Publications by authors named "Jeroen F Uleman"

Sleep plays an essential role in physiology, allowing the brain and body to restore itself. Despite its critical role, our understanding of the underlying processes in the sleeping human brain is still limited. Sleep comprises several distinct stages with varying depths and temporal compositions.

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Introduction: Systemic inflammation and endothelial dysfunction are potentially modifiable factors implicated in Alzheimer's disease (AD), which offer potential therapeutic targets to slow disease progression.

Methods: We investigated the relationship between baseline circulating levels of inflammatory (TNF-α, IL-1ß) and endothelial cell markers (VCAM-1, ICAM-1, E-selectin) and 18-month cognitive decline (ADAS-cog12) in 266 mild-to-moderate AD patients from the NILVAD study. We employed individual growth models to examine associations, potential mediation, and interaction effects while adjusting for confounders.

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This paper presents causal loop diagrams (CLDs) as tools for studying complex public health problems like health inequality. These problems often involve feedback loops-a characteristic of complex systems not fully integrated into mainstream epidemiology. CLDs are conceptual models that visualize connections between system variables.

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Despite extensive research efforts to mechanistically understand late-onset Alzheimer's disease (LOAD) and other complex mental health disorders, curative treatments remain elusive. We emphasize the multiscale multicausality inherent to LOAD, highlighting the interplay between interconnected pathophysiological processes and risk factors. Systems thinking methods, such as causal loop diagrams and systems dynamic models, offer powerful means to capture and study this complexity.

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Numerous clinical trials based on a single-cause paradigm have not resulted in efficacious treatments for Alzheimer's disease (AD). Recently, prevention trials that simultaneously intervened on multiple risk factors have shown mixed results, suggesting that careful design is necessary. Moreover, intensive pilot precision medicine (PM) trial results have been promising but may not generalize to a broader population.

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Orthostatic hypotension (OH) is an established and common cardiovascular risk factor for falls. An in-depth understanding of the various interacting pathophysiological pathways contributing to OH-related falls is essential to guide improvements in diagnostic and treatment opportunities. We applied systems thinking to multidisciplinary map out causal mechanisms and risk factors.

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Dysregulated inflammation underlies various diseases. Specialized pro-resolving mediators (SPMs) like Resolvin D1 (RvD1) have been shown to resolve inflammation and halt disease progression. Macrophages, key immune cells that drive inflammation, respond to the presence of RvD1 by polarizing to an anti-inflammatory type (M).

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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 and 148 causal links calibrated with empirical data from two studies.

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Background: Recent global meta-analyses show that 40% of dementia cases can be attributed to twelve modifiable risk factors.

Objective: To investigate how health promotion strategies may differ in specific populations, this study estimated population attributable fractions (PAFs) of these risk factors for dementia in cognitively normal (CN) individuals and individuals with mild cognitive impairment (MCI) in United States and Greek cohorts.

Methods: We re-analyzed data from the National Alzheimer's Coordinating Centre (NACC, n = 16,147, mean age 75.

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To face crises like the COVID-19 pandemic, resources such as personal protection equipment (PPE) are needed to reduce the infection rate and protect those in close contact with patients. The increasing demand for those products can, together with pandemic-related disruptions in the global supply chain, induce major local resource scarcities. During the first phase of the COVID-19 pandemic, we witnessed a reflex of 'our people first' in many regions.

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Complexity science and systems thinking are increasingly recognized as relevant paradigms for studying systems where biology, psychology, and socioenvironmental factors interact. The application of systems thinking, however, often stops at developing a conceptual model that visualizes the mapping of causal links within a system, e.g.

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Alzheimer's disease (AD) is a complex, multicausal disorder involving several spatiotemporal scales and scientific domains. While many studies focus on specific parts of this system, the complexity of AD is rarely studied as a whole. In this work, we apply systems thinking to map out known causal mechanisms and risk factors ranging from intracellular to psychosocial scales in sporadic AD.

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