Assessing tilavonemab efficacy in early Alzheimer's disease via longitudinal item response theory modeling
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2024-04
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<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>
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Zhou, Xiaoxiao, Haotian Zou, Michael W Lutz, Konstantin Arbeev, Igor Akushevich, Anatoli Yashin, Kathleen A Welsh-Bohmer, Sheng Luo, et al. (2024). Assessing tilavonemab efficacy in early Alzheimer's disease via longitudinal item response theory modeling. Alzheimer's & Dementia: Translational Research & Clinical Interventions, 10(2). 10.1002/trc2.12471 Retrieved from https://hdl.handle.net/10161/31148.
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Scholars@Duke
Haotian Zou
Konstantin Arbeev
Konstantin G. Arbeev received the M.S. degree in Applied Mathematics from Moscow State University (branch in Ulyanovsk, Russia) in 1995 and the Ph.D. degree in Mathematics and Physics (specialization in Theoretical Foundations of Mathematical Modeling, Numerical Methods and Programming) from Ulyanovsk State University (Russia) in 1999. He was a post-doctoral fellow in Max Planck Institute for Demographic Research in Rostock (Germany) before moving to Duke University in 2004 to work as a Research Scientist and a Senior Research Scientist in the Department of Sociology and the Social Science Research Institute (SSRI). He is currently an Associate Research Professor in SSRI. Dr. Arbeev's major research interests are related to three interconnected fields of biodemography, biostatistics and genetic epidemiology as pertains to research on aging. The focus of his research is on discovering genetic and non-genetic factors that can affect the process of aging and determine longevity and healthy lifespan. He is interested in both methodological advances in this research area as well as their practical applications to analyses of large-scale longitudinal studies with phenotypic, genetic and, recently, genomic information. Dr. Arbeev authored and co-authored more than 150 peer-reviewed publications in these areas.
Anatoli I. Yashin
Kathleen Anne Welsh-Bohmer
Dr. Kathleen Welsh-Bohmer is a Professor of Psychiatry with a secondary appointment in the Department of Neurology.
Clinically trained as a neuropsychologist, Dr. Welsh-Bohmer's research activities have been focused around developing effective prevention and treatment strategies to delay the onset of cognitive disorders occurring in later life. From 2006 through 2018 she directed the Joseph and Kathleen Bryan Alzheimer’s Center in the Department of Neurology. She also oversaw the neuropsychology scientific operations of a ground-breaking Phase III global clinical trial to delay the onset of early clinical symptoms of Alzheimer’s disease entitled the “TOMMORROW” study (Takeda Pharmaceutical Company funded) which concluded in 2018.
Currently, she directs the Alzheimer's disease therapeutic area within the Duke Clinical Research Institute and she collaborates actively with VeraSci, a Durham based company, to develop reliable digital cognitive and functional assessment tools of early Alzheimer's disease and related dementias. The methods her team is developing are informed by advances in neuroscience and technology and fill an information void in early pre-clinical Alzheimer's disease. Her work has implications for clinical practice and for the acceleration of global clinical trials aimed at the prevention of Alzheimer’s disease and related dementias.
Sheng Luo
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