Charting Frontotemporal Dementia: From Genes to Networks.

Abstract

Frontotemporal dementia (FTD) is a genetically and clinically heterogeneous syndrome that is characterized by overlapping clinical symptoms involving behavior, personality, language and/or motor functions and degeneration of the frontal and temporal lobes. The term frontotemporal lobar degeneration (FTLD) is used to describe the proteinopathies associated with clinical FTD. Emerging evidence from network-based neuroimaging studies, such as resting state functional MRI and diffusion tensor MRI studies, have implicated specific large-scale brain networks in the pathogenesis of FTD syndromes, suggesting a new paradigm for explaining the distributed and heterogeneous spreading patterns of pathological proteins in FTLD. In this review, we overview recent research on the study of FTD syndromes as connectivity disorders in symptomatic patients as well as genotype-specific changes in asymptomatic FTD-related gene mutation carriers. Characterizing brain network breakdown in these subjects using neuroimaging may help anticipate the diagnosis and perhaps prevent the devastating impact of FTD.