Medical Scientist-Programm 2022

Thema: "To assess risk profiles and protective factors in the development of neurodegenerative disease in patients with chronic insomnia, and to understand their underlying pathomechanisms"

Zusammenfassung:
Chronic Primary Insomnia (CPI) affects 6-10% of the adult population and predisposes patients to a 1.5 to 1.55-fold higher risk of developing Alzheimer’s Dementia (AD) in later life, making early identification of at-risk patients critical. However, this is difficult, as insomnia is a heterogeneous clinical symptom culminating in different insomnia phenotypes. This project therefore aims to assess whether different insomnia phenotypes are associated with different neurodegenerative risk profiles. Furthermore, the exact pathomechanisms underlying this neurodegenerative process are not clear. On the one hand, hyperarousal, which plays a prominent role in the aetiology of insomnia, leads to over activity of the stress axes, namely sympathetic over-activity and glucocorticoid excess, thereby accelerating neuronal loss and cerebral deposition of amyloid β. On the other hand, loss of slow-wave sleep, another hallmark of insomnia, downregulates glymphatic system activity in animal models, which lowers extracellular drainage capacity, thus leading to a build-up of amyloid β. Thus, the second objective is to uncover which pathomechanism underlies the neurodegenerative processes seen in CPI patients. Finally, some aspects of healthy sleep revealed by intact sleep microarchitecture, such as spindle density, cyclic alternating patterns, and amount of Rapid Eye Movement (REM) sleep, play a protective role in cognitive decline in healthy, older adults. The third aim of this study is thus to explore whether intact sleep microarchitecture also plays a protective role in cognitive decline in CPI.