This study investigates the optimal way to calculate anticholinergic burden using two calculators known as the Anticholinergic Cognitive Burden Scale and the Anticholinergic Loading Scale. The first aim of the study was to replicate extant literature that has suggested a significant, deleterious impact of anticholinergic burden on cognitive performance (Taylor-Rowan et al., 2022). It aims to find the more optimal calculator to see which one is a better predictor of cognitive performance, and specifically, cognitive impairment, as research has shown an association between anticholinergic burden and cognitive decline. This study aims to provide an optimal calculator to be used as a tool for physicians in their prescribing practices to most accurately predict the potential cognitive impact of medications with anticholinergic properties. Archival data was used from the Department of Psychiatry in the University of Chicago Medical Center to find each individual patient’s anticholinergic burden score, separately calculated using the Anticholinergic Cognitive Burden Scale and Anticholinergic Loading Scale protocols. The analysis showed no significant differences between burden and no burden groups and there were no correlations between anticholinergic burden and test scores on neuropsychological tests. We did not find a way to best predict cognitive performance. Future research should focus on longitudinal designs and moderating factors.