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WTC responders

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Some WTC 911 responders are suffering from PTSD and cognitive disorders many years after 911. Researchers are trying to determine why as they continue monitoring patients. Photo courtesy of Stony Brook WTC Health and Wellness Program

Twenty-two years after the September 11 World Trade Center attacks, responders who have suffered physical and cognitive illnesses resulting from exposures continue to be monitored by healthcare providers. Ongoing studies by investigators at the Stony Brook WTC Health and Wellness Program reveal that assessments of this patient population’s mental health and cognitive status remain on the forefront of research as we move further away from that fateful day of 9/11.

Benjamin Luft, MD, Director and Principal Investigator of the Stony Brook WTC Health and Wellness Program, and the Edmund D. Pellegrino Professor of Medicine at the Renaissance School of Medicine at Stony Brook University, and his colleagues study all aspects of responders’ health status. The program monitors approximately 13,000 WTC responders.

Previous research has shown that some responders may be experiencing cognitive difficulties earlier in life than the general population, and that PTSD, which remains one of their most common ailments, may be associated with cognitive problems and/or physical illnesses.

A compilation of new research published over the past year  suggests  the need to delve further into investigating the brain status of responders and their cognitive problems.

A study in the Journal of Geriatric Psychiatry and Neurology assessed more than 700 responders, many with chronic PTSD, and the relationship between having cortical atrophy and behavioral impairments. They found that individuals with PTSD start to experience more mental health symptoms as a secondary symptom to cognitive impairments. Specifically, responders with an increased risk of cortical atrophy showed behavioral impairment in motivation, mood, disinhibition, empathy and psychosis.

Published in Molecular Neurobiology, another study revealed that there are associations between WTC exposure duration and inflammation in the brains of responders among 99 responders who participated from 2017 to 2019, with the average age being only 56 years. Neuroinflammation was evident both in the hippocampus, a part of the brain that helps to regulate emotions and memory, and throughout much of the cerebral white matter.

A paper published in Psychological Medicine highlights research that may reveal a better way to  understand responders’ PTSD symptoms, as opposed to self-reporting or screening. This work found that by using an AI program that reads the words of responders can predict their current PTSD and even the future trajectory of the illness.

Moreover, WTC investigators are developing AI programs to identify and predict psychological symptoms from facial expressions and tone of voice. AI analyzes video recordings of WTC responders. Importantly, when these methods are fully developed, they may be able to offer objective diagnostic tests for PTSD and other mental disorders.

Many responders to date have experienced mild cognitive impairment in comparison to non-responders their age.

A study that measured a key aspect of brain chemistry — proteins or biomarkers often associated with dementia and Alzheimer’s Disease — may provide specific evidence that responders need to be monitored for earlier onset dementia.

Published in the Alzheimer’s Association’s Diagnosis, Assessment and Disease Monitoring, this study illustrates that among approximately 1,000 responders —  average age at 56.6 years, and some who have dementia — associations exist between WTC exposures and the prevalence of neurodegenerative proteins in their brains.

Lead author Sean Clouston, PhD, Professor in the Program of Public Health, and the Department of Family, Population, and Preventive Medicine, and colleagues found that 58 percent of responders with dementia had at least one elevated biomarker and nearly 3.5 percent had elevations in all biomarkers. The overall cohort had an increased risk of dementia associated with plasma biomarkers indicative of neurodegenerative disease.

Another core member of the Stony Brook research team, Pei-Fen Kean, PhD, Professor in the Department of Applied Mathematics and Statistics, is involved in several ongoing multi-omics research projects to help explicate pathophysiology of these disorders on molecular level and identify novel blood-based biomarkers. For example, a study in the Translational Psychiatry identified the metabolomic-proteomic signatures associated with PTSD to enhance understanding of the biological pathways implicated in PTSD.

As the collaborative work of the research teams affiliated with the Stony Brook WTC Health and Wellness Program moves forward, they will use previous findings and new methods to build their work to best assess the mental and physical health conditions of responders.

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This rendered image of the brain via a technique called diffusion tractography reveals parts of the brain’s white matter in a compilation of WTC responders experiencing cognitive impairment (CT). These areas depicted by various colors illustrate where the brain is more vulnerable to neurodegenerative processes. The different colors represent differences in the heath of various parts of the brain including the limbic system. Credit: Chuan Huang
Stony Brook-led imaging study sheds light on PTSD-associated mental decline

A study that assessed the brains of 99 World Trade Center (WTC) responders by using diffusion tractography, a 3-D imaging technique, showed that WTC responders with cognitive impairment (CI), a possible sign of dementia, and post-traumatic stress disorder (PTSD), have a different presentation of the white matter in their brains compared to responders with CI without PTSD. Led by researchers at Stony Brook University affiliated with the Stony Brook WTC Health and Wellness Program, the study suggests a specific form of dementia could be affecting WTC responders who also have PTSD. The findings are published early online in the Journal of Alzheimer’s Disease.

According to the authors, this is the first study to examine white matter alterations using connectometry in a sample of WTC responders in mid-life (average age: 56) with and without concurrent PTSD. The goal of the study was to examine and elucidate the extent to which white matter tract integrity might be impaired in WTC responders with CI and/or PTSD. Previously, the researchers had identified changes in white matter diffusivity in small numbers of responder patients.

“Our findings are by no means conclusive in terms of defining CI or dementia in WTC responders, and if this study provides evidence of a new form of dementia emerging,” says Sean Clouston, PhD, lead author and Associate Professor in the Program in Public Health, and in the Department of Family, Population, and Preventive Medicine at Stony Brook University.

“Overall, the study supports the view that responders with CI have neurological changes consistent with neurodegenerative disease, but they are inconclusive as to the type of disease,” he adds. “Our findings do show that dementia due to PTSD is clearly different from non-PTSD dementia in this responder population.”

Subjects in the study were matched by age, gender, occupation, race and education. Cognitive status was determined by using the Montreal Cognitive Assessment, and PTSD status was determined by using the Diagnostics and Statistics Manual-IV. The researchers used diffusion tensor imaging via a mMR scanner, and they used connectometry to examine whole-brain tract level differences in white matter integrity as reflected by fractional anistrophy (FA) values.

In summary, the team found that FA was negatively correlated with CI and PTSD status in the fornix, cingulum, forceps minor of the corpus callosum, and the right uncinate fasciculus. Additionally, FA was negatively correlated with PTSD status, regardless of the CI status in the superior thalamic radiation and the cerebellum.

The authors conclude that the brain imaging results “suggest that WTC responders with early-onset CI may be experiencing an early neurodegenerative process characterized by decreased FA in white matter tracts.”

The technique and other findings

Clouston and colleagues used the imaging technique diffusion tractography to examine how healthy axons are in the brain’s white matter. The technique helped to determine that responders with CI had signatures in their white matter that did not match patterns seen in old-age Alzheimer’s disease and other related dementias.

By using the imaging technique, they also compared responders with PTSD and dementia to those with dementia but without PTSD. The imaging revealed a lot of similarities between the groups but also showed a remarkable difference in the white matter of those with PTSD and dementia – showing evidence of cerebellar atrophy, a finding that is inconsistent with other studies of dementia.

The research for the study was supported in part by the National Institutes of Health’s National Institute on Aging (grant # R01AG049953), and the Centers for Disease Control and Prevention (grant # U010H011314) and the National Institute for Occupational Safety and Health, NIOSH, (grant # 200-2011-39361).

 

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