title: Functional Changes in the Language Network in Response to Increased Amyloid β Deposition in Cognitively Intact Older Adults.
abstract: Word finding symptoms are frequent early in the course of Alzheimer's disease and relate principally to functional changes in left posterior temporal cortex. In cognitively intact older adults, we examined whether amyloid load affects the network for language and associative-semantic processing. Fifty-six community-recruited subjects (52-74 years), stratified for apolipoprotein E and brain-derived neurotrophic factor genotype, received a neurolinguistic assessment, (18)F-flutemetamol positron emission tomography, and a functional MRI of the associative-semantic system. The primary measure of amyloid load was the cerebral-to-cerebellar gray matter standardized uptake value ratio in a composite cortical volume of interest (SUVR(comp)). The primary outcome analysis consisted of a whole-brain voxelwise linear regression between SUVR(comp) and fMRI response during associative-semantic versus visuoperceptual processing. Higher activity in one region, the posterior left middle temporal gyrus, correlated positively with increased amyloid load. The correlation remained significant when only the word conditions were contrasted but not for pictures. According to a stepwise linear regression analysis, offline naming reaction times correlated positively with SUVR(comp). A binary classification into amyloid-positive and amyloid-negative cases confirmed our findings. The left posterior temporal activity increase may reflect higher demands for semantic control in the presence of a higher amyloid burden.
authors.affiliation: Laboratory for Cognitive Neurology, KU Leuven, Belgium Alzheimer Research Centre KU Leuven, Leuven Institute of Neurodegenerative Disorders, KU Leuven, Belgium.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Adamczuk
authors.affiliation: Laboratory for Cognitive Neurology, KU Leuven, Belgium.
authors.forename: An-Sofie
authors.initials: AS
authors.lastname: De Weer
authors.affiliation: Laboratory for Cognitive Neurology, KU Leuven, Belgium Department of Experimental Psychology, Oxford University, UK.
authors.forename: Natalie
authors.initials: N
authors.lastname: Nelissen
authors.affiliation: Laboratory for Cognitive Neurology, KU Leuven, Belgium Alzheimer Research Centre KU Leuven, Leuven Institute of Neurodegenerative Disorders, KU Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Dupont
authors.affiliation: Alzheimer Research Centre KU Leuven, Leuven Institute of Neurodegenerative Disorders, KU Leuven, Belgium Radiology Department, UZ Leuven, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sunaert
authors.affiliation: Neurodegenerative Brain Diseases Group, VIB Department of Molecular Genetics, Antwerp, Belgium Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Belgium.
authors.forename: Karolien
authors.initials: K
authors.lastname: Bettens
authors.affiliation: Neurodegenerative Brain Diseases Group, VIB Department of Molecular Genetics, Antwerp, Belgium Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Belgium.
authors.forename: Kristel
authors.initials: K
authors.lastname: Sleegers
authors.affiliation: Neurodegenerative Brain Diseases Group, VIB Department of Molecular Genetics, Antwerp, Belgium Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.affiliation: Alzheimer Research Centre KU Leuven, Leuven Institute of Neurodegenerative Disorders, KU Leuven, Belgium Nuclear Medicine and Molecular Imaging Department, KU Leuven and UZ Leuven, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
authors.affiliation: Laboratory for Cognitive Neurology, KU Leuven, Belgium Alzheimer Research Centre KU Leuven, Leuven Institute of Neurodegenerative Disorders, KU Leuven, Belgium Neurology Department, UZ Leuven, Belgium.
authors.forename: Rik
authors.initials: R
authors.lastname: Vandenberghe
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000503:physiopathology*; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000503:physiopathology*; D006801:Humans; D007802:Language; D008279:Magnetic Resonance Imaging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods; D012660:Semantics
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides
keywords: 18F-flutemetamol; Alzheimer; amyloid PET; fMRI; semantic