ArticleJournal of pharmacokinetics and pharmacodynamics2014
An updated Alzheimer's disease progression model: incorporating non-linearity, beta regression, and a third-level random effect in NONMEM.
Article in Journal of pharmacokinetics and pharmacodynamics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- An updated overview of recent and ongoing deep brain stimulation (DBS) trials in patients with dementia: a systematic review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Pooled it
- Employing zero-inflated beta distribution in an exposure-response analysis of TYK2/JAK1 inhibitor brepocitinib in patients with plaque psoriasis.Journal of pharmacokinetics and pharmacodynamics · 2024Trial
- Characterization of exposure-Clinical Dementia Rating-Sum of Boxes relationship in subjects with early Alzheimer's disease from the aducanumab Phase 3 trials.Journal of pharmacokinetics and pharmacodynamics · 2023Trial
- Association of Amyloid Reduction After Donanemab Treatment With Tau Pathology and Clinical Outcomes: The TRAILBLAZER-ALZ Randomized Clinical Trial.JAMA neurology · 2022Trial
- Predicting the probability of successful efficacy of a dissociated agonist of the glucocorticoid receptor from dose-response analysis.Journal of pharmacokinetics and pharmacodynamics · 2016Trial
- The Potential of Disease Progression Modeling to Advance Clinical Development and Decision Making.Clinical pharmacology and therapeutics · 2025Review
- Bioavailability as Proof to Authorize the Clinical Testing of Neurodegenerative Drugs-Protocols and Advice for the FDA to Meet the ALS Act Vision.International journal of molecular sciences · 2024Review
- Onset of Alzheimer disease in apolipoprotein ɛ4 carriers is earlier in butyrylcholinesterase K variant carriers.BMC neurology · 2024Article
- Modeling Alzheimer's disease progression utilizing clinical trial and ADNI data to predict longitudinal trajectory of CDR-SB.CPT: pharmacometrics & systems pharmacology · 2023Observational
- Role of Disease Progression Models in Drug Development.Pharmaceutical research · 2022Review
- A large pragmatic trial is the right solution for testing anti-amyloid therapies for Alzheimer's disease.Journal of the American Geriatrics Society · 2022Article
- Influence of Subject-Specific Effects in Longitudinal Modelling of Cognitive Decline in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2022Article
- An Item Response Theory-Informed Strategy to Model Total Score Data from Composite Scales.The AAPS journal · 2021Article
- Comparison of Precision and Accuracy of Five Methods to Analyse Total Score Data.The AAPS journal · 2020Article
- Differential response to cytotoxic therapy explains treatment dynamics of acute myeloid leukaemia patients: insights from a mathematical modelling approach.Journal of the Royal Society, Interface · 2020Article
- Development of a Disease Progression Model for Leucine-Rich Repeat Kinase 2 in Parkinson's Disease to Inform Clinical Trial Designs.Clinical pharmacology and therapeutics · 2020Article
- Towards regulatory endorsement of drug development tools to promote the application of model-informed drug development in Duchenne muscular dystrophy.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- Misidentification Subtype of Alzheimer's Disease Psychosis Predicts a Faster Cognitive Decline.CPT: pharmacometrics & systems pharmacology · 2019Article
- Opening the debate on deep brain stimulation for Alzheimer disease - a critical evaluation of rationale, shortcomings, and ethical justification.BMC medical ethics · 2018Article
- Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis.Clinical and translational science · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our objective was to expand our understanding of the predictors of Alzheimer's disease (AD) progression to help design a clinical trial on a novel AD medication. We utilized the Coalition Against Major Diseases AD dataset consisting of control-arm data (both placebo and stable background AD medication) from 15 randomized double-blind clinical trials in mild-to-moderate AD patients (4,495 patients; July 2013). Our ADAS-cog longitudinal model incorporates a beta-regression with between-study, -subject, and -residual variability in NONMEM; it suggests that faster AD progression is associated with younger age and higher number of apolipoprotein E type 4 alleles (APOE*4), after accounting for baseline disease severity. APOE*4, in particular, seems to be implicated in the AD pathogenesis. In addition, patients who are already on stable background AD medications appear to have a faster progression relative to those who are not receiving AD medication. The current knowledge does not support a causality relationship between use of background AD medications and higher rate of disease progression, and the correlation is potentially due to confounding covariates. Although causality has not necessarily been demonstrated, this model can inform inclusion criteria and stratification, sample size, and trial duration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.