We tested the potential of task-based functional neuroimaging as a biomarker of emerging prefrontal brain changes in progranulin (GRN) mutations carriers. Five GRN mutation carriers free of frontotemporal dementia (FTD) and 11 non-carriers from families with FTD-GRN underwent functional MRI while solving matrix-reasoning problems. Mutation carriers displayed slower responses for more difficult problems and lower lateral prefrontal activation across all problems. Overall task-evoked posterior ventrolateral prefrontal activation predicted mutation status with 100% sensitivity and 91% specificity. Volumetric differences did not account for activation differences. Prefrontal activation may have utility as a biomarker in GRN mutation.
Background: Mutations in the progranulin (GRN) gene are a major cause of familial frontotemporal dementia. They result in a loss of progranulin levels and in GRN-related brain degenerative changes that unfold over years if not decades. The aim of our review was to summarize the evidence on emerging functional and structural brain abnormalities in carriers of GRN mutations. Summary: We performed a systematic search for studies that used at least one modality (structural MRI, fMRI, fluorodeoxyglucose positron emission tomography, diffusion tensor imaging) to compare mutation carriers to non-carrier controls. Our search produced 13 studies published between 2008 and 2017, the majority cross-sectional, with carrier sample sizes ranging from 5 to 65. Key Messages: The aggregate findings suggest that (1) measurable brain changes are detectable in at least some mutation carriers 20–25 years prior to disease onset; (2) functional/metabolic changes progress more consistently over time than structural changes; (3) the topographic pattern is anterior to posterior, not always asymmetric, and maps onto known functional networks.
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