OBJECTIVES/GOALS: To examine the relationship between chronic cadmium exposure and cognitive function in later life, we estimated the association of urinary cadmium concentration on composite cognitive score, an important marker of progression toward dementia, while accounting for diet and key co-pollutants tobacco use and lead exposure. METHODS/STUDY POPULATION: After excluding those missing cognitive data (141) or covariate data (190), we included 760 persons >/= 60 years of age from the National Health and Nutrition Examination Survey (NHANES), 2011-2014. Urinary cadmium reflects prolonged exposure: mean=0.41Î¼g/L (standard deviation (SD)= 0.46Î¼g/L). Concurrent with urine sampling, neuropsychological tests tapping memory, executive function, sustained attention and working memory were combined into a standardized z-score (mean 0, SD 1, 25th and 75th percentiles −0.68 and 0.72, respectively). We used linear models to estimate change in cognition per cadmium interquartile range, incorporating NHANES sampling weights, adjusting for demographic characteristics, diet, lead, and active tobacco use (classified by self-report or serum cotinine levels >10ng/mL). RESULTS/ANTICIPATED RESULTS: A baseline model showed that an IQR (0.38 Î¼g/L) increase in urinary cadmium exposure was associated with a 13% standard deviation lower cognitive z-score (95%CI: −0.19, −0.06), after adjusting for sampling weight and urinary creatinine (measure of urine dilution). This association was attenuated to 7% standard deviation lower cognitive z-score (95% CI −0.13, −0.02) after adjusting additionally for demographic characteristic of sex, age, age^2, race/ethnicity, marital status, education level, and poverty income ratio. Models further adjusted for smoking status (active/former/never), blood lead concentration, and key dietary sources of cadmium showed IQR increase in urinary cadmium exposure associated with 7% standard deviation lower cognitive z-score (95%CI: −0.14, −0.01). DISCUSSION/SIGNIFICANCE: Our findings suggest cadmium exposure is associated with lower cognitive scores even after accounting for confounding influence of diet, tobacco use and lead exposure. Alternate explanations include selection bias due to dropping persons missing needed variables and using concurrent cognitive measures rather than cognitive measures of over time.