To decipher the mechanisms of network-based neurodegeneration in Parkinson’s disease (PD) investigating the relationship between functional connectivity (FC) in healthy connectome and grey matter (GM) atrophy accumulation in mild PD patients, and to develop a predictive model for atrophy spreading in PD.

Propagation of progressive neuronal loss in PD may be a

multifactorial process depending on regional vulnerability and cell-to-cell spreading of misfolded

proteins.

86 mild-PD patients performed 3DT1-weighted brain MRI at baseline and

every year for 3 years. Functional brain connectome was estimated using resting-state functional

MRI in 60 controls. At each timepoint, regional GM atrophy was calculated in PD. In patients, the

“disease-exposure” (DE) to pathology of each brain region was defined as a function of FC with all

the connected regions in healthy connectome and the severity of atrophy of the connected regions in

patients. Partial correlations were tested between DE of each GM region at 1-year and 2-year

follow-up and atrophy progression at 2-year and 3-year follow-up. Prediction models of atrophy at

2-year and 3-year follow-up were estimated using stepwise regression models.

In mild PD patients, regional DE at 1-year correlated with atrophy accumulation at 2-year.

Furthermore, DE at 1-year and 2-year was associated with atrophy at 3-year. Models including DE

predict GM atrophy accumulation over 3 years in the caudate nucleus, frontal, parietal and temporal

brain regions.

This study showed that the functional organization of the brain connectome shapes the course of atrophy in the early stages of PD.

Supported by. This work was supported by the Ministry of ºÃÉ«ÏÈÉú, Science, and Technological Development of the Republic of Serbia [grant number #175090] and the Italian Ministry of Health [grant number # RF-2018-12366746].