In the human brain, butyrylcholinesterase (BuChE) is expressed in neurons and glia. For example, many nuclei in the human thalamus, with projections to the cerebral cortex, contain a large number of neurons with intense BuChE activity. Thalamocortical projections subserve a variety of cognitive functions. Due to genetic mutations, there are individuals who do not have detectable BuChE activity (silent BuChE). While the prevalence of silent BuChE is only 1:100,000 in European and American populations, it is 1:24 in the Vysya community in Coimbatore, India. To examine whether there are differences in cognitive functions between individuals with silent BuChE and those expressing normal BuChE (wild-type), twelve healthy individuals with silent BuChE and thirteen healthy individuals with wild-type BuChE, all from the Vysya community in Coimbatore, were tested for cognitive function using the Automated Neuropsychological Assessment Metrics test battery. The silent BuChE group was slightly faster on simple reaction tasks, but slower on a visual perceptual matching task. Furthermore, discriminant function analyses correctly classified 11/12 silent and 8/13 wild-type BuChE subjects (76% correct classification overall) based on BuChE status. Different profiles of cognitive test performance between individuals with silent and wild-type BuChE were observed. These observations suggest a function for BuChE in cognition.