Traumatic brain injury (TBI), common among military personnel, appears to not only result in cognitive dysfunction following the injury but to also have dire long-term consequences in aging. Individuals who experienced TBI earlier in life are at increased risk for developing dementia in older adulthood. This underscores the need to intervene to prevent dementia among individuals who previously experienced TBI, potentially by identifying ways to enhance cognitive reserve. The concept of cognitive reserve refers to qualities of an individual's cognitive capacity that can protect against cognitive decline, such as having higher educational and occupational attainment, better academic skills, and a more cognitively-stimulating lifestyle. In other older adult populations, greater cognitive reserve has been shown to reduce risk for dementia, even among older adults with Alzheimer's neuropathology. It remains to be investigated whether cognitive reserve can help buffer the neural system in aging against late-life cognitive impairment and dementia in individuals with a history of TBI. The research proposed for this Career Development Award-2 (CDA-2) aims to: 1) characterize cognitive function in older Veterans with a history of TBI by focusing on executive control, 2) identify aspects of cognitive reserve that promote cognitive resilience in older Veterans with a history of TBI, and 3) conduct a pilot intervention trial investigating whether a computerized executive control training intervention can improve cognitive function and enhance cognitive reserve in this population. This work will be accomplished in two studies. The first study is a cross-sectional comparison of 35 older Veterans (60-75 years old) with a history of repetitive mild TBI or at least one moderate TBI with 35 demographically-matched Veterans without TBI. These groups will be compared with respect to their performance on a cognitive battery designed to assess abilities involved in and related to executive control. We will also measure different aspects of cognitive reserve (i.e., education, occupational attainment, literacy, and engagement in cognitively-stimulating activities) to investigate the association between these factors and cognitive performance. The second study is a pilot intervention trial investigating a neuroscience-based computerized cognitive training intervention designed to target executive control. Sixty older Veterans (60-75 years old) with 1) a history of repetitive mild TBI or at least one moderate TBI and 2) subjective cognitive complaints or evidence of executive control deficits on objective testing will be randomly-assigned to the intervention or an active control condition (computerized word games) for four weeks. Using cognitive assessments and everyday functioning measures, we will investigate whether the intervention leads to improved cognitive performance, whether effects generalize to non-trained abilities and everyday functioning, and whether effects are maintained over a 3-month follow-up period. This program of research is designed to increase understanding of the role of cognitive reserve in protecting against TBI-associated cognitive impairment in late life and whether cognitive reserve can be enhanced with cognitive training. The applicant for this CDA-2 is a VA postdoctoral fellow who has studied predictors of cognitive aging. With this award, she aims to gain additional research experience and training to facilitate her career goal of becoming an independent VA investigator. The applicant seeks training in the conduction of TBI-focused research and intervention trials (e.g., randomized controlled trials) to investigate neuroscience-based cognitive training. The applicant's career goals are to become an expert in cognitive reserve and its effects in aging and how to promote cognitive reserve to prevent dementia in older Veterans, using TBI as the ideal clinical model to study these phenomena.

Public Health Relevance

Many older Veterans have sustained at least one traumatic brain injury (TBI) in their lifetimes, and older Veterans with a history of TBI are at heightened risk for developing dementia. It is therefore crucial to understand the impact of TBI on cognition in aging. It is also imperative to identify means to prevent Veterans from experiencing cognitive decline and developing dementia in older adulthood, especially among individuals at high-risk for dementia because of their TBI history. This research program will investigate cognitive functioning in older Veterans with a history of TBI, in order to understand what cognitive functions these Veterans may struggle with in their daily lives. This research will also investigate potential ways to encourage cognitive resilience in this population, with the goal of identifying ways to improve cognitive health and prevent, or at least delay, the onset of dementia among older Veterans with a history of TBI.

National Institute of Health (NIH)
Veterans Affairs (VA)
Veterans Administration (IK2)
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Career Development Program - Panel I (RRD8)
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Veterans Affairs Medical Center San Francisco
San Francisco
United States
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Kaup, Allison R; Xia, Feng; Launer, Lenore J et al. (2018) Occupational cognitive complexity in earlier adulthood is associated with brain structure and cognitive health in midlife: The CARDIA study. Neuropsychology 32:895-905
Kaup, Allison R; Peltz, Carrie; Kenney, Kimbra et al. (2017) Neuropsychological Profile of Lifetime Traumatic Brain Injury in Older Veterans. J Int Neuropsychol Soc 23:56-64
Kaup, Allison R; Yaffe, Kristine (2017) Reassuring News About Football and Cognitive Decline?: Not So Fast. JAMA Neurol 74:898-899
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Kaup, Allison R; Nettiksimmons, Jasmine; Yaffe, Kristine (2015) Diabetes Mellitus and Cognitive Resilience--Reply. JAMA Neurol 72:949-50