Neuroinflammation in World Trade Center responders at midlife: A pilot study using [¹⁸F]-FEPPA PET imaging

Background: Neuroinflammation has long been theorized to arise from exposures to fine particulate matter and to be modulated when individuals experience chronic stress, both of which are also though to cause cognitive decline in part as a result of neuroinflammation. Objectives: Hypothesizing that neuroinflammation might be linked to experiences at the World Trade Center (WTC) events, this study explored associations between glial activation and neuropsychological measures including post-traumatic stress disorder (PTSD) symptom severity and WTC exposure duration. Methods: Translocator protein 18-kDa (TSPO) is overexpressed by activated glial cells, predominantly microglia and astrocytes, making TSPO distribution a putative biomarker for neuroinflammation. Twenty WTC responders completed neuropsychological assessments and in vivo PET brain scan with [¹⁸F]-FEPPA. Generalized linear modeling was used to test associations between PTSD, and WTC exposure duratiioni as the predictor and both global and regional [¹⁸F]-FEPPA total distribution volumes as the outcomes. Result: Responders were 56.0 ​± ​4.7 years-old, and 75% were police officers on 9/11/2001, and all had at least a high school education. Higher PTSD symptom severity was associated with global and regional elevations in [¹⁸F]-FEPPA binding predominantly in the hippocampus (d ​= ​0.72, P ​= ​0.001) and frontal cortex (d ​= ​0.64, P ​= ​0.004). Longer exposure duration to WTC sites was associated with higher [¹⁸F]-FEPPA binding in the parietal cortex. Conclusion: Findings from this study of WTC responders at midlife suggest that glial activation is associated with PTSD symptoms, and WTC exposure duration. Future investigation is needed to understand the important role of neuroinflammation in highly exposed WTC responders.