Genetic Liability, Exposure Severity, and Post-Traumatic Stress Disorder Predict Cognitive Impairment in World Trade Center Responders

Article type: Research Article

Authors: Mann, Frank D.^{a; *} | Clouston, Sean A.P.^a | Cuevas, Adolfo^b | Waszczuk, Monika A.^c | Kuan, Pei-Fen^d | Carr, Melissa A.^e | Docherty, Anna R.^f | Shabalin, Andrea A.^f | Gandy, Sam E.^g | Luft, Benjamin J.^{e; h}

Affiliations: [a] Program in Public Health and Department of Family, Population, and Preventive Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA | [b] Center for Anti-Racism, Social Justice, and Public Health Department of Social and Behavioral Sciences, New York University, New York, NY, USA | [c] Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA | [d] Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA | [e] World Trade Center Program Clinical Center of Excellence, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA | [f] Department of Psychiatry, University of Utah, Salt Lake City, UT, USA | [g] Departments of Neurology and Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA | [h] Department of Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA

Correspondence: [*] Correspondence to: Dr. Frank D. Mann, Program in Public Health, 101 Nichols Rd., Health Sciences Center, #3-071, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, 11794, USA. E-mail: frank.mann@stonybrookmedicine.edu.

Abstract: Background: There is a high incidence of cognitive impairment among World Trade Center (WTC) responders, comorbid with post-traumatic stress disorder (PTSD). Yet, it remains unknown whether genetic liability for Alzheimer’s disease, PTSD, educational attainment, or for a combination of these phenotypes, is associated with cognitive impairment in this high-risk population. Similarly, whether the effects of genetic liability are comparable to PTSD and indicators of exposure severity remains unknown. Objective: In a study of 3,997 WTC responders, polygenic scores for Alzheimer’s disease, PTSD, and educational attainment were used to test whether genome-wide risk for one or more of these phenotypes is associated with cognitive impairment, controlling for population stratification, while simultaneously estimating the effects of demographic factors and indicators of 9/11 exposure severity, including symptoms of PTSD. Results: Polygenic scores for Alzheimer’s disease and educational attainment were significantly associated with an increase and decrease, respectively, in the hazard rate of mild cognitive impairment. The polygenic score for Alzheimer’s disease was marginally associated with an increase in the hazard rate of severe cognitive impairment, but only age, exposure severity, and symptoms of PTSD were statistically significant predictors. Conclusion: These results add to the emerging evidence that many WTC responders are suffering from mild cognitive impairments that resemble symptoms of Alzheimer’s disease, as genetic liability for Alzheimer’s disease predicted incidence of mild cognitive impairment. However, compared to polygenic scores, effect sizes were larger for PTSD and the type of work that responders completed during rescue and recovery efforts.

Keywords: Alzheimer’s disease, educational attainment, mild cognitive impairment, polygenic score, post-traumatic stress disorder

DOI: 10.3233/JAD-220892

Journal: Journal of Alzheimer's Disease, vol. 92, no. 2, pp. 701-712, 2023