Dataset Information

Older Patients with Alzheimer's Disease-Related Cortical Atrophy Who Develop Post-Operative Delirium May Be at Increased Risk of Long-Term Cognitive Decline After Surgery.

ABSTRACT:

Background

Older surgical patients with Alzheimer's disease (AD) dementia and delirium are at increased risk for accelerated long-term cognitive decline.

Objective

Investigate associations between a probabilistic marker of preclinical AD, delirium, and long-term cognitive decline.

Methods

The Successful Aging after Elective Surgery cohort includes older adults (?70 years) without dementia who underwent elective surgery. 140 patients underwent preoperative magnetic resonance imaging and had?6 months cognitive follow-up. Cortical thickness was measured in 'AD-Signature' regions. Delirium was evaluated each postoperative day by the Confusion Assessment Method. Cognitive performance was assessed using a detailed neuropsychological battery at baseline; months 1, 2, and 6; and every 6 months thereafter until 36 months. Using either a General Cognitive Performance composite (GCP) or individual test scores as outcomes, we performed linear mixed effects models to examine main effects of AD-signature atrophy and the interaction of AD-signature atrophy and delirium on slopes of cognitive change from post-operative months 2-36.

Results

Reduced baseline AD-signature cortical thickness was associated with greater 36-month cognitive decline in GCP (standardized beta coefficient, ? = -0.030, 95% confidence interval [-0.060, -0.001]). Patients who developed delirium who also had thinner AD signature cortex showed greater decline on a verbal learning test (? = -0.100 [-0.192, -0.007]).

Conclusion

Patients with the greatest baseline AD-related cortical atrophy who develop delirium after elective surgery appear to experience the greatest long-term cognitive decline. Thus, atrophy suggestive of preclinical AD and the development of delirium may be high-risk indicators for long-term cognitive decline following surgery.

SUBMITTER: Racine AM

PROVIDER: S-EPMC7304614 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Older Patients with Alzheimer's Disease-Related Cortical Atrophy Who Develop Post-Operative Delirium May Be at Increased Risk of Long-Term Cognitive Decline After Surgery.

Racine Annie M AM Touroutoglou Alexandra A Abrantes Tatiana T Wong Bonnie B Fong Tamara G TG Cavallari Michele M Travison Thomas G TG Gou Yun Y Marcantonio Edward R ER Alsop David C DC Jones Richard N RN Inouye Sharon K SK Dickerson Bradford C BC

Journal of Alzheimer's disease : JAD 20200101 1

<h4>Background</h4>Older surgical patients with Alzheimer's disease (AD) dementia and delirium are at increased risk for accelerated long-term cognitive decline.<h4>Objective</h4>Investigate associations between a probabilistic marker of preclinical AD, delirium, and long-term cognitive decline.<h4>Methods</h4>The Successful Aging after Elective Surgery cohort includes older adults (≥70 years) without dementia who underwent elective surgery. 140 patients underwent preoperative magnetic resonance ...[more]

PMID: 32250290

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Project description:BackgroundPost-operative delirium (POD), a common post-operative complication that affects up to 73. 5% of surgical patients, could prolong hospital stays, triple mortality rates, cause long-term cognitive decline and dementia, and boost medical expenses. However, the underlying mechanisms, especially the circuit mechanisms of POD remain largely unclear. Previous studies demonstrated that cannabis use might cause delirium-like behavior through the endocannabinoid system (eCBs), a widely distributed retrograde presynaptic neuromodulator system. We also found that the prelimbic (PrL) and intralimbic (IL) prefrontal cortex, a crucial hub for cognition and emotion, was involved in the eCBs-associated general anesthesia recovery.ObjectivesThe present study aimed to investigate the role of eCBs in POD development, and further clarify its neuronal specificity and circuit specificity attributed to POD.MethodsAccording to a previous study, 2 h of 1.4% isoflurane anesthesia and simple laparotomy were conducted to establish the POD model in C57/BL6 mice aged 8-12 weeks. A battery of behavioral tests, including the buried food, open field, and Y maze tests, were performed at 24 h before anesthesia and surgery (AS) and 6 and 9 h after AS. The behavioral results were calculated as a composite Z score for the POD assessment. To explore the dynamics of eCBs and their effect on POD regulation, an endocannabinoid (eCB) sensor was microinjected into the PrL, and the antagonists (AM281 and hemopressin) and agonist (nabilone) of type 1 cannabinoid receptor (CB1R), were administered systemically or locally (into PrL). Chemogenetics, combined Cre-loxP and Flp-FRT system, were employed in mutant mice for neuronal specificity and circuit specificity observation.ResultsAfter AS, the composite Z score significantly increased at 6 and 9 but not at 24 h, whereas blockade of CB1R systemically and intra-PrL could specifically decrease the composite Z score at 6 and 9 h after AS. Results of fiber photometry further confirmed that the activity of eCB in the PrL was enhanced by AS, especially in the Y maze test at 6 h post-operatively. Moreover, the activation of glutamatergic neurons in the PrL could reduce the composite Z score, which could be significantly reversed by exogenous cannabinoid (nabilone) at 6 and 9 h post-operatively. However, activation of GABAergic neurons only decreased composite Z score at 9 h post-operatively, with no response to nabilone application. Further study revealed the glutamatergic projection from mediodorsal thalamus (MD) to PrL glutamatergic neurons, but not hippocampus (HIP)-PrL circuit, was in charge of the effect of eCBs on POD.ConclusionOur study firstly demonstrated the involvement of eCBs in the POD pathogenesis and further revealed that the eCBs may regulate POD through the specific MDglu-PrLglu circuit. These findings not only partly revealed the molecular and circuit mechanisms of POD, but also provided an applicable candidate for the clinical prevention and treatment of POD.

Project description:This study aimed to determine the relationship between hemoglobin (Hb) concentration and post-operative delirium (POD) in elderly patients undergoing femoral neck fracture (FNF) surgery and to investigate whether the change in Hb concentration is associated with POD and the risk factors for POD. A total of 889 patients admitted with FNF between January 2016 and December 2020 were enrolled in this single-center, retrospective, case-control study. Hb concentrations were determined at admission and post-operative day 1 and the change in Hb concentration was defined as the absolute value of difference in pre-operative and post-operative Hb concentration. POD was assessed using the Confusion Assessment Method for the Intensive Care Unit (ICU) or the Confusion Assessment Method once a daily after surgery. The logistic regression analysis was performed for statistical analysis. In total, 172 (19.3%) patients developed POD and 151 (87.8%) patients developed POD within post-operative 3 days. Low pre-operative Hb concentration [p = 0.026, odds ratio (OR) = 0.978] and significant change in Hb concentration (p = 0.006, OR = 1.033) were significantly associated with POD. After excluding change in Hb concentration or pre-operative Hb concentration, neither of them was significantly associated with POD (p > 0.05). The interaction analysis of change in Hb concentration and pre-operative Hb concentration in the logistic regression model was negative. There was no significant relationship between post-operative Hb concentration and POD. Age (p < 0.001, OR = 1.072), stroke history (p = 0.003, OR = 2.489), post-operative ICU transfer (p = 0.007, OR = 1.981), and visual analog scale score within post-operative 2 days (p 1 = 0.016 and p 2 = 0.006) were independently associated with POD in the logistic regression analysis. Patients with low pre-operative Hb concentrations and high changes in Hb concentration seem to have an increased risk of POD and should receive more attention. Old age, stroke history, post-operative ICU transfer, and pain within post-operative 2 days were significantly associated with POD.

Project description:WHAT WE ALREADY KNOW ABOUT THIS TOPIC:Cardiac surgery is associated with cognitive decline and postoperative delirium. The relationship between postoperative delirium and cognitive decline after cardiac surgery is unclear WHAT THIS ARTICLE TELLS US THAT IS NEW:The development of postoperative delirium is associated with a greater degree of cognitive decline 1 month after cardiac surgery. The development of postoperative delirium is not a predictor of cognitive decline 1 yr after cardiac surgery. BACKGROUND:Delirium is common after cardiac surgery and has been associated with morbidity, mortality, and cognitive decline. However, there are conflicting reports on the magnitude, trajectory, and domains of cognitive change that might be affected. The authors hypothesized that patients with delirium would experience greater cognitive decline at 1 month and 1 yr after cardiac surgery compared to those without delirium. METHODS:Patients who underwent coronary artery bypass and/or valve surgery with cardiopulmonary bypass were eligible for this cohort study. Delirium was assessed with the Confusion Assessment Method. A neuropsychologic battery was administered before surgery, at 1 month, and at 1 yr later. Linear regression was used to examine the association between delirium and change in composite cognitive Z score from baseline to 1 month (primary outcome). Secondary outcomes were domain-specific changes at 1 month and composite and domain-specific changes at 1 yr. RESULTS:The incidence of delirium in 142 patients was 53.5%. Patients with delirium had greater decline in composite cognitive Z score at 1 month (greater decline by -0.29; 95% CI, -0.54 to -0.05; P = 0.020) and in the domains of visuoconstruction and processing speed. From baseline to 1 yr, there was no difference between delirious and nondelirious patients with respect to change in composite cognitive Z score, although greater decline in processing speed persisted among the delirious patients. CONCLUSIONS:Patients who developed delirium had greater decline in a composite measure of cognition and in visuoconstruction and processing speed domains at 1 month. The differences in cognitive change by delirium were not significant at 1 yr, with the exception of processing speed.

Project description:Introduction: Risk assessment for post-operative delirium (POD) is poorly developed. Improved metrics could greatly facilitate peri-operative care as costs associated with POD are staggering. In this preliminary study, we develop a novel stress-diathesis model based on comprehensive pre-operative psychiatric and neuropsychological testing, a blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) carbon dioxide (CO2) stress test, and high fidelity measures of intra-operative parameters that may interact facilitating POD. Methods: The study was approved by the ethics board at the University of Manitoba and registered at clinicaltrials.gov as NCT02126215. Twelve patients were studied. Pre-operative psychiatric symptom measures and neuropsychological testing preceded MRI featuring a BOLD MRI CO2 stress test whereby BOLD scans were conducted while exposing participants to a rigorously controlled CO2 stimulus. During surgery the patient had hemodynamics and end-tidal gases downloaded at 0.5 hz. Post-operatively, the presence of POD and POD severity was comprehensively assessed using the Confusion Assessment Measure -Severity (CAM-S) scoring instrument on days 0 (surgery) through post-operative day 5, and patients were followed up at least 1 month post-operatively. Results: Six of 12 patients had no evidence of POD (non-POD). Three patients had POD and 3 had clinically significant confusional states (referred as subthreshold POD; ST-POD) (score ≥ 5/19 on the CAM-S). Average severity for delirium was 1.3 in the non-POD group, 3.2 in ST-POD, and 6.1 in POD (F-statistic = 15.4, p < 0.001). Depressive symptoms, and cognitive measures of semantic fluency and executive functioning/processing speed were significantly associated with POD. Second level analysis revealed an increased inverse BOLD responsiveness to CO2 pre-operatively in ST-POD and marked increase in the POD groups when compared to the non-POD group. An association was also noted for the patient population to manifest leucoaraiosis as assessed with advanced neuroimaging techniques. Results provide preliminary support for the interacting of diatheses (vulnerabilities) and intra-operative stressors on the POD phenotype. Conclusions: The stress-diathesis model has the potential to aid in risk assessment for POD. Based on these initial findings, we make some recommendations for intra-operative management for patients at risk of POD.

Project description:ObjectivesTo investigate the global cortical and regional quantitative features of cortical neural architecture in the brains of patients with posterior cortical atrophy (PCA) and typical Alzheimer's disease (tAD) compared with elderly healthy controls (HC).MethodsA novel diffusion MRI method, that has been shown to correlate with minicolumnar organization changes in the cerebral cortex, was used as a surrogate of neuropathological changes in dementia. A cohort of 15 PCA patients, 23 tAD and 22 healthy elderly controls (HC) were enrolled to investigate the changes in cortical diffusivity among groups. For each subject, 3 T MRI T1-weighted images and diffusion tensor imaging (DTI) scans were analysed to extract novel cortical DTI derived measures (AngleR, PerpPD and ParlPD). Receiver operating characteristics (ROC) curve analysis and the area under the curve (AUC) were used to assess the group discrimination capability of the method.ResultsThe results showed that the global cortical DTI derived measures were able to detect differences, in both PCA and tAD patients compared to healthy controls. The AngleR was the best measure to discriminate HC from tAD (AUC?=?0.922), while PerpPD was the best measure to discriminate HC from PCA (AUC?=?0.961). Finally, the best global measure to differentiate the two patient groups was ParlPD (AUC?=?0.771). The comparison between PCA and tAD patients revealed a different pattern of damage within the AD spectrum and the regional comparisons identified significant differences in key regions including parietal and temporal lobe cortical areas. The best AUCs were shown by PerpPD right lingual cortex (AUC?=?0.856), PerpPD right superior parietal cortex (AUC?=?0.842) and ParlPD right lateral occipital cortex (AUC?=?0.826).ConclusionsDiagnostic group differences were found, suggesting that the new cortical DTI analysis method may be useful to investigate cortical changes in dementia, providing better characterization of neurodegeneration, and potentially aiding differential diagnosis and prognostic accuracy.

Dataset Information

Older Patients with Alzheimer's Disease-Related Cortical Atrophy Who Develop Post-Operative Delirium May Be at Increased Risk of Long-Term Cognitive Decline After Surgery.

Background

Objective

Methods

Results

Conclusion

Publications

Older Patients with Alzheimer's Disease-Related Cortical Atrophy Who Develop Post-Operative Delirium May Be at Increased Risk of Long-Term Cognitive Decline After Surgery.

Similar Datasets

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