Introduction: Trials to test disease-modifying treatments for frontotemporal dementia are eagerly awaited and sensitive instruments to assess potential treatment effects are increasingly urgent, yet lacking thus far. We aimed to identify gene-specific instruments assessing clinical onset and disease progression by comparing cognitive functioning between bvFTD patients across genetic mutations. Methods: We examined differences in 7 cognitive domains between bvFTD patients with GRN (n = 20), MAPT (n = 29) or C9orf72 (n = 31) mutations, and non-carriers (n = 24), and described longitudinal (M = 22.6 months, SD = 16.6) data in a subsample (n = 27). Results: Patients showed overall cognitive impairment, except memory recall, working memory and visuoconstruction. GRN patients performed lower on executive function (mean difference − 2.1; 95%CI − 4.1 to − 0.5) compared to MAPT and lower on attention compared to MAPT (mean difference − 2.5; 95%CI − 4.7 to − 0.3) and C9orf72 (mean difference − 2.4; 95%CI − 4.5 to − 0.3). Only MAPT patients were impaired on delayed recall (mean difference − 1.4; 95%CI − 2.1 to − 0.7). GRN patients declined rapidly on attention and memory, MAPT declined in confrontation naming, whereas C9orf72 patients were globally impaired but remained relatively stable over time on all cognitive domains. Discussion: This study shows gene-specific cognitive profiles in bvFTD, which underlines the value of neuropsychological tests as outcome measures in upcoming trials for genetic bvFTD.

Additional Metadata
Keywords Cognition, Frontotemporal dementia, FTD, Genetic, Neuropsychology
Persistent URL dx.doi.org/10.1007/s00415-020-09738-y, hdl.handle.net/1765/124885
Journal Journal of Neurology: official journal of the European Neurological Society
Citation
Poos, J.M, Jiskoot, L.C, Leijdersdorff, S.M.J, Seelaar, H, Panman, J.L, van der Ende, E.L, … van den Berg, E. (2020). Cognitive profiles discriminate between genetic variants of behavioral frontotemporal dementia. Journal of Neurology: official journal of the European Neurological Society. doi:10.1007/s00415-020-09738-y