Donepezil Improves Cognitive Performance in Healthy Pilots

July 11, 2002

July 12, 2002 — In a randomized, placebo-controlled trial reported in the July 9 issue of Neurology, donepezil, an acetylcholinesterase inhibitor used in Alzheimer's disease, significantly improved the performance of aircraft pilots. The findings pose ethical and practical questions of whether healthy individuals should use this drug to improve mental performance.

"Many older adults who will never develop Alzheimer's have cognitive impairments that impact their day-to-day functioning, and the demand is increasing for therapies to address this," lead author Jerome Yesavage, MD, from Stanford University in Palo Alto, California, says in a news release. "Many questions will come up."

In this double-blind, parallel group trial, 18 pilots with an average age of 52 years were trained to follow a complex series of instructions given during seven practice flights on a flight simulator. They were then randomized to treatment with placebo or donepezil, 5 mg/day for 30 days. On two additional flight simulator tests, retention for training was better in the donepezil group (P < .05).

This experimental design was chosen because flight simulators provide reliable, objective data, and because of the controversy over the Federal Aviation Administration (FAA) law requiring air transport pilots to retire when they reach age 60.

"There's no shortage of opinions about what the retirement age should be," Yesavage says. "However, there's very little data to support those opinions." Because the complex aviation tasks learned in this experiment were more difficult than those experienced in routine flight operations, he explains that these results may not be directly applicable to the retirement debate.

Although there were no adverse events with donepezil in this small study, Yesavage recommends doing larger studies, which would be more likely to reveal uncommon adverse effects. Confirming these findings may open a Pandora's box of legal, regulatory, and ethical issues.

"How will we pay for these therapies? Will it worsen the gap between the 'haves' and 'have-nots' when the rich are cognitively enhanced not only through better education, but also through drugs or other technologies?" Yesavage asks. "And how should the use of these therapies be regulated in settings beyond aviation or normal aging, such as chess matches or test-taking among college students?"

Neurology. 2002;59:123-125

Reviewed by Gary D. Vogin, MD


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