Abstract
Background Resilience in aging—the capacity to maintain cognition and function despite neuropathology—has been described through cognitive reserve, brain reserve, and maintenance. The dynamic Neurocognitive Adaptation (dNA) framework expands these constructs by defining resilience as a lifelong process of adaptive engagement across cognitive, physical, creative, and social domains that shape neural integrity and cognitive outcomes over time. Methods Fifty-eight older adults (39 cognitively normal, 19 with mild cognitive impairment) completed neuropsychological testing, amyloid assessment, and structural MRI. The dNA scale quantified engagement across seven life-course time windows. Hierarchical multiple regressions examined domain- and time-specific associations between dNA scores and cortical thickness or regional volumes (FreeSurfer 7.3.2), controlling for age, sex, education, and diagnosis. Exploratory mediation and moderation models tested indirect and interaction effects of demographic and diagnostic factors. Results Childhood (Time Window 1) emerged as a sensitive period: higher cognitive engagement is associated with stronger semantic fluency, and physical engagement is linked to a better episodic learning. Creative and physical engagement during childhood related to larger anterior and posterior cingulate and temporal-pole volumes. In adulthood and midlife (Time Windows 3–5), greater engagement was associated with thicker right lateral orbitofrontal cortex and larger lingual volumes. No mediation or moderation by sex, education, or diagnosis was observed. Conclusions Childhood and midlife emerge as sensitive periods linking multidomain engagement with later-life brain structure and cognition. The dNA framework provides a multidimensional, time-resolved model of resilience, illustrating how lifelong adaptive behaviors support neural integrity and cognitive health across aging and Alzheimer’s-disease risk.