ABSTRACT Direct trauma exposure is associated with negative physical and mental health consequences, including an increased risk of rapid decline of cognitive function, which may start early in midlife. Moreover, additional life traumas such as COVID-19, as well as chronic illnesses, have also been shown to accelerate cognitive aging. During the World Trade Center terror attack and its aftermath, tens of thousands of traditional first responders and other cleanup and recovery workers were exposed to the emotional trauma and to environmental toxicants, and they had high rates of subsequent physical and psychiatric disorders. The time to detect cognitive decline is before the onset of more obvious symptoms, so that the underlying neurodegeneration may be delayed or lessened. To evaluate the risk of cognitive decline, we will use remote web-based neuropsychological tasks to assess core cognitive functioning among the youngest first responders (N=1,200) in two waves, 40 months apart. The different levels of trauma exposure, and consequent physical and mental outcomes, which have been well documented, may imply different levels of premature cognitive decline risk among the responders which will be considered in our experimental design and analytical models. We plan to recruit first responders who received health services through the WTC Health Program, a majority of whom were police and non-traditional rescue, recovery and cleanup workers, and compare the risk of cognitive decline between these groups. In addition, a sub-group of responders and additional community controls (N=120) will participate in a neurocognitive study using EEG and MRI to elucidate the neurobiological mechanisms associate with premature cognitive decline. Specifically, we will include core cognitive tasks (attention and episodic memory) to determine the neuronal underpinnings of early cognitive changes and will obtain measures of brain morphology and connectivity. This study will generate scientifically robust information to guide clinical and public health actions focused on premature cognitive decline among the youngest responders. A better understanding of premature cognitive decline and of the most important pathways causing such decline has the potential to improve interventions that can reduce premature cognitive decline in this and other cohorts.