Abstract 15872: Association Between Cognition and Cardiovascular Function is Modified by Carnosine and Carnosine-Acrolein Conjugates

Background: Carnosine, a naturally occurring dipeptide found in highly metabolic tissues like skeletal muscles and brain can reduce oxidative stress caused by acrolein and particulate matter (PM) exposure. The role of carnosine and its acrolein-conjugates (propanol and propanal) maybe crucial in reducing the effects of PM2.5 air pollution on cardiovascular (CV) health. Methods: We analyzed data of 103 healthy participants from baseline (Visit # 2, before randomization) of the ongoing Nucleophilic Defense against Particulate Matter Toxicity (NEAT) clinical trial (NCT03314987) which investigates whether dietary supplementation of carnosine can protect against effects of PM2.5 air pollution. All participants underwent computerized cognitive test “Cognition”. The Cognition test includes 10 neurocognitive test batteries (Table 1) and assesses distinct domains of cognition. Tests scores were assessed in blinded fashion by the University of Pennsylvania team for individual batteries and a cumulative score. Two-tailed Spearman’s rho was used for correlation and Generalized Linear Models (GLM) with gamma distribution log-link was used for regression. Results: Cumulative cognition score showed a negative association with pulse pressure. Carnosine-propanol levels had a significant modifying effect (Figure 1). Stratified analysis showed that this relationship was significantly modified by low (B= -0.03, P=0.005) and medium (B= -0.016, P=0.046) carnosine-propanol levels. High levels of carnosine-propanol or carnosine-propanal did not show any effect on the cognition-pulse pressure. Indices of metabolic syndrome were also negatively associated with cumulative score (all P<0.05). Conclusions: Carnosine readily reacts with acrolein to reduce in-vivo oxidative stress by producing propanol and propanal aldehyde conjugates. Decrease in propanol conjugates is associated with higher CV health and in-turn higher cognitive outcomes.