title: Region-specific hierarchy between atrophy, hypometabolism, and β-amyloid (Aβ) load in Alzheimer's disease dementia.
abstract: Gray matter atrophy, glucose hypometabolism, and β-amyloid Aβ deposition are well-described hallmarks of Alzheimer's disease, but their relationships are poorly understood. The present study aims to compare the local levels of these three alterations in humans with Alzheimer's disease. Structural magnetic resonance imaging, (18)F-fluorodeoxyglucose positron emission tomography (PET), and (18)F-florbetapir PET data from 34 amyloid-negative healthy controls and 20 demented patients with a high probability of Alzheimer's disease etiology (attested using neuroimaging biomarkers as recently recommended) were analyzed. For each patient and imaging modality, age-adjusted Z-score maps were computed, and direct between-modality voxelwise comparison and correlation analyses were performed. Significant differences in the levels of atrophy, hypometabolism, and Aβ deposition were found in most brain areas, but the hierarchy differed across regions. A cluster analysis revealed distinct subsets of regions: (1) in the hippocampus, atrophy exceeded hypometabolism, whereas Aβ load was minimal; (2) in posterior association areas, Aβ deposition was predominant, together with high hypometabolism and lower but still significant atrophy; and (3) in frontal regions, Aβ deposition was maximal, whereas structural and metabolic alterations were low. Atrophy and hypometabolism significantly correlated in the hippocampus and temporo-parietal cortex, whereas Aβ load was not significantly related to either atrophy or hypometabolism. These findings provide direct evidence for regional variations in the hierarchy and relationships between Aβ load, hypometabolism, and atrophy. Altogether, these variations probably reflect the differential involvement of region-specific pathological or protective mechanisms, such as the presence of neurofibrillary tangles, disconnection, as well as compensation processes.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1077, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: La Joie
authors.forename: Audrey
authors.initials: A
authors.lastname: Perrotin
authors.forename: Louisa
authors.initials: L
authors.lastname: Barré
authors.forename: Caroline
authors.initials: C
authors.lastname: Hommet
authors.forename: Florence
authors.initials: F
authors.lastname: Mézenge
authors.forename: Méziane
authors.initials: M
authors.lastname: Ibazizene
authors.forename: Vincent
authors.initials: V
authors.lastname: Camus
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abbas
authors.forename: Brigitte
authors.initials: B
authors.lastname: Landeau
authors.forename: Denis
authors.initials: D
authors.lastname: Guilloteau
authors.forename: Vincent
authors.initials: V
authors.lastname: de La Sayette
authors.forename: Francis
authors.initials: F
authors.lastname: Eustache
authors.forename: Béatrice
authors.initials: B
authors.lastname: Desgranges
authors.forename: Gaël
authors.initials: G
authors.lastname: Chételat
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001284:Atrophy; D015415:Biomarkers; D001923:Brain Chemistry / Q000502:physiology; D004522:Educational Status; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D059906:Neuroimaging; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers