A longitudinal analysis of cerebral blood flow changes in genetic frontotemporal Dementia: Results from genfi

Abstract Background Mutations in the C9orf72, GRN, or MAPT genes are the most prevalent genetic causes of familial frontotemporal dementia (FTD). In a cross‐sectional study of genetic FTD, lower CBF was observed in presymptomatic FTD mutation carriers vs. controls from the same families in 6 regions of interest: the bilateral anterior cingulate cortex, the left medial temporal gyrus, the left and right insulae, and the left and right supramarginal gyri (Mutsaerts et. al. 2019). However, there have been no studies to date that identify longitudinal changes in CBF between FTD genetic subgroups (both presymptomatic and symptomatic) compared to controls. Method We compared longitudinal changes in CBF, as measured by ASL‐MRI, in 317 FTD mutation carriers (118 C9orf72, 141 GRN, and 58 MAPT) vs. 261 non‐carrier controls from the Genetic FTD Initiative (GENFI). Linear mixed effects models tested the main effect of carrier status, and its interaction with age, along with covariates of age, sex, site‐of‐scan against each subject’s mean regional cerebral blood flow within the regions of interest from Mutsaerts et al. (2019). Family membership was a random intercept in the model to control for similar genetic and environmental backgrounds. Result Differences between genetic subsets of FTD were apparent, with GRN carriers preferentially experiencing decreases within the salience network regions while MAPT carriers expressed differences within the left medial temporal gyrus and bilateral anterior cingulate gyrus. C9orf72 carriers only saw a decrease in CBF within the left insula. Significant interactions between carrier status and age were exclusively evident in MAPT carriers across all regions of interest. Conclusion Differentiating CBF signatures were found to exist between the genetic FTD subgroups, with the most prominent changes being seen in GRN and MAPT subsets. Evidence continues to mount that CBF may be a viable biomarker in the earlier detection and delineation of genetic FTD variants. References: Mutsaerts, H. J. M. M. et al. Cerebral perfusion changes in presymptomatic genetic frontotemporal dementia: a GENFI study. Brain 142, awz039 (2019).