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Background and Objectives: The phenotype of p.A53T-SNCA Parkinson's Disease (PD) mutation carriers appears more severe than that of iPD patients, however comprehensive comparative prospective studies are lacking. Here we conducted a longitudinal study to investigate, using multiple parameters, the progression of motor and nonmotor features of p.A53T-PD compared to iPD. Methods: Longitudinal 3-year data, concerning both motor and non-motor features, of 16 p.A53T-PD and 48 iPD, matched for age and disease duration at baseline, were downloaded from the Parkinson's Progression Markers Initiative (PPMI) database and compared between the two groups. Additionally, a cognitive composite score was generated by 5 cognitive tests, focused on executive/visuospatial function to better study cognitive change. Results: Neuropsychological assessments of global cognitive (MOCA), and especially executive/visuospatial function, reflected in the composite score, revealed significant cognitive decline in A53T-PD compared to iPD, but also across time for the group of A53T-PD. Autonomic dysfunction and items of MDS-UPDRS I, reflecting global cognitive function and psychotic features, were more prominent in A53T-PD. Motor assessments showed worse performance in A53T-PD, even though LEDD was significantly higher in A53T-PD. Discussion: The current longitudinal study indicates that A53T-PD represents a rapidly progressing subtype of PD, with accelerated decline in both motor and non-motor parameters, especially in cognitive function. Such data may set the stage for the application of targeted disease-modifying therapies in this particular subtype, in which the etiological link to alpha-synuclein is established, while generated data may be relevant to iPD, which is largely a sporadic synucleinopathy.
Simitsi et al. (Fri,) studied this question.