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Objective: Many interventions that exhibit therapeutic potential in preclinical Alzheimer’s disease (AD) research have not been proven effective clinically. One reason for this lack of translatability between animals and humans might be due to a failure to employ measures in animals that generalize to humans. The National Center for Toxicological Research (NCTR) has developed an operant test battery (OTB) designed to generate translational markers of complex brain function in rats, monkeys, and humans. The NCTR OTB has not, as yet, been used to assess cognitive function in persons with a diagnosis of AD. Thus, the purpose of this study was to assess the utility of the NCTR OTB to detect cognitive impairments in individuals with a diagnosis of AD. Methods: Seven participants with an AD diagnosis and 12 healthy adults (age ≥ 60), completed three operant tasks: Temporal Response Differentiation (TRD); Delayed Matching to Sample (DMTS); and Incremental Repeated Acquisition (IRA). These tasks were used to measure aspects of timing ability, short-term nonverbal memory and attention, and learning, respectively. Results: Persons with a diagnosis of Alzheimer’s disease performed significantly worse on all three tasks, displaying marked deficits in several areas of cognitive function. Conclusion: These results suggest that the NCTR OTB is capable of detecting cognitive impairments in individuals with AD and, therefore, is a useful tool for monitoring disease severity and progression and for screening compounds for cognitive enhancing effects in both preclinical and clinical research.