Bower, James H.

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.

Abstract Background Small studies suggest that constipation is a common symptom associated with a worse prognosis in patients with Parkinson's disease (PD). Objectives The aim was to compare the association between constipation, motor, and other non‐motor symptoms (NMS) in PD patients at baseline and in future. Methods Using the Fox Insight database, we compared baseline characteristics, risk of progressive motor symptoms, and incidence of NMS between PD patients with versus without constipation. Results Of 20,352 participants, 16,611 (82%) reported infrequent bowel movements and/or excessive straining, 15,594 (77%) had incomplete evacuation, and 14,165 (70%) reported both symptoms. Patients with constipation were generally older, white, women, had PD >5 years, and had higher NMS and comorbidity scores ( P < 0.001). Constipation was significantly associated with worse motor symptoms and most NMS , especially fecal incontinence (odds ratio [ OR] = 1.65; 95% confidence interval [CI], 1.49–1.82), dysphagia ( OR = 1.20; 95% CI = 1.12–1.29), talking/moving during sleep ( OR = 1.39; 95% CI = 1.30–1.48), and urinary urgency ( OR = 1.23; 95% CI = 1.16–1.32). Constipation was associated with a small, but statistically significant increased risk of some progressive motor symptoms. At a mean median follow‐up of 2.8 years, constipation was associated with an increased risk of incident gastrointestinal, autonomic, neuropsychiatric, sleep‐related, sensory NMS , such as dysphagia (hazard ratio [ HR] = 1.43; 95% CI = 1.35–1.51), fecal incontinence ( HR = 1.87; 95% CI = 1.74–2.01), falls ( HR = 1.44; 95% CI = 1.35–1.52), hallucinations ( HR = 1.65; 95% CI = 1.52–1.79), cognitive impairment ( HR = 1.38; 95% CI = 1.30–1.47), and talking/moving during sleep ( HR = 1.65; 95% CI = 1.55–1.75). Conclusions Constipation is a common symptom associated with severity of motor and other NMS and portends a worse prognosis in persons with PD.

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 Parkinsonism following hypoxic ischemic damage of the basal ganglia is an uncommon phenomenon that has been infrequently reported. However, only a few cases have noted improvement of symptoms with dopaminergic therapy. We report the clinical and imaging features of five patients with post-anoxic parkinsonism responsive to dopamine supplementation. Objective To describe a retrospective case series of five cases of dopamine-responsive post-anoxic parkinsonism. Methods We identified all the cases using the Mayo Clinic Data Management System utilizing advanced data explorer search engine for any patients evaluated for post anoxic parkinsonism and its associated acronyms from 2000–2024. Clinical features, neuroimaging, medication trials, and responses were obtained from chart review of identified patients. Results Five patients met the inclusion criteria. All patients underwent anoxic events followed by development of parkinsonism. Patients exhibited parkinsonism described as combinations of bradykinesia, rigidity, tremor, and postural instability. All patients underwent evaluation by a neurologist, MRI imaging, and treatment by dopaminergic agents. Of the five patients, four received carbidopa/levodopa whereas one received a dopamine agonist. All patients were clinically followed for a median of approximately 4 years and showed improvement in parkinsonism. Conclusions Parkinsonism following a hypoxic ischemic insult is a rare occurrence but response to dopaminergic therapy in those cases is even more scarcely described. Our cases series provides important implications for treatment options for patients with post anoxic parkinsonism.

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.

Importance The role of air pollution in risk and progression of Parkinson disease (PD) is unclear. Objective To assess whether air pollution is associated with increased risk of PD and clinical characteristics of PD. Design, Setting, and Participants This population-based case-control study included patients with PD and matched controls from the Rochester Epidemiology Project from 1998 to 2015. Data were analyzed from January to June 2024. Exposures Mean annual exposure to particulate matter with a diameter of 2.5 µm or less (PM 2.5 ) from 1998 to 2015 and mean annual exposure to nitrogen dioxide (NO 2 ) from 2000 to 2014. Main Outcomes and Measures Outcomes of interest were PD risk, all-cause mortality, presence of tremor-predominant vs akinetic rigid PD, and development of dyskinesia. Models were adjusted for age, sex, race and ethnicity, year of index, and urban vs rural residence. Results A total of 346 patients with PD (median [IQR] age 72 [65-80] years; 216 [62.4%] male) were identified and matched on age and sex with 4813 controls (median [IQR] age, 72 [65-79] years, 2946 [61.2%] male). Greater PM 2.5 exposure was associated with increased PD risk, and this risk was greatest after restricting to populations within metropolitan cores (odds ratio [OR], 1.23; 95% CI, 1.11-1.35) for the top quintile of PM 2.5 exposure compared with the bottom quintile. Greater NO 2 exposure was also associated with increased PD risk when comparing the top quintile with the bottom quintile (OR, 1.13; 95% CI, 1.07-1.19). Air pollution was associated with a 36% increased risk of akinetic rigid presentation (OR per each 1-μg/m 3 increase in PM 2.5 , 1.36; 95% CI, 1.02-1.80). In analyses among patients with PD only, higher PM 2.5 exposure was associated with greater risk for developing dyskinesia (HR per 1-μg/m 3 increase in PM 2.5 , 1.42; 95% CI, 1.17-1.73), as was increased NO 2 exposure (HR per 1 μg/m 3 increase in NO 2 , 1.13; 95% CI, 1.06-1.19). There was no association between PM 2.5 and all-cause mortality among patients with PD. Conclusions and Relevance In this case-control study of air pollution and PD, higher levels of PM 2.5 and NO 2 exposure were associated with increased risk of PD; also, higher levels of PM 2.5 exposure were associated with increased risk of developing akinetic rigid PD and dyskinesia compared with patients with PD exposed to lower levels. These findings suggest that reducing air pollution may reduce risk of PD, modify the PD phenotype, and reduce risk of dyskinesia.