Can small molecules provide truly effective enhancement of cognition? Current achievements and future directions.

INTRODUCTION: The prevalence of age-related diseases that implicate a deterioration of cognitive abilities is increasing. Moreover, cognitive decline occurs in numerous CNS disorders affecting patients at younger ages as well, resulting in reduced functional ability and quality of life. Despite the existence of few medications treating cognition, the need for efficacious treatment options to alleviate, halt or even prevent cognitive decline is generally unmet to date. Consequently, extensive research efforts are undertaken to identify medications that can effectively enhance cognition. AREAS COVERED: This review covers ongoing clinical trials for cognition and reflects on efforts undertaken to increase the success rates of procognitive drug treatment. The review discusses ways to optimize the drug development process for cognition enhancing agents at the preclinical to clinical interface and provides concrete examples. EXPERT OPINION: The existing efficacy readouts addressing cognition in preclinical research offer little translational validity to the clinical situation. In order to identify truly efficacious drug candidates, biomarkers need to be developed that directly address conserved mechanisms underlying cognitive performances. To this end, technologies such as neuroimaging or electroencephalography constitute promising entry points for identifying both the cognitive domain and the patient population most responsive to drug treatment.