Alzheimer's disease and its related dementias (ADRD) caused more than 110,000 deaths in 2017 making it the sixth most common cause of death. With an estimated lifetime risk of 40% in the U.S. population and an estimated cost of care exceeding $200 billion, ADRD is burdensome for individuals and their families, and costly to society. While work is increasingly determining risk and resilience factors for ADRD, little is known about causes of preclinical dementia. Life course researchers have posited that a lifetime of stressors can accumulate to cause increased incidence of ADRD and prodromal Mild Cognitive Impairment (MCI). We posit that chronic posttraumatic stress disorder (PTSD), a relatively common (prevalence=10%) memory disorder that is characterized by intrusive memories of past trauma accompanied by a heightened stress response, helps to provide a unique mechanism linking lifetime stressors with later onset of cognitive decline reminiscent of ADRD. Yet, while we know that PTSD predicts increased risk of MCI and related cognitive and physical symptoms, the reasons for this association remain opaque. Seeking to examine this conundrum, we began the first cognitive monitoring study (R01 AG049953) of a cohort of men and women without comorbid head trauma who participated in rescue and recovery work during and after the World Trade Center (WTC) attacks. Pilot work (n=34) developing the pipeline for this protocol has also found that WTC responders have increased plasma neurofilament-light compared to healthy controls, and that plasma tau was strongly associated with memory dysfunction (r=-0.6) in this sample. We posit that PTSD might cause a brain insult, thereby triggering an undirected immunological response ultimately resulting in increased neuropathology. !
There is increasing evidence suggesting that World Trade Center (WTC) responders may be experiencing increased levels of cognitive and physical impairments, commonly seen as early risk factors for Alzheimer's disease and other related dementias, and further identifies posttraumatic stress as a prelude to these conditions. Our ongoing work has identified neurodegeneration and microglial activation among the most severely impaired people in this cohort, but little is known about what is going on for those who are only now beginning to experience cognitive dysfunction. The proposed study will collect new data from a representative sample of WTC responders who have been cognitively monitored at the Stony Brook University site, in order to determine to what extent plasma markers of microglial activation, tauopathy, and neurofilament-light distribution is associated with cognitive dysfunction and MCI in WTC responders.
