Functional network connectivity predicts spreading of cortical atrophy in Parkinson's disease

Objective: To decipher the mechanisms of network-based neurodegeneration in Parkinson’s disease (PD) investigating the relationship between functional network connectivity (FC) in healthy brain connectome and cortical thinning in patients at the early disease stage, and to develop a predictive model for atrophy spreading in PD. Background: The neurodegenerative process in PD moves along neural networks, possibly reflecting the spread of toxic alphasynuclein molecules. Design/Methods: 86 early-stage PD patients performed 3D T1-weighted MRI at baseline and every year for 3 years. Resting state functional MRI (rs fMRI) was obtained from 60 age- and sex-matched controls at baseline. The brain was parcellated into 83 regions. Mean volumes for each region were calculated for PD patients and controls on 3D T1-weighted images. Regional percentage of atrophy in PD patients relative to controls was calculated at each time point: [1−(mean patient volumes/mean control volumes)]*100. Functional healthy connectome was estimated from rs fMRI in controls. In PD patients, the “disease exposure” (DE) to pathology of each brain region at each time point was defined as a function of FC of the region with the whole brain in healthy connectome and the severity of atrophy of the connected regions (i.e., the sum of the products of FC between i and all the other brain regions j in healthy subjects and atrophy percentage of the corresponding region j in patients). DE during the first and second year of follow up was used to predict atrophy at the subsequent time points. Results: In early-stage PD patients, regional DE at 1-year follow-up predicted atrophy accumulation at 2-year follow-up relative to baseline. Although atrophy at 3 years was increased relative to 2-year follow-up, its variation did not correlate with DE at any time point. Conclusions: Our study suggests that disease propagation in PD follows functional network connectivity. Disclosure: Dr. Agosta has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with EXCEMED– Excellence in Medical Education. Dr. Basaia has nothing to disclose. Dr. Zahedmanesh has nothing to disclose. Dr. Stojkovic has nothing to disclose. Dr. Stankovic has nothing to disclose. Dr. pica has nothing to disclose. Dr. Petrovic has nothing to disclose. Dr. Stefanova has nothing to disclose. Dr. Kostic has received personal compensation in an editorial capacity for Novartis Pharmaceuticals and Boehriner Ingelheim. Dr. Kostic has received research support from Valeant, Stada, Novartis Pharmaceuticals, and Boehriner Ingelheim. Dr. Filippi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in an editorial capacity for Journal of Neurology. Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche.