White matter connectivity in incident mild cognitive impairment: A diffusion spectrum imaging study of world trade center responders at midlife

Chuan Huang, Minos Kritikos, Sean A.P. Clouston, Yael Deri, Mario Serrano-Sosa, Lev Bangiyev, Stephanie Santiago-Michels, Sam Gandy, Mary Sano, Evelyn J. Bromet, Benjamin J. Luft

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish
Pages (from-to)1209-1219
Number of pages11
JournalJournal of Alzheimer's Disease
Issue number3
StatePublished - 2021


  • Alzheimer's disease
  • Diffusion spectrum imaging
  • Incident mild cognitive impairment
  • Midlife
  • White matter connectivity
  • World Trade Center responders


Dive into the research topics of 'White matter connectivity in incident mild cognitive impairment: A diffusion spectrum imaging study of world trade center responders at midlife'. Together they form a unique fingerprint.

Cite this