Abstract World Trade Center (WTC) responders were exposed to a mix of tiny dust particles as they participated in rescue and recovery efforts at the WTC in the aftermath of 9/11/2001. A significant number continue to suffer from Post- Traumatic Stress Disorder (PTSD) as a result of their experiences. These may have changed their expectations of brain health as they age. Our team has interrogated the potential for early signs of cognitive aging and has identified higher than expected burden of mild cognitive impairment (MCI) and, surprisingly, changes to physical functional limitations (PFL) common in both physical disability and in neurodegenerative disease. We propose that MCI is arising early because PTSD and inhaled particulate exposures have caused a neurodegenerative disease, resulting in increased Alzheimer’s disease neuropathology. We propose to conduct a large study of WTC-exposed Fire Department of the City of New York (FDNY) responders that includes cognitive functioning profiling alongside state-of-the-art proteomic studies of blood-based biomarkers alongside a PET/MRI study of 30 medically healthy WTC responders using two well-validated positron emission tomography (PET) ligands ([11C]-PiB to measure β-amyloid, and [18F]-Flortaucipir to measure tauopathy). Detailed cognitive testing will help to determine the level of cognitive dysfunction. Simultaneous structural MRI will be used to measure the extent of neurodegeneration. This study is timely because we are in a critical period when neuropathology is emerging and the etiology of the disease is still possible to determine.