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

•FTLD-tau and FTLD-TDP groups have distinct early loci of cortical atrophy.•In vivo biomarkers can distinguish early sites of atrophy between FTLD groups.•Subtypes within FTLD groups have divergent atrophy patterns as disease progresses.•Atrophy patterns from in vivo MRI correlate with postmortem pa...

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Published in:Neurobiology of aging 2022-05, Vol.113, p.95-107
Main Authors: Burke, Sarah E., Phillips, Jeffrey S., Olm, Christopher A., Peterson, Claire S., Cook, Phillip A., Gee, James C., Lee, Edward B., Trojanowski, John Q., Massimo, Lauren, Irwin, David J., Grossman, Murray
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creator Burke, Sarah E.
Phillips, Jeffrey S.
Olm, Christopher A.
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Massimo, Lauren
Irwin, David J.
Grossman, Murray
description •FTLD-tau and FTLD-TDP groups have distinct early loci of cortical atrophy.•In vivo biomarkers can distinguish early sites of atrophy between FTLD groups.•Subtypes within FTLD groups have divergent atrophy patterns as disease progresses.•Atrophy patterns from in vivo MRI correlate with postmortem pathology. Frontotemporal lobar degeneration (FTLD) includes clinically similar FTLD-tau or FTLD-TDP proteinopathies which lack in vivo markers for accurate antemortem diagnosis. To identify early distinguishing sites of cortical atrophy between groups, we retrospectively analyzed in vivo volumetric MRI from 42 FTLD-Tau and 21 FTLD-TDP patients and validated these findings with postmortem measures of pathological burden. Our frequency-based staging model revealed distinct loci of maximal early cortical atrophy in each group, including dorsolateral and medial frontal regions in FTLD-Tau and ventral frontal and anterior temporal regions in FTLD-TDP. Sørenson-Dice calculations between proteinopathy groups showed little overlap of phases. Conversely, within-group subtypes showed good overlap between 3R- and 4R-tauopathies, and between TDP-43 Types A and C for early regions with subtle divergence between subtypes in subsequent phases of atrophy. Postmortem validation found an association of imaging phases with pathologic burden within FTLD-tau (F(4, 238) = 17.44, p < 0.001) and FTLD-TDP (F(4,245) = 42.32, p < 0.001). These results suggest that relatively early, distinct markers of atrophy may distinguish FTLD proteinopathies during life. [Display omitted]
doi_str_mv 10.1016/j.neurobiolaging.2022.02.007
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Frontotemporal lobar degeneration (FTLD) includes clinically similar FTLD-tau or FTLD-TDP proteinopathies which lack in vivo markers for accurate antemortem diagnosis. To identify early distinguishing sites of cortical atrophy between groups, we retrospectively analyzed in vivo volumetric MRI from 42 FTLD-Tau and 21 FTLD-TDP patients and validated these findings with postmortem measures of pathological burden. Our frequency-based staging model revealed distinct loci of maximal early cortical atrophy in each group, including dorsolateral and medial frontal regions in FTLD-Tau and ventral frontal and anterior temporal regions in FTLD-TDP. Sørenson-Dice calculations between proteinopathy groups showed little overlap of phases. Conversely, within-group subtypes showed good overlap between 3R- and 4R-tauopathies, and between TDP-43 Types A and C for early regions with subtle divergence between subtypes in subsequent phases of atrophy. Postmortem validation found an association of imaging phases with pathologic burden within FTLD-tau (F(4, 238) = 17.44, p &lt; 0.001) and FTLD-TDP (F(4,245) = 42.32, p &lt; 0.001). These results suggest that relatively early, distinct markers of atrophy may distinguish FTLD proteinopathies during life. 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Frontotemporal lobar degeneration (FTLD) includes clinically similar FTLD-tau or FTLD-TDP proteinopathies which lack in vivo markers for accurate antemortem diagnosis. To identify early distinguishing sites of cortical atrophy between groups, we retrospectively analyzed in vivo volumetric MRI from 42 FTLD-Tau and 21 FTLD-TDP patients and validated these findings with postmortem measures of pathological burden. Our frequency-based staging model revealed distinct loci of maximal early cortical atrophy in each group, including dorsolateral and medial frontal regions in FTLD-Tau and ventral frontal and anterior temporal regions in FTLD-TDP. Sørenson-Dice calculations between proteinopathy groups showed little overlap of phases. Conversely, within-group subtypes showed good overlap between 3R- and 4R-tauopathies, and between TDP-43 Types A and C for early regions with subtle divergence between subtypes in subsequent phases of atrophy. 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1558-1497
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9241163
source ScienceDirect Freedom Collection 2022-2024
subjects Atrophy
Biomarkers
Frontotemporal Dementia - pathology
Frontotemporal lobar degeneration
Frontotemporal Lobar Degeneration - diagnostic imaging
Frontotemporal Lobar Degeneration - pathology
Humans
Magnetic resonance imaging
Percent area occupied
Retrospective Studies
Sporadic
Tau
tau Proteins
TDP-43
title Phases of volume loss in patients with known frontotemporal lobar degeneration spectrum pathology
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