Relationship between atrophy and β-amyloid deposition in Alzheimer disease

• Published in: Annals of neurology Vol. 67; no. 3; pp. 317 - 324
• Main Authors: Chételat, Gaël, Villemagne, Victor L., Bourgeat, Pierrick, Pike, Kerryn E., Jones, Gareth, Ames, David, Ellis, Kathryn A., Szoeke, Cassandra, Martins, Ralph N., O'Keefe, Graeme J., Salvado, Olivier, Masters, Colin L., Rowe, Christopher C.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.03.2010; Wiley-Liss
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Amyloid beta-Peptides - analysis; Amyloid beta-Peptides - metabolism; Atrophy - diagnostic imaging; Atrophy - metabolism; Atrophy - pathology; Benzothiazoles; Biological and medical sciences; Biomarkers - analysis; Biomarkers - metabolism; Brain - diagnostic imaging; Brain - metabolism; Brain - pathology; Cognition Disorders - diagnostic imaging; Cognition Disorders - metabolism; Cognition Disorders - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; Female; Humans; Magnetic Resonance Imaging; Male; Medical sciences; Neurology; Plaque, Amyloid - diagnostic imaging; Plaque, Amyloid - metabolism; Plaque, Amyloid - pathology; Positron-Emission Tomography; Predictive Value of Tests; Prognosis; Severity of Illness Index; Atrophy; Nervous system diseases; Alzheimer disease; Central nervous system disease; Degenerative disease; Amyloid; Cerebral disorder
• ISSN: 0364-5134; 1531-8249; 1531-8249
• DOI: 10.1002/ana.21955

Objective Elucidating the role of aggregated β‐amyloid in relation to gray matter atrophy is crucial to the understanding of the pathological mechanisms of Alzheimer disease and for the development of therapeutic trials. The present study aims to assess this relationship. Methods Brain magnetic resonance imaging and [11C]Pittsburgh compound B (PiB)‐positron emission tomography scans were obtained from 94 healthy elderly subjects (49 with subjective cognitive impairment), 34 patients with mild cognitive impairment, and 35 patients with Alzheimer disease. The correlations between global and regional neocortical PiB retention and atrophy were analyzed in each clinical group. Results Global and regional atrophy were strongly related to β‐amyloid load in participants with subjective cognitive impairment but not in patients with mild cognitive impairment or Alzheimer disease. Global neocortical β‐amyloid deposition correlated to atrophy in a large brain network including the hippocampus, medial frontal and parietal areas, and lateral temporoparietal cortex, whereas regional β‐amyloid load was related to local atrophy in the areas of highest β‐amyloid load only, that is, medial orbitofrontal and anterior and posterior cingulate/precuneus areas. Interpretation There is a strong relationship between β‐amyloid deposition and atrophy very early in the disease process. As the disease progresses to mild cognitive impairment and Alzheimer disease clinical stages, pathological events other than, and probably downstream from, aggregated β‐amyloid deposition might be responsible for the ongoing atrophic process. These findings suggest that antiamyloid therapy should be administered very early in the disease evolution to minimize synaptic and neuronal loss. ANN NEUROL 2010;67:317–324