Characterizing the Relationship Between Delirium and Biological Age in Traumatic Brain Injury: Implications for Cognitive Decline in Older Adults
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This is a Beeson K76 Career Development Award for Dr. Sara LaHue, a fellowship-trained inpatient neurologist (neurohospitalist) clinician-investigator. Dr. LaHue requests 5 years of salary and research support to provide protected time and training to study delirium risk factors and associated longitudinal clinical trajectories in older adults with acute mild traumatic brain injury (mTBI). Delirium is a sudden change in mental status affecting over 7 million hospitalized adults in the United States annually and is a major risk factor for Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD), functional and cognitive decline, and death. Dr. LaHue’s long-term goal is to become a leading expert in geriatric inpatient neurology, applying an aging biology lens to advance delirium diagnostics and therapeutics to improve health outcomes for older hospitalized adults. This project will advance her career development through investigating post- traumatic delirium as a high-impact, patient-focused outcome with substantive importance to both geriatrics and neurology. While Dr. LaHue is uniquely qualified to pursue her career goals, additional advanced training in four areas is critical for her success: (1) aging biology research methods, (2) geriatric TBI research methods, (3) advanced biostatistical methods, and (4) leadership. Dr. LaHue developed a rigorous 5-year training program with her exceptional mentoring team to gain this foundation. This application will provide preliminary data and tangible skills to support Dr. LaHue’s future NIH R01 applications and launch her independent research career. As a neurohospitalist caring for patients with delirium, Dr. LaHue recognized that patients with neurological disorders are disproportionately excluded from delirium research, limiting generalizability of existing research to these populations. Delirium affects nearly half of adults with mild-moderate TBI, yet existing knowledge is largely limited to moderate-severe TBI (despite mTBI accounting for >75% of US TBI cases) or young populations. There is a critical need to identify how baseline vulnerabilities, such as advanced biological age, inform delirium risk in geriatric TBI, and how delirium impacts both cognitive and functional outcomes, to optimize recovery for older adults with mTBI. To address these critical knowledge gaps, Dr. LaHue will investigate the following specific aims in a prospective cohort of older adults with acute mTBI: (1) identify whether biological age metrics are associated with post-traumatic delirium, (2) identify whether post- traumatic delirium is associated with longitudinal cognitive and physical function, and (3) determine the association between biological age, delirium, and longitudinal clinical outcomes. The findings will illuminate vulnerable subgroups that may benefit from targeted acute delirium management, inform clinical guidance for patients at risk for impaired recovery, and lay the foundation for a multicenter study to uncover mechanistic links between TBI, specific biological aging pathways, and delirium to inform future therapeutics.
