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© 2009 American Academy of Neurology In vivo mapping of amyloid toxicity in Alzheimer diseaseFrom the Laboratory of Epidemiology Neuroimaging and Telemedicine (G.B.F., M.L., A.C.) and Psychogeriatric Ward (G.B.F.), IRCCS Centro San Giovanni di Dio–FBF, Brescia, Italy; Associazione Fatebenefratelli per la Ricerca (G.B.F.), Rome, Italy; Medical Imaging Unit (A.C.), Biomedical Engineering Department, Mario Negri Institute for Pharmacological Research, Bergamo, Italy; Turku Positron Emission Tomography Centre (N.K., K.N., J.O.R.), University of Turku, Finland; and Department of Clinical Physiology and Nuclear Medicine (K.N.), PET and Cyclotron Unit, Copenhagen, Denmark. Address correspondence and reprint requests to Dr. Giovanni B. Frisoni, Laboratory of Epidemiology and Neuroimaging, IRCCS San Giovanni di Dio–FBF, via Pilastroni 4, I-25123 Brescia, Italy gfrisoni{at}fatebenefratelli.it Objective: To study the relationship between gray matter atrophy and amyloid deposition in Alzheimer disease (AD). Methods: Volumetric magnetic resonance (MR) and [11C]-PIB PET were acquired from 23 patients with AD and 17 healthy older persons. Standardized [11C]-PIB uptake values were coregistered to MR scans in a standard space. Decreased density of and increased [11C]-PIB uptake in the gray matter of patients with AD vs controls were assessed with both voxel-based (p < 0.05 corrected) and region-of-interest (ROI) analyses. The relationship between decreased density of and increased [11C]-PIB uptake in the gray matter was investigated with voxel-based Pearson r maps (thresholded at p < 0.05) and ROI linear regression plots. Results: Atrophy mapped to the hippocampus and increased [11C]-PIB uptake to large frontal, parietal, and posterior cingulate cortical areas. ROI analysis showed the largest effect size for atrophy in the hippocampus (2.01) and amygdala (1.27) and the highest effect size for [11C]-PIB uptake in frontal (2.66), posterior cingulate/retrosplenial (2.43), insular (2.41), and temporal (2.23) regions. In the hippocampus, [11C]-PIB uptake was significantly increased, but effect size was milder (1.72). Significant correlations between atrophy and increased [11C]-PIB uptake were found in the hippocampal (r = –0.54) and amygdalar ROIs (r = –0.40) but not in the frontal, temporal, posterior cingulate/retrosplenial, insular, and caudate ROIs (r between 0.04 and 0.25). Conclusion: The medial temporal lobe might be highly susceptible to amyloid toxicity, whereas neocortical areas might be more resilient.
Abbreviations: AD = Alzheimer disease; FDG = fluorodeoxyglucose; FWE = family-wise error; GM = gray matter; MNI = Montreal Neurological Institute; MR = magnetic resonance; ROI = region of interest.
Supplemental data at www.neurology.org Disclosure: The authors report no disclosures. Received October 22, 2008. Accepted in final form February 2, 2009. This article has been cited by other articles:
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