Problems in the search for cognition enhancers.

Drugs which enhance cognition may benefit the two largest groups of psychiatric patients who have been bypassed during the psychopharmacological revolution of the past 35 years: those with development mental disabilities and those with brains ravaged by senile dementias. But who among us would not benefit from such a drug, if indeed it could enhance normal performance? Establishing suitable animal models for developing such drugs has been a major problem. Lesioning experiments dictate the answers as well as the questions, delimiting the type of drug to remedy the defect. Other lesions which are less specific, such as anoxia or deficiency of some vitamin or metabolite, may not have particular relevance to the clinical situation. The best animal models would employ learning paradigms that mimic the problems encountered by the disabled patient. Testing new compounds in the clinic also has problems. Subjects should not be so deteriorated to require a miracle drug to show any effect. The characteristic variability in function of such patients must be taken into account, to assure that any changes are not simply within the normal range of variability. Thus, we may need a new kind of statistical approach to analyzing data, based more on individual responses than on group means. Finally, the end-points should be based on an improved quality of life both for patients and their caretakers. We need a different set of measurement criteria. Despite these difficulties the search for drugs which enhance cognition should not be delayed. The payoffs of success will be high for everyone.