Delineating the Trajectory of Cognitive Recovery From General Anesthesia in Older Adults: Design and Rationale of the TORIE (Trajectory of Recovery in the Elderly) Project

Mincer, Joshua S.; Baxter, Mark G.; McCormick, Patrick J.; Sano, Mary; Schwartz, Arthur E.; Brallier, Jess W.; Allore, Heather G.; Delman, Bradley N.; Sewell, Margaret; Kundu, Prantik; Tang, Cheuk Y.; Sanchez, Angela; Deiner, Stacie

doi:10.1213/ane.0000000000002427

Cited by 13 publications

(11 citation statements)

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“…To address the specific role of anesthesia in the absence of surgery on cognition in older adults, who have been identified at higher risk of postoperative neurocognitive disorders, we assessed cognitive recovery after general anesthesia in healthy adult volunteers by decade from 40 to 80 years of age. 10 The primary hypothesis is that the time to recovery increases across age decades from 40- to 80-year old based on the evidence that postoperative neurocognitive disorders are related to surgical stress and not anesthesia. Specifically, we examined whether there was an association between age group and time to recovery after adjusting for available confounding variables (gender, race, and education).…”

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confidence: 99%

Cognitive Recovery by Decade in Healthy 40- to 80-Year-Old Volunteers After Anesthesia Without Surgery

Baxter

Mincer

Brallier

et al. 2021

Anesthesia &Amp; Analgesia

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BACKGROUND: Postoperative delirium and postoperative cognitive dysfunction are the most common complications for older surgical patients. General anesthesia may contribute to the development of these conditions, but there are little data on the association of age with cognitive recovery from anesthesia in the absence of surgery or underlying medical condition. METHODS:We performed a single-center cohort study of healthy adult volunteers 40 to 80 years old (N = 71, mean age 58.5 years, and 44% women) with no underlying cognitive dysfunction. Volunteers underwent cognitive testing before and at multiple time points after 2 hours of general anesthesia consisting of propofol induction and sevoflurane maintenance, akin to a general anesthetic for a surgical procedure, although no procedure was performed. The primary outcome was time to recovery to cognitive baseline on the Postoperative Quality of Recovery Scale (PQRS) within 30 days of anesthesia. Secondary cognitive outcomes were time to recovery on in-depth neuropsychological batteries, including the National Institutes of Health Toolbox and well-validated paper-and-pencil tests. The primary hypothesis is that time to recovery of cognitive function after general anesthesia increases across decades from 40 to 80 years of age. We examined this with discrete-time logit regression (for the primary outcome) and linear mixed models for interactions of age decade with time postanesthesia (for secondary outcomes). RESULTS: There was no association between age group and recovery to baseline on the PQRS; 36 of 69 (52%) recovered within 60-minute postanesthesia and 63 of 69 (91%) by day 1. Hazard ratios (95% confidence interval) for each decade compared to 40-to 49-year olds were: 50 to 59 years, 1.41 (0.50-4.03); 60 to 69 years, 1.03 (0.35-3.00); and 70 to 80 years, 0.69 (0.25-1.88). There were no significant differences between older decades relative to the 40-to 49-year reference decade in recovery to baseline on secondary cognitive measures. CONCLUSIONS: Recovery of cognitive function to baseline was rapid and did not differ between age decades of participants, although the number in each decade was small. These results suggest that anesthesia alone may not be associated with cognitive recovery in healthy adults of any age decade. (Anesth Analg 2022;134:389-99) KEY POINTS• Question: Is time to recovery of baseline cognitive function after exposure to general anesthesia, without surgery, associated with age group? • Findings: Recovery of cognitive function to baseline was rapid and did not differ by age decade. • Meaning: General anesthesia alone is not associated with time to cognitive recovery in healthy adults of any age decade.

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confidence: 99%

Cognitive Recovery by Decade in Healthy 40- to 80-Year-Old Volunteers After Anesthesia Without Surgery

Baxter

Mincer

Brallier

et al. 2021

Anesthesia &Amp; Analgesia

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“…At baseline, linear correlation analysis showed that whole brain white matter FA had a significant negative correlation with age (p = 1.09e-5, R-sqr = 0.256) while MD (p = 4.07e-9, Rsqr = 0.410), AD (p = 5.781e-8, R-sqr = 0.362) and RD (p = 6.269e-9, R-sqr = 0.403) were positively correlated (Fig 3A). To visualize age differences we split up the data into 4 age groups [40-49 (n = 19), 50-59 (n = 18), 60-69 (n = 13), and 70-80 (n = 18)] as per the main protocol [5]. Group means of the DTI metrics are shown in Fig 3B . Multiple linear regression was used to investigate the relationship between change in FA, calculated as the value at 40 minutes after drug administration minus the baseline value, with age and sex.…”

Section: Resultsmentioning

confidence: 99%

“…This analysis is part of a larger study on the effects of anesthesia on cognitive function in the elderly in the absence of surgery (Trajectory of Recovery in the Elderly [TORIE] (Trajectory of Recovery in the Elderly), NIH 1R01AG046634, clinicaltrials.gov registration NCT 2275026). The full protocol for this study is published [ 5 ]. This study was approved by the Institutional Review Board of the Icahn School of Medicine at Mount Sinai (New York, NY, USA; IRB@mssm.edu , 212-824-8200).…”

Section: Methodsmentioning

confidence: 99%

“…Another situation where patients are scanned under anesthesia is in intraoperative MRI procedures [ 4 ]. We collected these data in the context of the TORIE (Trajectory of Recovery in the Elderly) study [ 5 ] which was designed to investigate the recovery of cognitive function after general anesthesia without surgery in healthy adults 40–80 years old, spanning the age range of individuals that are at elevated risk of postoperative neurocognitive disorders including Postoperative Delirium (PD) and Postoperative Cognitive Dysfunction (POCD) [ 6 , 7 ]. In this study we sought to analyze the effects of general anesthesia on brain white matter.…”

Section: Introductionmentioning

confidence: 99%

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Transient changes in white matter microstructure during general anesthesia

et al. 2021

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Cognitive dysfunction after surgery under general anesthesia is a well-recognized clinical phenomenon in the elderly. Physiological effects of various anesthetic agents have been studied at length. Very little is known about potential effects of anesthesia on brain structure. In this study we used Diffusion Tensor Imaging to compare the white matter microstructure of healthy control subjects under sevoflurane anesthesia with their awake state. Fractional Anisotropy, a white mater integrity index, transiently decreases throughout the brain during sevoflurane anesthesia and then returns back to baseline. Other DTI metrics such as mean diffusivity, axial diffusivity and radial diffusivity were increased under sevoflurane anesthesia. Although DTI metrics are age dependent, the transient changes due to sevoflurane were independent of age and sex. Volumetric analysis shows various white matter volumes decreased whereas some gray matter volumes increased during sevoflurane anesthesia. These results suggest that sevoflurane anesthesia has a significant, but transient, effect on white matter microstructure. In spite of the transient effects of sevoflurane anesthesia there were no measurable effects on brain white matter as determined by the DTI metrics at 2 days and 7 days following anesthesia. The role of white matter in the loss of consciousness under anesthesia will need to be studied and MRI studies with subjects under anesthesia will need to take these results into account.

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“…In fact, it was often the case that individual research groups were primarily interested only in emergence and or recovery but not both. While research into the neurophysiologic signatures of anesthetic-induced unconsciousness (Lee et al, 2013 ; Akeju et al, 2014a , b ; Pal et al, 2017 ) or the subsequent transition to waking (Solt et al, 2011 ; Safavynia et al, 2016 ) contributes to our understanding of the neural correlates of consciousness (Bonhomme et al, 2012 ; Pal et al, 2016 ), it is important to provide this work in the context of clinical anesthesiology and alongside studies focused on gaining a greater understanding of the potential adverse cognitive consequences (Mincer et al, 2017 ) or failure to reclaim the subject's pre-anesthesia baseline cognitive functions (Giattino et al, 2017 ). Standardized assessments for both emergence and recovery that go beyond simple cognitive and behavioral responses will be critical for understanding both processes.…”

Section: What Does It Mean To “Wake Up”? Observations On Regaining Comentioning

confidence: 99%

Waking Up to a New Model for Studying Neural Systems: What Emergence from Unconscious States Can Reveal about Brain Organization

García

Rothman

Fitzpatrick

2017

Front. Syst. Neurosci.

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Delineating the Trajectory of Cognitive Recovery From General Anesthesia in Older Adults: Design and Rationale of the TORIE (Trajectory of Recovery in the Elderly) Project

Abstract: The data acquired in this project will have both clinical and theoretical relevance regardless of the outcome by delineating the mechanism behind short-term recovery across the adult age lifespan, which will have major implications for our understanding of the effects of anesthetic drugs.

Cited by 13 publications

References 61 publications

Cognitive Recovery by Decade in Healthy 40- to 80-Year-Old Volunteers After Anesthesia Without Surgery

Cognitive Recovery by Decade in Healthy 40- to 80-Year-Old Volunteers After Anesthesia Without Surgery

Transient changes in white matter microstructure during general anesthesia

Waking Up to a New Model for Studying Neural Systems: What Emergence from Unconscious States Can Reveal about Brain Organization

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