Using Resting State Functional MRI to Predict Cognitive Decline among World Trade Center Responders

Dementia is the fifth most common cause of disability and death with a lifetime risk of 40% in the U.S. population. It is a costly disease, with estimates exceeding $236 billion annually, and is the only top cause of death for which neither a prevention nor cure is available. Dementia is typically preceded by milder forms of cognitive impairment (CI). Previous research by members of this investigative team have found that CI is more common among World Trade Center responders, relative to age-matched normative samples, approximating 12-14% in two separate studies. Further, among a different sample of 99 WTC responders in the Stony Brook health monitoring program (half of whom had CI) also studied by this team, reduced global mean cortical thickness and thickness across 21/34 subregions was found among those with CI. While the etiology of CI among WTC responders is unknown, preliminary data suggests that Alzheimer’s neuropathology may be one major source, as reflected in specific cognitive domains impacted (e.g., memory), as well as plasma biomarkers and atrophy of enthorhinal and temporal cortices. In addition to structural neuroimaging data, resting state functional MRI (RS-fMRI) data have been acquired among a sample of 99 WTC responders, approximately half of whom had CI at the time of scanning (Time Ascan). Given recent findings on the significance of RS data as a stable set of biomarkers for understanding disease risk, this proposal seeks first to leverage these existing data for determining RS connectivity differences among those with and without CI, as well as relationships with memory and processing speed. As a second aim, it will identify relationships among metrics of RS-fMRI network connectivity and cognition four years following the initial scan among 80 participants (Time Ascan®Time Bcog ). As an exploratory aim, it will characterize changes in RS network connectivity among 25 participants with progressing cognitive decline over four years and 25 with continued unimpaired cognition over four years by adding a RS-fMRI scan four years following the initial scan (Time Bscan) during the two-year study period. These results will inform a study that will aim to identify (with a larger sample) how and to what extent RS fMRI metrics can be used for predicting cognitive change in WTC responders.