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  Atrophy and structural covariance of the cholinergic basal forebrain in primary progressive aphasia

Teipel, S., Raiser, T., Riedl, L., Riederer, I., Schroeter, M. L., Bisenius, S., et al. (2016). Atrophy and structural covariance of the cholinergic basal forebrain in primary progressive aphasia. Cortex, 83, 124-135. doi:10.1016/j.cortex.2016.07.004.

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Teipel, Stefan1, 2, Author
Raiser, Theresa3, Author
Riedl, Lina4, Author
Riederer, Isabelle5, Author
Schroeter, Matthias L.6, 7, Author              
Bisenius, Sandrine6, 7, Author              
Schneider, Anja8, Author
Kornhuber, Johannes9, Author
Fliessbach, Klaus10, 11, Author
Spottke, Annika9, Author
Grothe, Michael J.1, 2, Author
Prudlo, Johannes12, Author
Kassubek, Jan13, Author
Ludolph, Albert13, Author
Landwehrmeyer, Bernhard13, Author
Straub, Sarah13, Author
Otto, Markus13, Author
Danek, Adrian2, Author
the FTLDc Study Group, Author              
1German Center for Neurodegenerative Diseases, Rostock, Germany, ou_persistent22              
2Department of Psychosomatic Medicine, University of Rostock, Germany, ou_persistent22              
3Department of Neurology, Ludwig Maximilians University Munich, Germany, ou_persistent22              
4Department of Psychiatry, TU Munich, Germany, ou_persistent22              
5Department of Neuroradiology, TU Munich, Germany, ou_persistent22              
6Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              
7Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, Leipzig, DE, ou_634549              
8Department of Psychiatry, Georg August University, Göttingen, Germany, ou_persistent22              
9Department of Psychiatry, Friedrich Alexander University Erlangen, Germany, ou_persistent22              
10German Center for Neurodegenerative Diseases, Bonn, Germany, ou_persistent22              
11Department of Psychiatry, University Bonn, Germany, ou_persistent22              
12Department of Neurology, University of Rostock, Germany, ou_persistent22              
13Department of Neurology, Ulm University, Germany, ou_persistent22              


Free keywords: Grey matter atrophy; Cholinergic system; Language; Multivariate analysis; MRI
 Abstract: Primary progressive aphasia (PPA) is characterized by profound destruction of cortical language areas. Anatomical studies suggest an involvement of cholinergic basal forebrain (BF) in PPA syndromes, particularly in the area of the nucleus subputaminalis (NSP). Here we aimed to determine the pattern of atrophy and structural covariance as a proxy of structural connectivity of BF nuclei in PPA variants. We studied 62 prospectively recruited cases with the clinical diagnosis of PPA and 31 healthy older control participants from the cohort study of the German consortium for frontotemporal lobar degeneration (FTLD). We determined cortical and BF atrophy based on high-resolution magnetic resonance imaging (MRI) scans. Patterns of structural covariance of BF with cortical regions were determined using voxel-based partial least square analysis. We found significant atrophy of total BF and BF subregions in PPA patients compared with controls [F(1, 82) = 20.2, p < .001]. Atrophy was most pronounced in the NSP and the posterior BF, and most severe in the semantic variant and the nonfluent variant of PPA. Structural covariance analysis in healthy controls revealed associations of the BF nuclei, particularly the NSP, with left hemispheric predominant prefrontal, lateral temporal, and parietal cortical areas, including Broca's speech area (p < .001, permutation test). In contrast, the PPA patients showed preserved structural covariance of the BF nuclei mostly with right but not with left hemispheric cortical areas (p < .001, permutation test). Our findings agree with the neuroanatomically proposed involvement of the cholinergic BF, particularly the NSP, in PPA syndromes. We found a shift from a structural covariance of the BF with left hemispheric cortical areas in healthy aging towards right hemispheric cortical areas in PPA, possibly reflecting a consequence of the profound and early destruction of cortical language areas in PPA.


Language(s): eng - English
 Dates: 2016-06-092016-02-042016-07-012016-07-162016-10
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.cortex.2016.07.004
PMID: 27509365
Other: Epub 2016
 Degree: -



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Title: Cortex
  Other : Cortex
Source Genre: Journal
Publ. Info: -
Pages: - Volume / Issue: 83 Sequence Number: - Start / End Page: 124 - 135 Identifier: DOI: 10.1016/j.cortex.2016.07.004
CoNE: https://pure.mpg.de/cone/journals/resource/954925393344