Donders Institute for Brain, Cognition and Behaviour
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Thesis defense Jeroen Uleman (Donders Series 626)

7 November 2023

Promotors: prof. dr. M.G.M. Olde Rikkert and prof. dr. ir. A.G. Hoekstra
Co-promotors: dr. R.J.F. Melis and dr. R. Quax

Disentangling Multicausality: A System Dynamics Approach to Alzheimer’s Disease

Conventional single-cause paradigms in Alzheimer's disease (AD) research have yielded limited success. Instead, the multiscale multicausality of AD is increasingly recognized and addressed in this thesis through a systems thinking approach. First, a causal loop diagram (CLD) was constructed via participatory group model building, engaging 15 interdisciplinary experts and a literature review. The CLD uncovered reinforcing feedback loops among various interconnected factors in AD. To transition from qualitative to quantitative analysis, a method was then developed for converting CLDs into system dynamics models. Applying this approach to the CLD identified modifiable risk factors like sleep quality and depressive symptoms as potential intervention points. An extension of the model was then used to explore multifactorial precision medicine interventions, finding a potential benefit of personalized approaches in AD prevention. This thesis highlights the potential of systems thinking and computational modeling in understanding AD's complexity and pinpointing potentially effective interventions.