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

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; World Trade Center Responders; cognitive impairment; diffusion tensor imaging; midlife; post-traumatic stress disorder; white matter connectometry.

Figure 1.

Flow Chart illustrating subject enrollment into study.

Figure 2.

Connectometry comparisons between WTC responders with Cognitively Impairment (CI+) [n=48] and those who were Cognitively Unimpaired (CI-) [n=51] responders, regardless of PTSD status, using three T-thresholds (T=2, 2.5, 3), identified that FA values were lower in responders with CI+ compared to CI- responders. Significantly different tracts included the left and right fornix, the right posterior thalamic radiation, and the middle cerebellar peduncle for all three T thresholds; and the forceps minor, the left posterior thalamic radiation, the right arcuate fasciculus, the left and right cingulum, and the right uncinate fasciculus for T<=2.5.

Figure 3.

Connectometry comparisons between WTC responders with PTSD+ (n=47) and PTSD- (n=52), regardless of cognitive status, using three T-thresholds (T=2, 2.5, 3) identified lower FA values in responders with PTSD when compared to responders without PTSD. Significantly different tracts included the left and right fornix, the right uncinate fasciculus, the forceps minor, the left and right cingulum, the left and right cerebellum, the right superior thalamic radiation, and the right inferior longitudinal fasciculus for T<=2.5; and the left superior thalamic radiation, the left inferior fronto-occipital fasciculus, and the left uncinate fasciculus, for T=2.

Figure 4.

Connectometry comparisons between WTC responders with Cognitive Impairment but no PTSD (CI+/PTSD-) [n=25] and no cognitive impairment or PTSD (CI-/PTSD-) [n=27] using three T-thresholds (T=2, 2.5, 3), identified that FA values were negatively associated with CI. Significantly different tracts included the left and right fornix, the right cingulum, and the right inferior longitudinal fasciculus for all three thresholds; and the left cingulum, the left cerebellum, the left inferior longitudinal fasciculus, the right posterior thalamic radiation, and the middle cerebellar peduncle for T≤2.5; with the forceps minor, and the left posterior thalamic radiation for T=2.

Figure 5.

Connectometry analysis of between WTC responders with Cognitive Impairment but no PTSD (CI+/PTSD-) [n=25] and those with both Cognitive Impairment and PTSD (CI+/PTSD+) [n=23], suggested that FA negatively correlated with responders with both CI+ and PTSD+ status. Significantly different tracts included the left and right fornix and the left cerebellum for all three thresholds: and the forceps minor, the right cerebellum, the left and right uncinate fasciculus and the left cingulum for T≤2.5. x