Endothelial bases of post-operative cognitive impairment in the elderly (EndOPCog)

• Applicant: Professorin Dr. Insa Feinkohl, Ph.D.
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Anaesthesiology ; Biological Psychiatry ; Epidemiology and Medical Biometry/Statistics ; Public Health, Healthcare Research, Social and Occupational Medicine
• Term: from 2020 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 438955240

Older people who undergo surgery often experience post-operative delirium (POD) or cognitive dysfunction (POCD). Yet, little is known of the pathophysiology underlying the conditions or of predisposing factors. Endothelial function is essential to maintaining healthy homeostasis of the body and the brain as a site with huge vascular surface. Consequently, systemic endothelial dysfunction (ED) has been associated with age-related cognitive impairment such as dementia. Yet the role of biomarkers of ED in the development of POD has only been investigated in a single small previous study and for POCD has never been investigated before. Here, I plan to close this gap in the research literature and thus expect to make a real contribution to the research field. I will test the hypothesis that systemic ED before surgery is associated with an increased risk of POD and POCD using data from the observational Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog) study. BioCog is the product of an EU-wide collaboration spanning 5 countries, tracking the cognitive and clinical development of 933 patients recruited between 2014 and 2017 from before surgery to 3 months after surgery and beyond. BioCog is unique, because it is among the largest studies of POD/POCD and is the largest study with brain imaging in its protocol globally. The study combines large sample size with detailed patient characterization with the overarching goal to determine why some patients are at POD/POCD risk whereas others are protected. Its findings will shed light on the pathophysiology of POD/POCD which is currently unknown and will additionally evaluate the prognostic value of pre-surgery risk factors for POD/POCD prediction. In the proposed work, I plan to measure 5 circulating biomarkers of systemic ED before surgery (which I have identified as relevant from the literature on age-related cognitive impairment) and assess their associations with and prognostic value for POD by 7-day follow-up/discharge (primary outcome) and POCD at 3 months after surgery (secondary outcome) in BioCog. I will also compare results for the 5 markers to determine whether some of those markers are more valuable for future research and clinical application. Importantly, I will go one step further and make full use of the BioCog data by testing the hypothesis that cerebrovascular damage determined on magnetic resonance imaging (MRI) is the driving force behind the hypothesized impact of systemic ED on POD/POCD risk. The project will form a natural progression from my current research focus on traditional vascular risk factors. This work is expected to i) help determine pathophysiological mechanisms underlying POD/POCD, and ii) identify biomarkers for use in POD/POCD risk prediction. With systemic ED as a risk factor that is modifiable through targeted intervention, the project is expected to result in knowledge for direct transfer to trial studies and clinical practice.

• DFG Programme: Research Grants