Autonomic Impairment and Risk of Mortality in Early-Onset Parkinson Disease
Capucine Piat1, Aidan Mullan2, Khaled Ghoniem4, Emanuele Camerucci5, Pierpaolo Turcano6, Jeremy Cutsforth-Gregory3, Eduardo Benarroch3, Rodolfo Savica3
1Neurology, Nantes University Hospital, 2Mayo Clinic, 3Neurology, Mayo Clinic, 4University of Illinois, 5Kansas University Medical Center, 6Rush University Medical Center
Objective:
To describe the frequency and time of onset of autonomic dysfunction relative to Parkinson Disease (PD) onset in Early-Onset Parkinson Disease (EOPD) and explore its association with mortality.
Background:
The majority of patients with PD experience some form of autonomic dysfunction, which has been associated with increased cardiovascular mortality.
Design/Methods:
We identified all incident PD cases with motor symptom onset before the age of 50 years (EOPD) evaluated at Mayo Clinic from 1990 to 2022. Sex- and age-matched controls were included for each patient. Medical records were reviewed to confirm clinical diagnosis and assess the presence and time of onset of autonomic symptoms, including constipation, bladder urgency, sweat dysfunction, orthostatic hypotension, and erectile dysfunction, relative to PD motor onset.
Results:
We included 829 EOPD patients and 829 controls. The median age at PD onset was 42 years (IQR=37-46). Autonomic symptoms were present in 63.4% of EOPD patients, compared to 27.0% of unaffected controls, and preceded motor symptoms in 91.4% of EOPD cases. Forty-seven percent of EOPD patients had constipation, 27.4% bladder urgency, 19.3% orthostatic hypotension, and 15.4% sweat dysfunction. Among male EOPD patients, 36.8% had erectile dysfunction. In EOPD, the presence of any symptoms of autonomic impairment was associated with a 3.06 increased mortality risk; for each additional such reported symptom the relative mortality risk increased by 63% (p < 0.001). EOPD patients with constipation or orthostatic hypotension had a 2.84 and 2.16 fold higher mortality risk, respectively, compared to EOPD patients without these symptoms.
Conclusions:
Autonomic impairment affects 63.4% of EOPD patients and is associated with a three-fold higher mortality risk, which increases with each additional autonomic failure symptom reported. In our EOPD cohort, autonomic symptoms were most commonly post-dromal features, contrasting with prodromal autonomic impairment seen in Late-Onset Parkinson disease.
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