Post-traumatic stress disorder (PTSD) is associated with a two to fourfold increase in the risk of dementia. This likely reflects both direct and indirect effects of PTSD on dementia pathologies. There is dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in PTSD, which may cause volume loss in amygdala, hippocampal, and prefrontal brain structures and promote Alzheimer’s Disease (AD) pathogenesis. PTSD is associated with a number of medical and lifestyle factors that are in themselves dementia risk factors, including hypertension, hyperlipidemia, type II diabetes, coronary artery disease, stroke, metabolic syndrome, chronic kidney disease, depression, substance abuse, obesity, and smoking. The two processes likely interact, such that chronic stress reduces the brain’s capacity to cope with new insults occurring during dementia processes. Finally there may be shared vulnerabilities for both illnesses, including psychosocial factors such as race/ethnicity, education, and gender. The work described here is a pilot study aimed at identifying those brain regions vulnerable to atrophy in older Veterans with PTSD and dementia, and determining neuropathological, medical, and psychosocial predictors of brain disease. To this end, we conducted a chart review study at the Greater Los Angeles VA Healthcare System (GLA VA). We identified 200 Veterans over the age of 60 who have completed clinical MRI brain scans. Patients were stratified into four groups based on dementia (DEM) and PTSD diagnoses (DEM+/PTSD+; DEM+/PTSD-; DEM-/PTSD+; DEM-/PTSD-). MRI scans were delineated into cortical and subcortical volumes. White matter hyperintensities (WMH), a biomarker of cerebrovascular disease, was quantified. FDG-PET scans (as available) were used to create an Alzheimer’s Disease (AD) biomarker. The primary analysis identified which brain regions are atrophic in DEM+/PTSD+ versus all other groups, to elucidate the neural signature of the combined diagnoses (aim 1). Subsequent analyses focus on the dementia groups (DEM+/PTSD+; DEM+/PTSD-), and the primary outcome will be whole brain volume, a marker of overall brain disease. For each group, the association between whole brain volume and dementia biomarkers (WMH and AD; aim 2), and whole brain volume and medical and psychosocial factors (aim 3, exploratory) will be assessed to determine the relative contribution these factors have on brain disease. We hypothesized that patients with PTSD and dementia would show smaller hippocampal and medial prefrontal cortical volume relative to those with dementia but no PTSD. We also hypothesized that DEM+/PTSD+ would show greater WMH burden than DEM+/PTSD-. In DEM+/PTSD+ whole brain volume will be predicted by both cerebrovascular and AD biomarkers, suggesting that while there may be a more prominent role for cerebrovascular disease, both pathologies are related to dementia risk in PTSD. Finally cardiovascular disease, metabolic disease, and lower education would predict smaller whole brain volume in DEM+/PTSD+, suggesting a role for both medical and psychosocial factors in disease expression. This preliminary work provided a first step in clarifying the mechanisms by which PTSD raises dementia risk. Importantly, the work described here supports optimal development of methods to refine the MRI data processing and chart review procedure, as well as preliminary analyses necessary for effect size estimates for a larger grant application. Ultimately this work saught to clarify the mechanisms by which risk factors translate to dementia, identifying priority areas for interventions in individuals with PTSD.