Longitudinal Progression of Atrophy in Non-Fluent Primary Progressive Aphasia Follows the Functional/Structural Speech Motor Network (P4.031)

Objective: We hypothesize that toxic proteins in non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) would spread transynaptically from an early epicenter to connected regions within the language network causing the progression of atrophy over time. To our knowledge, no longitudinal study has confirmed this hypothesis. Background: Functional intrinsic connectivity networks have helped in the prediction of neurodegeneration in different diseases by showing that patterns of atrophy mirror healthy functional network architectures. The language network is vulnerable to atrophy in nfvPPA, which is often linked to a tau-pathology. Design/Methods: the early epicenter was defined in a group of early nfvPPA (n=10) with the Voxel-based morphometry (VBM) analysis. From this region we derive the functional speech/language connectivity network in healthy controls. We then identify the underlying white matter fibers with diffusion tractography. Longitudinal gray matter (GM) and white matter (WM) changes were evaluated with a VBM longitudinal analysis on 34 nfvPPA. Finally we performed correlation analyses between volume changes in patients and the strength of the healthy network. Results: From the epicenter in the inferior frontal gyrus (IFG), the functional connectivity network in healthy controls comprises known areas involved in the speech/language function. Tractography delineated the WM pathways between the same regions. Significant longitudinal GM change was found in the left language-related regions and in the right IFG and precentral gyrus and the longitudinal WM change in the correspondent underlying regions. Significant correlations were found between GM changes in patients and the functional connectivity language network and between WM changes and fractional anisotropy along the language tracks. Conclusion: These findings suggest that the pattern of longitudinal progression of atrophy in nfvPPA reflects the anatomy of language functional network and support the hypothesis that the spread of degeneration occurs not only by contiguity but also following specific anatomical and functional network architectures. Disclosure: Dr. Mandelli has nothing to disclose. Dr. Vilaplana has nothing to disclose. Dr. Hubbard has nothing to disclose. Dr. Brown has nothing to disclose. Dr. Santos has nothing to disclose. Dr. Binney has nothing to disclose. Dr. Attygalle has nothing to disclose. Dr. Henry has nothing to disclose. Dr. Henry has received personal compensation for activities with StemCells, Inc. and Novartis. Dr. Rosen has nothing to disclose. Dr. Miller has nothing to disclose. Dr. Seeley has received personal compensation for activities with Biogen Idec. as a consultant. Dr. Gorno Tempini has received personal compensation in an editorial capacity for Co-Editor, Neuroimage Clinical.