Association of postoperative delirium with markers of neurodegeneration and brain amyloidosis: a pilot study

Rolandi, E; Cavedo, Enrica; Pievani, Michela; Galluzzi, Samantha; Ribaldi, Federica; Buckley, Christopher; Cunningham, Colm; Guerra, Ugo Paolo; Musarra, Monica; Morzenti, Sabrina; Magnaldi, S; Patassini, Mirko; Terragnoli, Flavio; Matascioli, Luca; Franzoni, Simone; Annoni, Giorgio; Carnevali, Lucio; Bellelli, Giuseppe; Frisoni, Giovanni B.

doi:10.1016/j.neurobiolaging.2017.09.020

Cited by 23 publications

(31 citation statements)

References 44 publications

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“…50 Delirium can acutely accelerate existing neurodegeneration; however, such pathologic changes in the vulnerable brain may be unique to delirium superimposed on dementia. In fact, delirium in nondemented patients does not induce long-term changes in A load, according to positron emission tomography (PET) imaging, 51,52 and similar findings are described when measuring CSF A biomarkers. 53,54 However, more detailed evaluation of vascular A pathology is required to determine if this is a protective response to acute trauma or a pathogenic hallmark of delirium superimposed on dementia, possibly F I G U R E 4 Orthopedic surgery triggers deficits in attention processes in CVN-AD mice and impairs neuronal markers.…”

Section: Fibrinogen Can Bind To the Cd11b Receptor Expressed On Micromentioning

confidence: 56%

Neurovascular and immune mechanisms that regulate postoperative delirium superimposed on dementia

Wang

Velagapudi

Kong

et al. 2020

Alzheimer's & Dementia

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Objective: The present work evaluates the relationship between postoperative immune and neurovascular changes and the pathogenesis of surgery-induced delirium superimposed on dementia. Background and rationale: Postoperative delirium is a common complication in many older adults and in patients with dementia including Alzheimer's disease (AD). The course of delirium can be particularly debilitating, while its pathophysiology remains poorly defined. Historical evolution: As of 2019, an estimated 5.8 million people of all ages have been diagnosed with AD, 97% of whom are >65 years of age. Each year, many of these patients require surgery. However, anesthesia and surgery can increase the risk for further cognitive decline. Surgery triggers neuroinflammation both in animal models and in humans, and a failure to resolve this inflammatory state may contribute to perioperative neurocognitive disorders as well as neurodegenerative pathology. Updated hypothesis: We propose an immunovascular hypothesis whereby dysregulated innate immunity negatively affects the blood-brain interface, which triggers delirium and thereby exacerbates AD neuropathology. Early experimental data: We have developed a translational model to study delirium superimposed on dementia in APPSwDI/mNos2 −/− AD mice (CVN-AD) after orthopedic surgery. At 12 months of age, CVN-AD showed distinct neuroimmune and vascular impairments after surgery, including acute microgliosis and amyloid-deposition. These changes correlated with attention deficits, a core feature of delirium-like behavior. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. c

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Section: Fibrinogen Can Bind To the Cd11b Receptor Expressed On Micromentioning

confidence: 56%

Neurovascular and immune mechanisms that regulate postoperative delirium superimposed on dementia

Wang

Velagapudi

Kong

et al. 2020

Alzheimer's & Dementia

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“…59 These findings suggest that the vulnerability of the brain for systemic inflammation-induced delirium is closely related to neurovascular rather than neurodegenerative pathology. Values are expressed as means ± SD or n/N (number with characteristic/total number with available data), and % is percentage.…”

Section: Discussionmentioning

confidence: 97%

“…57 This lack of evidence for an association of postoperative delirium with neurodegenerative markers is in line with studies reporting no evidence for an association of delirium with Abeta1-42, tau, or Ptau levels in cerebrospinal fluid 58 and brain amyloid quantified on positron emission tomography. 59 These findings suggest that the vulnerability of the brain for systemic inflammation-induced delirium is closely related to neurovascular rather than neurodegenerative pathology.…”

Section: Discussionmentioning

confidence: 97%

The trajectory of C‐reactive protein serum levels in older hip fracture patients with postoperative delirium

Slor

Witlox

Adamis

et al. 2019

Int J Geriat Psychiatry

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Objectives Important precipitating risk factors for delirium such as infections, vascular disorders, and surgery are accompanied by a systemic inflammatory response. Systemic inflammatory mediators can induce delirium in susceptible individuals. Little is known about the trajectory of systemic inflammatory markers and their role in the development and outcome of delirium. Methods This is a prospective cohort study of older patients undergoing acute surgery for hip fracture. Baseline characteristics were assessed preoperatively. During hospital admission, presence of delirium was assessed daily according to the Confusion Assessment Method criteria. This study compared the trajectory of serum levels of the C‐reactive protein (CRP) between people with and without postoperative delirium. Blood samples were taken at baseline and at postoperative day 1 through postoperative day 5. Results Forty‐one out of 121 patients developed postoperative delirium after hip fracture surgery. Longitudinal analysis of the trajectory of serum CRP levels using the Generalized Estimating Equations (GEE) method identified that higher CRP levels were associated with postoperative delirium. CRP levels were higher from postoperative day 2 through postoperative day 5. No significant differences in serum CRP levels were found when we compared patients with short (1‐2 days) and more prolonged delirium (3 days or more). Conclusions Delirium is associated with an increased systemic inflammatory response, and our results suggest that CRP plays a role in the underlying (inflammatory‐vascular) pathological pathway of postoperative delirium.

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“…Three biomarkers show a moderate positive associative trend with delirium: IL‐6, IL‐8, and CRP. Each of these biomarkers has been tied to the neuroinflammatory pathway and neurodegeneration, not only in delirium, but also in ADRD and other neurodegenerative disorders 19‐23 . Although these studies demonstrate a plausible pathway from delirium to continued neurodegeneration, it is important to consider the limitations.…”

Section: Discussionmentioning

confidence: 99%

A Systematic Review of Delirium Biomarkers and Their Alignment with the NIA‐AA Research Framework

Wang

Lindroth

Chan³

et al. 2020

J American Geriatrics Society

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To identify whether delirium biomarkers aligned with the National Institute on Aging-Alzheimerʼs Association (NIA-AA) research framework, a conceptual model that describes the use of diagnostic biomarkers for Alzheimerʼs disease and other related dementias (ADRD). DESIGN: Systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. SETTING: Acute care and outpatient settings. PARTICIPANTS: Adults diagnosed with delirium. METHODS AND MEASUREMENTS: MEDLINE, Psy-cInfo, Embase, and the Cochrane Library were searched for English-language studies published from January 2010 to February 2020. Studies included adults older than 18 years, identified delirium with a standardized assessment tool, and measured an ADRD biomarker. Independent reviewers determined whether an association between delirium and ADRD biomarker was found, the quality of biomarker data based on the REMARK (REporting recommendations for tumor MARKer prognostic studies) checklist, and the study bias based on the Newcastle-Ottawa Scale.RESULTS: A total of 61,256 citations were identified; 113 studies were included. Most studies did not examine amyloid, tau, or neurodegeneration biomarkers. Delirium may be associated with neurodegeneration biomarkers, but few to no studies found an association with amyloid and tau biomarkers. Delirium was not consistently associated with inflammatory biomarkers. The quality of biomarker data was moderate, and the risk of bias was moderate to high. Studies often did not collect prehospital and posthospital cognitive data. CONCLUSION: Most delirium diagnostic biomarker studies did not measure amyloid, tau, and/or neurodegenerative biomarkers, making characterization of the relationship between delirium and ADRD difficult. Future delirium biomarker diagnostic studies could improve the understanding of pathophysiologic links between delirium with other conditions affecting cognition.

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Association of postoperative delirium with markers of neurodegeneration and brain amyloidosis: a pilot study

Cited by 23 publications

References 44 publications

Neurovascular and immune mechanisms that regulate postoperative delirium superimposed on dementia

Neurovascular and immune mechanisms that regulate postoperative delirium superimposed on dementia

The trajectory of C‐reactive protein serum levels in older hip fracture patients with postoperative delirium

A Systematic Review of Delirium Biomarkers and Their Alignment with the NIA‐AA Research Framework

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