TY - JOUR
T1 - Application of Digital Cognitive Biomarkers for Alzheimer’s Disease
T2 - Identifying Cognitive Process Changes and Impending Cognitive Decline
AU - The Alzheimer's Disease Neuroimaging Initiative
AU - Bock, J. R.
AU - Hara, Junko
AU - Fortier, D.
AU - Lee, M. D.
AU - Petersen, R. C.
AU - Shankle, W. R.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2021/2
Y1 - 2021/2
N2 - Background: Recent Alzheimer’s disease (AD) trials have faced significant challenges to enroll pre-symptomatic or early stage AD subjects with biomarker positivity, minimal or no cognitive impairment, and likelihood to decline cognitively during a short trial period. Our previous study showed that digital cognitive biomarkers (DCB), generated by a hierarchical Bayesian cognitive process (HBCP) model, were able to distinguish groups of cognitively normal individuals with impending cognitive decline from those without. We generated DCBs using only baseline Auditory Verbal Learning Test’s wordlist memory (WLM) item response data from the Mayo Clinic Alzheimer’s Disease Patient Registry. Objectives: To replicate our previous findings, using baseline ADAS-Cog WLM item response data from the Alzheimer’s Disease Neuroimaging Initiative, and compare DCBs to traditional approaches for scoring word-list memory tests. DESIGN: Classified decliner subjects (n = 61) as those who developed amnestic MCI or AD dementia within 3 years of normal baseline assessment and non-decliner (n = 442) as those who did not. Measures: Evaluated the relative value of DCBs compared to traditional measures, using three analytic approaches to group differences: 1) logistic regression of summary scores per ADAS-Cog WLM task; 2) Bayesian modeling of summary scores; and 3) HBCP modeling to generate DCBs from item-level responses. RESULTS: The HBCP model produced posterior distributions of group differences, of which Bayes factor assessment identified three DCBs with notable group differences: Immediate Retrieval from Durable Storage, (BFds = 11.8, strong evidence); One-Shot Learning, (BFds = 4.5, moderate evidence); and Partial Learning (BFds = 2.9, weak evidence). In contrast, logistic regression of summary scores did not significantly discriminate between groups, and the Bayes factor assessment of modeled summary scores provided moderate evidence that the groups were equivalent (BFsd = 3.4, 3.1, 2.9, and 1.4, respectively). Conclusions: This study demonstrated DCBs’ ability to distinguish, at baseline, between impending cognitive decline and non-decline groups where individuals in both groups were classified as cognitively normal. This validated findings from our previous study, demonstrating DCBs’ advantages over traditional approaches. This study warrants further refinement of the HBCP DCBs to predict impending cognitive decline in individuals and other factors associated with AD, such as physical biomarker load.
AB - Background: Recent Alzheimer’s disease (AD) trials have faced significant challenges to enroll pre-symptomatic or early stage AD subjects with biomarker positivity, minimal or no cognitive impairment, and likelihood to decline cognitively during a short trial period. Our previous study showed that digital cognitive biomarkers (DCB), generated by a hierarchical Bayesian cognitive process (HBCP) model, were able to distinguish groups of cognitively normal individuals with impending cognitive decline from those without. We generated DCBs using only baseline Auditory Verbal Learning Test’s wordlist memory (WLM) item response data from the Mayo Clinic Alzheimer’s Disease Patient Registry. Objectives: To replicate our previous findings, using baseline ADAS-Cog WLM item response data from the Alzheimer’s Disease Neuroimaging Initiative, and compare DCBs to traditional approaches for scoring word-list memory tests. DESIGN: Classified decliner subjects (n = 61) as those who developed amnestic MCI or AD dementia within 3 years of normal baseline assessment and non-decliner (n = 442) as those who did not. Measures: Evaluated the relative value of DCBs compared to traditional measures, using three analytic approaches to group differences: 1) logistic regression of summary scores per ADAS-Cog WLM task; 2) Bayesian modeling of summary scores; and 3) HBCP modeling to generate DCBs from item-level responses. RESULTS: The HBCP model produced posterior distributions of group differences, of which Bayes factor assessment identified three DCBs with notable group differences: Immediate Retrieval from Durable Storage, (BFds = 11.8, strong evidence); One-Shot Learning, (BFds = 4.5, moderate evidence); and Partial Learning (BFds = 2.9, weak evidence). In contrast, logistic regression of summary scores did not significantly discriminate between groups, and the Bayes factor assessment of modeled summary scores provided moderate evidence that the groups were equivalent (BFsd = 3.4, 3.1, 2.9, and 1.4, respectively). Conclusions: This study demonstrated DCBs’ ability to distinguish, at baseline, between impending cognitive decline and non-decline groups where individuals in both groups were classified as cognitively normal. This validated findings from our previous study, demonstrating DCBs’ advantages over traditional approaches. This study warrants further refinement of the HBCP DCBs to predict impending cognitive decline in individuals and other factors associated with AD, such as physical biomarker load.
KW - Bayesian modeling
KW - Wordlist memory test
KW - clinical trial
KW - digital cognitive biomarkers
KW - preclinical Alzheimer’s disease
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UR - http://www.scopus.com/inward/citedby.url?scp=85095953792&partnerID=8YFLogxK
U2 - 10.14283/jpad.2020.63
DO - 10.14283/jpad.2020.63
M3 - Article
C2 - 33569557
AN - SCOPUS:85095953792
SN - 2426-0266
VL - 8
SP - 123
EP - 126
JO - The journal of prevention of Alzheimer's disease
JF - The journal of prevention of Alzheimer's disease
IS - 2
ER -