Short-Term Practice Effects on Cognitive Tests Across the Late Life Cognitive Spectrum and How They Compare to Biomarkers of Alzheimer’s Disease

Article type: Research Article

Authors: Duff, Kevin^{a; b; *} | Hammers, Dustin B.^c | Koppelmans, Vincent^d | King, Jace B.^e | Hoffman, John M.^{b; e; f}

Affiliations: [a] Department of Neurology, Layton Aging and Alzheimer’s Disease Center, Oregon Health & Science University, Portland, OR, USA | [b] Department of Neurology, Center for Alzheimer’s Care, Imaging and Research, University of Utah, Salt Lake City, UT, USA | [c] Department of Neurology, Indiana University School of Medicine, Indiana, USA | [d] Department of Psychiatry, University of Utah, Salt Lake City, UT, USA | [e] Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT, USA | [f] University of Utah Center for Quantitative Cancer Imaging, Huntsman Cancer Institute, Salt Lake City, UT, USA

Correspondence: [*] Correspondence to: Kevin Duff, 3181 SW Sam Jackson Park Rd (Mail code: CR131), Portland, OR 97239, USA. Tel.: +1 503 494 6975; Fax: +1 503 494 7499; E-mail: [email protected].

Abstract: Background: Practice effects on cognitive testing in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) remain understudied, especially with how they compare to biomarkers of AD. Objective: The current study sought to add to this growing literature. Methods: Cognitively intact older adults (n = 68), those with amnestic MCI (n = 52), and those with mild AD (n = 45) completed a brief battery of cognitive tests at baseline and again after one week, and they also completed a baseline amyloid PET scan, a baseline MRI, and a baseline blood draw to obtain APOE ɛ4 status. Results: The intact participants showed significantly larger baseline cognitive scores and practice effects than the other two groups on overall composite measures. Those with MCI showed significantly larger baseline scores and practice effects than AD participants on the composite. For amyloid deposition, the intact participants had significantly less tracer uptake, whereas MCI and AD participants were comparable. For total hippocampal volumes, all three groups were significantly different in the expected direction (intact > MCI > AD). For APOE ɛ4, the intact had significantly fewer copies of ɛ4 than MCI and AD. The effect sizes of the baseline cognitive scores and practice effects were comparable, and they were significantly larger than effect sizes of biomarkers in 7 of the 9 comparisons. Conclusion:Baseline cognition and short-term practice effects appear to be sensitive markers in late life cognitive disorders, as they separated groups better than commonly-used biomarkers in AD. Further development of baseline cognition and short-term practice effects as tools for clinical diagnosis, prognostic indication, and enrichment of clinical trials seems warranted.

Keywords: Alzheimer’s disease, amyloid, biomarkers, brain imaging, effect sizes, mild cognitive impairment, neuropsychological testing, practice effects

DOI: 10.3233/JAD-231392

Journal: Journal of Alzheimer's Disease, vol. 99, no. 1, pp. 321-332, 2024