Cognitive Aging Trajectories in Survivors of Trauma

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Dementia and the prodromal stages of cognitive decline, together, affect approximately 25-30% of older adults across the United States (U.S.). Posttraumatic Stress Disorder (PTSD) has been linked to a 111% increased risk of developing dementia of any type, even after controlling for potential confounders such as traumatic brain injury (TBI). Therefore, PTSD may be an important target for early prevention of cognitive decline and potential progression to dementia. Most studies on PTSD and cognition have used a cross-sectional study design and have not examined important potential effect modifiers (e.g., sex and APOE4 carrier status), leaving a gap in our fundamental understanding of the effect of PTSD on longitudinal trajectories of cognitive functioning. Further, although PTSD is more prevalent in women, most research on PTSD and cognition has been conducted in men. This proposal is of timely public health importance, as the pre-pandemic lifetime prevalence of PTSD in the U.S. was 6%, but post-pandemic epidemiological findings have indicated a rise to approximately 32% among young adults. COVID-19 events have also resulted in PTSD symptoms without meeting Diagnostics and Statistical Manual of Mental Disorders, 5th edition (DSM-5) Criterion A. Therefore, critical research gaps in our understanding of the effect of PTSD on cognitive aging include: 1) prospective investigation wherein temporal sequencing and rate of cognitive decline can be evaluated in the context of PTSD, 2) testing the potential modifying effects of sex and APOE4 carrier status on the relationship between PTSD status and cognitive decline and, 3) understanding whether Criterion A is necessary when determining the relationship between PTSD and cognitive decline. Aims 1 and 2 will leverage existing data from the National Alzheimer's Coordinating Center (NACC). In adults aged 55+ years, multilevel modeling and interaction analyses will determine the impact of PTSD status on trajectories, rate, and temporal sequence of domain-specific cognitive decline and will test sex and APOE4 carrier status as potential effect modifiers. For Aim 3, men and women participants, aged 65+, with and without Criterion A trauma, will be recruited and multiple regression will be used to unambiguously clarify if PTSD severity (Criteria B through E) is associated with cognitive functioning without meeting Criterion A. This K01 award will provide training and mentorship in aging health, cognitive aging, sex-specific health effects of PTSD, neuropsychology of PTSD, longitudinal study design, and advanced statistics and propel the PI to become an independent investigator with expertise in the effects of traumatic stress and biopsychosocial factors on cognitive aging, with a sex-specific focus and in alignment with Goals B-3, B-4, and F-4 of NIA’s Strategic Directions 2020-2025.