Cognitively normal older individuals with the lowest cognitive activity have amyloid burden that resembles that of patients with Alzheimer disease (AD). A, Carbon 11–labeled Pittsburgh Compound B ([11C]PiB) indices, reflecting amyloid deposition, in 10 patients with AD and 11 young controls were compared with older controls, who were subdivided into tertiles based on past cognitive activity scores. Within older controls, the cognitive activity tertiles differed from one another (P = .001 by the Kruskal-Wallis test) such that the lowest tertile had higher [11C]PiB uptake than the middle tertile (P = .04 by the Mann-Whitney test) and the top tertile (P = .001 by the Mann-Whitney test). The middle and highest tertiles were marginally different (P = .06). Patients with AD had higher [11C]PiB levels compared with older controls overall (P < .001) and young controls (P < .001). Young controls had lower [11C]PiB levels than older controls overall (P = .04). B, Regions in which past cognitive activity is inversely associated with [11C]PiB (blue; P = .001, cluster size = 100 voxels; controlling for age, sex, and years of education) overlaid, for comparison, on the set of regions used to calculate the mean cortical [11C]PiB indices for each study participant (cyan), which are plotted in A and listed in Table 2.