title: Cholinergic depletion and basal forebrain volume in primary progressive aphasia.
abstract: Primary progressive aphasia (PPA) is a heterogeneous syndrome with various neuropathological causes for which no medical treatment with proven efficacy exists. Basal forebrain (BF) volume loss has been reported in PPA but its relation to cholinergic depletion is still unclear. The primary objective of this study was to investigate whether cholinergic alterations occur in PPA variants and how this relates to BF volume loss. An academic memory clinic based consecutive series of 11 PPA patients (five with the semantic variant (SV), four with the logopenic variant (LV) and two with the nonfluent variant (NFV)) participated in this cross-sectionalin vivoPET imaging study together with 10 healthy control subjects. Acetylcholinesterase (AChE) activity was quantitatively measured in the neo- and allocortex using N-[11C]-Methylpiperidin-4-yl propionate (PMP)-PET with arterial sampling and metabolite correction. Whole brain and BF volumes were quantified using voxel-based morphometry on high-resolution magnetic resonance imaging (MRI) scans. In the PPA group, only LV cases showed decreases in AChE activity levels compared to controls. Surprisingly, a substantial number of SV cases showed significant AChE activity increases compared to controls. BF volume did not correlate with AChE activity levels in PPA. To conclude, in our sample of PPA patients, LV but not SV was associated with cholinergic depletion. BF atrophy in PPA does not imply cholinergic depletion.
authors.affiliation: Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Herestraat 49, Box 1027, Leuven 3000, Belgium; Alzheimer Research Centre, KU Leuven, Herestraat 49, Leuven 3000, Belgium; Leuven Institute of Neuroscience and Disease, Herestraat 49, Leuven 3000, Belgium.
authors.forename: Jolien
authors.initials: J
authors.lastname: Schaeverbeke
authors.affiliation: Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Herestraat 49, Box 1027, Leuven 3000, Belgium; Alzheimer Research Centre, KU Leuven, Herestraat 49, Leuven 3000, Belgium; Leuven Institute of Neuroscience and Disease, Herestraat 49, Leuven 3000, Belgium.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Evenepoel
authors.affiliation: Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Herestraat 49, Box 1027, Leuven 3000, Belgium; Neurology Department, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium.
authors.forename: Rose
authors.initials: R
authors.lastname: Bruffaerts
authors.affiliation: Leuven Institute of Neuroscience and Disease, Herestraat 49, Leuven 3000, Belgium; Nuclear Medicine and Molecular Imaging, KU Leuven and University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
authors.affiliation: Nuclear Medicine and Molecular Imaging, KU Leuven and University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium; Laboratory of Radiopharmaceutical Chemistry, KU Leuven, Herestraat 49, Leuven 3000, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.affiliation: Neurology Department, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Dries
authors.affiliation: Pathology Department, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tousseyn
authors.affiliation: Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Herestraat 49, Box 1027, Leuven 3000, Belgium; Experimental Psychology Department, Oxford University, 9 South Parks Road, Oxford OX1 3UD, United Kingdom.
authors.forename: Natalie
authors.initials: N
authors.lastname: Nelissen
authors.affiliation: Radiology Department, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium.
authors.forename: Ronald
authors.initials: R
authors.lastname: Peeters
authors.affiliation: Alzheimer Research Centre, KU Leuven, Herestraat 49, Leuven 3000, Belgium; Old Age Psychiatry Department, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vandenbulcke
authors.affiliation: Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Herestraat 49, Box 1027, Leuven 3000, Belgium; Alzheimer Research Centre, KU Leuven, Herestraat 49, Leuven 3000, Belgium; Leuven Institute of Neuroscience and Disease, Herestraat 49, Leuven 3000, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Dupont
authors.affiliation: Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Herestraat 49, Box 1027, Leuven 3000, Belgium; Alzheimer Research Centre, KU Leuven, Herestraat 49, Leuven 3000, Belgium; Leuven Institute of Neuroscience and Disease, Herestraat 49, Leuven 3000, Belgium; Neurology Department, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium.
authors.forename: Rik
authors.initials: R
authors.lastname: Vandenberghe
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000328:Adult; D000368:Aged; D018888:Aphasia, Primary Progressive / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D001284:Atrophy / Q000473:pathology; D066187:Basal Forebrain / Q000000981:diagnostic imaging / Q000473:pathology*; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011422:Propionates
chemical_list: D002250:Carbon Radioisotopes; D011422:Propionates; C099183:N-methylpiperidin-4-yl propionate; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase; Basal forebrain; Kinetic modeling; N-[11C]-Methylpiperidin-4-yl propionate; PET; Primary progressive aphasia