The longitudinal progression of autonomic dysfunction in Parkinson's disease: A 7-year study

Abstract

BackgroundAutonomic dysfunction, including gastrointestinal, cardiovascular, and urinary dysfunction, is often present in early Parkinson's Disease (PD). However, the knowledge of the longitudinal progression of these symptoms, and the connection between different autonomic domains, is limited. Furthermore, the relationship between the presence of autonomic symptoms in early-stage PD and olfactory dysfunction, a possible marker of central nervous system involvement, has not been fully investigated.ObjectivesWe aimed to investigate the occurrence and progression of autonomic dysfunction in recently diagnosed (< 2 years) untreated PD patients and determine any coexistence of symptoms in individual patients. We also investigated the relationship between autonomic symptoms, olfactory dysfunction, and motor impairment.MethodsData were obtained from the Parkinson's Progression Markers Initiative (PPMI) database. Autonomic dysfunction was measured using the Scales for Outcomes in Parkinson's Disease (SCOPA-AUT). Symptom frequency and mean scores over 7 years were determined. The simultaneous occurrence of different autonomic symptoms was also examined. Finally, the relationships between SCOPA-AUT scores, olfactory dysfunction, and motor impairment were investigated using the University of Pennsylvania Smell Identification Test (UPSIT) and the Movement Disorder Society—Unified Parkinson's Disease Rating Scale (MDS-UPDRS), respectively.ResultsFollow-up data were available for 7 years for 171 PD patients and for 5 years for 136 HCs. Mean SCOPA-AUT score increased significantly from baseline to the 7-year follow-up for each autonomic domain, except for female sexual dysfunction. Most patients reported three or more autonomic symptoms. Common clusters of symptoms were composed of combinations of gastrointestinal, urinary, thermoregulatory, and sexual dysfunction. At baseline, greater SCOPA-AUT total score was associated with lower UPSIT scores (r = −0.209, p = 0.006) and with greater total MDS-UDPRS III score (r = 0.218, p = 0.004).ConclusionsAutonomic dysfunction, often with coexistence of autonomic manifestations, is common in early PD and progressively worsens over the first 7 years of disease, suggesting that these symptoms should be addressed with appropriate treatments early in the disease. The association between greater autonomic dysfunction and greater olfactory impairment, coupled with the association with more severe motor scores at baseline, indicates that patients who show more severe autonomic dysfunction could also have more severe involvement of the central nervous system at the time of diagnosis.

Both brain network topology and striatal dopamine depletion mediate the effects of autonomic dysfunction on disease burden of Parkinson’s disease

“…[29] In current study, we found autonomic dysfunction was positively associated with HY stages and UPDRS-III scores, which was in agreement with previous studies showing that autonomic dysfunction was associated with faster motor progression. [9] We found autonomic symptoms were positively associated with ESS scores, which was supported by a recent study showing that more severe EDS in PD patients was in parallel with more worsened autonomic symptoms. [41] A previous study showed that female sex, high HY stage, high UPDRS total and subtotal scores, and cognitive decline were significantly associated with depressive symptoms.…”

“…[5–8] In addition, it has been shown that more severe autonomic dysfunction at baseline was associated with future worse olfaction loss and greater overall disease burden. [9] Moreover, the severity of autonomic symptoms was independently associated with impairments in activities of daily living and health-related quality of life. [6, 10] Therefore, the clinical diagnosis and treatment of autonomic dysfunction is extremely important in PD management.…”

Predictors for early‐onset psychotic symptoms in patients newly diagnosed with Parkinson's disease without psychosis at baseline: A 5‐year cohort study

“… 27 , 28 , 29 , 30 The accumulation of α‐synuclein in the ENS has been found to correlate with cell death in the autonomic nervous system and is suggested to lead to autonomic dysfunction in the GI domain. 27 Based on the ENS‐first etiology of PD (the initial α‐synuclein pathology within the ENS), 31 researchers proposed that the pathologic change first happens in the GI system and then ascends through the vagus nerve to the brainstem which is closely related to the formation of hallucinations. 9 , 28 , 32 , 33 , 34 Our findings provide more evidence to support the theory that degeneration of the brainstem is associated with psychosis in PD, and autonomic dysfunction and pRBD in PD may be driven by similar neurobiological mechanisms.…”

“…GI autonomic dysfunction has been proposed as a prodromal non‐motor symptom of PD. Evidence has pointed to abnormal α‐synuclein accumulating not only in the brain but also in the enteric nervous system (ENS) 27–30 . The accumulation of α‐synuclein in the ENS has been found to correlate with cell death in the autonomic nervous system and is suggested to lead to autonomic dysfunction in the GI domain 27 .…”

“…Evidence has pointed to abnormal α‐synuclein accumulating not only in the brain but also in the enteric nervous system (ENS) 27–30 . The accumulation of α‐synuclein in the ENS has been found to correlate with cell death in the autonomic nervous system and is suggested to lead to autonomic dysfunction in the GI domain 27 . Based on the ENS‐first etiology of PD (the initial α‐synuclein pathology within the ENS), 31 researchers proposed that the pathologic change first happens in the GI system and then ascends through the vagus nerve to the brainstem which is closely related to the formation of hallucinations 9,28,32–34 .…”