Project Summary World Trade Centers (WTC) responders exposed to extreme psychological trauma have high rates of PTSD, which is independently associated both with cognitive impairment and with significant alteration in the brain. In the Stony Brook WTC Health Program cohort, nearly 20% of responders developed DSM-IV PTSD since 9/11. Their current average age is 54, placing them at the cusp of the risk period for cognitive decline. In order to provide a baseline for anticipated cognitive changes, the Stony Brook arm of the WTC Health Program began assessing cognitive functioning in 2014. In the first 2,400 responders screened with the Montreal Cognitive Assessment (MoCA), the rate of moderate-to-severe cognitive impairment (scores <20) was 2.6%, and the association with WTC-PTSD was highly significant. WTC responders were also exposed to a mix of neurotoxic airborne particles of different size including respirable, nano-sized and ultrafine, metals, PCB, dioxins and solvents. Recent literature shows that nanoparticles, defined as a particle <0.1?m in at least one dimension, can reach the brain through the olfactory pathway and cause long-term neuro-degeneration. Therefore, neurotoxicity may be due to chronic neuro-inflammation caused by oxidative stress induced by the inhaled particles and via involvement of immune system. The purpose of this application is to better understand brain dysfunction among responders with cognitive impairment and Post Traumatic Stress Disorders. That is, similar to the growing body of research on veterans with PTSD, it is of fundamental importance to determine if there are unique structural patterns in the brain associated with cognitive impairment in WTC responders. We thus propose to use in vivo magnetic resonance imaging (MRI) techniques, including functional MRI (fMRI) and positron emission tomography (PET/MRI) imaging to examine these patterns. This application is a pilot study of 120 SBU-WTC responders, 30 with cognitive impairment (MoCA <20) and PTSD, 30 with cognitive impairment without PTSD, 30 with normal cognitive functioning (MoCA>26) and PTSD, 30 with normal cognitive functioning without PTSD. All responders will be matched on age and occupation as well as 30 non-WTC exposed, matched controls with MoCA scores >26. We hope to improve the understanding of mechanisms underlying the potential neuro-cognitive effect from WTC exposure. The ultimate goal of this project is to provide a basis to prevent potential WTC responders' mental health deterioration. The study results will also provide important and novel information for the understanding and prevention of neurodegenerative disorders in the population at large.