Avoid or Embrace? Practice Effects in Alzheimer's Disease Prevention Trials

Area of Science:

• Neuroscience
• Clinical Trials
• Cognitive Science

Background:

• Slowing cognitive decline is a key outcome in Alzheimer's disease (AD) clinical trials.
• Cognitive endpoints are often selected based on observational studies.
• Practice effects, or improvements from repeated testing, can significantly impact trial results, especially in cognitively unimpaired participants.

Purpose of the Study:

• To compare practice effects in a clinical trial setting versus observational studies for Alzheimer's disease prevention.
• To understand how practice effects may differ between trial and observational study designs.
• To inform the selection and modeling of cognitive endpoints in AD prevention trials.

Main Methods:

• Analysis of data from the DIAN-TU-001 clinical trial (TU) and the DIAN-Observational (OBS) study.
• Comparison of practice effects on key cognitive outcomes between asymptomatic mutation carriers in the TU and matched participants in the OBS study.
• Assessment of practice effects across the trial duration and consideration of alternate instrument forms.

Main Results:

• Asymptomatic mutation carriers in the TU demonstrated persistent practice effects throughout the trial.
• Practice-related improvements were significantly larger on certain cognitive tests in the TU compared to the OBS study.
• Observed differences suggest that practice effects may be underestimated in observational studies due to less frequent assessments and absence of drug expectancy effects.

Conclusions:

• Practice effects in Alzheimer's disease prevention trials may be underestimated by observational studies.
• Cognitive endpoint selection for AD prevention trials requires careful consideration of practice effects, potentially by using trial data with similar assessment frequencies.
• Strategies like using alternate instrument forms or directly modeling practice effects are crucial for accurate outcome interpretation in AD clinical trials.