Delirium and <scp>A</scp>lzheimer disease: A proposed model for shared pathophysiology

Fong, Tamara G.; Vasunilashorn, Sarinnapha; Libermann, Towia A.; Marcantonio, Edward R.; Inouye, Sharon K.

doi:10.1002/gps.5088

Cited by 35 publications

(39 citation statements)

References 56 publications

(97 reference statements)

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“…A potential explanation for this observation is that following the acute phase of delirium (ie, POD2), some patients recover, with normalization of NfL by PO1MO, but others have ongoing elevation in NfL and go on to have ongoing cognitive decline. 4 Not all patients with higher NfL at baseline and POD2 reach the highest level of NfL at PO1MO. However, whereas a nested case-control sample optimizes delirium analyses, the design limits the analyses of other outcomes; thus, the finding on 1-month cognitive function should be interpreted with caution.…”

Section: Cam-s = Confusionmentioning

confidence: 90%

“…We have previously hypothesized that neuronal injury may represent a final common pathway for disparate pathophysiologic processes that occur during acute delirium. 4 In delirium, synaptic or neuronal injury may occur through a variety of mechanisms, including excitotoxicity, oxidative stress, and/or inflammation among other effects. 5,35,36 In this study, we examined 4 potential plasma biomarkers of neuronal injury, NfL, GFAP, UCHL-1, and tau, and found only NfL to be altered in association with surgery and delirium.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3] Knowledge of delirium pathophysiology is limited, but emerging evidence suggests neuronal injury may play a role. 4,5 Increasingly, fluid biomarkers of neuronal injury have been studied in a range of conditions, including traumatic brain injury (TBI), 6 multiple sclerosis, 7,8 stroke, 9 and neurodegenerative disease. 7 In delirium, prior studies examining plasma markers of neuronal injury have been mixed.…”

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confidence: 99%

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Association of Plasma Neurofilament Light with Postoperative Delirium

Fong

Vasunilashorn

Ngo

et al. 2020

Annals of Neurology

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for the SAGES Study Group Objective: To examine the association of the plasma neuroaxonal injury markers neurofilament light (NfL), total tau, glial fibrillary acid protein, and ubiquitin carboxyl-terminal hydrolase L1 with delirium, delirium severity, and cognitive performance. Methods: Delirium case-no delirium control (n = 108) pairs were matched by age, sex, surgery type, cognition, and vascular comorbidities. Biomarkers were measured in plasma collected preoperatively (PREOP), and 2 days (POD2) and 30 days postoperatively (PO1MO) using Simoa technology (Quanterix, Lexington, MA). The Confusion Assessment Method (CAM) and CAM-S (Severity) were used to measure delirium and delirium severity, respectively. Cognitive function was measured with General Cognitive Performance (GCP) scores. Results: Delirium cases had higher NfL on POD2 and PO1MO (median matched pair difference = 16.2pg/ml and 13.6pg/ml, respectively; p < 0.05). Patients with PREOP and POD2 NfL in the highest quartile (Q4) had increased risk for incident delirium (adjusted odds ratio [OR] = 3.7 [95% confidence interval (CI) = 1.1-12.6] and 4.6 [95% CI = 1.2-18.2], respectively) and experienced more severe delirium, with sum CAM-S scores 7.8 points (95% CI = 1.6-14.0) and 9.3 points higher (95% CI = 3.2-15.5). At PO1MO, delirium cases had continued high NfL (adjusted OR = 9.7, 95% CI = 2.3-41.4), and those with Q4 NfL values showed a −2.3 point decline in GCP score (−2.3 points, 95% CI = −4.7 to −0.9). Interpretation: Patients with the highest PREOP or POD2 NfL levels were more likely to develop delirium. Elevated NfL at PO1MO was associated with delirium and greater cognitive decline. These findings suggest NfL may be useful as a predictive biomarker for delirium risk and long-term cognitive decline, and once confirmed would provide pathophysiological evidence for neuroaxonal injury following delirium.

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Section: Cam-s = Confusionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Association of Plasma Neurofilament Light with Postoperative Delirium

Fong

Vasunilashorn

Ngo

et al. 2020

Annals of Neurology

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“…The method to address heterogeneity of studied populations is needed, because it remains unclear whether different precipitants of delirium (infection vs surgery) result in differing pathophysiology (e.g., postoperative delirium in a fairly healthy older adult vs a younger ICU patient with a complicated medical course). Future studies should consider focusing on a specific patient population, using statistical methods to control for differences, or using matched case‐control design in a limited resource environment 42 …”

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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“…Alzheimer's disease (AD), the most common cause of dementia [6], is characterized by the accumulation of amyloid β (Aβ) and hyper-phosphorylation of the Tau protein, with additional reduced acetylcholine levels and cerebral blood flow [2,7]. Furthermore, modifications in the blood-brain barrier (BBB), oxidative stress, mitochondrial impairment, neuroinflammation, and alterations in the insulin signaling have been observed in this condition [8].…”

Section: Introductionmentioning

confidence: 99%

Influence of the Mediterranean and Ketogenic Diets on Cognitive Status and Decline: A Narrative Review

et al. 2020

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Alzheimer’s disease (AD) is the most common form of senile dementia, accounting for up to 70% of dementia cases. AD is a slowly progressive disease, which causes global mental deterioration by affecting various cognitive areas. A growing body of evidence has demonstrated that lifestyle habits and nutritional patterns could delay the natural course of the neurodegeneration process. There is no single dietary pattern unequivocally proven to prevent AD. Nevertheless, epidemiological data suggest that by adopting several dietary habits, especially if accompanied with a healthy lifestyle, the negative consequences of AD could potentially be delayed. Alongside with others, two specific eating patterns have been well investigated concerning their potential beneficial effect on cognitive status: the Mediterranean diet (MedDi) and the Ketogenic Diet (KD). Despite the different underlying mechanisms, both of them have demonstrated a fairly profitable role in reducing or delaying cognitive impairment. The aim of the present narrative review is to overview the existing research on the efficacy of MedDi and KD against AD-related cognitive decline, focusing on the proposed protective mechanisms of action. Although the current knowledge on this complex topic does not allow us, at this point, to make exhaustive conclusions, this information could be of help in order to better characterize the possible role of MedDi and KD as nonpharmacological therapies in the treatment of AD and, more generically, of neurodegenerative disorders.

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Delirium and Alzheimer disease: A proposed model for shared pathophysiology

Cited by 35 publications

References 56 publications

Association of Plasma Neurofilament Light with Postoperative Delirium

Association of Plasma Neurofilament Light with Postoperative Delirium

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

Influence of the Mediterranean and Ketogenic Diets on Cognitive Status and Decline: A Narrative Review

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