A worldwide study of subcortical shape as a marker for clinical staging in Parkinson's disease.
Laansma MA., Zhao Y., van Heese EM., Bright JK., Owens-Walton C., Al-Bachari S., Anderson TJ., Assogna F., van Balkom TD., Berendse HW., Cendes F., Dalrymple-Alford JC., Debove I., Dirkx MF., Druzgal J., Emsley HCA., Fouche J-P., Garraux G., Guimarães RP., Helmich RC., Hu M., van den Heuvel OA., Isaev D., Kim H-B., Klein JC., Lochner C., McMillan CT., Melzer TR., Newman B., Parkes LM., Pellicano C., Piras F., Pitcher TL., Poston KL., Rango M., Ribeiro LF., Rocha CS., Rummel C., Santos LSR., Schmidt R., Schwingenschuh P., Squarcina L., Stein DJ., Vecchio D., Vriend C., Wang J., Weintraub D., Wiest R., Yasuda CL., Jahanshad N., Thompson PM., van der Werf YD., Gutman BA.
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.