Localization of Network-Level Atrophy in Preclinical Alzheimer's Disease

Brain atrophy may precede symptoms in Alzheimer's disease (AD), but it remains unclear whether atrophy in this preclinical stage falls within a distinct brain network or is associated with transitional cognitive changes. We investigated cortical thickness in cognitively unimpaired older adults with varying amyloid-β accumulation and estimated the connectivity of each individual's atrophy pattern using a large normative connectome (n = 1000). A distinct network was connected to atrophy patterns in amyloid-β-positive (n = 1242) versus negative (n = 536) participants. This preclinical AD network was similar to a previously published atrophy network associated with AD dementia (r = 0.8284, p = 0.016). In leave-one-out cross-validation, atrophy patterns connected to the preclinical AD network were associated with lower cognitive performance (p = 0.0018), greater subjective cognitive decline (p < 0.001), and amyloid-β levels (p < 0.001). Atrophy in preclinical AD maps to a network similar to AD dementia that is associated with amyloid-β and cognition, demonstrating an atrophy-related network across the continuum of AD.