TY  - JOUR
A1  - Diehl-Schmid, Janine
A1  - Licata, Abigail
A1  - Goldhardt, Oliver
A1  - Förstl, Hans
A1  - Yakushew, Igor
A1  - Otto, Markus
A1  - Anderl-Straub, Sarah
A1  - Beer, Ambros
A1  - Ludolph, Albert Christian
A1  - Landwehrmeyer, Georg Bernhard
A1  - Levin, Johannes
A1  - Danek, Adrian
A1  - Fliessbach, Klaus
A1  - Spottke, Annika
A1  - Fassbender, Klaus
A1  - Lyros, Epameinondas
A1  - Prudlo, Johannes
A1  - Krause, Bernd Joachim
A1  - Volk, Alexander
A1  - Edbauer, Dieter
A1  - Schroeter, Matthias Leopold
A1  - Drzezga, Alexander
A1  - Kornhuber, Johannes
A1  - Lauer, Martin
A1  - Grimmer, Timo
T1  - FDG-PET underscores the key role of the thalamus in frontotemporal lobar degeneration caused by C9ORF72 mutations
JF  - Translational Psychiatry
N2  - C9ORF72 mutations are the most common cause of familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). MRI studies have investigated structural changes in C9ORF72-associated FTLD (C9FTLD) and provided first insights about a prominent involvement of the thalamus and the cerebellum. Our multicenter, 18F-fluorodeoxyglucose positron-emission tomography study of 22 mutation carriers with FTLD, 22 matched non-carriers with FTLD, and 23 cognitively healthy controls provided valuable insights into functional changes in C9FTLD: compared to non-carriers, mutation carriers showed a significant reduction of glucose metabolism in both thalami, underscoring the key role of the thalamus in C9FTLD. Thalamic metabolism did not correlate with disease severity, duration of disease, or the presence of psychotic symptoms. Against our expectations we could not demonstrate a cerebellar hypometabolism in carriers or non-carriers. Future imaging and neuropathological studies in large patient cohorts are required to further elucidate the central role of the thalamus in C9FTLD.
KW  - diagnostic markers
KW  - psychiatric disorders
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225308
VL  - 9
ER  - 
TY  - JOUR
A1  - Semler, Elisa
A1  - Anderl-Straub, Sarah
A1  - Uttner, Ingo
A1  - Diehl-Schmid, Janine
A1  - Danek, Adrian
A1  - Einsiedler, Beate
A1  - Fassbender, Klaus
A1  - Fliessbach, Klaus
A1  - Huppertz, Hans-Jürgen
A1  - Jahn, Holger
A1  - Kornhuber, Johannes
A1  - Landwehrmeyer, Bernhard
A1  - Lauer, Martin
A1  - Muche, Rainer
A1  - Prudlo, Johannes
A1  - Schneider, Anja
A1  - Schroeter, Matthias L.
A1  - Ludolph, Albert C.
A1  - Otto, Markus
T1  - A language-based sum score for the course and therapeutic intervention in primary progressive aphasia
JF  - Alzheimer's Research & Therapy
N2  - Background
With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions.

Methods
We assessed 28 patients with nonfluent variant PPA, 17 with semantic variant PPA, 13 with logopenic variant PPA, and 28 healthy controls in detail for 1 year. The most informative neuropsychological assessments were combined to a sum score, and associations between brain atrophy were investigated followed by a sample size calculation for clinical trials.

Results
Significant absolute changes up to 20% in cognitive tests were found after 1 year. Semantic and phonemic word fluency, Boston Naming Test, Digit Span, Token Test, AAT Written language, and Cookie Test were identified as the best markers for disease progression. These tasks provide the basis of a new PPA sum score. Assuming a therapeutic effect of 50% reduction in cognitive decline for sample size calculations, a number of 56 cases is needed to find a significant treatment effect. Correlations between cognitive decline and atrophy showed a correlation up to r = 0.7 between the sum score and frontal structures, namely the superior and inferior frontal gyrus, as well as with left-sided subcortical structures.

Conclusion
Our findings support the high performance of the proposed sum score in the follow-up of PPA and recommend it as an outcome measure in intervention studies.
KW  - frontotemporal dementia
KW  - cognitive neuropsychology in dementia
KW  - assessment of cognitive disorders/dementia
KW  - volumetric MRI
KW  - aphasia
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236277
VL  - 10
ER  -