Objective: To investigate longitudinal brain morphometric trajectories across Parkinson disease (PD) clinical subtypes

Background: We developed a PD multi-domain classification based on motor and non-motor features yielding ‘motor only,’ ‘psychiatric & motor’ and ‘cognitive & motor’ subtypes [1, 2]. Previously, we demonstrated brain morphometric differences between the subtypes at baseline [3]. Here, we examine longitudinal intra-individual morphometric differences across subtypes. We hypothesized that intra-individual trajectories of brain volumes and cortical thickness differ across PD subtypes.

Method: Participants completed T1 structural MRIs on a 3T MRI scanner at baseline then every 1-3 years. We used FreeSurfer v7.3 software to obtain cortical thickness and brain volume measures, with quality control and manual edits as necessary. To assess whether the rate of change in morphometric measures differed among subtypes, we used hierarchical linear models. In addition to modeling time, subtype group and their interaction, predictors included age and disease duration at baseline, sex, education, and total intracranial volume as appropriate. A participant’s intercept and time-slope were specified as random effects i.e. specific to each participant’s data and thus varied across individuals.

Results: The ‘cognitive & motor’ subtype (N=94; 48 with follow-up MRIs) showed significantly higher rate of left & right lateral ventricular enlargement and accelerated whole brain atrophy compared to both ‘motor only’ (N=98; 79) and ‘psychiatric & motor’ (N=21; 11) subtypes (p<0.05). Additionally, specific regions showed more longitudinal atrophy in the ‘cognitive & motor’ subtype compared to the other two subtypes–left hippocampus and right cerebellar cortex and compared to ‘motor only’ subtype including right hippocampus, left cerebellar cortex and left thalamus (p<0.05). Global and most regional cortical thickness measures did not differ in their rate of atrophy across subtypes.

Conclusion: The ‘cognitive & motor’ PD subtype shows ventricular enlargement and accelerated brain atrophy compared to the other subtypes. Despite baseline analysis indicating decreased cortical thickness in various regions in ‘cognitive & motor’ compared to ‘motor only’ subtype [3], the rate of cortical thinning seems to be uniform across subtypes. This may be due to accelerated cortical thinning in this subtype early in the disease process.

References: 1. Campbell MC, Myers PS, Weigand AJ, Foster ER, Cairns NJ, Jackson JJ, Lessov-Schlaggar CN, Perlmutter JS. Parkinson disease clinical subtypes: key features & clinical milestones. Ann Clin Transl Neurol. 2020 Aug;7(8):1272-1283. doi: 10.1002/acn3.51102. Epub 2020 Jun 29. PMID: 32602253; PMCID: PMC7448190.

2. Myers PS, Jackson JJ, Clover AK, Lessov-Schlaggar CN, Foster ER, Maiti B, Perlmutter JS, Campbell MC. Distinct progression patterns across Parkinson disease clinical subtypes. Ann Clin Transl Neurol. 2021 Aug;8(8):1695-1708. doi: 10.1002/acn3.51436. Epub 2021 Jul 26. PMID: 34310084; PMCID: PMC8351397.

3. Eid AM, Grossen S, Tanenbaum A, Hood J, Hwang H, Cash T, Lessov-Schlaggar C, Kotzbauer P, Perlmutter J, & Campbell M. Regional brain volume differences across Parkinson disease clinical subtypes [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/regional-brain-volume-differences-across-pd-clinical-subtypes/. Accessed February 17, 2025. https://doi.org/10.1002/mds.29953

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-brain-morphometric-trajectories-across-parkinson-disease-clinical-subtypes/