In order to better understand the pathologic mechanisms by which Posttraumatic Stress Disorder (PTSD) leads to poor health outcomes in older adults, this study will investigate the influence of chronic PTSD on signatures of aging at neural, cognitive, somatic, and behavioral levels of analysis. Chronic PTSD in older adults leads to increased risk of mortality from cardiovascular disease, metabolic syndrome, diabetes mellitus, and ulcerative gastrointestinal disease. PTSD appears to promote aging-associated syndromes such as frailty, and older patients with PTSD exhibit faster cognitive decline and have twice the risk of dementia compared to individuals without PTSD. In addition, laboratory studies report accelerated biological signatures of aging in PTSD patients, including shortened leukocyte telomere length, increases in pro-inflammatory cytokines, and increased oxidative stress. PTSD is associated with similar anatomical brain changes to those occurring with cognitive aging, including bilateral hippocampal volume reductions, specifically affecting the dentate gyrus (DG) and CA3 subregion, and increased microvascular lesions (white matter hyperintensities [WMH]). These observations suggest that the adverse health and functional outcomes associated with chronic PTSD in older patients may be explained by a deleterious interaction between pathophysiologic changes underlying PTSD and the biology of aging, the end result of which is to accelerate senescence throughout the body and particularly in the brain. However, no prior study has explicitly tested this hypothesis by examining indices of aging in older adults with and without PTSD. We hypothesize that chronic PTSD, over and above other contributing factors, accelerates biological aging in the brain and body, leading to adverse behavioral consequences such as frailty and cognitive decline. To test these hypotheses, 150 individuals will be recruited who are aged ?50 and diagnosed with PTSD. A control group of 150 age-, sex-, and trauma exposure-matched subjects without PTSD will be recruited and assessed. Included subjects will undergo comprehensive neuropsychological assessment and cerebral blood volume functional magnetic resonance imaging (CBV-fMRI) to assess regional hippocampal metabolic activity and function. Structural MRI will be performed to quantify WMH, regional brain volume, and cortical thickness, while resting state fMRI will measure functional connectivity within hippocampal networks. PTSD subjects and controls will be compared on measures of aging within the following domains: neural (DG CBV, WMH, morphology), cognitive (processing speed, memory, executive function, pattern separation), somatic (peripheral inflammatory markers, leukocyte telomere length, and measures of oxidative stress), and behavioral (grip strength, gait speed, fatigue levels). By elucidating the interaction of chronic PTSD with aging processes, data from this project may contribute to the development of rationally designed, personalized, and age-appropriate novel treatments.

Public Health Relevance

Chronic PTSD increases mortality risk from medical diseases, promotes aging-associated syndromes such as frailty, and is linked to faster cognitive decline in older adults. One strong possibility is that PTSD leads to these adverse health outcomes by accelerating biological aging in the brain and body. This study will investigate the interplay between aging processes and PTSD, which may help identify novel therapeutic targets to promote healthier aging trajectories for PTSD patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH111596-03
Application #
9772564
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Rowland, Laura Marie
Project Start
2017-09-01
Project End
2022-07-31
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032