Biopsychosocial Mechanisms of Successful Aging

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It is well-known that in most people, cognitive abilities decline with age. With the elderly population growing (20% of Americans will be over 65 by 2030), this represents a significant public health concern. However, not all older adults show this pattern of decline. We and others have demonstrated that some individuals seem to be resilient to age-related decline, even in the setting of biomarkers of Alzheimer’s disease (AD) neuropathologic changes. Understanding the factors that promote resilience in older adults could point to new approaches to achieve healthy aging in all adults. In our recent studies of aging, we identified substantial heterogeneity within older adults in memory performance and both brain anatomy and connectivity, such that some older participants (60-80 yrs.) were indistinguishable from young adults (18-32). These remarkable individuals offer the opportunity to investigate the biobehavioral mechanisms that contribute to successful aging. Our findings indicated that successful agers (who showed preserved anatomy within and connectivity between multiple limbic and paralimbic structures that subserve motivation, affect, and cognition) exhibited a distinct neural response to challenging tasks when compared to typical agers. Crucially, successful agers also differed in their subjective experience of the task, rating the arousal caused by the task as significantly more pleasant. Together, these results suggest that individual differences in the response to increasing arousal during difficult cognitive tasks contribute meaningfully to cognitive outcomes in aging. Here, we introduce the Arousal along the Challenge/Threat Continuum (ACT-C) model, which hypothesizes that arousal can be helpful or harmful to cognition, depending on how it is expressed in the brain and the body In this proposal, we will test the central hypothesis of the ACT-C model, that individual differences in the experience of affect, and its neurobiological and autonomic physiological correlates predicts cognitive performance in aging. We propose that increased effort and cognitive performance will be associated with a tendency to subjectively experience arousal more as challenge than as threat (Aim 1), an autonomic physiological response to difficult tasks previously associated with a challenge interpretation (i.e. decreased vascular resistance, Aim 2), and a neural ‘challenge’ pattern involving increased mid-cingulate activity and communication between networks (Aim 3). Crucially, we predict that these motivational, physiological, and neural factors will be associated with improved performance even in individuals with evidence of preclinical AD. This research, if successful, will provide much-needed insight into the biological mechanisms by which affect and motivation support cognitive aging. The outcomes of this research could point the way to neural and physiological biomarkers predicting successful aging, which could be used to evaluate interventions to promote successful aging, including in people with biomarker evidence of Preclinical AD.