Analyses proceeded in several steps that involved data from 380 participants (336 using structural MRI and 44 using amyloid-PIB PET and structural MRI). First, in a large primary sample of participants (N = 144), we explored the entire cortical mantle to identify areas of thinning in a relatively homogeneous sample of participants with mild AD (N = 29) compared with nondemented older controls (OC, N = 115). This initial analysis identified a cortical signature of AD—a spatially distributed set of specific regions with AD-related thinning. Regions of interest (ROIs) were defined to capture the spatially distributed pattern of cortex most affected by AD. Then, to investigate the consistency of cortical thinning in AD, we applied these a priori ROIs to 3 new samples of AD participants and OC (total N = 123). Each independent sample was recruited and evaluated at a different clinical site and scanners involved 2 different field strengths (1.5 and 3 T), similar to multicenter studies such as clinical trials. To explore the progression of AD, we next applied the a priori ROIs to another sample of individuals with Incipient and very mild AD dementia (N = 69) to determine the degree to which these regions are affected in the earliest clinical stages of disease progression. The relationship of regional cortical thinning to severity of symptoms was also investigated by correlational analysis between ROI thickness and the Clinical Dementia Rating scale Sum-of-Boxes (Morris et al. 1997 (link)), a measure of severity of cognitive and functional impairments in daily life. A pooled analysis was performed of all 267 mild AD patients and OC to provide a stable, highly precise estimate of the spatial distribution and magnitude of thinning in the cortical signature of AD. Finally, “AD-signature” regional thickness was investigated in a group of OC individuals known to harbor brain amyloid from PIB-PET scanning and compared with a group of OC individuals without brain amyloid.
The overall data collection and analysis procedure is depicted in a flowchart in Figure 1. Demographic and clinical data for the participants are presented in Table 1.