Figure 5. MRI cortical thinning is reflective of cortical neuropathological burden at autopsy.

A: Scatterplot portrays a significant negative relationship between pathology burden (i.e. normalized %AO) and cortical thickness z-scores from antemortem MRI in regions matching autopsy sampling across pathology groups (beta = −0.04, SE = 0.01, p = 0.007). The fit line represents the linear association between cortical thickness z-scores (x-axis) and normalized %AO (y-axis) in corresponding regions, and has been derived in a linear mixed effects model³⁶ accounting for multiple measurements from the same patient as well as one covariate (i.e. time from scan to autopsy), which may confound the linear association between the two measurements. Data points are color-coded by pathology (i.e. FTLD-TDP = blue, FTLD-Tau = red). B: Heat-map shows relative MRI cortical thinning in left-hemisphere ROIs matching five standard core regions sampled at autopsy in FTLD-TDP and FTLD-Tau. Regions are color-coded by relative severity of cortical thinning as compared to healthy controls (scale bars = z-scores) within pathology groups. Group means are obtained from 11 patients (5 FTLD-TDP, 6 FTLD-Tau) with available antemortem structural MRI. Among these core ROIs, FTLD-TDP has greatest core-region atrophy in left OFC (mean = −3.78 ± 2.25), while FTLD-Tau has greatest core-region atrophy in left MFC (mean = −2.10 ± 1.53), validating our postmortem findings. Regions of greatest core-region atrophy are marked with an asterisk (*). Legend: FTLD-Tau = frontotemporal lobar degeneration with inclusions of the tau protein; FTLD-TDP = frontotemporal lobar degeneration with inclusions of the transactive response DNA-binding protein 43; normalized %AO = percentage area occupied by pathology after normalization [0;1].