INTRODUCTION: We aimed to determine whether cognitively unimpaired (CU) amyloid- beta-positive (Aβ+) individuals display decreased practice effects on serial neuropsychological testing. METHODS: We included 209 CU participants from three research centers, 157 Aβ- controls and 52 Aβ+ individuals. Participants underwent neuropsychological assessment at baseline and annually during a 2-year follow-up. We used linear mixed-effects models to analyze cognitive change over time between the two groups, including time from baseline, amyloid status, their interaction, age, sex, and years of education as fixed effects and the intercept and time as random effects. RESULTS: The Aβ+ group showed reduced practice effects in verbal learning (β = -1.14, SE = 0.40, p = 0.0046) and memory function (β = -0.56, SE = 0.19, p = 0.0035), as well as in language tasks (β = -0.59, SE = 0.19, p = 0.0027). DISCUSSION: Individuals with normal cognition who are in the Alzheimer's continuum show decreased practice effects over annual neuropsychological testing. Our findings could have implications for the design and interpretation of primary prevention trials. HIGHLIGHTS: This was a multicenter study on practice effects in asymptomatic Aβ+ individuals. We used LME models to analyze cognitive trajectories across multiple domains. Practice-effects reductions might be an indicator of subtle cognitive decline. Implications on clinical and research settings within the AD field are discussed.