TOPLINE:

Autonomic dysfunction affected 63% of patients with early-onset Parkinson’s disease (EOPD) and was associated with a threefold higher risk for mortality in a new cohort study. Each additional autonomic symptom was linked to a 50% increased risk for mortality, with constipation and orthostatic intolerance showing the strongest associations.

METHODOLOGY:

• A retrospective case-control cohort study used Mayo Clinic Health System medical records from 1990 to 2022 for more than 1600 participants (63% male), half of whom had EOPD and the other half acting as the sex-matched healthy control group. The median age at onset or index was 42 years, and the median follow-up duration was 18 years.
• EOPD was defined as motor symptom onset at or before 50 years of age on the basis of at least two of four cardinal symptoms: rest tremor, rigidity, bradykinesia, or impaired postural reflexes.
• Autonomic dysfunction was assessed using documented symptoms, such as constipation, bladder urgency, orthostatic intolerance, sweat dysfunction, and erectile dysfunction (ED).
• The frequency and timing (before or after motor symptom onset) of autonomic symptoms were compared between patients and control individuals.

TAKEAWAY:

• Autonomic dysfunction was more common in patients with EOPD than in the control individuals (63% vs 27%, respectively), and 91% vs 70.5% of these participants developed autonomic dysfunction after motor symptom onset. Among men, 37% vs 0.2% of the groups developed ED (P < .001). In both groups, constipation was the most common and sweat dysfunction the least common symptom.
• Among those with no autonomic symptom at index, the risk of developing autonomic symptoms was fourfold higher in patients with EOPD than in control individuals (hazard ratio [HR], 4.30), with the highest differences in the risk for orthostatic intolerance (HR, 5.90), constipation (HR, 4.30), bladder urgency (HR, 3.85), and sweat dysfunction (HR, 2.62; P < .001 for all).
• Presence of any autonomic symptom was associated with an increased risk for mortality (HRs, 2.71 in patients with EOPD and 3.57 in control individuals), and each additional autonomic symptom further increased the risk (HRs, 1.50 and 1.82, respectively; P < .001 for all).
• In both patients with EOPD and the control group, constipation (HR, 3.22 vs 3.50) and orthostatic intolerance (HR, 2.78 vs 5.44) showed the strongest associations with increased mortality risk (P < .001 for all), whereas bladder urgency and ED showed no significant associations with risk in either group.

IN PRACTICE:

“In our cohort, autonomic symptoms appeared most commonly after motor onset, contrasting with prodromal autonomic impairment seen in late-onset Parkinson’s disease,” the investigators of the study wrote.

They added that “further studies on systematic screening and treatment of autonomic dysfunction should be considered in this population to ensure the best outcome” for those with EOPD.

SOURCE:

The study was led by Capucine Piat, MD, Mayo Clinic, Rochester, Minnesota. It was published online on December 31 in Annals of Neurology.

LIMITATIONS:

The retrospective nature of the study may have led to underreporting of autonomic symptoms. The non-population-based design limited generalizability, whereas the rare nature of EOPD would have required a larger sample size for a population-based study. Only a small number of patients with EOPD underwent formal autonomic testing, limiting conclusions from electrophysiologic data. Additionally, missing data on the cause of death for many deceased participants restricted the understanding of the autonomic dysfunction-mortality association. Data on some potential confounders, such as autoimmune diseases, cognitive impairment, and genetic mutations, were also unavailable.

DISCLOSURES:

No funding information was provided for the study. The investigators reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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