title: Mapping 3-year changes in gray matter and metabolism in Aβ-positive nondemented subjects.
abstract: Gray matter (GM) atrophy and brain glucose hypometabolism are already detected in the predementia stages of Alzheimer's disease (AD), but the regional and longitudinal associations between the two are not well understood. Here, we analyzed the patterns of longitudinal atrophy (magnetic resonance imaging [MRI]) and (18)F-Fluorodeoxyglucose-positron emission tomography ([18F]FDG-PET) metabolism decline in 40 cognitively healthy control (HC) and 52 mildly impaired (mild cognitive impairment [MCI]) subjects during 3 years. Based on cerebrospinal fluid and brain amyloid-PET, the subjects were divided into amyloid-beta (Aβ)- and Aβ+ subgroups. In voxel-based and region of interest analyses, we compared the 3-year rates of change in GM and glucose metabolism between Aβ-subgroups, within each diagnostic group. In joint-independent component analyses, we assessed the patterns of covariation between longitudinal change in GM volume and glucose metabolism. MCI-Aβ+ showed faster atrophy than MCI-Aβ- within the temporal, medial temporal, and medial parietal lobes. HC-Aβ+ showed faster atrophy within the precuneus than HC-Aβ-. For FDG-PET metabolism, MCI-Aβ+ exhibited faster decline than MCI-Aβ- in temporoparietal regions, whereas no differences between HC subgroups were observed. Joint-independent component analysis showed that accelerated atrophy and metabolism decline correlated across distant brain regions for MCI-Aβ+. In conclusion, abnormally increased levels of Aβ in nondemented subjects were associated with accelerated decline in both GM and glucose metabolism, where both types of neurodegeneration progress in spatially divergent patterns.
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilian-University (LMU), Munich, Germany. Electronic address: miguel.caballero@med.uni-muenchen.de.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Araque Caballero
authors.affiliation: Department of Nuclear Medicine, Klinikum der Universität München, Ludwig-Maximilian-University (LMU), Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Brendel
authors.affiliation: Department of Nuclear Medicine, Klinikum der Universität München, Ludwig-Maximilian-University (LMU), Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Delker
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilian-University (LMU), Munich, Germany.
authors.forename: Jinyi
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Nuclear Medicine, Klinikum der Universität München, Ludwig-Maximilian-University (LMU), Munich, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Rominger
authors.affiliation: Department of Nuclear Medicine, Klinikum der Universität München, Ludwig-Maximilian-University (LMU), Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilian-University (LMU), Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.affiliation: Department of Radiology, VA Medical Center, Center for Imaging of Neurodegenerative Diseases, University of California, SanFrancisco, CA, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilian-University (LMU), Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ewers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001284:Atrophy; D060825:Cognitive Dysfunction / Q000378:metabolism / Q000473:pathology; D005260:Female; D005947:Glucose / Q000378:metabolism; D066128:Gray Matter / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D005947:Glucose
keywords: Alzheimer's; Longitudinal; Multimodal; Multivariate; Neurodegeneration; Neuroimaging