DTI Connectometry Analysis Reveals White Matter Changes in Cognitively Impaired World Trade Center Responders at Midlife

Article type: Research Article

Authors: Kritikos, Minos^{a; 1} | Huang, Chuan^{b; 1} | Clouston, Sean A.P.^{a; *} | Pellecchia, Alison C.^c | Santiago-Michels, Stephanie^c | Carr, Melissa A.^c | Hagan, Thomas^b | Kotov, Roman^d | Gandy, Sam^{f; g; h} | Sano, Mary^{g; h} | Horton, Meganⁱ | Bromet, Evelyn J.^d | Lucchini, Roberto G.^e | Luft, Benjamin J.^{c; 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] Department of Radiology, Renaissance School of Medicine at Stony Brook, Stony Brook, NY, USA | [c] Stony Brook World Trade Center Wellness Program, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA | [d] Department of Psychiatry, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA | [e] Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinair, New York, NY, USA | [f] James J Peters VA Medical Center, Bronx, NY, USA | [g] Department of Psychiatry and Mount Sinai Alzheimer’s Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA | [h] Center for Cognitive Health and Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA | [i] Department of Environmental Medicine and Public Health, 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. Sean Clouston, 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. Tel.: +1 631 444 6593; Fax: +1 631 444 3480; E-mail: sean.clouston@stonybrookmedicine.edu.

Note: [1] These authors contributed equally to this work.

Abstract: Background:More than 8% of responders who participated in the search and rescue efforts at the World Trade Center (WTC) following 9/11 developed early-onset cognitive impairment (CI). Approximately 23% were also diagnosed with chronic post-traumatic stress disorder (PTSD). Objective:To shed light on the pathophysiology of these WTC-related conditions, we examined diffusion connectometry to identify altered white matter tracts in WTC responders with CI and/or PTSD compared to unaffected responders. Methods:99 WTC responders (mean age 56 years) consisting of CI-/PTSD- (n = 27), CI+/PTSD- (n = 25), CI-/PTSD+ (n = 24), and CI+/PTSD+ (n = 23) were matched on age, sex, occupation, race, and education. Cognitive status was determined using the Montreal Cognitive Assessment and PTSD status was determined using the DSM-IV SCID. Diffusion tensor imaging was acquired on a 3T Siemens Biograph mMR scanner. Connectometry analysis was used to examine whole-brain tract-level differences in white matter integrity as reflected by fractional anisotropy (FA) values after adjusting for confounders. Results:Analyses identified 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. Furthermore, FA was negatively correlated with PTSD status, regardless of CI status in the superior thalamic radiation and the cerebellum. Conclusion:This is the first connectometry study to examine altered white matter tracts in a sample of WTC responders with CI and/or PTSD. Results from this study suggest that WTC responders with early-onset CI may be experiencing an early neurodegenerative process characterized by decreased FA in white matter tracts.

Keywords: Alzheimer’s disease, cognitive impairment, diffusion tensor imaging, midlife, post-traumatic stress disorder, white matter connectometry, World Trade Center Responders

DOI: 10.3233/JAD-220255

Journal: Journal of Alzheimer's Disease, vol. 89, no. 3, pp. 1075-1089, 2022