Abstract

Objective Autonomic symptoms are common in α-synuclein disorders: multiple system atrophy (MSA), Parkinson's disease (PD), dementia with Lewy bodies (DLB), and Parkinson's disease with dementia (PDD). These symptoms may precede the motor findings/clinical diagnosis by years. Erectile dysfunction (ED) is an autonomic symptom that has rarely been studied in these α-synuclein disorders. In this population-based, case-control study, we investigated the association between premonitory erectile dysfunction surfacing prior to the clinical-motor manifestations of these α-synucleinopathies. Methods We used the medical record-linkage system of the Rochester Epidemiology Project to identify cases of α-synucleinopathies in Olmsted County from 1991 to 2010. Each male case was matched by age (±1 year) of symptom onset and sex to a control. We reviewed complete medical records of cases and controls to detect erectile dysfunction prior to the clinical-motor onset of α-synucleinopathies of any type. We used conditional logistic regression to calculate the odds ratio of all α-synucleinopathies, as well as by type, adjusting for diabetes, coffee, and smoking. Results A history of male erectile dysfunction was associated with 1.5-fold increased odds of an α-synucleinopathy diagnosis of any type in univariate analyses (p=0.06). When stratifying α-synucleinopathies by type, early erectile dysfunction was most frequent in MSA cases than matched controls (45% vs. 9%). Premotor phase ED was next most frequent among the DLB cases (46% vs. 27% among the controls; OR = 2.83, p=0.03; when adjusted for diabetes, smoking, and coffee, OR = 2.98, p=0.04). Premotor phase ED was not significantly associated with PD or PDD. Conclusions Early erectile dysfunction may be a premotor symptom of MSA and DLB, reflecting premonitory dysautonomia. It was not associated with premotor PD or PDD.

Highlights

  • Alpha-synuclein inclusions are the pathological hallmark of a group of neurodegenerative diseases including Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) [1]. ese four disorders have a very prolonged course, and the α-synuclein neuropathology typically begins years before the clinical-motor onset [2,3,4]

  • erectile dysfunction (ED) had been diagnosed in 92 cases (32.5%) and 70 controls (24.7%), yielding an odds ratio (OR) of 1.47 among all α-synucleinopathies (Table 1). is finding remained insignificant after adjusting for diabetes, smoking, and coffee (p 0.06)

  • Given that clinical and pathological evidence of dysautonomia has been a hallmark of the PD and PDD premotor phase, we assessed whether another autonomic symptom, ED, surfaced before the clinical picture of these α-synuclein disorders became apparent

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Summary

Introduction

Alpha-synuclein inclusions are the pathological hallmark of a group of neurodegenerative diseases including Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) [1]. ese four disorders have a very prolonged course, and the α-synuclein neuropathology typically begins years before the clinical-motor onset [2,3,4]. Alpha-synuclein inclusions are the pathological hallmark of a group of neurodegenerative diseases including Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) [1]. Ese four disorders have a very prolonged course, and the α-synuclein neuropathology typically begins years before the clinical-motor onset [2,3,4]. Nonmotor symptoms may surface during the preclinical phase, and this includes autonomic dysfunction [5,6,7,8]. Limited dysautonomia may predate the motor symptoms by up to 20 years [5, 9]. Dysautonomia is common among all the α-synucleinopathies. Erectile dysfunction (ED) is an autonomic symptom, it has largely been overlooked among these disorders. ED has been observed in DLB and MSA [7, 11]

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