title: Brain atrophy in primary progressive aphasia involves the cholinergic basal forebrain and Ayala's nucleus.
abstract: Primary progressive aphasia (PPA) is characterized by left hemispheric frontotemporal cortical atrophy. Evidence from anatomical studies suggests that the nucleus subputaminalis (NSP), a subnucleus of the cholinergic basal forebrain, may be involved in the pathological process of PPA. Therefore, we studied the pattern of cortical and basal forebrain atrophy in 10 patients with a clinical diagnosis of PPA and 18 healthy age-matched controls using high-resolution magnetic resonance imaging (MRI). We determined the cholinergic basal forebrain nuclei according to Mesulam's nomenclature and the NSP in MRI reference space based on histological sections and the MRI scan of a post-mortem brain in cranio. Using voxel-based analysis, we found left hemispheric cortical atrophy in PPA patients compared with controls, including prefrontal, lateral temporal and medial temporal lobe areas. We detected cholinergic basal forebrain atrophy in left predominant localizations of Ch4p, Ch4am, Ch4al, Ch3 and NSP. For the first time, we have described the pattern of basal forebrain atrophy in PPA and confirmed the involvement of NSP that had been predicted based on theoretical considerations. Our findings may enhance understanding of the role of cholinergic degeneration for the regional specificity of the cortical destruction leading to the syndrome of PPA.
authors.affiliation: Department of Psychosomatic Medicine, University Medicine Rostock, Gehlsheimer Str. 20, 18147 Rostock, Germany; DZNE, German Center for Neurodegenerative Diseases, Rostock, Germany. Electronic address: stefan.teipel@med.uni-rostock.de.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Teipel
authors.affiliation: Department of Clinical Radiology, University Hospitals - Grosshadern, Ludwig-Maximilians Universität, Munich, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Flatz
authors.affiliation: Department of Neurology, Ludwig-Maximilians Universität, Munich, Germany.
authors.forename: Nibal
authors.initials: N
authors.lastname: Ackl
authors.affiliation: Department of Psychosomatic Medicine, University Medicine Rostock, Gehlsheimer Str. 20, 18147 Rostock, Germany; DZNE, German Center for Neurodegenerative Diseases, Rostock, Germany.
authors.forename: Michel
authors.initials: M
authors.lastname: Grothe
authors.affiliation: Department of Psychosomatic Medicine, University Medicine Rostock, Gehlsheimer Str. 20, 18147 Rostock, Germany; DZNE, German Center for Neurodegenerative Diseases, Rostock, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Kilimann
authors.affiliation: Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience (TCIN), Laboratory of Neuroimaging & Biomarker Research, Trinity College Dublin, The Adelaide and Meath Hospital incorporating the National Children's Hospital (AMiNCH), Dublin, Ireland, UK.
authors.forename: Arun L W
authors.initials: AL
authors.lastname: Bokde
authors.affiliation: Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: Lea
authors.initials: L
authors.lastname: Grinberg
authors.affiliation: Department of Radiology, University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: Edson
authors.initials: E
authors.lastname: Amaro
authors.affiliation: DZNE, German Center for Neurodegenerative Diseases, Rostock, Germany.
authors.forename: Vanja
authors.initials: V
authors.lastname: Kljajevic
authors.affiliation: Department of Neurosurgery, University of Sao Paulo Medical School, Sao Paulo, Brazil; Morphological Brain Research Unit, Department of Psychiatry, University Würzburg, Würzburg, Germany.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Alho
authors.affiliation: Hochschule Fresenius, Hamburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Knels
authors.affiliation: Department of Neurology, University of Mannheim, Mannheim, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Ebert
authors.affiliation: Morphological Brain Research Unit, Department of Psychiatry, University Würzburg, Würzburg, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Heinsen
authors.affiliation: Department of Neurology, Ludwig-Maximilians Universität, Munich, Germany.
authors.forename: Adrian
authors.initials: A
authors.lastname: Danek
mesh_terms: D000368:Aged; D018888:Aphasia, Primary Progressive / Q000473:pathology*; D001284:Atrophy; D001921:Brain / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology*; D002799:Cholinergic Fibers / Q000473:pathology*; D056344:Executive Function; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000473:pathology; D016548:Prosencephalon / Q000473:pathology*; D013702:Temporal Lobe / Q000473:pathology
keywords: Cholinergic system; Diagnosis; Language; Nucleus subputaminalis; Post-mortem MRI; Primary progressive aphasia