Focal Temporal Pole Atrophy and Network Degeneration in Semantic Variant Primary Progressive Aphasia (I7.003)

Objective: The goal of this study was to identify the precise focal point of neurodegeneration in Semantic Variant Primary Progressive Aphasia (svPPA) and to elucidate the selective vulnerability of large-scale networks to neuropathology. Background: Despite a wealth of neuroimaging research that has associated svPPA with a distributed pattern of cortical atrophy that is most prominent in the left anterior temporal pole, there is little consensus regarding which region within this heterogeneous structure is most damaged, which may indicate the putative origin of neurodegeneration. Furthermore, no studies have attempted to assess the reliability of effects across multiple samples of patients with svPPA. Methods: We used cortical thickness analysis to precisely localize the maximal atrophy point in svPPA. We further investigated the reliability of the localization of this focal atrophy point in two independent samples, and the overlap of the maximal atrophy point between individual subjects. We then used resting-state functional connectivity in healthy young adults to assess the intrinsic network connectivity of this region. Results: The maximal atrophy point in both svPPA patient samples was localized to the same region of the left temporal pole. Notably, 100[percnt] of individuals in both svPPA samples had their maximal atrophy point in the same temporopolar region. The focal atrophy point identified in our cortical thickness analysis anchored a network of brain regions in healthy adults that closely resembled the cortical atrophy pattern of svPPA patients. Furthermore, in both patient samples, the magnitude of cortical atrophy within a given brain region was predicted by that region’s strength of connectivity to the focal atrophy point in healthy adults Conclusions: Our results provide novel evidence for the network neurodegeneration hypothesis, suggesting that the progression of neurodegeneration in svPPA not only follows the topography of large-scale networks but also prioritizes the strongest connections from the site of origin. Disclosure: Dr. Collins has nothing to disclose. Dr. Montal has nothing to disclose. Dr. Gorno Tempini has received personal compensation in an editorial capacity for Co-Editor, Neuroimage Clinical. Merck, consultant, En Vivo, consultant, Forum (consultant).