Subtypes of brain change in aging and their associations with cognition and Alzheimer's disease biomarkers.

Structural brain changes underlie cognitive changes and interindividual variability in cognition in older age. By using structural MRI data-driven clustering, we aimed to identify subgroups of cognitively unimpaired older adults based on brain change patterns and assess how changes in cortical thickness, surface area, and subcortical volume relate to cognitive change. We tested (1) which brain structural changes predict cognitive change (2) whether these are associated with core cerebrospinal fluid (CSF) Alzheimer's disease biomarkers, and (3) the degree of overlap between clusters derived from different structural modalities in 1899 cognitively healthy older adults followed up to 16 years. We identified four groups for each brain feature, based on the degree of a main longitudinal component of decline. The minimal overlap between features suggested that each contributed uniquely and independently to structural brain changes in aging. Cognitive change and baseline cognition were associated with cortical area change, whereas higher baseline levels of phosphorylated tau and amyloid-β related to changes in subcortical volume. These results may contribute to a better understanding of different aging trajectories.