Widespread Cortical Thinning in Parkinson's Disease: Findings from the ENIGMA-Parkinson's Disease Working Group

Objective: To assess the effect of Parkinson’s Disease on in-vivo cortical thickness measures in a large multicenter study. Background: Parkinson’s disease (PD) is a progressive neurodegenerative disease, affecting 10 million people worldwide. The primary cause of PD is the degeneration of dopamine-containing neurons in the basal ganglia and substantia nigra, which are involved in the control of movement, learning, behavior and emotions. Brain MRI-based biomarkers of PD have been proposed, but, given their modest effect sizes, smaller studies have had inconsistent results. Here, we present initial results from the multi-center ENIGMA Parkinson’s disease working group using harmonized meta-analysis. Design/Methods: To assess cortical thickness measures from brain MRI, we used the FreeSurfer 5.3 pipeline. In-vivo measures of cortical thickness for each of 68 regions in the Desikan-Killiany atlas were extracted independently at four ENIGMA-PD sites: USC (Parkinson’s Progression Markers Initiative, PPMI), PD-UNICAMP (Campinas, Brazil), BernPD (Bern, Switzerland), and VUmc (Amsterdam). The study included 575 PD patients, 386 controls (559 M, 402 F, ages 27–95). Site-level analysis was performed using the ENIGMA-PD pipeline (enigma.usc.edu/ongoing/enigma-parkinsons), controlling for Sex, Age, Sex-by-Age. We meta-analyzed the 4 sites’ results using METAL software, Bonferroni-correcting for the 68 comparisons. Results: Cortical thinning is widespread in PD. Effects are especially prevalent in the parietal association areas (inferior parietal lobule, p=2.2×10 −8 , Cohen’s D=0.38 (left), p=2.35×10 −5 , D=0.30 (right)), supplementary and premotor cortices (superior frontal gyrus, p=4.26×10 −7 , D=0.37 (left), p=1.75×10 −6 , D=0.34), inferior temporal areas (p=3.15×10 −8 , D=0.37 (left), p=5.6×10 −8 , D=0.38 (right)), precuneus (p=3.1×10 −6 , D=0.31 (left), p=3.54×10 −5 , D=0.29 (right)) and posterior cingulate (p=2.8×10 −5 , D=0.29 (right), p=3.2×10 −4 , D=0.24 (left)). Conclusions: We present a large multi-site study of PD effects on cortical thickness. The study confirms several PD hypotheses: atrophy in parietal association and premotor cortices (SMA), which has previously been associated with reduced striatal F-DOPA uptake, and particularly associated with rigidity and bradykinesia. Study Supported by: NIH U54 EB020403 Grant - The ENIGMA Center for Worldwide Medicine, Imaging and Genomics Disclosure: Dr. Gutman has nothing to disclose. Dr. Bright has nothing to disclose. Dr. Rummel has nothing to disclose. Dr. ROCHA has nothing to disclose. Dr. Debove has nothing to disclose. Dr. Yasuda has nothing to disclose. Dr. Guimaraes has nothing to disclose. Dr. Bergo has nothing to disclose. Dr. D9Abreu has nothing to disclose. Dr. Poston has nothing to disclose. Dr. Wiest has nothing to disclose. Dr. Cendes has nothing to disclose. Dr. Thompson has nothing to disclose. Dr. van der Werf has nothing to disclose. Dr. Parkinson9s Disease Working Gr has nothing to disclose.