Using practice effects for targeted trials or sub-group analysis in Alzheimer's disease: How practice effects predict...

Area of Science:

• Neuroscience
• Clinical Trials
• Cognitive Science

Background:

• Alzheimer disease (AD) and mild cognitive impairment (MCI) are progressive neurodegenerative conditions.
• Clinical trials in AD and MCI often rely on cognitive assessments to measure disease progression and treatment efficacy.
• Practice effects, improvements in cognitive test scores due to repeated testing, can influence the interpretation of trial results.

Purpose of the Study:

• To determine the prevalence of practice effects in individuals with AD or MCI.
• To assess the impact of practice effects on cognitive decline.
• To evaluate how practice effects influence clinical trial design and sample size calculations.

Main Methods:

• Utilized a meta-database of 18 studies, including ADCS and ADNI participants.
• Defined practice effects by improvement in the first two ADAS-Cog11 scores.
• Compared cognitive progression (ADAS-Cog11, CDR SB) between participants with and without practice effects.
• Investigated the impact on sample size estimation.

Main Results:

• Practice effects were observed in 39.0% of AD participants and 53.3% of MCI participants.
• Participants without practice effects showed greater cognitive decline over 2 years compared to those with practice effects.
• Sample size estimations varied by over 35% depending on the presence of practice effects.

Conclusions:

• Practice effects are prevalent and significantly impact cognitive progression measures in AD and MCI.
• These effects must be considered in the planning of future AD and MCI clinical trials.
• Strategies such as targeted trials or stratification analysis based on practice effects may improve trial power and accuracy.