Characterizing postoperative cognitive dysfunction in the elderly

In the Netherlands, yearly more than 400.000 elderly patients undergo surgery. An estimated ten percent of these patients develops long-lasting postoperative cognitive dysfunction (POCD), associated with a reduced quality of life, increased dependency and worse prognosis. Currently, there is no treatment for POCD.
A good understanding of the underlying mechanisms of POCD is essential to develop adequate (preventive) therapies. In this thesis we investigate the hypothesis that, in parallel to a local inflammatory response, necessary for wound healing, an inflammatory response (neuroinflammation) occurs in the brain. This neuroinflammation disturbs sensitive brain areas of vulnerable patients, resulting in dysfunction in specific cognitive domains.
A unique rat-model for POCD was developed to study the influence of surgery on multiple brain regions and cognitive domains. We found that in healthy adult rats with a low risk for POCD minor and temporary (neuro)inflammation and cognitive impairment occur after surgery. A potential break-through in POCD research is the finding that the presence of risk factors for POCD lead to a longer-lasting and more generalized postoperative neuroinflammation and cognitive dysfunction. Such risk factors include aging, more severe surgery and prior infection. These results are translated to the clinical setting with a patient study, revealing that also in surgical patients POCD in specific domains is associated with the inflammatory response to surgery.
The studies presented in this thesis promote interpretation of postoperative cognitive complaints and provide new insights into the mechanism underlying POCD, opening new avenues for therapeutic approaches.