Clinical Phenotype Imprints on Brain Atrophy Progression in Parkinson’s Disease

There is much controversy about the link between motor symptom progression and the plethora of reported brain atrophy patterns in idiopathic Parkinson’s disease (PD). The main goal of this study is to provide empirical evidence for unique and common contributions of clinical phenotype characteristics on the dynamic changes of brain structure over time. We analyzed the behavioral and magnetic resonance imaging (MRI) data of PD patients (n = 22) and healthy individuals (n = 21) acquired two years apart through the computational anatomy framework of longitudinal voxel-based morphometry (VBM). This analysis revealed a symmetrical bi-hemispheric pattern of accelerated grey matter decrease in PD extending through the insula, parahippocampal gyrus, medial temporal lobes and the precuneus. We observed a hemisphere-specific correlation between the established scores for motor symptoms severity and the rate of atrophy within motor regions, which was further differentiated by the clinical phenotype characteristics of PD patients. Baseline cerebellum anatomy differences between the tremor-dominant and akineto-rigid PD remained stable over time and can be regarded as trait rather than state-associated features. We interpret the observed pattern of progressive brain anatomy changes as mainly linked to insular areas that determine together with basal ganglia the motor and non-motor phenotype in PD. Our findings provide empirical evidence for the sensitivity of computational anatomy to dynamic changes in PD, offering additional opportunities to establish reliable models of disease progression.