Rates of lobar atrophy in asymptomatic MAPT mutation carriers

Qin Chen, Bradley F Boeve, Matthew Senjem, Nirubol Tosakulwong, Timothy G Lesnick, Danielle Brushaber, Christina Dheel, Julie Fields, Leah Forsberg, Ralitza Gavrilova, Debra Gearhart, Jonathan Graff-Radford, Neill R Graff-Radford, Clifford R Jack Jr, David T Jones, David S Knopman, Walter K Kremers, Maria Lapid, Rosa Rademakers, Jeremy Syrjanen, Adam L Boxer, Howie Rosen, Zbigniew K Wszolek, Kejal Kantarci, LEFFTDS Consortium, Qin Chen, Bradley F Boeve, Matthew Senjem, Nirubol Tosakulwong, Timothy G Lesnick, Danielle Brushaber, Christina Dheel, Julie Fields, Leah Forsberg, Ralitza Gavrilova, Debra Gearhart, Jonathan Graff-Radford, Neill R Graff-Radford, Clifford R Jack Jr, David T Jones, David S Knopman, Walter K Kremers, Maria Lapid, Rosa Rademakers, Jeremy Syrjanen, Adam L Boxer, Howie Rosen, Zbigniew K Wszolek, Kejal Kantarci, LEFFTDS Consortium

Abstract

Introduction: The aim of this study was to investigate the rates of lobar atrophy in the asymptomatic microtubule-associated protein tau (MAPT) mutation carriers.

Methods: MAPT mutation carriers (n = 14; 10 asymptomatic, 4 converters from asymptomatic to symptomatic) and noncarriers (n = 13) underwent structural magnetic resonance imaging and were followed annually with a median of 9.2 years. Longitudinal changes in lobar atrophy were analyzed using the tensor-based morphometry with symmetric normalization algorithm.

Results: The rate of temporal lobe atrophy in asymptomatic MAPT mutation carriers was faster than that in noncarriers. Although the greatest rate of atrophy was observed in the temporal lobe in converters, they also had increased atrophy rates in the frontal and parietal lobes compared to noncarriers.

Discussion: Accelerated decline in temporal lobe volume occurs in asymptomatic MAPT mutation carriers followed by the frontal and parietal lobe in those who have become symptomatic. The findings have implications for monitoring the progression of neurodegeneration during clinical trials in asymptomatic MAPT mutation carriers.

Keywords: Asymptomatic; Frontotemporal dementia; Longitudinal; MAPT; Magnetic resonance image.

Figures

Fig. 1
Fig. 1
Lobar volume plotted against age at MRI. Data point trajectories for individual MAPT mutation carriers (top panel) and the predicted volumes (cm3) from the mixed models for each group (bottom panel) are shown. The blue line represents for the asymptomatic group who remained asymptomatic during the course of the study; the red line represents for the asymptomatic MAPT mutation carriers who converted; the black line represents the noncarriers. The noncarriers are not plotted in the top panel to show the data from the MAPT mutation carriers with clarity. Abbreviations: MAPT, microtubule-associated protein tau; MRI, magnetic resonance imaging.
Fig. 2
Fig. 2
Voxel-based analysis showed greater annualized rates of cortical atrophy in all MAPT mutation carriers compared to noncarriers. The results are shown at P < .05 after using the false discovery rate correction for multiple comparisons. Abbreviation: MAPT, microtubule-associated protein tau.

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Source: PubMed

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