Structural Brain Changes in Pre-Clinical FTD MAPT Mutation Carriers

Abstract

Background: Frontotemporal dementia (FTD) is the second most common cause of early-onset neurodegenerative dementia. Several studies have focused on early imaging changes in FTD patients, but once subjects meet full criteria for FTD diagnosis, structural changes are generally widespread.

Objective: This study aims to determine the earliest structural brain changes in asymptomatic MAPT MUTATION carriers.

Methods: This is a cross-sectional multicenter study comparing global and regional brain volume and white matter integrity in a group of MAPT mutation preclinical carriers and controls. Participants belong to multiple generations of six families with five MAPT mutations. All participants underwent a medical examination, neuropsychological tests, genetic analysis, and a magnetic resonance scan (3T, scout, T1-weighted image followed by EPI (BOLD), MPRAGE, DTI, FLAIR, and ASL sequences).

Results: Volumes of five cortical and subcortical areas were strongly correlated with mutation status: temporal lobe (left amygdala, left temporal pole), cingulate cortex (left rostral anterior cingulate gyrus, right posterior cingulate), and the lingual gyrus in the occipital lobe. We did not find significant differences in whole brain volume, white matter hyperintensities volume, and white matter integrity using DTI analysis.

Conclusion: Temporal lobe, cingulate cortex and the lingual gyrus seem to be early targets of the disease and may serve as biomarkers for FTD prior to overt symptom onset.

Keywords: Atrophy; MAPT mutation; brain atrophy; early detection; frontotemporal lobar degeneration.

Fig. 1.

Multivariate analysis: Elastic net. Percentage of selection over 500 Bootstrap iterations. In Elastic-net model, 10/89 ROIs are selected into the model. Over 500 iteration bootstrapping, 5 measures are constantly selected (with over 80% selection rate), demonstrating a potential strong association with mutation status. This is a recalculation of selection percentage based on the bootstrap results. The column ‘Either’ is a surrogate measure of the % selection for either left or right hemisphere of the specific ROI. When considering bilateral selection %, the results remain the same as considering both hemispheres separately. It could be shown from the graph that for those ROIs, the bilateral ROIs seems not competing with each other.