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Multicenter Study
. 2025 Mar;21(3):e70016.
doi: 10.1002/alz.70016.

Decreased practice effects in cognitively unimpaired amyloid betapositive individuals: a multicenter, longitudinal, cohort study

Adrià Tort-Merino  1   2 , Agnès Pérez-Millan  1   2   3 , Neus Falgàs  1   2 , Sergi Borrego-Écija  1   2 , Diana Esteller  1 , Bea Bosch  1   2 , Magdalena Castellví  1 , Jordi Juncà-Parella  1   2 , Andrea Del Val-Guardiola  1 , Guadalupe Fernández-Villullas  1   2 , Anna Antonell  1   2 , María Belén Sanchez-Saudinós  4 , Sara Rubio-Guerra  4 , Nuole Zhu  4 , María García-Martínez  5 , Ana Pozueta  5 , Ainara Estanga  6 , Mirian Ecay-Torres  6 , Carolina López de Luis  6 , Mikel Tainta  6 , Miren Altuna  6 , Eloy Rodríguez-Rodríguez  2   5   7 , Pascual Sánchez-Juan  8 , Pablo Martínez-Lage  6 , Alberto Lleó  4 , Juan Fortea  4 , Ignacio Illán-Gala  4 , Mircea Balasa  1   2 , Albert Lladó  1   2 , Lorena Rami  1   2 , Raquel Sánchez-Valle  1   2
Affiliations
Multicenter Study

Decreased practice effects in cognitively unimpaired amyloid betapositive individuals: a multicenter, longitudinal, cohort study

Adrià Tort-Merino et al. Alzheimers Dement. 2025 Mar.

Abstract

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.

Keywords: Alzheimer's disease; cognition; early detection; neuropsychological assessment; practice effects; subtle cognitive decline.

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Conflict of interest statement

The authors declare no conflicts of interest in connection with this paper. Author disclosures are available in the Supporting Information.

Figures

FIGURE 1
FIGURE 1
Sample composition flowchart.
FIGURE 2
FIGURE 2
Baseline neuropsychological performance among the study groups. Data are presented in z‐scores for visualization purposes to standardize performance across all tests and present them on a common scale (error bars represent SD). Trail Making Test scores are shown inverted. CERAD, Consortium to Establish a Registry for Alzheimer's Disease; FCSRT, Free and Cued Selective Reminding Test; VOSP, Visual Object and Space Perception Battery.
FIGURE 3
FIGURE 3
Linear mixed‐effects model plots at individual and population levels. Linear mixed‐effects model plot showing predicted population tendency (thick line) and predicted individual trajectories (thin line) according to amyloid status. Individual lines are lighter/darker depending on number of observations with the same results. FCSRT, Free and Cued Selective Reminding Test.
FIGURE 4
FIGURE 4
Linear mixed‐effects models on effect of phosphorylated tau. Linear mixed‐effects model plot showing predicted population tendency (thick line) and predicted individual trajectories (thin line) according to amyloid status. Individual lines are lighter/darker depending on number of observations with the same results. FCSRT, Free and Cued Selective Reminding Test.
See this image and copyright information in PMC

References

    1. Dodge HH, Wang CN, Chang CCH, Ganguli M. Terminal decline and practice effects in older adults without dementia: the MoVIES project. Neurology. 2011;77(8):722‐730. doi:10.1212/WNL.0b013e31822b0068 - DOI - PMC - PubMed
    1. Duff K, Beglinger LJ, Moser DJ, Paulsen JS, Schultz SK, Arndt S. Predicting cognitive change in older adults: the relative contribution of practice effects. Arch Clin Neuropsychol. 2010;25(2):81‐88. doi:10.1093/arclin/acp105 - DOI - PMC - PubMed
    1. Wilson RS, Beckett LA, Bennett DA, Albert MS, Evans DA. Change in cognitive function in older persons from a community population: relation to age and Alzheimer disease. Arch Neurol. 1999;56(10):1274. doi:10.1001/archneur.56.10.1274 - DOI - PubMed
    1. Wilson RS, Li Y, Bienias JL, Bennett DA. Cognitive decline in old age: separating retest effects from the effects of growing older. Psychol Aging. 2006;21(4):774‐789. doi:10.1037/0882-7974.21.4.774 - DOI - PubMed
    1. Cooper DB, Lacritz LH, Weiner MF, Rosenberg RN, Cullum CM. Category fluency in mild cognitive impairment: reduced effect of practice in test‐retest conditions. Alzheimer Dis Assoc Disord. 2004;18(3):120. doi:10.1097/01.wad.0000127442.15689.92 - DOI - PubMed

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