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Even in the absence of pathology such as Alzheimer's disease, aging is associated with cognitive decline. Nevertheless, some older individuals appear to maintain their cognitive abilities, raising the question of what neural factors might promote "successful" cognitive aging (SCA). From the current literature, it is unclear whether there are unique neural factors that give rise to individual differences in SCA, or whether the same neural factors relate to cognition across adulthood. Little is known about the relative importance of different aspects of neural integrity (i.e. brain structure, task-related functional response, and functional connectivity) to promoting SCA or how different neural factors interact in their contribution to SCA. We aimed to characterize the neural signature of SCA, defined by working memory performance. Sixty-four healthy adults, ages 23 to 78, underwent structural and functional magnetic resonance imaging during a working memory task. We focused on measuring the cortical thickness and surface area of the dorsolateral prefrontal cortex (DLPFC) and task-related activation within the DLPFC including laterality effects. We also focused on the "default-mode network" by measuring task-related deactivation in the medial prefrontal cortex (MPFC), functional connectivity between the MPFC and posterior cingulate (PC), and MPFC structure. We aimed to determine how these neural measures related to working memory and whether or not these brain-cognition relationships differed by age. We also explored the relative contribution of and inter-relationships between these neural measures in predicting SCA. Larger DLPFC surface area, greater left and right DLPFC activation, more bilateral DLPFC activation, and greater MPFC deactivation were each associated with better working memory performance. These brain-cognition relationships did not differ with age, thus SCA did not result from a unique neural signature but occurred when older adults maintained the same brain-cognition relationships present throughout adulthood. Results of multivariate analyses showed how different aspects of the neural system (i.e., brain structure and function) work together to achieve good cognitive function in aging. Right DLPFC activation and MPFC deactivation were the strongest contributors to SCA, suggesting that brain-based interventions should focus on preventing or reversing age-related alterations in those aspects of the neural system
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