White Matter Connectivity in Incident Mild Cognitive Impairment: A Diffusion Spectrum Imaging Study of World Trade Center Responders at Midlife

• Published in: Journal of Alzheimer's disease Vol. 80; no. 3; pp. 1209 - 1219
• Main Authors: Huang, Chuan, Kritikos, Minos, Clouston, Sean A.P., Deri, Yael, Serrano-Sosa, Mario, Bangiyev, Lev, Santiago-Michels, Stephanie, Gandy, Sam, Sano, Mary, Bromet, Evelyn J., Luft, Benjamin J.
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.01.2021
• Subjects: Brain - diagnostic imaging; Brain - pathology; Cognitive Dysfunction - diagnostic imaging; Cognitive Dysfunction - etiology; Cognitive Dysfunction - pathology; Diffusion Tensor Imaging; Emergency Responders; Female; Humans; Incidence; Male; Middle Aged; September 11 Terrorist Attacks; White Matter - diagnostic imaging; White Matter - pathology; incident mild cognitive impairment; white matter connectivity; diffusion spectrum imaging; midlife; Alzheimer’s disease; World Trade Center responders
• ISSN: 1387-2877; 1875-8908
• DOI: 10.3233/JAD-201237

Background: Individuals who participated in response efforts at the World Trade Center (WTC) following 9/11/2001 are experiencing elevated incidence of mild cognitive impairment (MCI) at midlife. Objective: We hypothesized that white matter connectivity measured using diffusion spectrum imaging (DSI) would be restructured in WTC responders with MCI versus cognitively unimpaired responders. Methods: Twenty responders (mean age 56; 10 MCI/10 unimpaired) recruited from an epidemiological study were characterized using NIA-AA criteria alongside controls matched on demographics (age/sex/occupation/race/education). Axial DSI was acquired on a 3T Siemen’s Biograph mMR scanner (12-channel head coil) using a multi-band diffusion sequence. Connectometry examined whole-brain tract-level differences in white matter integrity. Fractional anisotropy (FA), mean diffusivity (MD), and quantified anisotropy were extracted for region of interest (ROI) analyses using the Desikan-Killiany atlas. Results: Connectometry identified both increased and decreased connectivity within regions of the brains of responders with MCI identified in the corticothalamic pathway and cortico-striatal pathway that survived adjustment for multiple comparisons. MCI was also associated with higher FA values in five ROIs including in the rostral anterior cingulate; lower MD values in four ROIs including the left rostral anterior cingulate; and higher MD values in the right inferior circular insula. Analyses by cognitive domain revealed nominal associations in domains of response speed, verbal learning, verbal retention, and visuospatial learning. Conclusions: WTC responders with MCI at midlife showed early signs of neurodegeneration characterized by both increased and decreased white matter diffusivity in regions commonly affected by early-onset Alzheimer’s disease.