Exploring Cognitive Impairment among 9/11-exposed Individuals

Research is emerging that suggests an increase in the risk of cognitive decline among individuals who were exposed to the 9/11 terrorist attacks. This decline, known as mild cognitive impairment (MCI), is common in aging populations but varies greatly from person to person. More research is needed to determine whether MCI in the 9/11 population is caused by their exposure, other factors, or represents a normal pattern of aging.

About the WTC Health Program

The World Trade Center (WTC) Health Program is a limited health benefits program for qualifying health conditions related to the 9/11 attacks and the aftermath. It provides medical monitoring and treatment of eligible responders, initial health evaluations for eligible survivors, and medical monitoring and treatment for survivors who have health conditions certified by the Program. The WTC Health Program is administered by the Director of the National Institute for Occupational Safety and Health (NIOSH). As of June 30, 2021, there are over 112,000 persons enrolled in the WTC Health Program.

A qualifying health condition is a diagnosed illness or health condition (including mental health conditions) for which a member’s exposure to airborne toxins, any other hazard, or any other adverse condition resulting from the 9/11 terrorist attacks is substantially likely to be a significant factor in aggravating, contributing to, or causing the illness or health condition (42 CFR §88.1). These conditions comprise a large group of aerodigestive disorders, mental health conditions, musculoskeletal disorders, many types of cancers, and acute traumatic injuries that have been linked to the terrorist attacks. The list of health conditions can be found in Title 42, Part 88 of the Code of Federal Regulations under paragraph 42 CFR §88.15, List of WTC-Related Health Conditions. Some common health conditions are chronic rhinosinusitis, gastroesophageal reflux disease (GERD), cancer, asthma, sleep apnea, post-traumatic stress disorder (PTSD), anxiety disorder, and major depressive disorder.

Mild Cognitive Impairment

While definitions differ, mild cognitive impairment (MCI) is best described as an intermediate clinical state between normal cognitive function and dementia. MCI usually precedes dementia; however, not all patients with MCI will progress to dementia and not all dementia patients will have a previous diagnosis of MCI.

Cognitive decline is a common characteristic of aging. The prevalence of MCI is significant, ranging from 4% to 19% of persons aged 65 or older. The 9/11-exposed population is entering an age in which cognitive dysfunction is becoming more clinically relevant; therefore, research in this area is expanding.

Growing evidence suggests that 9/11-exposed first responders may be at increased risk of early onset cognitive impairment typically seen at older ages. However, these studies are subject to several important limitations; therefore, alternative explanations of study findings, such as bias from systematic and random errors, cannot be ruled out.

On October 2019, the WTC Health Program held a 2-day scientific workshop to review the current science on MCI, discuss the evidence of increased risk in the 9/11-exposed population, identify research gaps, and discuss potential risk management strategies. For a detailed summary of the workshop, see the article A Workshop on Cognitive Aging and Impairment in the 9/11-Exposed Population.

Two potential pathways for WTC-related cognitive impairment have been hypothesized. First, unremitting, and chronic symptoms of WTC-related PTSD among individuals who experienced the attacks, or participated in the subsequent rescue, recovery and rehabilitation efforts may progress to MCI. This pathway is supported by previous studies of combat veterans that found associations between PTSD and cognitive impairment. Second, toxic exposures to WTC dust and particulate matter might also be a cause, based on growing evidence from animal and human studies linking air pollution to potential neurological effects. Of these, the existing evidence from WTC health research is strongest for a potential link between chronic PTSD and MCI.

Limitations

There are several important limitations in existing studies. Many studies use cross-sectional designs that provide little information on cause and effect. Among incidence studies, many lacked adequate information on baseline risk, cognitive impairment definitions have varied, and few data are available to characterize age-stratified rates, especially at younger ages. Other limitations are a lack of a non-WTC exposed comparison group, small sample sizes (e.g., lack of statistical power), and imprecise exposure assessment. See A Workshop on Cognitive Aging and Impairment in the 9/11-Exposed Population for more information.

Next Steps

More research is needed to clarify causal mechanisms for potential WTC-related MCI. Future research will also characterize MCI progression and disease burden in the 9/11 population. Future research projects are needed to address several important limitations in existing studies, such as inconsistent definitions of cognitive impairment, inadequate information characterizing baseline risks, exposure misclassification, and a lack of non-exposed comparison groups. Advancements in neuroimaging and biomarker research offers potential improvements in surveillance and diagnostic cost and capability. Similarly, advances in molecular sciences (e.g., genomics, epigenomics, proteomics) may uncover data that inform causation and possibly lead to better care.

The 2019 workshop stimulated collaboration and initiated new ideas that, along with input from other scientists and stakeholders, will be useful in planning research on cognitive decline and other issues related to aging in the 9/11-exposed population. To build research capacity, the WTC Health Program is pursuing an agenda that targets a broad range of studies that characterize the health burden and inform treatment. The research goals are to maximize available resources through collaboration, improve the understanding of the risk and underlying etiology of cognitive impairment among WTC Health Program members, and to develop risk reduction and mitigation strategies.

The following exploratory/developmental research grants related to cognitive impairment under the joint announcement of the WTC Health Program and the National Institute on Aging (NIA) were funded by NIA during the 2021 funding cycle.

• Trauma Exposure and Cognitive Impairment: Understanding Polygenic Liability and the Causative and Moderating Effects of Exposure, PTSD, and Psychiatric Comorbidity in WTC Responders
• Using Artificial Intelligence to Identify Accelerated Brain Aging in World Trade Center Responders
• Using Resting State Functional MRI to Predict Cognitive Decline among World Trade Center Responders
• Physical and Mental Health Pathways to Cognitive Decline in World Trade Center Responders: The Roles of Pulmonary Function and Post-Traumatic Stress Disorder

Please visit the WTC Health Program Research Gateway for more information on NIOSH funded research projects that help answer critical questions about MCI and other health conditions.

Robert D. Daniels, PhD, CHP, is Associate Director for Science in the World Trade Center Health Program.

Travis Kubale, PhD, is the Associate Director, Research Planning & Care Integration in the World Trade Center Health Program.