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Background  TDP-43 type C is one of the pathological forms of frontotemporal lobar degeneration (FTLD) and mainly associated clinically with the semantic variant of primary progressive aphasia (svPPA). We aimed to define in vivo the sequential pattern of neuroanatomical involvement in a cohort of patients with FTLD-TDP type C pathology.    Methods  We extracted the volumes of a set of cortical and subcortical regions from MRI scans of 19 patients with  post mortem  confirmed TDP-43 type C pathology (all with left hemisphere-predominant atrophy at baseline). In the initial development phase, we used w-scores computed from 81 cognitively normal controls to define a set of sequential stages of neuroanatomical involvement within the FTLD-TDP type C cohort where a w-score of < − 1.65 was considered abnormal. In a subsequent validation phase, we used 31 follow-up scans from 14 of the 19 patients in the same cohort to confirm the staging model.    Results  Four sequential stages were identified in the initial development phase.  Stage 1  was defined by atrophy in the left amygdala, medial temporal cortex, temporal pole, lateral temporal cortex and right medial temporal cortex;  Stage 2  by atrophy in the left supratemporal cortex;  Stage 3  by atrophy in the right anterior insula; and  Stage 4  by atrophy in the right accumbens. In the validation phase, calculation of w-scores in the longitudinal scans confirmed the staging system, with all patients either staying in the same stage or progressing to a later stage at follow-up.    Conclusion  In vivo imaging is able to detect distinct stages of neuroanatomical involvement in FTLD-TDP type C pathology. Using an imaging-derived staging system allows a more refined stratification of patients with svPPA during life.

In vivo staging of frontotemporal lobar degeneration TDP-43 type C pathology