This grant will guide best clinical practice in Australia, revolutionize our understanding of the mechanisms through which acute illness and surgery alter the cognitive trajectory, and lead international efforts in trials on the prevention of delirium. It will significantly expand the breadth of Professor Sanders research program and accelerate the depth of accumulated knowledge for the field. The timing of this work is critical as (1) biospecimens and imaging data are ready for analysis; (2) there is a significant knowledge gap in these areas of research; (3) my mechanistic evidence suggests novel preventative measures for delirium that can be implemented rapidly and cost-effectively; and (4) in Australia, we can optimise best clinical practice for preventing delirium.
This program of research encompasses three projects: a) translate delirium research into national standards and a collaborative research network; b) determine whether cumulative hospitalisations lead to chronic inflammation and neurodegeneration that mediate long-term cognitive decline using UK biobank data and c) conduct new trials informed by discovery, research collaboration and new networks
Ultimately, this grant will guide best clinical practice on perioperative neuroprotection in Australia, revolutionize our understanding of the mechanisms through which acute illness and surgery alter the cognitive trajectory, and lead international efforts in trials on the prevention of delirium.
Professor Robert Sanders, The University of Sydney, NSW
Associate investigators
Associate Professor Lis Evered, St Vincents Hospital, Melbourne
Professor Andrew Davidson, Royal Children’s Hospital, Melbourne
Professor Gideon Caplan, University of NSW
The project was awarded $A100,000 through the ANZCA research grants program for 2023.
Completed in 2024 and leading to a publication in The Lancet Health Longevity, this program aimed to guide best clinical practice in Australia, revolutionize understanding of acute illness and surgery mechanisms altering cognitive trajectory, and lead international trials on delirium prevention, addressing a significant knowledge gap.
The first project, translating research into national standards and a collaborative network, led to a paper describing Australian views of the European Society of Anaesthesiology and Intensive Care perioperative guidelines being accepted by Anaesthesia & Intensive Care, and an active consumer group in partnership with the ANZCA Clinical Trials Network (CTN).
The second project aimed to determine whether cumulative hospitalisations lead to chronic inflammation, neurodegeneration, and long-term cognitive decline, using UK Biobank data from 2006-2023. Primary outcomes were hippocampal volume and white matter hyperintensities, and surgeries were calculated cumulatively from eight years before baseline.
With 492,802 participants included and 46,706 undergoing MRI, small adverse associations with cognition were found per surgery. Surgeries were associated with smaller hippocampal volume, greater white matter hyperintensities volume, and neurodegeneration of the insula and superior temporal cortex.
The team concluded that surgeries are generally safe, but cumulatively associated with cognitive decline, and that neurodegeneration and perioperative brain health should be prioritised for older, vulnerable, and multiple-surgery patients.
The third project, conducting new trials informed by discovery, collaboration and new networks, led to the NHMRC-CTC-funded DECIDE trial investigating dexmedetomidine and delirium-free survival after cardiac surgery. An adaptive platform trial is being set up including an agreement on the required simulations, for which the team is seeking further funding.
This program has fundamentally advanced scientific knowledge of brain health and current best practice, defined the scope of potential cognitive harm and brain degeneration that may follow surgery, and evaluated the suitability of current guidelines for protecting brain health in Australian practice.
The team is now designing new trials to define therapies to protect our patients.
Taylor J, Robledo KP, Medel V, Heller G, Payne T, Wehrman J, Casey C, Yang PF, Krause BM, Lennertz R, Naismith S, Teixeira-Pinto A, Sanders RD. Association between surgical admissions, cognition, and neurodegeneration in older people: a population-based study from the UK Biobank. Lancet Healthy Longev. 2024 Sep;5(9):100623. doi: 10.1016/j.lanhl.2024.07.006. Epub 2024 Sep 5.PMID: 39245058