Frontotemporal lobar degeneration (FTLD) syndromes are highly heterogeneous and overlapping in their clinical phenotype and brain morphometry. Thus, utilizing a transdiagnostic approach to capture the heterogeneous nature of FTLD is important for understanding and treating FTLD syndromes. The primary hypothesis of this study was that syndromes associated with FTLD are multidimensional rather than discrete clinical entities. From the Pick’s disease and Progressive Supranuclear Palsy Prevalence and Incidence (PiPPIN) study dataset, 310 patients with a syndrome likely to be caused by FTLD were assessed via behavioural, cognitive, and neuroimaging measures. A data-driven analysis of cross-sectional phenotypes showed that common syndromes associated with FTLD exist as a multidimensional spectrum in terms of their clinical features and structural brain changes. A subset of these patients was also assessed four years later and showed greater overlap across all FTLD syndromes at follow-up. Taking on a spectral, or a transdiagnostic, approach, therefore, can be critical to effectively capture the individual differences in FTLD syndromes for further understanding disease aetiology and progression and for targeted treatments.

Murley, A. G., Coyle-Gilchrist, I., Rouse, M. A., Jones, P. S., Li, W., Wiggins, J., Lansdall, C., Rodríguez, P. V., Wilcox, A., Tsvetanov, K. A., Patterson, K., Ralph, M. A. L., & Rowe, J. B. (2020). Redefining the multidimensional clinical phenotypes of frontotemporal lobar degeneration syndromes. BRAIN, 143, 1555–1571. https://doi.org/10.1093/brain/awaa119