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      A Real-Time Neurophysiologic Stress Test for the Aging Brain: Novel Perioperative and ICU Applications of EEG in Older Surgical Patients

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          Abstract

          As of 2022, individuals age 65 and older represent approximately 10% of the global population [ 1], and older adults make up more than one third of anesthesia and surgical cases in developed countries [ 2, 3]. With approximately > 234 million major surgical procedures performed annually worldwide [ 4], this suggests that > 70 million surgeries are performed on older adults across the globe each year. The most common postoperative complications seen in these older surgical patients are perioperative neurocognitive disorders including postoperative delirium, which are associated with an increased risk for mortality [ 5], greater economic burden [ 6, 7], and greater risk for developing long-term cognitive decline [ 8] such as Alzheimer’s disease and/or related dementias (ADRD). Thus, anesthesia, surgery, and postoperative hospitalization have been viewed as a biological “stress test” for the aging brain, in which postoperative delirium indicates a failed stress test and consequent risk for later cognitive decline (see Fig. 3). Further, it has been hypothesized that interventions that prevent postoperative delirium might reduce the risk of long-term cognitive decline. Recent advances suggest that rather than waiting for the development of postoperative delirium to indicate whether a patient “passed” or “failed” this stress test, the status of the brain can be monitored in real-time via electroencephalography (EEG) in the perioperative period. Beyond the traditional intraoperative use of EEG monitoring for anesthetic titration, perioperative EEG may be a viable tool for identifying waveforms indicative of reduced brain integrity and potential risk for postoperative delirium and long-term cognitive decline. In principle, research incorporating routine perioperative EEG monitoring may provide insight into neuronal patterns of dysfunction associated with risk of postoperative delirium, long-term cognitive decline, or even specific types of aging-related neurodegenerative disease pathology. This research would accelerate our understanding of which waveforms or neuronal patterns necessitate diagnostic workup and intervention in the perioperative period, which could potentially reduce postoperative delirium and/or dementia risk. Thus, here we present recommendations for the use of perioperative EEG as a “predictor” of delirium and perioperative cognitive decline in older surgical patients.

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          The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

          The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia. Copyright © 2011. Published by Elsevier Inc.
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            NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease

            In 2011, the National Institute on Aging and Alzheimer’s Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer’s disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer’s Association to update and unify the 2011 guidelines. This unifying update is labeled a “research framework” because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer’s Association Research Framework, Alzheimer’s disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.
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              Event-related EEG/MEG synchronization and desynchronization: basic principles.

              An internally or externally paced event results not only in the generation of an event-related potential (ERP) but also in a change in the ongoing EEG/MEG in form of an event-related desynchronization (ERD) or event-related synchronization (ERS). The ERP on the one side and the ERD/ERS on the other side are different responses of neuronal structures in the brain. While the former is phase-locked, the latter is not phase-locked to the event. The most important difference between both phenomena is that the ERD/ERS is highly frequency band-specific, whereby either the same or different locations on the scalp can display ERD and ERS simultaneously. Quantification of ERD/ERS in time and space is demonstrated on data from a number of movement experiments.
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                Author and article information

                Contributors
                miles.berger@duke.edu
                Journal
                Neurotherapeutics
                Neurotherapeutics
                Neurotherapeutics
                Springer International Publishing (Cham )
                1933-7213
                1878-7479
                12 July 2023
                12 July 2023
                July 2023
                : 20
                : 4
                : 975-1000
                Affiliations
                [1 ]GRID grid.189509.c, ISNI 0000000100241216, Department of Anesthesiology, , Duke University Medical Center, ; Duke South Orange Zone Room 4315B, Box 3094, Durham, NC 27710 USA
                [2 ]GRID grid.189509.c, ISNI 0000000100241216, Duke Aging Center, , Duke University Medical Center, ; Durham, NC USA
                [3 ]GRID grid.189509.c, ISNI 0000000100241216, Duke/UNC Alzheimer’s Disease Research Center, , Duke University Medical Center, ; Durham, NC USA
                [4 ]GRID grid.26009.3d, ISNI 0000 0004 1936 7961, School of Medicine, , Duke University, ; Durham, NC USA
                [5 ]GRID grid.413105.2, ISNI 0000 0000 8606 2560, Department of Anaesthesia and Acute Pain Medicine, , St Vincent’s Hospital, ; Melbourne, VIC Australia
                [6 ]GRID grid.1008.9, ISNI 0000 0001 2179 088X, Department of Critical Care, School of Medicine, , University of Melbourne, ; Melbourne, Australia
                [7 ]GRID grid.5386.8, ISNI 000000041936877X, Weill Cornell Medicine, ; New York, NY USA
                [8 ]GRID grid.15276.37, ISNI 0000 0004 1936 8091, Clinical and Health Psychology, , University of Florida, ; Gainesville, FL USA
                [9 ]GRID grid.15276.37, ISNI 0000 0004 1936 8091, Norman Fixel Institute for Neurological Diseases, , University of Florida, ; Gainesville, FL USA
                [10 ]GRID grid.239395.7, ISNI 0000 0000 9011 8547, Department of Neurology, , Beth Israel Deaconess Hospital, ; Boston, MA USA
                [11 ]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Department of Anesthesiology and Critical Care, Perelman School of Medicine, , University of Pennsylvania, ; Philadelphia, PA USA
                [12 ]GRID grid.412451.7, ISNI 0000 0001 2181 4941, Department of Medicine and Aging Sciences, , University G d’Annunzio of Chieti-Pescara, ; Chieti, Italy
                [13 ]GRID grid.4777.3, ISNI 0000 0004 0374 7521, School of Medicine, Dentistry and Biomedical Sciences, , Queen’s University Belfast, ; Belfast, UK
                [14 ]GRID grid.7841.a, Department of Physiology and Pharmacology “Vittorio Erspamer”, , Sapienza University of Rome, ; Rome, Italy
                [15 ]San Raffaele of Cassino, Cassino, FR Italy
                Author information
                http://orcid.org/0000-0002-2386-5061
                Article
                1401
                10.1007/s13311-023-01401-4
                10457272
                37436580
                c2e247f4-8808-46f2-b8b3-ea68d6f26952
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 29 May 2023
                Categories
                Review
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                © The American Society for Experimental Neurotherapeutics, Inc. 2023

                Neurology
                delirium,anesthesia,dementia,alzheimer’s disease,neurophysiology,cognitive impairment
                Neurology
                delirium, anesthesia, dementia, alzheimer’s disease, neurophysiology, cognitive impairment

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