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Cognitive Trajectories in Preclinical and Prodromal Alzheimer's Disease Related to Amyloid Status and Brain Atrophy: A Bayesian Approach.

Journal of Alzheimer's disease reports

Authors: Stefan J Teipel, Martin Dyrba, Fedor Levin, Slawek Altenstein, Moritz Berger, Aline Beyle, Frederic Brosseron, Katharina Buerger, Lena Burow, Laura Dobisch, Michael Ewers, Klaus Fliessbach, Ingo Frommann, Wenzel Glanz, Doreen Goerss, Daria Gref, Niels Hansen, Michael T Heneka, Enise I Incesoy, Daniel Janowitz, Deniz Keles, Ingo Kilimann, Christoph Laske, Andrea Lohse, Matthias H Munk, Robert Perneczky, Oliver Peters, Lukas Preis, Josef Priller, Ayda Rostamzadeh, Nina Roy, Matthias Schmid, Anja Schneider, Annika Spottke, Eike Jakob Spruth, Jens Wiltfang, Emrah Düzel, Frank Jessen, Luca Kleineidam, Michael Wagner

BACKGROUND: Cognitive decline is a key outcome of clinical studies in Alzheimer's disease (AD).

OBJECTIVE: To determine effects of global amyloid load as well as hippocampus and basal forebrain volumes on longitudinal rates and practice effects from repeated testing of domain specific cognitive change in the AD spectrum, considering non-linear effects and heterogeneity across cohorts.

METHODS: We included 1,514 cases from three cohorts, ADNI, AIBL, and DELCODE, spanning the range from cognitively normal people to people with subjective cognitive decline and mild cognitive impairment (MCI). We used generalized Bayesian mixed effects analysis of linear and polynomial models of amyloid and volume effects in time. Robustness of effects across cohorts was determined using Bayesian random effects meta-analysis.

RESULTS: We found a consistent effect of amyloid and hippocampus volume, but not of basal forebrain volume, on rates of memory change across the three cohorts in the meta-analysis. Effects for amyloid and volumetric markers on executive function were more heterogeneous. We found practice effects in memory and executive performance in amyloid negative cognitively normal controls and MCI cases, but only to a smaller degree in amyloid positive controls and not at all in amyloid positive MCI cases.

CONCLUSIONS: We found heterogeneity between cohorts, particularly in effects on executive functions. Initial increases in cognitive performance in amyloid negative, but not in amyloid positive MCI cases and controls may reflect practice effects from repeated testing that are lost with higher levels of cerebral amyloid.

© 2023 – The authors. Published by IOS Press.

PMID: 37849637

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