. Donepezil and flight simulator performance: effects on retention of complex skills. Neurology. 2002 Jul 9;59(1):123-5. PubMed.


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  1. This paper documents an effect that probably has been known for some time, i.e. that inhibition of acetylcholinesterase may improve memory in nondemented individuals. The effect size is, however, a major issue. This is a function not only of drug, dosage, target population, but also of the sensitivity of measurement. In this study the measurement is highly quantified and has been sensitive to a number of drug effects (alcohol, marijuana, nicotine). So one is left with the question of about how large is the effect. Our collaborator Martin Mumenthaler has been comparing effect sizes across studies and feels this effect is about the same size (though in the opposite direction) of alcohol hangover. This is not to say this should be a treatment for hangover! But, it is one attempt to get a handle on the size of a subtle drug effect. ‑ Jerome Yesavage

    Food for further thought: "Although the results of this study do not suggest that current cholinergic drugs are useful for nondemented adults, it is hard to predict what drugs will be developed in the future. In their conclusion, the authors raise much thornier questions that ought to be discussed in public forums sooner rather than later: "Even though our results need to be replicated in larger samples, if cognitive enhancement becomes possible in intellectually intact individuals, significant legal, regulatory, and ethical questions will emerge. To date, cholinesterase inhibitors have been used primarily for the treatment of AD. Recently, they have been considered as palliative approaches for individuals at risk for AD, such as those with mild cognitive impairment. However, many older adults, who will never have AD, have cognitive impairments that impact their day-to-day functioning, and there is an increasing demand for therapeutic interventions to remediate such deficits. How should one pay for such interventions? Will we further worsen the divisions between the "have" and "have-nots" when the rich are cognitively enhanced not only through better education but also through drugs or other technologies? Finally, how should one regulate the use of such agents in settings and populations beyond aviation and normal aging, such as chess matches or test taking among college students?" (From Yesavage et al. 2002)

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