18F-Florbetaben uptake suggests a unique amyloidosis in World Trade Center responders

Introduction: The search-and-rescue operations following the collapse of the World Trade Center (WTC) exposed responders to emotionally and mentally taxing conditions and a toxic environment. Now, more than two-decades after the attack, approximately 23% of these volunteers have a higher prevalence of post-traumatic stress disorder (PTSD) and mild cognitive impairment, a precursor to Alzheimer's disease and related dementias (ADRD).

Previous studies in this population have investigated neuroinflammation and neurodegeneration through magnetic resonance imaging (MRI) and positron emission tomography (PET). Furthermore, serological analyses in this cohort indicate an immune response potentially in response to the toxic particulate matter from the dust. These results suggest that neuroinflammation was correlated with time spent at the disaster site in key regions often associated with MCI, but not PTSD. Furthermore, MCI in this population was associated with decreased fractional anisotropy (FA) and cortical thickness (CT), both common measures of neurodegeneration. Therefore, there may be a unique etiology of MCI in responders. In this PET/MR study of WTC responders, we assess the amyloid load to explain clinical phenotypes and to determine if amyloid distribution in responders is consistent with ADRD.

Methods: Thirty-five WTC responders participated in this study, aged 45-65 at the time of the study. The subjects' cognition status was determined using the COGSTATE battery. Of these volunteers, we determined that 18 subjects were cognitively unimpaired (CU), while 17 subjects had MCI.

Responders were intravenously injected with FBB approximately 1 hour before imaging. Scans were acquired using a 3T Siemens Biography mMR. PET images were attenuation corrected using the Boston Method, reconstructed with 20-minute window between approximately 90 - 110 minutes post-injection. The PET images were registered to the subjects' T1-weighted MR scan and segmented using Desikan-Killiany atlas with FreeSurfer v7.1.1. Regional standardized uptake values (SUVs) were partial volume corrected and normalized by cerebellar gray. A WTC-relevant meta-ROI was defined based on previous imaging results in this population. This meta-ROI consists of the inferior frontal gyrus, most of temporal parietal cortex, cingulate, amygdala, hippocampus, pallidum, putamen, and ventral diencephalon. We compared the results of our meta-ROI against the Centiloid values, as well as examined the correlation between regional SUVRs and physical measures of neurodegeneration between MCI and CU responders.

Results: Using the Centiloid numbers, we were unable to differentiate between MCI and CU responders (p=0.341). However, the WTC meta-ROI was able to determine a difference between these cohorts (p=0.025). Correlations between regional amyloid deposition and domains of cognition generally show a stronger association with the WTC meta-ROI than the Centiloid, particularly in reaction speed.

Conclusions: While some aspects of MCI in WTC responders are consistent with ADRD, such as increased amyloid load, the presentation of amyloidosis is not entirely consistent with ADRD. First, there is no increased FBB uptake in the Centiloid meta-ROI, and amyloid deposition was consistently correlated with memory and throughput. These results imply that there may be a unique neuropathology of CI in the WTC responder population.

• Download figure
• Open in new tab
• Download powerpoint