Objective: To investigate brain morphometric differences across Parkinson disease (PD) clinical subtypes.

Background: We developed a PD subtype classification with three subtypes that includes motor and non-motor features based on multi-domain classification [1, 2]. Here, we examined volumetric differences across these three distinct PD clinical subtypes, ‘motor only,’ ‘psychiatric & motor’ and ‘cognitive & motor.’  We hypothesized that these PD subtypes differ in their regional cortical thickness and subcortical volumes.

Method: Participants completed T1 (MPRAGE) structural MRIs OFF PD medications on a 3T MRI scanner. We used FreeSurfer v7.3 automated atlas-registration and volume segmentation software to obtain cortical thickness and subcortical volumes, with quality control checks and manual edits as necessary. Analyses of covariance (ANCOVA) compared regional cortical thickness and subcortical volumes (corrected for total intracranial volume) across subtypes, with age, sex, education, and time since motor onset as covariates. Significant group differences were followed with post-hoc pairwise comparisons using multiple comparison correction with Benjamini-Hochberg adjusted p < 0.05.

Results: The ‘cognitive & motor’ subtype (N=62) showed significantly decreased cortical thickness compared to each of ‘motor only’ (N=116) and ‘psychiatric & motor’ (N=27) subtypes in left parahippocampal (p = 0.025 & 0.016), left fusiform (p = 0.027 & 0.037), and left lingual (p = 0.02 & 0.011) regions, and compared to ‘motor only’ subtype in right entorhinal (p = 0.043), right inferior parietal (p = 0.03), and right lateral occipital (p = 0.024) regions.

Conclusion: The ‘cognitive & motor’ PD subtype had decreased cortical thickness in temporoparietooccipital regions compared to the other two subtypes, suggesting this subtype exhibits a unique pattern of posterior cortical volume loss. Longitudinal analyses may reveal additional differences in brain atrophy across PD subtypes.

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.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/regional-brain-volume-differences-across-pd-clinical-subtypes/