Cognitive impairment after surgery occurs frequently in the large number of increasingly elderly patients undergoing cardiac surgery every year. Postoperative cognitive deficit (POCD) is present in 36-50% of patients in the early phases after surgery and has been shown to adversely impact quality of life as much as one year after surgery. The objective of our multidisciplinary Neurological Outcome Research Group is to understand the mechanisms underlying neurologic and neurocognitive dysfunction after cardiac surgery and to reduce the incidence of these devastating outcomes. Despite substantial advancement in technology, pharmacology, and perioperative organ protection leading to reductions in mortality associated with cardiac surgery, the incidence of POCD has changed little over the last ten years. While multiple etiologic factors have been proposed for this neurological injury including cerebral embolic processes and hypoperfusion, the role of brain amyloid burden has never been examined. Because cardiac surgery generally takes place in the aged, it is possible that the cognitive dysfunction seen in surgical patients is a form of mild cognitive impairment (MCI), a condition characterized by accumulation of amyloid beta-fibrils. Thus the primary aim of our study is to determine the relationship between b-amyloid deposition and POCD using positron emission tomography (PET) and a newer PET tracer with a high affinity for b-amyloid fibrils. Secondarily, we will assess regional patterns of amyloid deposition in patients with POCD and compare these patterns with a previously imaged group of 40 MCI subjects and 40 elderly controls. Little is more devastating to a patient or the patient's family than to have a successful operation that prolongs life, but is complicated by cognitive impairment resulting in a diminished quality of life and loss of functional independence. The results of our study will be invaluable to the prevention of POCD in that we will define the role of regional amyloid burden in POCD using functional imaging markers that reveal the earliest neuronal changes and thus generate new mechanistic insights.

Public Health Relevance

Cognitive impairment is a common complication of cardiac surgery. In this research proposal, we plan to determine the relationship between brain amyloid plaque formation and postoperative cognitive dysfunction. Understanding this relationship may generate new treatments to prevent cognitive decline and thus improve quality of life and functional independence for the large number of elderly surgical patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HL108280-02
Application #
8306387
Study Section
Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
Program Officer
Danthi, Narasimhan
Project Start
2011-07-25
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2012
Total Cost
$235,500
Indirect Cost
$85,500
Name
Duke University
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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Kertai, Miklos D; Qi, Wenjing; Li, Yi-Ju et al. (2016) Gene signatures of postoperative atrial fibrillation in atrial tissue after coronary artery bypass grafting surgery in patients receiving β-blockers. J Mol Cell Cardiol 92:109-15
Kertai, Miklos D; Zhou, Shan; Karhausen, Jörn A et al. (2016) In Reply. Anesthesiology 125:438-9
Bartels, Karsten; Li, Yi-Ju; Li, Yen-Wei et al. (2015) Apolipoprotein epsilon 4 genotype is associated with less improvement in cognitive function five years after cardiac surgery: a retrospective cohort study. Can J Anaesth 62:618-26
Berger, Miles; Nadler, Jacob W; Browndyke, Jeffrey et al. (2015) Postoperative Cognitive Dysfunction: Minding the Gaps in Our Knowledge of a Common Postoperative Complication in the Elderly. Anesthesiol Clin 33:517-50
Stafford-Smith, Mark; Li, Yi-Ju; Mathew, Joseph P et al. (2015) Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci. Kidney Int 88:823-32
Kertai, Miklos D; Li, Yi-Ju; Ji, Yunqi et al. (2015) Genome-wide association study of new-onset atrial fibrillation after coronary artery bypass grafting surgery. Am Heart J 170:580-90.e28
Klinger, Rebecca Y; Thunberg, Christopher A; White, William D et al. (2015) Intraoperative Magnesium Administration Does Not Reduce Postoperative Atrial Fibrillation After Cardiac Surgery. Anesth Analg 121:861-7
Fontes, Monique T; McDonagh, David L; Phillips-Bute, Barbara et al. (2014) Arterial hyperoxia during cardiopulmonary bypass and postoperative cognitive dysfunction. J Cardiothorac Vasc Anesth 28:462-6
McDonagh, David L; Berger, Miles; Mathew, Joseph P et al. (2014) Neurological complications of cardiac surgery. Lancet Neurol 13:490-502

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