title: Atrophy and structural covariance of the cholinergic basal forebrain in primary progressive aphasia.
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.
authors: German Center for Neurodegenerative Diseases (DZNE) - Rostock/Greifswald, Rostock, Germany; Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany. Electronic address: stefan.teipel@med.uni-rostock.de.
authors: Stefan
authors: S
authors: Teipel
authors: Department of Neurology, University of Munich, Munich, Germany.
authors: Theresa
authors: T
authors: Raiser
authors: Department of Psychiatry, Technical University of Munich, Munich, Germany.
authors: Lina
authors: L
authors: Riedl
authors: Department of Neuroradiology, Technical University of Munich, Munich, Germany.
authors: Isabelle
authors: I
authors: Riederer
authors: Clinic of Cognitive Neurology, University of Leipzig, Leipzig, Germany; Max Planck Institute for Human Cognitive & Brain Sciences, Leipzig, Germany.
authors: Matthias L
authors: ML
authors: Schroeter
authors: Clinic of Cognitive Neurology, University of Leipzig, Leipzig, Germany; Max Planck Institute for Human Cognitive & Brain Sciences, Leipzig, Germany.
authors: Sandrine
authors: S
authors: Bisenius
authors: Department of Psychiatry, University of Göttingen, Göttingen, Germany.
authors: Anja
authors: A
authors: Schneider
authors: Department of Psychiatry, University of Erlangen, Erlangen, Germany.
authors: Johannes
authors: J
authors: Kornhuber
authors: German Center for Neurodegenerative Diseases (DZNE) - Bonn, Bonn, Germany; Department of Psychiatry, University of Bonn, Bonn, Germany.
authors: Klaus
authors: K
authors: Fliessbach
authors: German Center for Neurodegenerative Diseases (DZNE) - Bonn, Bonn, Germany.
authors: Annika
authors: A
authors: Spottke
authors: German Center for Neurodegenerative Diseases (DZNE) - Rostock/Greifswald, Rostock, Germany; Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany.
authors: Michel J
authors: MJ
authors: Grothe
authors: Department of Neurology, University of Rostock, Rostock, Germany.
authors: Johannes
authors: J
authors: Prudlo
authors: Department of Neurology, University of Ulm, Ulm, Germany.
authors: Jan
authors: J
authors: Kassubek
authors: Department of Neurology, University of Ulm, Ulm, Germany.
authors: Albert
authors: A
authors: Ludolph
authors: Department of Neurology, University of Ulm, Ulm, Germany.
authors: Bernhard
authors: B
authors: Landwehrmeyer
authors: Department of Neurology, University of Ulm, Ulm, Germany.
authors: Sarah
authors: S
authors: Straub
authors: Department of Neurology, University of Ulm, Ulm, Germany.
authors: Markus
authors: M
authors: Otto
authors: Department of Neurology, University of Munich, Munich, Germany.
authors: Adrian
authors: A
authors: Danek
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018888:Aphasia, Primary Progressive / Q000000981:diagnostic imaging / Q000473:pathology*; D001284:Atrophy / Q000000981:diagnostic imaging / Q000473:pathology; D066187:Basal Forebrain / Q000000981:diagnostic imaging / Q000473:pathology*; D059329:Cholinergic Neurons / Q000473:pathology*; D005260:Female; D006801:Humans; D007802:Language; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests
keywords: Cholinergic system; Grey matter atrophy; Language; MRI; Multivariate analysis