O2‐09‐06: Trajectory of Lobar Atrophy in Asymptomatic and Symptomatic Grn Mutation Carriers: a Longitudinal Tbm‐syn Study
Year: 2019
Type: article
Study design: Observational Study
Abstract: Mutations in the progranulin (GRN) gene are a major cause of familial frontotemporal lobar degeneration (FTLD). Our objective was to determine the rates of lobar cortical atrophy in the asymptomatic and symptomatic GRN mutations carriers. Participants of this study were enrolled in the Mayo Alzheimer's Disease Research Center (ADRC) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) studies at the Mayo Clinic site. We identified 13 GRN mutation carriers (8 asymptomatic, 5 symptomatic) and non-carriers (n=10) from 6 individual families who had at least 2 serial T1-weighted structural MRIs and were followed annually with a median of 4.12 years (range 1.02 to 9.78 years). A total of 86 MRI scans were included. Longitudinal changes in lobar cortical volume were analyzed using the tensor-based morphometry with symmetric normalization (TBM-SyN) algorithm. Linear mixed-effect models were used to model cortical volume change over time among 3 groups accounting for within-family correlations. The annual rates of frontal (p<0.05) and parietal (p<0.01) lobe cortical atrophy were higher in asymptomatic GRN mutation carriers than non-carriers. The symptomatic GRN mutation carriers also had increased rates of atrophy in the frontal (p<0.01) and parietal lobe (p<0.01) cortices than non-carriers. In addition, greater rates of cortical atrophy was observed in the temporal lobe cortices of symptomatic GRN mutation carriers than non-carriers (p<0.001) (Figure 1).
Source: Alzheimer s & Dementia
Authors: Qin Chen, Bradley F. Boeve, Matthew L. Senjem, Nirubol Tosakulwong, Timothy G. Lesnick, Danielle Brushaber, Christina Dheel, Julie A. Fields, Leah K. Forsberg, Ralitza H. Gavrilova, Debra Gearhart, Jonathan Graff-Radford, Neill R. Graff-Radford, Clifford R. Jack, David T. Jones, David S. Knopman, Walter K. Kremers, Maria I. Lapid, Rosa Rademakers, Jeremy Syrjanen, Adam L. Boxer, Howard J. Rosen, Zbigniew Wszolek, Kejal Kantarci
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2981244061