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The Association of Blood-Brain Barrier Breakdown with Sleep Apnea and Postoperative Delirium

血脑屏障破坏与睡眠呼吸暂停和术后谵妄的关系

基本信息

批准号：
10456198
负责人：
Michael Joseph Devinney
金额：
$ 16.1万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10456198
关键词：
Age Albumins Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk American Anesthesia procedures Animal Model Animals Apnea Attention Blood Blood - brain barrier anatomy Blood capillaries Brain Breathing Cerebrospinal Fluid Clinical Research Cognitive Conscious Delirium Dementia Diagnosis Diffusion Disease Elderly Endothelium Enrollment Exhibits FDA approved Feasibility Studies Foundations Functional disorder Funding Future Geriatrics Goals Grant Hip Fractures Home Impaired cognition Incidence Inflammation Mediators Interruption Lead Link Measurement Measures Mediating Mediator of activation protein Mentors Morbidity - disease rate Neuraxis Neurocognitive Obstructive Sleep Apnea Operative Surgical Procedures Outcome Study Pathway interactions Patients Peripheral Pharmaceutical Preparations Play Postoperative Period Prevalence Prospective Studies Quality of life Risk Risk Factors Role Sampling Secondary to Serum Severities Sleep Sleep Apnea Syndromes Syndrome Testing Tight Junctions Toxin Training Water age related blood-brain barrier permeabilization career development cognitive function cohort in vitro Model indexing mild cognitive impairment modifiable risk mortality neuroinflammation neuropathology novel therapeutics older patient postoperative delirium prevent relating to nervous system skills systemic inflammatory response therapy development tool

项目摘要

ABSTRACT Blood-brain barrier (BBB) breakdown occurs in older patients after anesthesia/surgery, and could increase risk for postoperative delirium. BBB breakdown could play a role in postoperative delirium because 1) anesthesia/surgery are associated with BBB breakdown and 2) BBB breakdown is associated with neuroinflammation, which has been linked to delirium and Alzheimer’s disease (AD). The BBB, which normally restricts diffusion of large molecules into the central nervous system, can be assessed by measuring large molecules, such as albumin, in the cerebrospinal (CSF). BBB breakdown results in an increased CSF-to-serum ratio of albumin (Qalbumin). Increased Qalbumin is associated with neuroinflammation, increased AD risk, and accelerated cognitive decline. Although BBB breakdown is theorized to play a role in postoperative delirium, no studies have yet determined whether postoperative delirium is associated with BBB breakdown (ie, increased Qalbumin). One potentially modifiable risk factor for BBB breakdown is obstructive sleep apnea (OSA), characterized by repeated interruptions in breathing during sleep, that is associated with postoperative delirium, mild cognitive impairment, and accelerated AD pathology. Since OSA is a frequently undiagnosed, highly prevalent (~50% of older adults) disorder, OSA could represent a pervasive, yet treatable, risk factor for BBB breakdown.Thus, we will also determine whether OSA patients have increased preoperative BBB breakdown (ie, Qalbumin), which could potentially predispose OSA patients to postoperative delirium. The overall aim of this study is to measure the magnitude of blood-brain barrier (BBB) breakdown in older adults undergoing non-cardiac surgery, and determine the extent that BBB breakdown is associated with OSA and postoperative delirium severity. To test these hypotheses, I will prospectively study 200 non-cardiac surgery patients over age 60 from my ongoing foundation-funded study: Sleep Apnea, Neuroinflammation, and cognitive Dysfunction Manifesting After Non-cardiac surgery (SANDMAN), and my mentor’s larger NIA K76-funded study. These patients already undergo preoperative OSA testing, pre- and postoperative blood/CSF sampling, and delirium assessment. Leveraging this unique, existing cohort and cerebrospinal fluid samples makes these proposed studies feasible as all the samples will already be collected by the anticipated grant period. Our findings will help us understand mechanisms of OSA-related neurocognitive dysfunction, and eventually inform the development of therapies to reduce postoperative delirium and to help prevent AD for >16 million older Americans who undergo surgery every year

摘要