Monthly At-Home Computerized Cognitive Testing to Detect Diminished Practice Effects in Preclinical Alzheimer's Disease

Frontiers in Aging Neuroscience

Aging Neuroscience

Paul Maruff¹  Craig E. Stark²  Michael A. Yassa²  Michael J. Properzi³  Roos J. Jutten³  Rebecca E. Amariglio⁴  Reisa A. Sperling⁴  Kathryn V. Papp⁴  Dorene M. Rentz⁴  Keith A. Johnson⁵  Rachel F. Buckley⁶  Jessie F. Fu⁷  Danielle V. Mayblyum⁷ 

[1] CogState Ltd., Melbourne, VIC, Australia;The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia;Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA, United States;Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States;Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States;Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States;Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States;Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States;Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States;Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, VIC, Australia;Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States;

关键词: computerized testing;    remote assessment;    practice effects;    digital biomarkers;    preclinical AD;   

DOI  :  10.3389/fnagi.2021.800126

 received in 2021-10-22, accepted in 2021-12-14,  发布年份 2022

来源: Frontiers

【 摘 要 】

Introduction: We investigated whether monthly assessments of a computerized cognitive composite (C3) could aid in the detection of differences in practice effects (PE) in clinically unimpaired (CU) older adults, and whether diminished PE were associated with Alzheimer's disease (AD) biomarkers and annual cognitive decline.Materials and Methods: N = 114 CU participants (age 77.6 ± 5.0, 61% female, MMSE 29 ± 1.2) from the Harvard Aging Brain Study completed the self-administered C3 monthly, at-home, on an iPad for one year. At baseline, participants underwent in-clinic Preclinical Alzheimer's Cognitive Composite-5 (PACC5) testing, and a subsample (n = 72, age = 77.8 ± 4.9, 59% female, MMSE 29 ± 1.3) had 1-year follow-up in-clinic PACC5 testing available. Participants had undergone PIB-PET imaging (0.99 ± 1.6 years before at-home baseline) and Flortaucipir PET imaging (n = 105, 0.62 ± 1.1 years before at-home baseline). Linear mixed models were used to investigate change over months on the C3 adjusting for age, sex, and years of education, and to extract individual covariate-adjusted slopes over the first 3 months. We investigated the association of 3-month C3 slopes with global amyloid burden and tau deposition in eight predefined regions of interest, and conducted Receiver Operating Characteristic analyses to examine how accurately 3-month C3 slopes could identify individuals that showed >0.10 SD annual decline on the PACC-5.Results: Overall, individuals improved on all C3 measures over 12 months (β = 0.23, 95% CI [0.21–0.25], p < 0.001), but improvement over the first 3 months was greatest (β = 0.68, 95% CI [0.59–0.77], p < 0.001), suggesting stronger PE over initial repeated exposures. However, lower PE over 3 months were associated with more global amyloid burden (r = −0.20, 95% CI [−0.38 – −0.01], p = 0.049) and tau deposition in the entorhinal cortex (r = −0.38, 95% CI [−0.54 – −0.19], p < 0.001) and inferior-temporal lobe (r = −0.23, 95% CI [−0.41 – −0.02], p = 0.03). 3-month C3 slopes exhibited good discriminative ability to identify PACC-5 decliners (AUC 0.91, 95% CI [0.84–0.98]), which was better than baseline C3 (p < 0.001) and baseline PACC-5 scores (p = 0.02).Conclusion: While PE are commonly observed among CU adults, diminished PE over monthly cognitive testing are associated with greater AD biomarker burden and cognitive decline. Our findings imply that unsupervised computerized testing using monthly retest paradigms can provide rapid detection of diminished PE indicative of future cognitive decline in preclinical AD.

【 授权许可】

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Copyright © 2022 Jutten, Rentz, Fu, Mayblyum, Amariglio, Buckley, Properzi, Maruff, Stark, Yassa, Johnson, Sperling and Papp.