Postoperative Cognitive Dysfunction (POCD)
INTERACTION OF AGE-RELATED BRAIN CHANGES, ANESTHETICS AND INFLAMMATION
Brain Protection
Postoperative Cognitive Dysfunction (POCD) describes a potential decline of cognitive performance after surgery under anesthesia, which can affect episodic memory as well as learning and concentration performance. Postoperative cognitive dysfunction is a serious health problem in the elderly. Based on demographic changes, as a result of which the population structure has changed significantly in recent decades and will continue to change in the future, age-related surgeries, such as knee or hip replacements or procedures for circulatory disorders, are steadily increasing and account for a disproportionate share of surgical procedures requiring anesthesia. In addition, because of their age, this group of patients is characterized by numerous changes in the brain (e.g., elevation of inflammatory markers that could adversely affect cognition) that may contribute to an increased risk of POCD. However, the current state of science on POCD is relatively limited, and further research is needed to improve understanding of the causes, risk factors, diagnosis, and treatment of POCD. Thus, new insights that enable personalized prediction, prevention, and treatment development are urgently needed. Here, we hypothesize that the stress response pathway plays a mechanistic role in POCD, either as a) an independent mechanism or through b) interaction with preexisting amyloid pathology that triggers a surgically induced imbalance between excitation and inhibition (hyperexcitability) with resulting dysfunction of cognitive circuitry. In this context, the non-invasive method of transcutaneous vagus nerve stimulation (taVNS) can help to reduce the elevated inflammatory markers. The goal is to better understand the interplay between brain function, subclinical AD pathology, and their interaction with anesthetics and to develop appropriate interventions.
What we want to achieve
Our Project Goals
Influence of transcutaneous auricular vagus nerve stimulation (taVNS) on neuroinflammation in POCD
Post-operative cognitive dysfunction (POCD) is accompanied by neuroinflammation, e.g. activation of the inflammatory markers TNFα/NF-κB IL-1ß, IL-6, which can lead to impairment of the blood-brain barrier and thus to migration of macrophages into the hippocampus (HC) and subsequently to memory impairment. These inflammatory reactions can be attenuated via the vagus nerve (VN), e.g., via the cholinergic anti-inflammatory pathway (CAP, vagal efferents). In animal studies a reduction of inflammation markers, such as TNFa, IL-ß, IL6, could already be brought about due to invasive vagus nerve stimulation (iVNS). Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive method for stimulating the VN. Two small electrodes are applied mainly in the area of the inner ear called cymba conchae (CC), as this area has nerve fibre connections to the VN exclusively and projects to the noradrenergic system of the locus coeruleus via the brainstem. We expect that stimulation will increase noradrenergic levels and will have an anti-inflammatory effect by inhibiting microglial activation and suppressing the production of pro-inflammatory mediators.
Identification of risk factors for POCD
An important risk factor for POCD is the presence of cognitive impairment prior to surgery, which can range from mild cognitive impairment (MCI) to dementia. However, cognitive deficits such as MCI are difficult to characterise in routine care due to a lack of appropriate cognitive testing procedures. The diagnosis of POCD is based on the results of analogue neuropsychological testing procedures collected before surgery, as well as at different time points after surgery.
The aim of our project is to use digital assessments with high-frequency data collection to detect variations in cognitive performance before and after surgery in order to identify sensitive time windows for therapeutic interventions. In addition, we would like to determine biomarkers in the blood that can provide information about neuronal damage before and after surgery and enable us to investigate a possible interaction with the anaesthetic used.
Project Team
Prof. Dr. Emrah Düzel
Prof. Dr. Christoph Lohmann
M.Sc. Mareike Ludwig
Dr. Margit Rudolf
Dr. Judith Wesenberg
Publications
Current challenges in reliably targeting the noradrenergic locus coeruleus using transcutaneous auricular vagus nerve stimulation (taVNS)
Autonomic NeuroscienceSupport our research
Become a study participant!
How do our brains, our bodies and our environment interact? How do physical illnesses affect our mental performance? And why are we more efficient on some days than others?
We would like to get to the bottom of these questions together with you. Register now and take part in exciting studies.
