Simulating the multicausality of Alzheimer's disease with system dynamics

• DOI: 10.1002/alz.12923
• Publication Date: 2023-02-16T12:00:20Z
• Authors: Jeroen F. Uleman; René J. F. Melis; Eva Ntanasi; Nikolaos Scarmeas; Alfons G. Hoekstra; Rick Quax; Marcel G. M. Olde...
• Keywords: 03 medical and health sciences; 0302 clinical medicine; Alzheimer Disease; Risk Factors; Radboudumc 1: Alzheimer`s disease DCMN: Donders Center for Medical Neuroscience; 610; Radboudumc 18: Healthcare improvement science Geriatrics; Radboud University Medical Center; Humans; Cognitive Dysfunction

Abstract Introduction In Alzheimer's disease (AD), cognitive decline is driven by various interlinking causal factors. Systems thinking could help elucidate this multicausality and identify opportune intervention targets. Methods We developed a system dynamics model (SDM) of sporadic AD with 33 factors 148 links calibrated empirical data from two studies. tested the SDM's validity ranking outcomes on 15 modifiable risk to sets 44 9 validation statements based meta‐analyses observational randomized controlled trials, respectively. Results The SDM answered 77% 78% correctly. Sleep quality depressive symptoms yielded largest effects which they were connected through strong reinforcing feedback loops, including via phosphorylated tau burden. Discussion SDMs can be constructed validated simulate interventions gain insight into relative contribution mechanistic pathways.