Konsortium zur Erforschung der frontotemporalen Lobärdegeneration

Otto, Markus; Ludolph, Albert C.; Landwehrmeyer, G. Bernhard; Förstl, Hans; Diehl‐Schmid, Janine; Neumann, Manuela; Kretzschmar, Hans A.; Schroeter, Matthias L.; Kornhuber, Johannes; Danek, Adrian

doi:10.1007/s00115-011-3261-3

Cited by 42 publications

(29 citation statements)

References 21 publications

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“…A total of 77 participants from the cohort of the German consortium for frontotemporal lobar degeneration ( Otto et al, 2011 ) were included in the study: 13 symptomatic C9orf72 mutation carriers (8 FTD, 2 ALS, 3 FTD/ALS), 45 with sporadic FTD ( Medford and Critchley, 2010 ) or FTD/ALS ( Snowden et al, 2015 ) in whom a pathological C9orf72 expansion, MAPT or GRN mutation has been excluded and 19 healthy elderly control subjects. Diagnosis was made according to current international consensus criteria ( Brooks et al, 2000 ; Rascovsky et al, 2011 ).…”

Section: Methodsmentioning

confidence: 99%

Atrophy in the Thalamus But Not Cerebellum Is Specific for C9orf72 FTD and ALS Patients – An Atlas-Based Volumetric MRI Study

Schönecker

Neuhofer

Otto

et al. 2018

Front. Aging Neurosci.

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Background: The neuropathology of patients with frontotemporal dementia (FTD) or amyotrophic lateral sclerosis (ALS) due to a C9orf72 mutation 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 to C9orf72 mutation 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 affected C9orf72 FTD, 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 in C9orf72 mutation carriers goes beyond the expected atrophy in the prefrontal and temporal subregion and is in good agreement with the cortical atrophy pattern described in C9orf72 mutation 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 differentiating C9orf72 mutation carriers from patients with sporadic FTD.

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Section: Methodsmentioning

confidence: 99%

Atrophy in the Thalamus But Not Cerebellum Is Specific for C9orf72 FTD and ALS Patients – An Atlas-Based Volumetric MRI Study

Schönecker

Neuhofer

Otto

et al. 2018

Front. Aging Neurosci.

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“…Data were provided by the multi-centric FTLD consortium’s study Germany ( Otto et al, 2011 1 ). The cohort included 86 patients diagnosed with possible and probable bvFTD according to Rascovsky et al (2011) and 43 healthy age-matched control subjects.…”

Section: Methodsmentioning

confidence: 99%

“…To investigate the relevance of social cognition in diagnosing bvFTD clinically, we examined the discriminatory diagnostic power for several neuropsychological tests in a large sample of bvFTD patients compared with age-matched healthy subjects from the multi-centric FTLD consortium’s study Germany ( Otto et al, 2011 ). We applied the new diagnostic criteria for bvFTD ( Rascovsky et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

A Modified Reading the Mind in the Eyes Test Predicts Behavioral Variant Frontotemporal Dementia Better Than Executive Function Tests

Schroeter

Pawelke

Bisenius

et al. 2018

Front. Aging Neurosci.

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Behavioral variant frontotemporal dementia (bvFTD) is characterized by deep alterations in behavior and personality. Although revised diagnostic criteria agree for executive dysfunction as most characteristic, impairments in social cognition are also suggested. The study aimed at identifying those neuropsychological and behavioral parameters best discriminating between bvFTD and healthy controls. Eighty six patients were diagnosed with possible or probable bvFTD according to Rascovsky et al. (2011) and compared with 43 healthy age-matched controls. Neuropsychological performance was assessed with a modified Reading the Mind in the Eyes Test (RMET), Stroop task, Trail Making Test (TMT), Hamasch-Five-Point Test (H5PT), and semantic and phonemic verbal fluency tasks. Behavior was assessed with the Apathy Evaluation Scale, Frontal Systems Behavioral Scale, and Bayer Activities of Daily Living Scale. Each test’s discriminatory power was investigated by Receiver Operating Characteristic curves calculating the area under the curve (AUC). bvFTD patients performed significantly worse than healthy controls in all neuropsychological tests. Discriminatory power (AUC) was highest in behavioral questionnaires, high in verbal fluency tasks and the RMET, and lower in executive function tests such as the Stroop task, TMT and H5PT. As fluency tasks depend on several cognitive functions, not only executive functions, results suggest that the RMET discriminated better between bvFTD and control subjects than other executive tests. Social cognition should be incorporated into diagnostic criteria for bvFTD in the future, such as in the International Classification of Diseases (ICD)-11, as already suggested in the Diagnostic and Statistical Manual for Mental Disorders (DSM)-5.

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“…Disease severity was 5.5 ± 3.5 or 7.7 ± 4.2 as measured with the Clinical Dementia Rating scale (CDR) and the FTLD-modified Clinical Dementia Rating scale (FTLD-CDR). The data was retrieved from the German FTLD Consortium, a prospective multicenter study on FTLD (http://www.ftld.de; Otto et al, 2011). Fifty-two (twenty-four female) control subjects were recruited overall, thirty subjects from the different centers in the German FTLD Consortium's study and, additionally, twenty-two from the Max-Planck-Institute Leipzig database.…”

Section: Methodsmentioning

confidence: 99%

Predicting behavioral variant frontotemporal dementia with pattern classification in multi-center structural MRI data

Meyer

Mueller

Stuke

et al. 2017

NeuroImage: Clinical

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PurposeFrontotemporal lobar degeneration (FTLD) is a common cause of early onset dementia. Behavioral variant frontotemporal dementia (bvFTD), its most common subtype, is characterized by deep alterations in behavior and personality. In 2011, new diagnostic criteria were suggested that incorporate imaging criteria into diagnostic algorithms. The study aimed at validating the potential of imaging criteria to individually predict diagnosis with machine learning algorithms.Materials & methodsBrain atrophy was measured with structural magnetic resonance imaging (MRI) at 3 Tesla in a multi-centric cohort of 52 bvFTD patients and 52 healthy control subjects from the German FTLD Consortium's Study. Beside group comparisons, diagnosis bvFTD vs. controls was individually predicted in each subject with support vector machine classification in MRI data across the whole brain or in frontotemporal, insular regions, and basal ganglia known to be mainly affected based on recent meta-analyses. Multi-center effects were controlled for with a new method, “leave one center out” conjunction analyses, i.e. repeatedly excluding subjects from each center from the analysis.ResultsGroup comparisons revealed atrophy in, most consistently, the frontal lobe in bvFTD beside alterations in the insula, basal ganglia and temporal lobe. Most remarkably, support vector machine classification enabled predicting diagnosis in single patients with a high accuracy of up to 84.6%, where accuracy was highest in a region-of-interest approach focusing on frontotemporal, insular regions, and basal ganglia in comparison with the whole brain approach.ConclusionOur study demonstrates that MRI, a widespread imaging technology, can individually identify bvFTD with high accuracy in multi-center imaging data, paving the road to personalized diagnostic approaches in the future.

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Konsortium zur Erforschung der frontotemporalen Lobärdegeneration

Cited by 42 publications

References 21 publications

Atrophy in the Thalamus But Not Cerebellum Is Specific for C9orf72 FTD and ALS Patients – An Atlas-Based Volumetric MRI Study

Atrophy in the Thalamus But Not Cerebellum Is Specific for C9orf72 FTD and ALS Patients – An Atlas-Based Volumetric MRI Study

A Modified Reading the Mind in the Eyes Test Predicts Behavioral Variant Frontotemporal Dementia Better Than Executive Function Tests

Predicting behavioral variant frontotemporal dementia with pattern classification in multi-center structural MRI data

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