Aschenbrenner, Andrew J;
Hassenstab, Jason;
Wang, Guoqiao;
Li, Yan;
Xiong, Chengjie;
McDade, Eric;
Clifford, David B;
... Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU); + view all
(2022)
Avoid or Embrace? Practice Effects in Alzheimer's Disease Prevention Trials.
Frontiers in Aging Neuroscience
, 14
, Article 883131. 10.3389/fnagi.2022.883131.
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Abstract
Demonstrating a slowing in the rate of cognitive decline is a common outcome measure in clinical trials in Alzheimer’s disease (AD). Selection of cognitive endpoints typically includes modeling candidate outcome measures in the many, richly phenotyped observational cohort studies available. An important part of choosing cognitive endpoints is a consideration of improvements in performance due to repeated cognitive testing (termed “practice effects”). As primary and secondary AD prevention trials are comprised predominantly of cognitively unimpaired participants, practice effects may be substantial and may have considerable impact on detecting cognitive change. The extent to which practice effects in AD prevention trials are similar to those from observational studies and how these potential differences impact trials is unknown. In the current study, we analyzed data from the recently completed DIAN-TU-001 clinical trial (TU) and the associated DIAN-Observational (OBS) study. Results indicated that asymptomatic mutation carriers in the TU exhibited persistent practice effects on several key outcomes spanning the entire trial duration. Critically, these practice related improvements were larger on certain tests in the TU relative to matched participants from the OBS study. Our results suggest that the magnitude of practice effects may not be captured by modeling potential endpoints in observational studies where assessments are typically less frequent and drug expectancy effects are absent. Using alternate instrument forms (represented in our study by computerized tasks) may partly mitigate practice effects in clinical trials but incorporating practice effects as outcomes may also be viable. Thus, investigators must carefully consider practice effects (either by minimizing them or modeling them directly) when designing cognitive endpoint AD prevention trials by utilizing trial data with similar assessment frequencies.
| Type: | Article |
|---|---|
| Title: | Avoid or Embrace? Practice Effects in Alzheimer's Disease Prevention Trials |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fnagi.2022.883131 |
| Publisher version: | https://doi.org/10.3389/fnagi.2022.883131 |
| Language: | English |
| Additional information: | Copyright © 2022 Aschenbrenner, Hassenstab, Wang, Li, Xiong, McDade, Clifford, Salloway, Farlow, Yaari, Cheng, Holdridge, Mummery, Masters, Hsiung, Surti, Day, Weintraub, Honig, Galvin, Ringman, Brooks, Fox, Snyder, Suzuki, Shimada, Gräber and Bateman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | practice effects, Alzheimer’s disease, clinical trials, learning, assessment frequency, alternative forms |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10152837 |
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