A worldwide study of subcortical shape as a marker for clinical staging in Parkinson’s disease

Laansma, Max A. and Zhao, Yuji and van Heese, Eva M. and Bright, Joanna K. and Owens-Walton, Conor and Al-Bachari, Sarah and Anderson, Tim J. and Assogna, Francesca and van Balkom, Tim D. and Berendse, Henk W. and Cendes, Fernando and Dalrymple-Alford, John C. and Debove, Ines and Dirkx, Michiel F. and Druzgal, Jason and Emsley, Hedley C. A. and Fouche, Jean-Paul and Garraux, Gaëtan and Guimarães, Rachel P. and Helmich, Rick C. and Hu, Michele and van den Heuvel, Odile A. and Isaev, Dmitry and Kim, Ho-Bin and Klein, Johannes C. and Lochner, Christine and McMillan, Corey T. and Melzer, Tracy R. and Newman, Benjamin and Parkes, Laura M. and Pellicano, Clelia and Piras, Fabrizio and Pitcher, Toni L. and Poston, Kathleen L. and Rango, Mario and Ribeiro, Leticia F. and Rocha, Cristiane S. and Rummel, Christian and Santos, Lucas S. R. and Schmidt, Reinhold and Schwingenschuh, Petra and Squarcina, Letizia and Stein, Dan J. and Vecchio, Daniela and Vriend, Chris and Wang, Jiunjie and Weintraub, Daniel and Wiest, Roland and Yasuda, Clarissa L. and Jahanshad, Neda and Thompson, Paul M. and van der Werf, Ysbrand D. and Gutman, Boris A. (2024) A worldwide study of subcortical shape as a marker for clinical staging in Parkinson’s disease. npj Parkinson's Disease, 10 (1): 223. ISSN 2373-8057

Abstract

Alterations in subcortical brain regions are linked to motor and non-motor symptoms in Parkinson’s disease (PD). However, associations between clinical expression and regional morphological abnormalities of the basal ganglia, thalamus, amygdala and hippocampus are not well established. We analyzed 3D T1-weighted brain MRI and clinical data from 2525 individuals with PD and 1326 controls from 22 global sources in the ENIGMA-PD consortium. We investigated disease effects using mass univariate and multivariate models on the medial thickness of 27,120 vertices of seven bilateral subcortical structures. Shape differences were observed across all Hoehn and Yahr (HY) stages, as well as correlations with motor and cognitive symptoms. Notably, we observed incrementally thinner putamen from HY1, caudate nucleus and amygdala from HY2, hippocampus, nucleus accumbens, and thalamus from HY3, and globus pallidus from HY4–5. Subregions of the thalami were thicker in HY1 and HY2. Largely congruent patterns were associated with a longer time since diagnosis and worse motor symptoms and cognitive performance. Multivariate regression revealed patterns predictive of disease stage. These cross-sectional findings provide new insights into PD subcortical degeneration by demonstrating patterns of disease stage-specific morphology, largely consistent with ongoing degeneration.