Vemuri P, Lesnick TG, Knopman DS, et al. - Using the population-based Mayo Clinic Study of Aging, researchers studied the multifactorial processes underlying cognitive aging based on the assumption that multiple causal pathways and mechanisms (amyloid, vascular, and resilience) influence longitudinal cognitive decline in each individual by worsening brain health. One thousand two hundred thirty elderly patients (aged ≥ 50 years) were identified with an average of 4.9 years of clinical follow-up and with amyloid positron emission tomography, diffusion tensor imaging, and structural MRI scans. Through their effects on cortical thinning and worsening cognition, all pathways (amyloid, vascular, resilience) converged, explaining patterns in cognitive decline. Resilience and vascular pathways (aging process, gender differences, education/occupation, and systemic vascular health) had a major impact on white matter microstructural integrity. Levels of education/occupation contributed through systemic vascular health to the integrity of white matter. Worsening integrity of white matter has contributed to significant cortical thinning and subsequently cognitive longitudinal decline. An integrated framework was developed to assist explain the dynamic and complex process of cognitive aging by considering key causal pathways. Such an approach is important both for a better understanding of cognitive aging processes and will help to develop successful strategies of intervention.