Statistical Model of Dynamic Markers of the Alzheimer’s Pathological Cascade

Abstract Objectives Alzheimer’s disease (AD) is a progressive disease reflected in markers across assessment modalities, including neuroimaging, cognitive testing, and evaluation of adaptive function. Identifying a single continuum of decline across assessment modalities in a single sample is statis...

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Bibliographic Details
Published in:The journals of gerontology. Series B, Psychological sciences and social sciences Psychological sciences and social sciences, 2018-08, Vol.73 (6), p.964-973
Main Authors: Balsis, Steve, Geraci, Lisa, Benge, Jared, Lowe, Deborah A, Choudhury, Tabina K, Tirso, Robert, Doody, Rachelle S
Format: Article
Language:English
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The Journal of Gerontology: Psychological Sciences
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Summary:Abstract Objectives Alzheimer’s disease (AD) is a progressive disease reflected in markers across assessment modalities, including neuroimaging, cognitive testing, and evaluation of adaptive function. Identifying a single continuum of decline across assessment modalities in a single sample is statistically challenging because of the multivariate nature of the data. To address this challenge, we implemented advanced statistical analyses designed specifically to model complex data across a single continuum. Method We analyzed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI; N = 1,056), focusing on indicators from the assessments of magnetic resonance imaging (MRI) volume, fluorodeoxyglucose positron emission tomography (FDG-PET) metabolic activity, cognitive performance, and adaptive function. Item response theory was used to identify the continuum of decline. Then, through a process of statistical scaling, indicators across all modalities were linked to that continuum and analyzed. Results Findings revealed that measures of MRI volume, FDG-PET metabolic activity, and adaptive function added measurement precision beyond that provided by cognitive measures, particularly in the relatively mild range of disease severity. More specifically, MRI volume, and FDG-PET metabolic activity become compromised in the very mild range of severity, followed by cognitive performance and finally adaptive function. Conclusion Our statistically derived models of the AD pathological cascade are consistent with existing theoretical models.
ISSN:1079-5014
1758-5368
DOI:10.1093/geronb/gbx156