Assessing tilavonemab efficacy in early Alzheimer's disease via longitudinal item response theory modeling

Zhou, Xiaoxiao

Zou, Haotian

Lutz, Michael W

Arbeev, Konstantin

Akushevich, Igor

Yashin, Anatoli

Welsh-Bohmer, Kathleen A

Luo, Sheng

2024-06-07T13:07:13Z

2024-06-07T13:07:13Z

2024-04

<jats:title>Abstract</jats:title><jats:sec><jats:title>INTRODUCTION</jats:title><jats:p>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by declines in cognitive and functional severities. This research utilized the Clinical Dementia Rating (CDR) to assess the influence of tilavonemab on these deteriorations.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>Longitudinal Item Response Theory (IRT) models were employed to analyze CDR domains in early‐stage AD patients. Both unidimensional and multidimensional models were contrasted to elucidate the trajectories of cognitive and functional severities.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>We observed significant temporal increases in both cognitive and functional severities, with the cognitive severity deteriorating at a quicker rate. Tilavonemab did not demonstrate a statistically significant effect on the progression in either severity. Furthermore, a significant positive association was identified between the baselines and progression rates of both severities.</jats:p></jats:sec><jats:sec><jats:title>DISCUSSION</jats:title><jats:p>While tilavonemab failed to mitigate impairment progression, our multidimensional IRT analysis illuminated the interconnected progression of cognitive and functional declines in AD, suggesting a comprehensive perspective on disease trajectories.</jats:p></jats:sec><jats:sec><jats:title>Highlights</jats:title><jats:p><jats:list> <jats:list-item><jats:p>Utilized longitudinal Item Response Theory (IRT) models to analyze the Clinical Dementia Rating (CDR) domains in early‐stage Alzheimer's disease (AD) patients, comparing unidimensional and multidimensional models.</jats:p></jats:list-item> <jats:list-item><jats:p>Observed significant temporal increases in both cognitive and functional severities, with cognitive severity deteriorating at a faster rate, while tilavonemab showed no statistically significant effect on either domain's progression.</jats:p></jats:list-item> <jats:list-item><jats:p>Found a significant positive association between the baseline severities and their progression rates, indicating interconnected progression patterns of cognitive and functional declines in AD.</jats:p></jats:list-item> <jats:list-item><jats:p>Introduced the application of multidimensional longitudinal IRT models to provide a comprehensive perspective on the trajectories of cognitive and functional severities in early AD, suggesting new avenues for future research including the inclusion of time‐dependent random effects and data‐driven IRT models.</jats:p></jats:list-item> </jats:list></jats:p></jats:sec>

2352-8737

2352-8737

https://hdl.handle.net/10161/31148

en

Wiley

Alzheimer's & Dementia: Translational Research & Clinical Interventions

10.1002/trc2.12471

https://creativecommons.org/licenses/by-nc/4.0

Assessing tilavonemab efficacy in early Alzheimer's disease via longitudinal item response theory modeling

Journal article

Zou, Haotian|0000-0002-3595-8716

Arbeev, Konstantin|0000-0002-4195-7832

Welsh-Bohmer, Kathleen A|0000-0003-1824-0179

Luo, Sheng|0000-0003-4214-5809

2

Duke

School of Medicine

Staff

Basic Science Departments

Biostatistics & Bioinformatics

Biostatistics & Bioinformatics, Division of Biostatistics

Published

10