In vivo mapping of amyloid toxicity in Alzheimer disease

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.