Phases of volume loss in patients with known frontotemporal lobar degeneration spectrum pathology

Area of Science:

• Neuroimaging
• Neuropathology
• Neurodegenerative Diseases

Background:

• Frontotemporal lobar degeneration (FTLD) encompasses clinically similar FTLD-tau and FTLD-TDP proteinopathies.
• Accurate antemortem diagnosis is challenging due to a lack of reliable in vivo markers.

Purpose of the Study:

• To identify early, distinguishing sites of cortical atrophy between FTLD-tau and FTLD-TDP proteinopathies using in vivo volumetric MRI.
• To validate imaging findings with postmortem pathological burden.

Main Methods:

• Retrospective analysis of volumetric MRI data from 42 FTLD-Tau and 21 FTLD-TDP patients.
• Development of a frequency-based staging model to map atrophy patterns.
• Validation using postmortem measures of pathological burden.

Main Results:

• Distinct loci of maximal early cortical atrophy were identified: dorsolateral/medial frontal for FTLD-Tau and ventral frontal/anterior temporal for FTLD-TDP.
• Minimal overlap in atrophy phases between the two main proteinopathy groups.
• Within-group subtypes (3R/4R-tauopathies, TDP-43 Types A/C) showed good early overlap with subtle later divergence.
• Postmortem validation confirmed associations between imaging phases and pathological burden in both FTLD-tau and FTLD-TDP.

Conclusions:

• Early, distinct patterns of cortical atrophy identified via MRI can help differentiate FTLD proteinopathies during a patient's lifetime.
• These imaging markers offer potential for improved antemortem diagnosis and understanding of disease progression.