness, head trauma and dementia HR 2.1 (CI: 1.9-2.4). In those with anxiety, the presence of depression, hypotension, tremor, rigidity, balance impairment, constipation, sleep disturbance, fatigue, and cognitive impairment were associated with an increased risk of developing PD. The risk of developing PD was at least doubled in people with anxiety compared to those without. The clinical features of those who developed PD can help identify patients presenting with anxiety who are in the prodromal phase of PD.

Association of antihypertensives and Parkinson's disease in a primary care population matched for underlying diagnosis.

To examine the association of several antihypertensive medication classes with incidence of Parkinson's disease (PD), taking into account possible underlying conditions. In a case-control study based on a large primary care database and including 21,981 PD cases and 21,981 non-PD controls matched for age, sex, and possible treatment indications associations with different antihypertensive medication groups, including diuretics, betablockers, calcium channel blockers, angiotensin-converting enzyme inhibitors and angiotensin-II receptor-blockers and PD were examined. Antihypertensive medications overall were associated with a lower risk of subsequent diagnosis of PD (OR: 0.94, 95% CI 0.90-0.97), with the negative association most significant for medications acting on the renin-angiotensin-aldosterone system. A positive association with diagnosis of PD was only seen for betablockers and restricted to those with relatively young age and not in those with longer treatment duration. When taking into account underlying diagnoses, antihypertensive medications overall were associated with a reduced incidence of PD.

Therapeutic Potential of Natural Flavonoids: Pharmacological Targets, Signaling Pathways, Molecular Mechanisms, and Clinical Perspective on Parkinson's Disease

Abstract: Parkinson’s disease (PD) is a prominent area of study within the field of neurology, particularly neurodegenerative disease (ND). The peak incidence of PD occurs in those over the age of 45, and the disease’s prevalence rises continuously with age, the incidence of PD has skyrocketed over the world. A slow decline in neural function characterizes NDs, but the pathophysiological mechanisms behind this decline remain elusive. Because the pathophysiological mechanisms behind neurodegeneration are intricate, the clinical issue of finding efficient, multi-target treatments still exists. Furthermore, adequate neuroprotective medicines are currently scarce, necessitating the development of new therapeutic agents. There is currently no medicine for PD that is without side effects. The ability of natural flavonoids to lower the risk of PD has contributed to an increase in their popularity in recent years, models both in vivo and in vitro. Flavonoids are multi-target natural substances that affect distinct pathogenic pathways in neurodegeneration. As a result, the emphasis has turned to discovering natural product inhibitors for the treatment of PD. The majority of the results pointed to flavonoids' beneficial role in the treatment of PD and no adverse events were reported. This review offered scientific data on the protective and preventative functions of flavonoids. It has been demonstrated that flavonoids have a neuroprotective effect by activating anti-apoptotic mechanisms that target mitochondrial dysfunction and produce neurotrophic factors. In addition to having antioxidant, anti-inflammatory, and protective dopaminergic neurons. Even though no evidence using flavonoids as a treatment might reverse the abnormal phenotypes of PD patients, it was also indicated that flavonoids might be promising natural remedies for PD prevention and could be used as therapeutic agents against PD.

Causal association between long-term exposure to air pollution and incident Parkinson’s disease

Epidemiological evidence for long-term air pollution exposure and Parkinson’s disease (PD) is controversial, and analysis of causality is limited. We identified 293,888 participants who were free of PD at baseline in the UK Biobank (2006–2010). Time-varying air pollution [fine particulate (PM2.5) and ozone (O3)] exposures were estimated using spatio-temporal models. Incident cases of PD were identified using validated algorithms. Four methods were used to investigate the associations between air pollution and PD, including (1) standard time-varying Cox proportional-hazard model; (2) Cox models weighted by generalized propensity score (GPS) and inverse-probability weights (IPW); (3) instrumental variable (IV) analysis; and (4) negative control outcome analysis. During a median of 11.6 years of follow-up, 1822 incident PD cases were identified. Based on standard Cox regression, the hazard ratios (95% confidence interval) for a 1 µg/m3 or ppb increase in PM2.5 and O3 were 1.23 (1.17, 1.30) and 1.02 (0.98, 1.05), respectively. Consistent results were found in models weighted by GPS and IPW, and in IV analysis. There were no significant associations between air pollution and negative control outcomes. This study provides evidence to support a causal association between PM2.5 exposure and PD. Mitigation of air pollution could be a protective measure against PD.

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.

Prediabetes and the incidence of Parkinson's disease: A meta-analysis.

Diabetes has been associated with an elevated risk of Parkinson's disease (PD), yet the relationship between prediabetes (PreD) and the incidence of PD in the adult population remains unclear. Therefore, a systematic review and meta-analysis was conducted to evaluate if PreD is also associated with a higher risk of PD. We conducted comprehensive searches of the PubMed, Embase, and Web of Science databases to identify relevant observational studies with longitudinal follow-up. The random-effects model was employed to synthesize the data, mitigating the potential impact of study heterogeneity on the outcomes. Our analysis incorporated seven datasets from five cohort studies, encompassing 18,170,592 adult participants without a PD diagnosis at baseline. Among them, 2,432,148 (13.3%) had PreD. During the follow-up, a total of 46,682 patients were diagnosed with PD. The pooled results indicated that PreD was associated with an increased incidence of PD (risk ratio [RR] 1.09, 95% confidence interval [CI] 1.02 - 1.16; P = 0.02; I2 = 52%), after adjusting for potential confounding factors such as age, sex, body mass index (BMI), and smoking. Subsequent pilot subgroup analyses suggested that the association between PreD and PD might not be significantly influenced by the country of the study, its design, age or sex of the participants, definition of PreD, or the quality scores of the study (P for subgroup difference all > 0.05). In conclusion, adult population with PreD may have a mildly increased risk of developing PD compared to those with normoglycemia.

Risk of Parkinson disease in stroke patients: A nationwide cohort study in South Korea.

Previous studies have examined the risk of stroke in patients with Parkinson disease (PD), but the incidence of PD onset among stroke patients and its risk according to severity of poststroke disabilities have scarcely been investigated. This study aims to determine whether the risk of PD is increased among stroke patients using a retrospective cohort with a large population-based database. We used data collected by the Korean National Health Insurance Service from 2010 to 2018 and examined 307,361 stroke patients and 380,917 sex- and age-matched individuals without stroke to uncover the incidence of PD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI), and the risk of PD was compared according to presence and severity of disability. During 4.31 years of follow-up, stroke patients had a 1.67 times higher risk of PD compared to individuals without stroke (adjusted HR = 1.67, 95% CI = 1.57-1.78). The risk of PD was greater among stroke patients with disabilities than among those without disabilities, even after adjustment for multiple covariates (adjusted HR = 1.72, 95% CI = 1.55-1.91; and adjusted HR = 1.66, 95% CI = 1.56-1.77, respectively). Our study demonstrated an increased risk of PD among stroke patients. Health professionals need to pay careful attention to detecting movement disorders as clues for diagnosing PD.

Association of time spent outdoors with the risk of Parkinson’s disease: a prospective cohort study of 329,359 participants

BackgroundStudies on the association between time spent outdoors and the development of Parkinson’s disease (PD) are lacking, and whether this relationship differs in different subgroups (age, sex) remains unclear.ObjectiveWe here examined the association between time spent outdoors and the incidence of PD in different seasons.MethodsThis study included 329,359 participants from the UK Biobank. Data regarding hours spent outdoors during a typical day were obtained through questionnaires. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) for the association between exposure to outdoors duration and PD incidence. Restricted cubic spline was used to explore the potential nonlinear relationship between time spent outdoors and PD risk. To explore the potential mechanisms of time spent outdoors effecting the risk of PD incidence, their association with serum vitamin D was further analysed separately.ResultsDuring a median follow-up of 13.57 years, 2,238 participants developed PD. In summer, time spent outdoors > 5.0 h/day was associated with a reduced PD risk compared with ≤ 2.0 h/day (HR = 0.84, 95% CI, 0.74–0.95). In winter too, time spent outdoors > 2.0 h/day was also associated with a reduced PD risk compared with ≤ 1.0 h/day (HR = 0.85, 95% CI, 0.76–0.94). For annual average time spent outdoors, participants who went outdoors for more than 3.5 h/day had a reduced PD risk than those who went outdoors for ≤ 1.5 h/day (HR = 0.85, 95% CI, 0.75–0.96). Additionally, sex and age differences were observed in the association between time spent outdoors and the PD risk. Moreover, Time spent outdoors was observed to be positively associated with serum vitamin D levels. Compared with serum vitamin D-deficient participants, the risk of PD was reduced by 15% in the sufficient participants.ConclusionIn the total population, higher time spent outdoors was linked to a reduced PD risk. However, this association may vary among different age or sex groups.

Hair color, family history of melanoma, and the risk of Parkinson's disease: An analysis update

BackgroundA shared biological component between melanoma and Parkinson's disease (PD) has been suggested. Yet, epidemiological evidence is scarce. ObjectiveTo examine the association of hair color and family history of melanoma, two strong predictors of melanoma risk, with the occurrence of PD. MethodsWe followed 131,342 women and men for ∼30 years for the development of PD. We calculated the cumulative incidence of PD from ages 40 to 90 according to hair color, and estimated the hazard ratio of PD according to hair color and family history of melanoma. ResultsHair color was not strongly associated with the risk of PD, especially at advanced ages. In contrast, individuals with a family history of melanoma had a 1.4-fold higher risk of PD compared to those without a history. ConclusionsOur results support the hypothesis of a shared biological component between PD and melanoma. Both pigmentary and non-pigmentary pathways may play a role.

The association between migraine and Parkinson's disease: a nationwide cohort study.

Clinical studies have suggested an association between migraine and the occurrence of Parkinson's disease (PD). However, it is unknown whether migraine affects PD risk. We aimed to investigate the incidence of PD in patients with migraine and to determine the risk factors affecting the association between migraine and PD incidence. Using the Korean National Health Insurance System database (2002-2019), we enrolled all Koreans aged ≥40 years who participated in the national health screening program in 2009. International Classification of Diseases (10th revision) diagnostic codes and Rare Incurable Diseases System diagnostic codes were used to define patients with migraine (within 12 months of enrollment) and newly diagnosed PD. We included 214,193 patients with migraine and 5,879,711 individuals without migraine. During 9.1 years of follow-up (55,435,626 person-years), 1,973 (0.92%) and 30,664 (0.52%) individuals with and without migraine, respectively, were newly diagnosed with PD. Following covariate adjustment, patients with migraine showed a 1.35-fold higher PD risk than individuals without migraine. The incidence of PD was not significantly different between patients with migraine with aura and those without aura. In males with migraine, underlying dyslipidemia increased the risk of PD (p=0.012). In contrast, among females with migraine, younger age (<65 years) increased the risk of PD (p=0.038). Patients with migraine were more likely to develop PD than individuals without migraine. Preventive management of underlying comorbidities and chronic migraine may affect the incidence of PD in these patients. Future prospective randomized clinical trials are warranted to clarify this association.

Use of dipeptidyl peptidase-4 inhibitors was associated with a lower risk of Parkinson’s disease in diabetic patients

Diabetes mellitus is a risk factor for Parkinson's disease (PD). While animal studies have supported the benefits of incretin-based therapies, including dipeptidyl peptidase-4 (DPP4) inhibitors, in PD, clinical research has yielded controversial results. This cohort study aimed to assess the relationship between PD incidence and the utilization of DPP4 inhibitor in diabetic patients. Using Taiwan's National Health Insurance Research Database from 2009 to 2018, diabetic patients receiving metformin plus at least one second-line oral antidiabetic (OAD) were enrolled. The patients were categorized as DPP4 inhibitor users and non-users. Propensity score matching was employed to establish a 1:1 ratio between DPP4 inhibitor users and non-users. Among the 205,910 patients enrolled, 149 were diagnosed with PD during follow-up. The incidence rate was 0.29 per 1000 person-years for DPP4 inhibitor users and 0.55 per 1000 person-years for the non-users. DPP4 inhibitor users exhibited a significantly lower risk of PD (adjusted hazard ratio, 0.51; 95% CI 0.39–0.68). Among DPP4 inhibitor users, vildagliptin showed the strongest correlation with a reduction in the risk of PD. This study demonstrates that the use of DPP4 inhibitors along with metformin in diabetic patients is associated with a lower risk of PD compared to those using other OADs.

Association between Self-Reported Oral Health and Parkinson’s Disease: Evidence from UK Biobank

Objectives: Oral health problem is prevalent in the elderly population which is also at high risk of Parkinson’s disease (PD). However, the association between self-reported oral health and PD is still unclear. We aimed to explore the association between baseline self-reported oral health (mouth ulcers, painful gums, bleeding gums, loose teeth, toothache, dentures) and future incidence of PD. Methods and Participants: Participants were enrolled in the UK Biobank from 2006 to 2010 and those without PD at baseline were included in the current study. We used Cox regression analysis to explore the question and adjusted for age, sex, body mass index, smoking, drinking, ethnicity, education, socioeconomic status, and average total household income before tax. Results: We included 421,180 participants with a mean age of 56.26 years old, and 46.5% of them were male. And 2,339 participants were diagnosed with PD in the follow-up. Mouth ulcers, loose teeth, dentures, toothache, and bleeding gums were not related to the risk of PD. Painful gums were related to a higher risk of PD (HR: 1.39, 95% CI: 1.12–1.72, p = 0.003), and similar results were reached after adjusting for gene risk (HR: 1.39, 95% CI: 1.12–1.73, p = 0.003), or source of diagnosis (HR: 1.39, 95% CI: 1.12–1.72, p = 0.002), and time of diagnosis (HR: 1.29, 95% CI: 1.03–1.63, p = 0.02). Conclusions: Our study has demonstrated a substantial correlation between painful gums and elevated susceptibility to PD, underscoring the potential advantages of implementing oral health interventions for decreasing the risk of PD.