O3‐03‐05: Longitudinal Mri and Neuropsychological Changes in Symptomatic Frontotemporal Lobar Degeneration Subjects With Mutations in Mapt, Pgrn, and C9orf72
Year: 2014
Type: article
Study design: Observational Study
Abstract: Familial frontotemporal lobar degeneration (f-FTLD) is commonly caused by mutations in MAPT, progranulin (PGRN) and C9ORF72. Our objectives were to compare imaging and neuropsychological progression among these three mutation groups to prepare for clinical trials. Available neuroimaging data on f-FTLD patients evaluated at Mayo Clinic were reviewed and analyzed. In order to compare longitudinal changes in frontotemporal volume (FTV) and ventricular volume (VV) in symptomatic MAPT, PGRN and C9ORF72 mutation carriers, the Symmetric Diffeomorphic Image Normalization method was used for normalization of serial scans to obtain Tensor Based Morphometry (TBM-SyN) maps. We also compared baseline and longitudinal data on the Controlled Oral Word Association Test (COWAT), Trailmaking Test B (TMT B), Boston Naming Test (BNT) and Category Fluency (Cat Fl) in f-FTLD mutation carriers among subjects. We used linear mixed models with random slopes and intercepts to analyze longitudinal clinical and imaging data with years from baseline as the time scale. MR data was available for 21 MAPT kindred subjects (age 50 ± 12 years, 57% male), 11 PGRN subjects (age 64 ± 9 years, 45% male) and 11 C9ORF72 subjects (age 62 ± 10 years, 55% male). PGRN mutation carriers had a greater rate of change in FTV compared to MAPT (p=0.01); with a trend compared to C9ORF72 (p=0.07). (Figure 1) VV change was greater in PGRN subjects compared to MAPT (p<0.001); and C9ORF72 subjects (p=0.003). While all mutation carriers declined on neuropsychological measures, there was no difference in baseline or rate of change on the COWAT or Cat Fl among the three groups. Rates of changes were greater in PGRN carriers on the BNT compared to MAPT carriers, and greater in MAPT carriers on the TMT B compared to C9ORF72 subjects. These findings suggest that among symptomatic f-FTLD subjects with mutations in MAPT, PGRN and C9ORF72: 1) FTV decreases and VV increases in a measurable and relatively linear fashion using TBM-SyN maps, 2) the rate of volume change is greater for PGRN than for MAPT and C9ORF72 mutation carriers, 3) the rate of volume change is similar between MAPT and C9ORF72 mutation carriers, 4) all mutation carriers have declining performance on key neuropsychological measures. Volume in frontotemporal region over time for individual subjects by group.
Source: Alzheimer s & Dementia
Authors: Jonathan Graff‐Radford, David Jones, Stephen Weigand, Scott Przybelski, Jennifer Louise Whitwell, Mathew Senjem, David S. Knopman, Neill R. Graff‐Radford, Keith Josephs, Zbigniew Wszolek, Prashanthi Vemuri, Julie A. Fields, Tanis J. Ferman, John Lucas, Val J. Lowe, Ralitza Gavrilova, Karen Kuntz, Mariely DeJesus Hernandez, Matthew Baker, Rosa Rademakers, Ronald Carl Petersen, Kejal Kantarci, Clifford Jack, Bradley F. Boeve
Institutions: Mayo Clinic, Mayo Clinic in Florida
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2035303840