Comparison of disease progression between brain-predominant Parkinson's disease versus Parkinson's disease with body-involvement phenotypes

Abstract

Recently, new disease phenotyping has been proposed based on the origin site of α-synuclein pathology in Parkinson's disease (PD). In addition, a great deal of evidences suggested of parallel degeneration in the central nervous system and peripheral nervous system in PD. The myocardial uptake pattern of ¹²³I-meta-iodobenzylguanidine can be a surrogate imaging biomarker for the peripheral nervous system involvement in PD. This study aimed to compare the clinical progression between brain-predominant PD (br-PD) and PD with body-involvement (bo-PD) phenotypes according to the onset of cardiac sympathetic denervation (CSD); the bo-PD group was defined as having the early onset of CSD and the br-PD phenotype was defined as those without initial CSD but later developed CSD in subsequent scans (the delayed onset of CSD). Clinical chracteristics, dopamine transporter activity, and non-motor manifestations were compared between the groups. Motor symptoms and cognitive functions at the initial and follow-up tests [3.1 (±1.4) years interval] were compared between the groups. This study included 29 br-PD and 103 bo-PD patients. Symptoms of rapid-eye-movement sleep behavior disorder, excessive daytime sleepiness, constipation, and orthostatic hypotension were more frequent in the bo-PD than in the br-PD group. The Unified Parkinson's Disease Rating Scale part III score was higher at the initial and increased more steeply during the follow-up period in the bo-PD patients than in the br-PD patients. Although the general cognitive status was not much different between the groups at initial and follow-up, each group showed statistically different cognitive domain profiles and progression patterns. The results demonstrated that the bo-PD group had more severe initial symptoms and steeper motor deterioration than the br-PD group, which indicated that there may be the more pathological involvements of central and peripheral nervous systems in the bo-PD group.

Keywords: Cardiac sympathetic denervation; Disease progression; Parkinson's disease; Phenotype.