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BRIEF COMMUNICATIONS: J. A. Yesavage, M. S. Mumenthaler, J. L. Taylor, L. Friedman, R. O’Hara, J. Sheikh, J. Tinklenberg, and P. J. Whitehouse Donepezil and flight simulator performance: Effects on retention of complex skills Neurology 2002; 59: 123-125 [Abstract] [Full text] [PDF]

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Donepezil and flight simulator performance: Effects on retention of complex skills

Bernhard J. Connemann   (18 February 2003)

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Martin S. Mumenthaler, J. A. Yesavage, J. L. Taylor, L. Friedman, R. O’Hara, J. Sheikh, J. Tinklenberg, and P. J. Whitehouse   (18 February 2003)

Donepezil and flight simulator performance: Effects on retention of complex skills 18 February 2003
Bernhard J. Connemann Dept. Psychiatry, University of Ulm, Germany Send Correspondence to journal: Re: Donepezil and flight simulator performance: Effects on retention of complex skills bernhard.connemann{at}medizin.uni-ulm.de Bernhard J. Connemann	I read the article by Yesavage et al. [1] with interest because I have a private pilot license. The efficacy of acetylcholinesterase inhibitors in healthy persons is of interest as is the performance of aircraft pilots. Correspondingly, the authors argue with the “face validity” of the task which they believe exceeds that of so-called “mere laboratory measures of cognition”. The perceived high validity of the task or, more precisely, of this complex bundle of tasks does not imply similarly high qualities with regard to other test-theoretical properties. In many cases, there is an inverse relation between validity and “face validity”, and repeat reliability of a measurement. It is necessary to isolate functions and to develop “laboratory tests”. Most of our current knowledge probably rests upon our ability to sub-divide questions. Therefore, the introductory notes relating to reliability of measurements and “face validity” of tasks appear to be misleading. Both validity and reliability of the score in use have not been evaluated. There is clear indication of a low reliability in the data. Since measurements were not repeated under truly identical conditions, but only after a month of training, performance might well increase not only with donepezil but also with placebo or even without any further intervention. This is the main scientific reason for introducing a placebo group. Decreasing performance with placebo in the given setting, however, is difficult to understand except as the visible expression of a high measurement error and a low repeat reliability. Thus, the observed worsening with placebo probably represents nothing else than a random effect, and so does the improvement with donepezil which was even substantially lower. Unfortunately, the authors preferred to ignore this important problem and to treat their results as if proven. On the contrary, in view of the questionable quality of the data, I would strongly recommend not to draw any conclusions except that more scientifically rigorous studies are needed. References 1. Yesavage JA, Mumenthaler MS, Taylor JL, Friedman L, O'Hara R, Sheikh J, Tinklenberg J, Whitehouse PJ. Donepezil and flight simulator performance: effects on retention of complex skills. Neurology 2002;59:123 -125.
Reply to Connemann 18 February 2003
Martin S. Mumenthaler Dept. of Psychiatry and Behavioral Sciences, Stanford University, CA, J. A. Yesavage, J. L. Taylor, L. Friedman, R. O’Hara, J. Sheikh, J. Tinklenberg, and P. J. Whitehouse Send Correspondence to journal: Re: Reply to Connemann msm{at}stanford.edu Martin S. Mumenthaler, et al.	We appreciate the opportunity to elucidate our position. We agree with Dr. Connemann that most of the current knowledge of human cognition come from laboratory tests that isolate specific functions and that isolated cognitive tests are valuable. However, we emphasize that the main goal of our study was to determine whether donepezil improves pilots’ overall flight performance, an approach that is complementary to testing isolated functions. For that reason we chose to test the pilots’ performance in a flight simulator. We believe that because our Frasca 141 flight simulator is a popular, Federal Aviation Administration (FAA) - approved pilot-training device, it has face validity. It allows our subjects to use their “real world skills and knowledge”, which may not be possible in a conventional laboratory task such as four-choice reaction time. At the same time we recognize that even sophisticated flight simulators are not airplanes, and that we have not conducted any studies to validate our flight simulator scores with scores collected during “real” flights. In our discussion we emphasize that our results should not be interpreted as a recommendation for the use of donepezil as a drug to improve flight performance. Dr. Connemann states that reliability of our flight scores has not been evaluated and that there is a clear indication of low reliability in the data themselves. We disagree. We have evaluated the test-retest reliability of our flight scores in prior work. For example, using the same flight simulator, and measuring the same flight scores as in the present study, we tested 24 female pilots twice within two weeks and evaluated test-retest reliability [2]. The correlation coefficient of the flight summary scores between the two test days (test-retest reliability coefficient) was 0.66, indicating acceptable reliability. In another study testing our flight summary score, with 100 men and women between 50- 69 years of age, we achieved a high test-retest reliability coefficient of 0.76 between two flights performed on the same day [3]. The test-retest reliability of our flight summary score falls in the range of comparable, established human cognitive tests [4, 5]. Our flight tasks are more difficult than those experienced in routine flight operations. Between baseline and post treatment (30 days), the pilots had no opportunity to practice and therefore were unable to retain some of the skills learned in our flight simulator. We believe that the performance decline between baseline and the 30-day post treatment test in the placebo group is a result of lack of practice during that period. This led us to conclude that the significantly better retention of learned flight simulator skills in the donepezil group was drug induced. References 2. Mumenthaler MS, O'Hara R, Taylor JL, Yesavage JA (2001) Relationship between variation in estradiol and progesterone levels across the menstrual cycle and human performance. Psychopharmacology 155: 198-203 3. Taylor JL, O'Hara R, Mumenthaler MS, Yesavage JA (2000): Relationship of CogScreen-AE to flight simulator performance and pilot age. Aviation, Space, and Environmental Medicine 71: 373-380 4. Dikmen SS, Heaton RK, Grant I, Temkin NR (1999) Test-retest reliability and practice effects of expanded Halstead-Reitan Neuropsychological Test Battery. J Int Neuropsychol Soc 5: 346-56 5. Tornatore JB, Hill E, Laboff JA, Hammond KW (2002) Automated screening for Mild Cognitive Impairment and Alzheimer's Disease. Poster: Presented at The 8th International Conference on Alzheimer’s Disease and Related Disorders, Stockholm, Sweden 2002, Abstract Number: 637