Deficits in cognitive functioning are considered one of the most debilitating aspects of aging, and prevent older adults from leading productive and meaningful lives. Although many changes occur over the normal course of aging, recent work in cognitive neuroscience has implicated a central role for inhibition, one of several ?executive functions? that enable an individual to resist interference from task-irrelevant information in the service of goals. Deficits in inhibitory processes may have direct implications for older adults' ability to function independently in daily life, a key factor in considering institutional care. Despite work exploring age-related changes to inhibitory processes, inconsistent findings have prevented a theoretical consensus from being reached. Until the mechanisms supporting inhibitory abilities are fully understood, it will not be feasible to construct maximally effective interventions to strengthen inhibitory skills in the individuals who need these skills the most, and ultimately to promote successful cognitive aging. This K99/R00 presents a research and training program that will support the applicant on a path towards becoming an independent investigator focused on characterizing inhibitory processes in cognitively ?normal? aging (i.e., aging in the absence of dementia or neurologic disorder). Cross-sectional and longitudinal structural equation models will test relationships between age, inhibitory ability, biomarkers for Alzheimer's Disease (AD), global and domain specific measures of cognition, and quantified measures of cortical thickness. The activities in this application will supplement the candidate's strong existing background in cognitive psychology and cognitive neuroscience and are set in a resource-rich environment that will provide the applicant with expertise in (1) structural equation modeling, (2) neuroimaging data analysis of cortical thickness in an aged population and multivariate brain-behavior analysis techniques, (3) biomarkers for age-related neuropathological disorders including AD and 4) the responsible conduct of research. The combination of the environment, training plan, research strategy and mentorship team will not only provide the candidate with a spectrum of new methods and skills that will establish her as an independent research scientist, but will also produce a body of knowledge that will clarify how inhibitory processes are affected in aging. This knowledge, in turn, may lead to targets for interventions aimed at reducing age-related cognitive morbidity and improving quality of life in the rapidly expanding U.S. aging population.

Public Health Relevance

Mounting evidence suggests that age-related changes to cognition may in part be due to underlying deficits in inhibitory processes, or the ability to filter out unwanted or conflicting thoughts, actions or behaviors. Using a combination of biobehavioral methods and advanced statistical modeling, the proposed research aims to characterize inhibitory function in clinically healthy older adults, and to identify how morphological brain changes and biomarkers of Alzheimer's Disease contribute to inhibitory processes. The ultimate goal is to determine which aspects of inhibitory function are most sensitive to normal aging, which may enable the development of interventions that promote cognitive wellbeing and mitigate cognitive morbidity in older adults.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
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Stoeckel, Luke
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University of Southern California
Los Angeles
United States
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