F4‐04‐04: Subcortical Shape Analysis for Joint Biomarker Discovery

Abstract

target the default mode network, a set of interconnected brain areas implicated in monitoring and memory retrieval. Conversely, variants of FTD target different networks; for example, the behavioral variant of FTD, which is characterized by impulsivity and disordered emotional regulation, targets a brain network implicated in reward and motivation. Methods: We used the Parkinson's Progression Markers Initiative (PPMI), a large open-source database of imaging and clinical data in de novo PD patients. We performed deformation based morphometry and independent component analysis to identify areas showing atrophy in PD patients compared to control subjects. Results: Striatum, basal forebrain, amygdala, hippocampus, insula and anterior cingulate cortex demonstrated atrophy in proportion to clinical disease severity, consistent with the scheme proposed by Braak from postmortem data. We also show that these regions form a connected intrinsic network. Moreover, we show that disease patterns follow brain connectomics, compatible with an epicenter in the substantia nigra. Finally we find that cognitive impairment at visit 2 is associated with progression of atrophy in the entorhinal cortex. Conclusions: PD, like AD and FTD, demonstrates a pattern of disease atrophy compatible with the network spread hypothesis. Disease spread from the PD network to the AD network may herald the onset of dementia.