Citations

Objective Dysautonomia affects many patients with Parkinson's disease and correlates with increased cardiovascular mortality. We describe the frequency and onset time of autonomic dysfunction relative to disease onset in early‐onset Parkinson's disease (EOPD) and explore its association with mortality. Methods We identified all incident Parkinson cases with motor‐symptom onset before age 50 years evaluated at the Mayo Clinic Health System (1990–2022) including sex‐ and age‐matched controls for each patient. Medical record review confirmed clinical diagnosis and assessed the presence and onset of autonomic symptoms, relative to Parkinson onset. Results We included 829 patients with EOPD and 829 healthy controls. The median age at disease onset was 42 years (interquartile range [IQR] = 37–46 years). Autonomic symptoms were present in 63.4% of patients, compared with 27.0% of unaffected controls, and proceeded motor symptoms in 91.4%. Forty‐seven percent of patients with early‐onset Parkinson's disease had constipation, 27.4% had bladder urgency, 19.3% had orthostatic intolerance, and 15.4% had sweat dysfunction. Among male patients, 36.8% had erectile dysfunction. In our EOPD population only, the presence of any autonomic‐impairment symptoms correlated with a 2.71‐fold increased mortality risk; each additional reported symptom increased the relative mortality risk by 50% ( p < 0.001). Patients with constipation or orthostatic intolerance had a 3.22‐ and 2.78‐fold higher mortality than patients without these symptoms. Interpretation Autonomic impairment affects 63.4% of patients with EOPD and carries a 3‐fold higher mortality risk, which increases with every additional autonomic symptom reported. In our cohort, autonomic symptoms appeared most commonly after motor onset, contrasting with prodromal autonomic impairment seen in late‐onset Parkinson's disease (LOPD). ANN NEUROL 2026;99:964–975

Background Early onset Parkinson's disease (EOPD), defined as Parkinson's disease (PD) diagnosed before age 50, often presents unique challenges compared to late-onset PD, particularly with regard to non-motor symptoms. Psychosis in EOPD is associated with increased functional impairment and may lead to a higher mortality risk. Objective Our study is aimed to determine the prevalence of psychosis in EOPD patients and its impact on all-cause mortality, along with examining the effects of antipsychotic medications and Selective Serotonin Reuptake Inhibitors (SSRIs) on mortality in EOPD patients. Methods Our retrospective cohort included EOPD patients diagnosed between 1990 and 2022 at Mayo Clinic, Rochester, Minnesota. Psychosis was defined using the National Institute of Neurological Disorders and Stroke/the National Institute of Mental Health (NINDS/NIMH) Work Group criteria. Cox proportional hazards models were used to analyze the association of psychosis and medications with mortality. Results Of 829 patients with EOPD, 158 (19.1%) developed psychosis at a median of 12.1 years after PD motor symptom onset. Psychosis was significantly associated with increased mortality in unadjusted (HR = 4.31, 95% CI: 2.59–7.18, p < 0.001) and adjusted (HR = 3.55, 95% CI: 2.10–6.01, p < 0.001) models. No significant difference in mortality risk was observed between patients treated with antipsychotics or SSRIs versus those who were not. Conclusions Psychosis is a possible complication in EOPD and is associated with a significant increase in all-cause mortality. The use of antipsychotics and SSRIs did not significantly alter the mortality risk in these patients. Further research is needed to understand the mechanisms driving this association and to develop tailored interventions.

Importance The role of pesticide exposure from golf courses in Parkinson disease (PD) risk remains unclear. Objective To assess whether proximity to golf courses is associated with increased PD risk and to use information on groundwater vulnerability and municipal well locations to investigate drinking water contamination as a potential route of exposure. Design, Setting, and Participants This case-control study included patients with incident PD and matched controls from the Rochester Epidemiology Project from 1991 to 2015. Data were analyzed between June and August 2024. Exposures Distance to golf courses, living in water service areas with a golf course, living in water service areas in vulnerable groundwater regions, living in water service areas with shallow municipal wells, and living in water service areas with a municipal well on a golf course. Main Outcome and Measures Risk of incident PD. All models adjusted for age, sex, race and ethnicity, year of index, median household income, and urban or rural category. Results A total of 419 incident PD cases were identified (median [IQR] age, 73 [65-80] years; 257 male [61.3%]) with 5113 matched controls (median [IQR] age, 72 [65-79] years; 3043 male [59.5%]; 4504 White [88.1%]). After adjusting for patient demographics and neighborhood characteristics, living within 1 mile of a golf course was associated with 126% increased odds of developing PD compared with individuals living more than 6 miles away from a golf course (adjusted odds ratio [aOR], 2.26; 95% CI, 1.09-4.70). Individuals living within water service areas with a golf course had nearly double the odds of PD compared with individuals in water service areas without golf courses (aOR, 1.96; 95% CI, 1.20-3.23) and 49% greater odds compared with individuals with private wells (aOR, 1.49; 95% CI, 1.05-2.13). Additionally, individuals living in water service areas with a golf course in vulnerable groundwater regions had 82% greater odds of developing PD compared with those in nonvulnerable groundwater regions (aOR, 1.82; 95% CI, 1.09-3.03). Conclusions and Relevance In this population-based case-control study, the greatest risk of PD was found within 1 to 3 miles of a golf course and risk generally decreased with distance. Associations with the largest effect sizes were in water service areas with a golf course and in vulnerable ground water regions.

Background Parkinson's disease (PD) is a progressive degenerative disease affecting people at any age; however, it is generally more prevalent in older age groups. Younger individuals, especially women, are facing significant challenges that pertain to pregnancy. Unfortunately, the available information is limited and supported mostly by anecdotical experience. Objective To gain insight into the interaction between early-onset PD and pregnancy. Methods We report on a case series of women, diagnosed with PD, that underwent pregnancy to explore the disease catachrestic, natural history, and different challenges associated with these unique group of people. Results We identified a total of 9 participants who met our inclusion criteria, who had gone through a total of 12 pregnancies after onset of PD motor symptoms. In 10 out of 12 pregnancies, participants did not use any PD medication; throughout 1 pregnancy, a participant used pramipexole and throughout 1 pregnancy, a participant used levodopa/carbidopa. Conclusions Our study supports the importance of further multicentric studies on pregnant women with PD to prospectively collect data on complications, birth outcomes, lactation, and PD severity.