Our proposed project focuses on understanding the concepts of reserve and resilience, switching from a static perspective often applied in the literature to dynamic adaptation to the environment. Our validated dynamic Neurocognitive Adaptation (dNA) Scale will explore how individuals are engaged in protective cognitive and leisure activities, throughout their lifetime, and the relationship between these behaviors and gold-standard neuropsychological-neurophysiological markers of cognitive health, to understand presentation and mechanisms of individual adaptation to the environment through life. Neuropsychological measures of working memory and executive functions will be used to assess cognitive flexibility, while graph theoretical metrics of functional connectivity (FC) will be used to assess neurophysiological efficiency. Together, these components will give us a measure of neurocognitive adaptation, which is likely to clarify mechanisms of AD resilience. We will further investigate the role of AD risk factors and early pathology (amyloid, inflammation) in moderating effects of adaptive behavior on outcomes. Furthermore, as women show different structural and functional reserve characteristics, we will include sex as a factor when examining individual dynamic adaptation to the environment. The objective of this proposal is to investigate multiple domains (cognitive, physical, creative, and social) in 7-time windows from childhood (0-10 years old) to old age (+ 65 years old), exploring individual adaptation to the environment and its potential protective factors against neurodegeneration. Testing convergent validity of the dNA against gold-standard neuropsychological tests and fMRI measures of executive function in aging is an important innovation, and lays a foundation for implementing the dNA in at-risk and AD populations. The rationale for this project is that the concept of reserve is mostly static, based on unmodifiable variables (IQ and formal education), and poorly suited for understanding the role of time in this protective role. From our perspective, environment and learning change through the lifetime dynamically, as does individual subjective adaptation to environment. Specific Aim 1 will determine association of adaptation profiles with education and gold standard measures of cognitive flexibility, such as working memory, problem solving, setshifting, and inhibition in cognitively Healthy Controls (HCs). Our hypothesis is that greater maintenance in activities through lifetime will relate to higher education and better cognitive flexibility and peripheral inflammation will moderate this effect. Specific Aim 2 will establish association of adaptation profiles and gold standard measures of neurophysiological efficiency through fMRI (FC) and graph theoretical metrics during resting state. Our hypothesis is that greater maintenance in activities through lifetime will relate to better segregation of the Default ...