Abstract
We recently investigated a cross-sectional relationship between the function of a selected set of brain regions and cognition in older adults with excellent memory capacity (a.k.a., Supernormals), and revealed that a unique brain map covering anterior and posterior regions in Supernormals protected their cognition from Alzheimer’s disease (AD) pathology (Lin et al., 2017, Cortex). In the present study, we continued the validation of the longitudinal relationship between the brain map and cognition and AD pathology in Supernormals. We hypothesized that an over-time stable brain map involving anterior and posterior regions would differentiate Supernormals from their cognitively normal or abnormal counterparts, and such a brain map would link to AD pathology. Here, we identified 22 Supernormals, 25 with normal cognition (NC), 70 with amnestic mild cognitive impairment (MCI) and 28 with AD. Multivariate pattern based searchlight analysis of resting-state functional MRI data was applied to identify brain regions with constantly high discriminative powers between Supernormals and NC over 2 years. The regions included right cerebellum, left middle temporal gyrus, right middle frontal gyrus, right precuneus, right precentral gyrus. The brain map composed by these regions predicted multiple cognitive assessments and their longitudinal changes with 51% to 82% accuracy, discriminated NC, MCI and AD at 62% to 78%, and predicted beta-amyloid/pTau at 71%. Our findings suggest that applying searchlight analysis with longitudinal resting-state imaging data from Supernormals construct a brain map that sheds lights on understanding Alzheimer’s disease associated neurodegeneration.