Early Autonomic Symptoms Predict Functional Decline in Parkinson’s Disease Independent of Dopaminergic Therapy

Abstract

Introduction: Parkinson’s disease (PD) has variable progression; identifying determinants of functional decline in PD is needed for accurate prognostication. Autonomic symptoms can result from dopaminergic therapy but may also independently predict functional decline. Methods: The sample included individuals with newly diagnosed PD in Parkinson’s Progression Markers Initiative. Autonomic symptoms were measured with the Scales-for-Outcomes-in-Parkinson’s-Disease-Autonomic (SCOPA-AUT). Presence/absence of autonomic symptoms for SCOPA-AUT total scale and seven subscales was defined, and baseline demographic/clinical data were compared between groups with and without autonomic symptoms. Time-to-functional-dependence, or Schwab-and-England Activities-of-Daily-Living (SE-ADL) ≤70, was compared between groups using hazard models, adjusting for covariates including time-varying levodopa-equivalent daily dosage. If a subscale was associated with a significant subhazard ratio (SHR), hazard models for items in that subscale were generated and gender was evaluated as an effect modifier. Results: 399 participants were included. Over a median of 72 months (range 6–84), 91 (22.81%) reached SE-ADL ≤70. SCOPA-AUT total/gastrointestinal/urinary/pupillomotor scales were associated with SE-ADL ≤70; respective multivariable SHRs (95% CI, p value) were 1.98 (1.06–3.70, 0.03), 1.71 (1.04–2.81, 0.03), 1.94 (1.25–3.01, <0.01), 2.56 (1.24–5.31, 0.01). Individual items in the gastrointestinal and urinary scales drove associations. Urinary scale associations were seen in males only. Conclusions: Symptoms of gastrointestinal, urinary, pupillomotor dysfunction are associated with functional decline risk in PD, independent of dopaminergic therapy. Detailed assessments of autonomic symptomatology should be utilized in studies attempting to refine predictive models of PD progression.