Does amyloid deposition produce a specific atrophic signature in cognitively normal subjects?

The objective of our study was to evaluate whether cognitively normal (CN) elderly participants showing elevated cortical beta-amyloid (A beta) deposition have a consistent neuroanatomical signature of brain atrophy that may characterize preclinical Alzheimer's disease (AD). 115 CN participants who were A beta-positive (CN+) by amyloid PET imaging; 115 CN participants who were A beta-negative (CN-); and 88 A beta-positive mild cognitive impairment or AD participants (MCI/AD+) were identified. Cortical thickness (FreeSurfer) and gray matter volume (SPM5) were measured for 28 regions-of-interest (ROIs) across the brain and compared across groups. ROIs that best discriminated CN- from CN+ differed for FreeSurfer cortical thickness and SPM5 gray matter volume. Group-wise discrimination was poor with a high degree of uncertainty in terms of the rank ordering of ROIs. In contrast, both techniques showed strong and consistent findings comparing MCI/AD+ to both CN- and CN+ groups, with entorhinal cortex, middle and inferior temporal lobe, inferior parietal lobe, and hippocampus providing the best discrimination for both techniques. Concordance across techniques was higher for the CN- and CN+ versus MCI/AD+ comparisons, compared to the CN- versus CN+ comparison. The weak and inconsistent nature of the findings across technique in this study cast doubt on the existence of a reliable neuroanatomical signature of preclinical AD in elderly PiB-positive CN participants. (C) 2013 The Authors. Published by Elsevier Inc. Open access under CC BY license.