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An important research application of amyloid imaging with positron emission tomography (PET) is detection of the earliest evidence of fibrillar amyloid-beta (Aβ) deposition. Use of amyloid PET for this purpose, requires a reproducible method for defining a cutoff that separates individuals with no significant Aβ deposition from those in which Aβ deposition has begun. We previously reported the iterative outlier approach (IO) for the analysis of Pittsburgh Compound-B (PiB) PET data. Developments in amyloid imaging since the initial report of IO have led us to re-examine the generalizability of this method. IO was developed using full-dynamic atrophy-corrected PiB PET data obtained from a group of control subjects with a fairly distinct separation between PiB-positive [PiB(+)] and PiB-negative [PiB(−)] subjects. Methods We tested the performance of IO using late-summed tissue ratio data with atrophy correction or with an automated template method without atrophy correction and tested the robustness of the method when applied to a cohort of older subjects in which separation between PiB(+) and PiB(−) subjects was not so distinct. Results The IO method did not perform consistently across analyses and performed particularly poorly when separation was less clear. We found that a sparse k-means (SKM) cluster analysis approach performed significantly better; performing more consistently across methods and subject cohorts. We also compared SKM to a consensus visual read approach and found very good correspondence. Conclusion The visual read and SKM methods, applied together, may optimize the identification of early Aβ deposition. These methods have the potential to provide a standard approach to the detection of PiB-positivity that is generalizable across centers.

Attentional control, motor planning abilities, and executive cognitive functions (ECF) rapidly decline with age. In particular, older adults experience difficulty in manipulating selected motor responses in the presence of conflicting or distracting information. To examine age-related changes in the neural substrates of the attentional and motor planning components of ECF, we assessed the patterns of brain activation in 8 cognitively normal older adults (mean age 81.5) and 20 young individuals (mean age 23.0) while they responded to low and high loads of attentional demands of the Preparing to Overcome Prepotency (POP) task. In the POP task, the selection of one out of two possible motor responses in the presence of increasing attentional task loads determines the accuracy of the performance. Older individuals were slower than young adults (P0.001) but achieved a strikingly high accuracy similar to the young group (P = 0.2), regardless of the task load. Both groups showed a load-related fMRI signal increase in the anterior cingulate cortex (ACC), posterior parietal cortex (PPC: Brodmann areas 7 and 40), and dorsolateral prefrontal cortex (dLPFC: Brodmann areas 9, 45, and 46) bilaterally. Compared to young individuals, older adults had lower activation in dLPFC (Brodmann areas 9, 45, and 46: P = 0.007, P = 0.043, and P = 0.040) and Brodmann area 7, P = 0.002. Activation in Brodmann areas 40 and ACC was similar in the two groups (P0.05). Among older adults, the most successful performers were those who responded to increasing task loads with greater activation in PPC (Brodmann area 40), despite lower dLPFC activation. Older adults who are able to perform executive control tasks as well as young adults, also seem to implement speed-accuracy trade-off strategies which may rely on increased parietal activation.