This is a K76 Beeson career development award for Dr. Miles Berger, a geriatric neuro- anesthesiologist with a focus on postoperative cognitive disorders. Each year >16 million older Americans undergo anesthesia and surgery, and up to 40% of these patients develop postoperative cognitive dysfunction (POCD), a syndrome of postoperative thinking and memory deficits. Although distinct from delirium, POCD (like delirium) is associated with decreased quality of life, long term cognitive decline, early retirement, increased mortality, and a possible increased risk for developing dementia such as Alzheimer?s disease. We need strategies to prevent POCD, but first, we need to understand what causes it. A dominant theory holds that brain inflammation causes POCD, but little work has directly tested this theory in humans. Our preliminary data strongly suggest that there is significant postoperative neuro-inflammation in older adults who develop POCD. In this K76 award, we will prospectively obtain pre- and post-operative cognitive testing, fMRI imaging and CSF samples in 200 surgical patients over age 65. This will allow us to evaluate the role of specific neuro-inflammatory processes in POCD, its underlying brain connectivity changes, and postoperative changes in cerebrospinal fluid (CSF) Alzheimer?s disease (AD) biomarkers, such as the microtubule-associated protein tau. This project will advance understanding of neuro-inflammatory processes in POCD and clarify the potential link(s) between these processes and postoperative changes in AD pathology, in line with the National Institute of Aging?s mission to understand aging and fight cognitive decline due to AD. During this K76 grant period, Dr. Berger will also complete an individually tailored MS degree in Translational Research that will include training in immunology methods, fMRI imaging, cognitive neuroscience, geroscience, and physician leadership. This career development plan will give Dr. Berger the transdisciplinary skills to pursue his longer term goal of improving postoperative cognitive function for the more than 16 million older Americans who have anesthesia and surgery each year.

Public Health Relevance

More than 16 million older Americans undergo anesthesia and surgery each year. Up to 40% of these patients develop postoperative cognitive dysfunction (POCCD), a syndrome of thinking and memory deficits that last for weeks to months after surgery, and which is associated with long term cognitive decline and a possible increased risk of developing Alzheimer?s disease. In this project, we seek to better understand inflammation within the central nervous system (i.e. brain and spinal cord) after surgery, and to discover whether it is associated with POCD.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Project #
5K76AG057022-04
Application #
9898206
Study Section
Special Emphasis Panel (ZAG1)
Program Officer
Roberts, Luci
Project Start
2017-07-15
Project End
2022-03-31
Budget Start
2020-05-15
Budget End
2021-03-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Duke University
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Devinney, Michael J; Mathew, Joseph P; Berger, Miles (2018) Postoperative Delirium and Postoperative Cognitive Dysfunction: Two Sides of the Same Coin? Anesthesiology 129:389-391
Berger, Miles; Terrando, Niccolò; Smith, S Kendall et al. (2018) Neurocognitive Function after Cardiac Surgery: From Phenotypes to Mechanisms. Anesthesiology 129:829-851
Browndyke, Jeffrey N; Berger, Miles; Smith, Patrick J et al. (2018) Task-related changes in degree centrality and local coherence of the posterior cingulate cortex after major cardiac surgery in older adults. Hum Brain Mapp 39:985-1003
Giattino, Charles M; Gardner, Jacob E; Sbahi, Faris M et al. (2017) Intraoperative Frontal Alpha-Band Power Correlates with Preoperative Neurocognitive Function in Older Adults. Front Syst Neurosci 11:24
Berger, Miles; Ponnusamy, Vikram; Greene, Nathaniel et al. (2017) The Effect of Propofol vs. Isoflurane Anesthesia on Postoperative Changes in Cerebrospinal Fluid Cytokine Levels: Results from a Randomized Trial. Front Immunol 8:1528
Browndyke, Jeffrey N; Berger, Miles; Harshbarger, Todd B et al. (2017) Resting-State Functional Connectivity and Cognition After Major Cardiac Surgery in Older Adults without Preoperative Cognitive Impairment: Preliminary Findings. J Am Geriatr Soc 65:e6-e12
Berger, Miles; Nadler, Jacob W; Friedman, Allan et al. (2016) The Effect of Propofol Versus Isoflurane Anesthesia on Human Cerebrospinal Fluid Markers of Alzheimer's Disease: Results of a Randomized Trial. J Alzheimers Dis 52:1299-310
Berger, Miles; GarcĂ­a, Paul S (2016) Anesthetic Suppression of Thalamic High-Frequency Oscillations: Evidence that the Thalamus Is More Than Just a Gateway to Consciousness? Anesth Analg 122:1737-9