COGNITIVE AND NEURAL MECHANISMS OF THE ACCELERATED AGING PHENOTYPE IN PTSD

Abstract

Introduction Posttraumatic Stress Disorder (PTSD) affects 6.8% of adults in the United States and is associated with high rates of disability, comorbid medical and psychiatric disorders, and suicide. Older adults make up an increasingly large proportion of PTSD patients as the population skews older and Veterans from recent conflicts age. PTSD in older adults is often chronic, leads to increased mortality from cardiovascular disease and other medical conditions, and promotes adverse aging associated syndromes such as frailty. Moreover, older PTSD patients exhibit faster cognitive decline and have twice the risk of dementia compared to individuals without PTSD. Accelerated biological aging may explain these findings, as PTSD is associated with similar brain changes to those occurring with cognitive aging, including bilateral hippocampal volume reductions specifically in the cornu ammonis 3 (CA3) and dentate gyrus (DG) sub-regions and increased microvascular lesions (white matter hyperintensities). The goal of this presentation is to describe ongoing work from our laboratories characterizing the mechanisms by which PTSD accelerates aging cognitively and physically. We will present data linking cognitive dysfunction in PTSD with indicators of brain health such as DG CBV and increased white matter hyperintensities and physical decline with increased levels of inflammation and oxidative stress. Methods To date. N=17 adults 50 years and older with PTSD and N=9 trauma exposed healthy controls (TEHCs) have undergone testing to assess cognitive function and physical performance. Neuropsychological testing and magnetic resonance imaging (MRI) including cerebral blood volume (CBV)-fMRI were used to assess cognitive function and brain health. Neuropsychology testing included a modified form of the Benton Visual Retention Task (ModBent), a task that has been validated as a measure of DG function relative to age. Tasks such as gait speed and tests of strength, including grip strength and the short physical performance battery, were used to assess physical decline. Inflammatory markers IL-6, CRP, and telomere length, and urinary isoprostanes, a measure of oxidative stress, were also used to examine physical decline. Measures were compared between the PTSD patients and trauma exposed healthy controls. We expect to substantially increase the sample size available for presentation by the time of the Annual Meeting. Results Enrolled PTSD subjects to date show deficits in every cognitive domain when compared to the TEHC, particularly on measures of processing speed and executive function, where their performance is > 1 SD below that of age-matched TEHCs. CBV fMRI (N=15) analyzed to date shows PTSD patients to have diminished DG CBV compared to TEHC, and lower DG CBV is associated with increasing symptom severity as measured by the Clinician Administered PTSD Scale (r=-0.49). Reaction time on ModBent increased (worsened) with increasing symptom severity (r=0.50). Overall hippocampus volume is smaller in PTSD patients than TEHC (d=-.23), although PTSD patients have on average greater ICV (d=0.30). PTSD patients also display deficits in every physical performance task compared to the TEHC patients and report reduced physical activity and worse physical conditions. PTSD patients have higher levels of inflammatory markers IL-6 (d=0.18) and CRP (d=0.25) as well as urinary isoprostanes (d=0.05), a marker of oxidative stress. Conclusions These data indicate that PTSD, particularly chronic PTSD, is associated with unhealthy aging trajectories. These findings are consistent with the hypothesis that older adults with PTSD have marked neurocognitive and physiologic performance decrements compared to age-matched TEHC. This research was funded by NIMH. PDF: http://submissions.mirasmart.com/Verify/AAGP2019/Original/AAGP2019-000325/AAGP2019-000325_Fig1.pdf