Clinical and Neuroanatomical Characteristics of Individuals with Frontotemporal Dementia and the C9orf72 Repeat Expansion (P6.240)

Objective: To characterize symptom profiles and structural brain changes of individuals with the C9orf72 repeat expansion and bvFTD or FTD-ALS. Background: The C9orf72 repeat expansion is a recently discovered autosomal genetic alteration that is associated with some familial cases of behavioral variant frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis (ALS). Methods: Subjects included 10 individuals with bvFTD or FTD-ALS and the C9orf72 repeat expansion, eight of whom had structural MRIs for analysis. Freesurfer 5.3 was used to process images and extract structural measures using standard workflows. Selected subcortical and cortical regions were compared to those in a set of normal older adults using unpaired two sample t-tests and corrections for multiple comparisons. Single subject cortical thickness maps were also constructed to evaluate regions of atrophy compared to normal older adults, using a generalized linear model. Clinical histories were reviewed regarding criteria for bvFTD and psychotic symptoms. Results: Subcortical volumes including the bilateral thalami, hippocampi, and amygdalae, but not cerebellar cortices, were significantly diminished in subjects (p-adjusted < 0.05). Cortical thickness analyses revealed significant bilateral atrophy most prominent in orbitofrontal, superior frontal, and middle temporal regions. Nine patients satisfied clinical criteria for possible bvFTD, four had delusions, and three had mild auditory hallucinations. Conclusion: In this sample, individuals with the C9orf72 repeat expansion and bvFTD or FTD-ALS demonstrated significant atrophy in subcortical regions and frontotemporal cortices, and had a moderate prevalence of psychotic symptoms, which is atypical for bvFTD but has been described in patients with this genetic alteration.