Atrophy in the Thalamus But Not Cerebellum Is Specific forFTD and ALS Patients - An Atlas-Based Volumetric MRI Study

TY - JOUR

T1 - Atrophy in the Thalamus But Not Cerebellum Is Specific forFTD and ALS Patients - An Atlas-Based Volumetric MRI Study

AU - Schönecker, Sonja

AU - Neuhofer, Christiane

AU - Otto, Markus

AU - Ludolph, Albert

AU - Kassubek, Jan

AU - Landwehrmeyer, Bernhard

AU - Anderl-Straub, Sarah

AU - Semler, Elisa

AU - Diehl-Schmid, Janine

AU - Prix, Catharina

AU - Vollmar, Christian

AU - Fortea, Juan

AU - Huppertz, Hans-Jürgen

AU - Arzberger, Thomas

AU - Edbauer, Dieter

AU - Feddersen, Berend

AU - Dieterich, Marianne

AU - Schroeter, Matthias L

AU - Volk, Alexander E

AU - Fließbach, Klaus

AU - Schneider, Anja

AU - Kornhuber, Johannes

AU - Maler, Manuel

AU - Prudlo, Johannes

AU - Jahn, Holger

AU - Boeckh-Behrens, Tobias

AU - Danek, Adrian

AU - Klopstock, Thomas

AU - Levin, Johannes

AU - FTLD Consortium Germany

PY - 2018

Y1 - 2018

N2 - Background: The neuropathology of patients with frontotemporal dementia (FTD) or amyotrophic lateral sclerosis (ALS) due to aC9orf72mutation is characterized by two distinct types of characteristic protein depositions containing either TDP-43 or so-called dipeptide repeat proteins that extend beyond frontal and temporal regions. Thalamus and cerebellum seem to be preferentially affected by the dipeptide repeat pathology unique toC9orf72mutation carriers.Objective: This study aimed to determine if mutation carriers showed an enhanced degree of thalamic and cerebellar atrophy compared to sporadic patients or healthy controls.Methods: Atlas-based volumetry was performed in 13 affectedC9orf72FTD, ALS and FTD/ALS patients, 45 sporadic FTD and FTD/ALS patients and 19 healthy controls. Volumes and laterality indices showing significant differences between mutation carriers and sporadic patients were subjected to binary logistic regression to determine the best predictor of mutation carrier status. Results: Compared to sporadic patients, mutation carriers showed a significant volume reduction of the thalamus, which was most striking in the occipital, temporal and prefrontal subregion of the thalamus. Disease severity measured by mini mental status examination (MMSE) and FTD modified Clinical Dementia Rating Scale Sum of Boxes (FTD-CDR-SOB) significantly correlated with volume reduction in the aforementioned thalamic subregions. No significant atrophy of cerebellar regions could be detected. A logistic regression model using the volume of the prefrontal and the laterality index of the occipital subregion of the thalamus as predictor variables resulted in an area under the curve (AUC) of 0.88 while a model using overall thalamic volume still resulted in an AUC of 0.82.Conclusion: Our data show that thalamic atrophy inC9orf72mutation carriers goes beyond the expected atrophy in the prefrontal and temporal subregion and is in good agreement with the cortical atrophy pattern described inC9orf72mutation carriers, indicating a retrograde degeneration of functionally connected regions. Clinical relevance of the detected thalamic atrophy is illustrated by a correlation with disease severity. Furthermore, the findings suggest MRI volumetry of the thalamus to be of high predictive value in differentiatingC9orf72mutation carriers from patients with sporadic FTD.

AB - Background: The neuropathology of patients with frontotemporal dementia (FTD) or amyotrophic lateral sclerosis (ALS) due to aC9orf72mutation is characterized by two distinct types of characteristic protein depositions containing either TDP-43 or so-called dipeptide repeat proteins that extend beyond frontal and temporal regions. Thalamus and cerebellum seem to be preferentially affected by the dipeptide repeat pathology unique toC9orf72mutation carriers.Objective: This study aimed to determine if mutation carriers showed an enhanced degree of thalamic and cerebellar atrophy compared to sporadic patients or healthy controls.Methods: Atlas-based volumetry was performed in 13 affectedC9orf72FTD, ALS and FTD/ALS patients, 45 sporadic FTD and FTD/ALS patients and 19 healthy controls. Volumes and laterality indices showing significant differences between mutation carriers and sporadic patients were subjected to binary logistic regression to determine the best predictor of mutation carrier status. Results: Compared to sporadic patients, mutation carriers showed a significant volume reduction of the thalamus, which was most striking in the occipital, temporal and prefrontal subregion of the thalamus. Disease severity measured by mini mental status examination (MMSE) and FTD modified Clinical Dementia Rating Scale Sum of Boxes (FTD-CDR-SOB) significantly correlated with volume reduction in the aforementioned thalamic subregions. No significant atrophy of cerebellar regions could be detected. A logistic regression model using the volume of the prefrontal and the laterality index of the occipital subregion of the thalamus as predictor variables resulted in an area under the curve (AUC) of 0.88 while a model using overall thalamic volume still resulted in an AUC of 0.82.Conclusion: Our data show that thalamic atrophy inC9orf72mutation carriers goes beyond the expected atrophy in the prefrontal and temporal subregion and is in good agreement with the cortical atrophy pattern described inC9orf72mutation carriers, indicating a retrograde degeneration of functionally connected regions. Clinical relevance of the detected thalamic atrophy is illustrated by a correlation with disease severity. Furthermore, the findings suggest MRI volumetry of the thalamus to be of high predictive value in differentiatingC9orf72mutation carriers from patients with sporadic FTD.

KW - Journal Article

U2 - 10.3389/fnagi.2018.00045

DO - 10.3389/fnagi.2018.00045

M3 - SCORING: Journal article

C2 - 29599716

VL - 10

SP - 45

JO - FRONT AGING NEUROSCI

JF - FRONT AGING NEUROSCI

SN - 1663-4365

ER -