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Psychiatry Res. 2014 Mar 30;221(3):187-94. doi: 10.1016/j.pscychresns.2013.10.003. Epub 2013 Dec 6.

Brain atrophy in primary progressive aphasia involves the cholinergic basal forebrain and Ayala's nucleus.

Author information

1
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.
2
Department of Clinical Radiology, University Hospitals - Grosshadern, Ludwig-Maximilians Universität, Munich, Germany.
3
Department of Neurology, Ludwig-Maximilians Universität, Munich, Germany.
4
Department of Psychosomatic Medicine, University Medicine Rostock, Gehlsheimer Str. 20, 18147 Rostock, Germany; DZNE, German Center for Neurodegenerative Diseases, Rostock, Germany.
5
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.
6
Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil.
7
Department of Radiology, University of Sao Paulo Medical School, Sao Paulo, Brazil.
8
DZNE, German Center for Neurodegenerative Diseases, Rostock, Germany.
9
Department of Neurosurgery, University of Sao Paulo Medical School, Sao Paulo, Brazil; Morphological Brain Research Unit, Department of Psychiatry, University Würzburg, Würzburg, Germany.
10
Hochschule Fresenius, Hamburg, Germany.
11
Department of Neurology, University of Mannheim, Mannheim, Germany.
12
Morphological Brain Research Unit, Department of Psychiatry, University Würzburg, Würzburg, Germany.

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.

KEYWORDS:

Cholinergic system; Diagnosis; Language; Nucleus subputaminalis; Post-mortem MRI; Primary progressive aphasia

PMID:
24434193
PMCID:
PMC4086659
DOI:
10.1016/j.pscychresns.2013.10.003
[Indexed for MEDLINE]
Free PMC Article

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