Magnetic Resonance Imaging Signatures of Tissue Pathology in Frontotemporal Dementia

Abstract

The pathologic substrates of frontotemporal dementia (FTD) are difficult to predict in vivo. To determine whether different pathologic substrates of FTD have distinct patterns of regional atrophy on magnetic resonance imaging (MRI). Retrospective case study. The Institute of Neurology, University College London, and the Institute of Psychiatry, King's College London. Patients Twenty-one cases of FTD selected on pathologic grounds (9 with ubiquitin-positive [tau- and alpha-synuclein-negative] inclusions [FTD-U], 7 with Pick disease [PiD], and 5 with familial FTD with tau exon 10+16 mutations [tau exon 10+16]) and 20 healthy controls were studied. Patterns of gray matter atrophy in each group as assessed by voxel-based morphometry (VBM) and a blinded visual assessment of each MRI study. All pathologic substrates were associated with atrophy that involved the inferior and medial temporal and inferior frontal lobes. Additionally, specific VBM signatures were identified for each subgroup: FTD-U was associated with asymmetric (left > right) temporal lobe atrophy, PiD was associated with severe dorsolateral bifrontal atrophy, and tau exon 10+16 was associated with asymmetric (right > left) medial temporal lobe atrophy. The VBM findings were supported by blinded visual assessment. These findings suggest that MRI patterns of regional gray matter atrophy constitute signatures of tissue pathology in FTD.