Cognitive and Functional Change Over Time in Cognitively Healthy Individuals According to Alzheimer Disease Biomarker-Defined Subgroups
Mark A. Dubbelman, Heleen M.A. Hendriksen, John Harrison, Everard G.B. Vijverberg, Niels D. Prins, Lior A. Kroeze, Lois Ottenhoff, Mardou M.S.S.A. Van Leeuwenstijn, Inge M.W. Verberk, Charlotte E. Teunissen, Elsmarieke van de Giessen, Argonde C. van Harten, Wiesje M. van der Flier, Sietske A.M. Sikkes
Abstract
BACKGROUND AND OBJECTIVES: It is unclear to what extent cognitive outcome measures are sensitive to capture decline in Alzheimer disease (AD) prevention trials. We aimed to analyze the sensitivity to changes over time of a range of neuropsychological tests in several cognitively unimpaired, biomarker-defined patient groups. METHODS: ) were reported as outcome of interest. We analyzed change over time with full follow-up, as well as with follow-up limited to 1.5 and 3 years. RESULTS: range -0.12 to -0.62) in all groups, except plasma p-tau-positive individuals. When limiting original follow-up duration, many effects disappeared or even flipped direction. DISCUSSION: In conclusion, functional, composite, and neuropsychological outcome measures across all cognitive domains detect changes over time in various biomarker-defined groups, with changes being most evident among individuals with more AD pathology. AD prevention trials should use sufficiently long follow-up duration and/or more sensitive outcome measures to optimally capture subtle cognitive changes over time.