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- W4380893955 abstract "Abstract Background White matter signal abnormalities (WMSA) are frequently observed on magnetic resonance imaging (MRI) scans of people with frontotemporal dementia (FTD). We hypothesized that carriers of mutations in progranulin (GRN+) , chromosome 9 open reading frame 72 ( C9orf72+) and microtubule associated protein tau ( MAPT+) have increased rates of progression of WMSA compared to non‐carrier individuals prior to onset of dementia, and that different mutations may have different rates of WMSA accumulation. Method Participants were recruited through the ARTFL‐LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) Study. We selected participants with Clinical Dementia Rating scale (CDR) scores of 0 and 0.5. If a participant developed FTD during the follow‐up, we only analyzed observations collected before the conversion. WMSA were defined as hyperintensities on FLAIR MRI. Total WMSA volumes were normalized to the respective intracranial volumes. We used a linear mixed effects model, with random intercepts and slopes, to compare the baseline burden and the longitudinal progression of total WMSA volumes between mutation carriers and controls. The model was adjusted for baseline age, sex, education, baseline Montreal Cognitive Assessment (MoCA) scores, and MRI acquisition sites. Result We analyzed MRI data from 199 participants who had at least two MRI visits (46 C9orf72+ , 17 GRN+ , 35 MAPT+ , 101 non‐carrier controls; up to five years of follow‐up). We did not find significant group differences in baseline demographic features, except that MAPT+ was younger than non‐carrier controls (average age: C9orf72+ = 47, GRN+ = 56, MAPT+ = 40, controls = 47). Baseline WMSA volumes were not significantly different between mutation carriers and controls. Longitudinally, the rates of WMSA volume increase in C9orf72+ and MAPT+ were comparable to controls; whereas, GRN+ had higher rates of WMSA volume increases compared to controls (p = 0.01). Conclusion WMSA may accumulate at higher rates in GRN+ prior to the onset of FTD, which is consistent with the frequent presence of white matter diseases observed in symptomatic FTD patients with GRN mutations. Future work is warranted to investigate the association between white matter structural changes and cognitive/psychiatric changes in FTD mutation carriers." @default.
- W4380893955 created "2023-06-17" @default.
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- W4380893955 date "2023-06-01" @default.
- W4380893955 modified "2023-09-27" @default.
- W4380893955 title "Progression of white matter signal abnormalities in predementia frontotemporal dementia mutation carriers" @default.
- W4380893955 doi "https://doi.org/10.1002/alz.068038" @default.
- W4380893955 hasPublicationYear "2023" @default.
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