Longitudinal neuroimaging and neuropsychological profiles of frontotemporal dementia with C9ORF72 expansions

摘要

Introduction Frontotemporal dementia (FTD) is a common cause of early-onset dementia with a significant genetic component, as underlined by the recent identification of repeat expansions in the gene C9ORF72 as a major cause of FTD and motor neuron disease. Understanding the neurobiology and clinical phenomenology of this novel mutation is currently a major research focus. However, few data are available concerning the longitudinal evolution of this genetic disease. Here we present longitudinal neuropsychological and neuroimaging data on a cohort of patients with pathological repeat expansions in C9ORF72 . Methods Following a review of the University College London FTD DNA database, 20 cases were retrospectively identified with a C9ORF72 expansion. Twelve cases had longitudinal neuropsychology data available and six of these cases also had longitudinal volumetric brain magnetic resonance imaging. Cortical and subcortical volumes were extracted using FreeSurfer. Rates of whole brain, hemispheric, cerebellar and ventricular change were calculated for each subject. Nonlinear fluid registration of follow-up to baseline scan was performed to visualise longitudinal intra-subject patterns of brain atrophy and ventricular expansion. Results Patients had low average verbal and performance IQ at baseline that became impaired (Conclusion Disease evolution in C9ORF72 -associated FTD is linked neuropsychologically with increasing involvement of parietal and amnestic functions, and neuroanatomically with rather diffuse and variable cortical and central atrophy but more consistent involvement of the cerebellum and thalamus. These longitudinal profiles are consistent with disease spread within a distributed subcortical network and demonstrate the feasibility of longitudinal biomarkers for tracking the evolution of the C9ORF72 mutation phenotype.