Abstract P328: Hepatocyte Growth Factor and Incident Cognitive Impairment: The Reasons for Geographic and Racial Differences in Stroke (REGARDS)

Abstract

Background: Cognitive impairment is a major public health burden in the U.S., and Black adults experience a disproportionate burden of cognitive impairment, including dementia. Hepatocyte growth factor (HGF) is a tyrosine kinase receptor MET agonist with neuroprotective properties, including peptide synthesis, neuronal regeneration, and inflammation reduction. Recombinant HGF aids endothelial repair and combats tissue fibrosis in mice. A positive HGF/MET pathway modulator (fosgonimeton) is in Phase 2 clinical trials for mild to moderate Alzheimer’s disease. We investigated the link between circulating HGF and incident cognitive impairment (ICI) in a national cohort study. Methods: REGARDS enrolled a cohort of 30,239 Black and White adults aged ≥45 in 2003-2007. ICI was identified using a 3-test battery administered every 2 years. Excluding participants with baseline cognitive impairment or stroke, with a mean follow-up of 3.5 years, 432 ICI cases and 520 controls were identified and HGF was measured in their baseline blood samples. Logistic regression estimated odds ratios (OR) of ICI by continuous HGF and also per quartile of HGF, controlling for known confounders. We assessed sex*HGF and race*HGF interactions on ICI. Restricted Cubic (RC) splines illustrated potential non-linear relationships. Results: Higher HGF was not associated with greater ICI risk in any model ( Figure ). There was no observed significant sex*HGF (P=0.58) or race*HGF interactions (P=0.19). RC splines visualized a possible non-linear relationship between lower HGF and higher risk of ICI relative to the median HGF level. Conclusions: In a prospective study of HGF in adults free from stroke or cognitive impairment, there was no clear association between higher HGF and ICI, though possible nonlinear associations might exist at low levels. This suggests that pharmaceuticals augmenting HGF pathways may benefit in primary prevention of ICI. Confirmatory studies are needed.