Abstract
1573
Objectives: Recent studies have identified a high risk of cognitive impairment (CI) among responders to the 9/11/2001 attacks at the World Trade Center (WTC). This study presents results from a clinical case series addressing the etiology behind these observations. This study examined preliminary results collected from a pilot study of WTC responders with CI (WTC-CI), whose burden of β-amyloid (Aβ) or tau deposition and neurodegeneration in cortical regions of interest (ROI’s) was assessed to determine whether or not it followed hallmarks of Alzheimer’s disease (AD) neuropathology.
Methods: Twelve WTC-CI responders with Montreal Cognitive Assessment (MoCA) score <23, were recruited in two independent pilot studies using simultaneous magnetic resonance imaging (MRI) and positron emission tomography (PET). Two groups of six responders each received intravenous injection of either [18F]-Florbetaben (FBB) to measure Aβ deposition, or [18F]-Flortaucipir (FTP) to measure tau deposition. Quantitative analysis employed standardized uptake value ratios (SUVR) to measure cortical deposition of either radiotracer in bilateral regions of interest. Aβ (A+) and tau (T+) scan positivity were determined qualitatively by a board-certified neuroradiologist and quantitatively using validated methods and cutoffs. Neurodegeneration was assessed utilizing semi-quantitative automatic brain parcellation routine in Neuroquant™ with age/sex-corrected volumetric percentiles reported.
Results: Twelve WTC-CI responders were aged 54.92 ± 5.38 years old; 5 were female. Qualitative brain PETMR imaging analysis identified three amyloid and three tau-positive readings. Quantitative analyses identified one centiloid (CL) positive subject with concurrent SUVR amyloid positivity, one CL negative with concurrent SUVR amyloid positivity and three subjects with SUVR tau positivity consistent with Braak Stage I tauopathy. MRI bi-hemispheric analysis identified frontal, occipital and temporal lobes and inferior temporal gyri and the entorhinal cortex below the 10th percentile of age/sex matched norms. The hippocampus showed the least degeneration across cortical regions; the entorhinal cortex showed the most. Correlation analyses suggested strong associations between elevated FBB in the parietal lobe and hippocampus with neurodegeneration in the amygdala and temporal pole, respectively, and elevated FTP in the temporal lobe with neurodegeneration in the hippocampus and amygdala.
Conclusions: These analyses identified reductions in whole brain volume in twelve responders with WTC-CI, with substantial neurodegeneration across many, though not all ROI’s, and associations evident in Aβ and tau deposition across ROIs. These results may suggest that the etiology of WTC-CI is an entorhinal focused, hippocampal-sparing type of neurodegenerative disease.