An hypothesis on the role of glucose in the mechanism of action of cognitive enhancers.

This review presents evidence that some cognition enhancing drugs produce their beneficial effects on learning and memory by increasing the availability of glucose for uptake and utilization into the brain. The hypothesis further suggests that many cognition enhancing drugs act through a peripheral mechanism rather than directly on the brain. The general hypothesis is supported by four independent and converging pieces of evidence: 1) Some cognition enhancing drugs may not cross the blood-brain barrier, but can still facilitate memory; 2) Some cognition enhancing drugs are effective only when injected peripherally, but not when injected directly into the brain; 3) Many cognition enhancing drugs are not effective after adrenalectomy; 4) Cognitive function is correlated with glucose regulation in aged animals and humans. These four lines of research have implications for the role of glucose in the action of specific cognitive enhancers.