GR.3 Distinct longitudinal brain atrophy trajectories in parkinson’s disease clinical subtypes: insight towards precision medicine

Background: Parkinson’s disease (PD) varies widely across individuals in terms of clinical manifestations and course of progression. We aimed to compare patterns of brain atrophy between PD clinical subtypes using longitudinally acquired brain MRIs. Methods: We used T1-weighted MRIs from Parkinson’s Progression Markers Initiative (PPMI) on 134 PD individuals and 60 healthy controls with at least two MRIs. Patients were classified into three clinical subtypes at de novo stage using validated subtyping criteria based on major motor and non-motor classifiers (early cognitive impairment, RBD, dysautonomia): mild-motor predominant (n=74), intermediate (n=44), and diffuse-malignant (n=16). Deformation-based morphometry (DBM) maps were calculated and mixed effect models were used to examine the interaction between PD subtypes and rate of atrophy across brain regions over time, controlling for sex and age at baseline. Results: Individuals with ‘diffuse malignant’ PD showed a significantly higher rate of atrophy across multiple brain regions, including lateral nucleus of the forebrain, precuneus, paracentral lobule, inferior temporal gyrus, fusiform gyrus, and lateral hemisphere of the cerebellum (FDR corrected p<0.05). Conclusions: We demonstrated an accelerated atrophy pattern within several brain regions in ‘diffuse malignant’ PD subtype. These findings suggest the presence of a more diffuse multidomain neurodegenerative process in a subgroup of people with PD, favoring the existence of diverse underlying pathophysiologies.