Alteration of posteromedial cortico-thalamic connectivity in moderate staged Parkinson disease identified by early-phase Florbetaben PET

1555 Purpose: Parkinson’s disease (PD) is the most common neurodegenerative disease impaired in the dopaminergic system. Parkinson9s disease is known to be implicated in the striatal-thalamo-cortical circuits. However, the alteration of brain connectivity during disease progression has not been clearly evaluated. Amyloid PET tracers have a high first-pass influx rate due to its lipophilicity, so early phase imaging show high concordance with perfusion SPECT and even with FDG PET because of perfusion-metabolism coupling, thus theoretically can be used for brain connectivity study. The purpose of this study is to evaluate brain connectivity alteration in moderate-severe staged PD compared with mild staged PD using early phase florbetaben (FBB) PET imaging. Methods: Eighty-three patients suffering from Parkinson9s disease or parkinsonism, who had FBB PET were retrospectively reviewed. Among 56 patients who were clinically diagnosed as idiopathic Parkinson9s disease, one patient was excluded due to left occipital malacia. Early phase 10 min FBB PET scans were normalized by SPM8 using an FDG PET template. The normalized brains were parcellated to 166 regions-of-interest (ROI) using the Automated Anatomical Labeling 3 atlas. Brain connectivity analysis with the posterior cingulate cortex (PCC), which is a hub of default mode network (DMN), as a seed ROI was performed based on statistical dependence among ROIs, using partial correlation adjusted with age. The permutation with 12,000 randomizations of labels was done to do non-parametric statistical tests to evaluate the group difference of brain connectivity in mild (Hoehn & Yahr stage 1,2) vs. moderate (Hoehn & Yahr stage 3) PD. Two-sided P-value less than 0.05 was regarded as statistically significant. Multiple comparison problem was controlled as a false-discovery rate (FDR) less than 0.05. Results: Two groups of 38 patients in the mild PD group (median age 68y, range 50-87yy) and 17 patients in the moderate PD gorup (median age 76y, range 63-86yy) were analyzed their group-specific connectivities. The total scores of UPDRS were significantly different between the mild PD group (22 ± 10) and moderate PD group (48 ± 21), respectively (P 0.05). Conclusions: Increased integrity of the posteromedial cortical (PCC)-thalamic connectivity in the moderate PD group suggests that dysfunction of DMN may be related to the progression of PD. To our knowledge, this is the first study applicating early-phase FBB PET in brain connectivity research.