scholarly journals Cerebrospinal Fluid Proteome Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction

2021 ◽  
Vol 80 (3) ◽  
pp. 1281-1297
Author(s):  
Keith W. VanDusen ◽  
Yi-Ju Li ◽  
Victor Cai ◽  
Ashley Hall ◽  
Sarah Hiles ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
Cognitive Dysfunction ◽  
Pathway Analysis ◽  
Cognitive Deficits ◽  
Postoperative Cognitive Dysfunction ◽  
Neurologic Diseases ◽  
Proteome Changes ◽  
Coagulation Pathway ◽  
Over Time

Background: Postoperative cognitive dysfunction (POCD), a syndrome of cognitive deficits occurring 1–12 months after surgery primarily in older patients, is associated with poor postoperative outcomes. POCD is hypothesized to result from neuroinflammation; however, the pathways involved remain unclear. Unbiased proteomic analyses have been used to identify neuroinflammatory pathways in multiple neurologic diseases and syndromes but have not yet been applied to POCD. Objective: To utilize unbiased mass spectrometry-based proteomics to identify potential neuroinflammatory pathways underlying POCD. Methods: Unbiased LC-MS/MS proteomics was performed on immunodepleted cerebrospinal fluid (CSF) samples obtained before, 24 hours after, and 6 weeks after major non-cardiac surgery in older adults who did (n = 8) or did not develop POCD (n = 6). Linear mixed models were used to select peptides and proteins with intensity differences for pathway analysis. Results: Mass spectrometry quantified 8,258 peptides from 1,222 proteins in > 50%of patient samples at all three time points. Twelve peptides from 11 proteins showed differences in expression over time between patients with versus without POCD (q < 0.05), including proteins previously implicated in neurodegenerative disease pathophysiology. Additionally, 283 peptides from 182 proteins were identified with trend-level differences (q < 0.25) in expression over time between these groups. Among these, pathway analysis revealed that 50 were from 17 proteins mapping to complement and coagulation pathways (q = 2.44*10–13). Conclusion: These data demonstrate the feasibility of performing unbiased mass spectrometry on perioperative CSF samples to identify pathways associated with POCD. Additionally, they provide hypothesis-generating evidence for CSF complement and coagulation pathway changes in patients with POCD.

scholarly journals Cerebrospinal Fluid Proteomic Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction

2020 ◽  
Author(s):  
Keith W. VanDusen ◽  
Wenjing Qi ◽  
Yi-ju Li ◽  
Victor Cai ◽  
Ashley Hall ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
Cognitive Dysfunction ◽  
Cognitive Deficits ◽  
Mixed Model ◽  
Postoperative Cognitive Dysfunction ◽  
Neurologic Diseases ◽  
Patient Groups ◽  
Coagulation Pathway ◽  
Over Time

Abstract Background: Postoperative cognitive dysfunction (POCD) is a syndrome of cognitive deficits that occurs in 10-40% of patients age > 60 within 1-12 months after surgery, hypothesized to be caused in part by neuroinflammation. However, the specific neuroinflammatory pathways involved remain unclear. Unbiased mass spectrometry-based proteomic analyses have been used to identify neuro-inflammatory pathways in multiple neurologic diseases and syndromes but have not yet been used in the POCD field. Thus, we used unbiased mass spectrometry-based proteomics to compare cerebrospinal fluid (CSF) samples from patients with and without POCD to identify potential neuroinflammatory pathways for further investigation in future studies. Methods: We performed unbiased LC-MS/MS proteomics on immunodepleted CSF samples obtained before, 24 hours, and 6 weeks after major non-cardiac surgery in older adults who developed (n=8) or did not develop POCD (n=6). General linear mixed models were used to identify peptides and proteins with intensity differences between groups or over time by groups. Kyoto Encyclopedia of Genes and Genomes analysis was used to identify pathways containing proteins/peptides with q values < 0.25 in the mixed model. Results: Mass spectrometry quantified 8258 peptides from 1222 proteins in >50% of patient samples at all three time points. Twelve peptides from 11 proteins showed differences in expression over time between groups (POCD vs non-POCD) at q < 0.05, including several from proteins previously implicated in neurodegenerative disease pathophysiology. Additionally, 283 peptides from 182 proteins were identified with trend-level differences (q < 0.25) in expression over time between these patient groups. Of these 283 peptides with trend-level significance, pathway analysis revealed that 50 of them were from 17 proteins that mapped to the complement and coagulation pathways (q=2.44*10-13).Conclusions: These data demonstrate the feasibility of performing unbiased mass spectrometry on perioperative CSF samples to identify peptides, proteins, and pathways associated with POCD. Additionally, they provide hypothesis-generating evidence for CSF complement and coagulation pathway changes in patients with POCD.

scholarly journals Flow Cytometry Characterization of Cerebrospinal Fluid Monocytes in Patients With Postoperative Cognitive Dysfunction

2019 ◽  
Vol 129 (5) ◽  
pp. e150-e154 ◽  
Author(s):  
Miles Berger ◽  
David M. Murdoch ◽  
Janet S. Staats ◽  
Cliburn Chan ◽  
Jake P. Thomas ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cerebrospinal Fluid ◽  
Cognitive Dysfunction ◽  
Postoperative Cognitive Dysfunction

Cerebrospinal Fluid Biomarker for Alzheimer Disease Predicts Postoperative Cognitive Dysfunction

2016 ◽  
Vol 124 (2) ◽  
pp. 353-361 ◽  
Author(s):  
Lisbeth Evered ◽  
Brendan Silbert ◽  
David A. Scott ◽  
David Ames ◽  
Paul Maruff ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Alzheimer Disease ◽  
Cognitive Dysfunction ◽  
Postoperative Cognitive Dysfunction ◽  
Adverse Outcomes ◽  
Reliable Change Index ◽  
Enzyme Linked Immunosorbent Assay ◽  
Neurofilament Light ◽  
Cut Point ◽  
Significant Difference

Abstract Background Postoperative cognitive dysfunction (POCD) affects 16 to 21% of the elderly 3 months after anesthesia and surgery and is associated with adverse outcomes. The exact cause of POCD remains unknown. The authors hypothesized that elderly individuals with Alzheimer disease (AD) neuropathology, identified by cerebrospinal fluid (CSF) analysis, would have increased the risk for POCD. Methods CSF samples were collected from 59 patients 60 yr or older who received combined spinal and general anesthesia for elective total hip replacement. Patients underwent neuropsychological testing preoperatively and at 7 days, 3 months, and 12 months postoperatively. POCD at 3 months and cognitive decline at 12 months were calculated by using the reliable change index. CSF amyloid β1–42 (Aβ1–42), total-tau, phosphorylated-tau, and neurofilament light were assayed with enzyme-linked immunosorbent assay methods. Results POCD was identified in 5 of 57 patients (8.8%) at 3 months. For Aβ1–42, 11 patients were below the cut-point for AD neuropathology of whom 3 were classified with POCD (27.3%; 95% CI, 6.0 to 61%), whereas of the 46 patients above the cut-point, 2 were classified with POCD (4.3%; 95% CI, 0.5 to 14.8%) (P = 0.01). There was no significant difference in the incidence of POCD in relation to the cut-points for any of the other analytes. Conclusions Low CSF Aβ1–42 may be a significant predictor of POCD at 3 months. This indicates that patients with AD neuropathology even in the absence of clinically detectable AD symptoms may be susceptible to POCD.

scholarly journals The Effect of Dexmedetomidine on Cognitive Function and Protein Expression of Aβ, p-Tau, and PSD95 after Extracorporeal Circulation Operation in Aged Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Zhang ◽  
Yong Lin ◽  
Qing Liu ◽  
Xuemei Yuan ◽  
Anqiong Mao ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Prefrontal Cortex ◽  
Cognitive Function ◽  
Protein Expression ◽  
Cognitive Dysfunction ◽  
Extracorporeal Circulation ◽  
Postoperative Cognitive Dysfunction ◽  
Favorable Outcome ◽  
Neurologic Complications ◽  
Aged Rats

Postoperative cognitive dysfunction (POCD) is a kind of serious neurologic complications and dexmedetomidine has a certain effect on POCD. However, functional mechanism of dexmedetomidine on POCD still remains unclear, so the research mainly studied the effect of dexmedetomidine on cognitive function and protein expression in hippocampus and prefrontal cortex cerebrospinal fluid after extracorporeal circulation operation in aged rats. We Found that, compared with POCD group, the cognitive function was improved in POCD + Dex group. We speculate that dexmedetomidine could improve the cognitive function after extracorporeal circulation operation in aged rats and Aβ, p-Tau, and PSD95 protein might have contributed to this favorable outcome.

Cerebrospinal Fluid Biomarker for Alzheimer Disease Predicts Postoperative Cognitive Dysfunction

2016 ◽  
Vol 60 (5) ◽  
pp. 195-196 ◽  
Author(s):  
Lisbeth Evered ◽  
Brendan Silbert ◽  
David A. Scott ◽  
David Ames ◽  
Paul Maruff ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Alzheimer Disease ◽  
Cognitive Dysfunction ◽  
Postoperative Cognitive Dysfunction ◽  
Fluid Biomarker

Postoperative Cognitive Dysfunction In Older Alcoholics

2007 ◽  
Author(s):  
Judith A. Hudetz ◽  
Diane Reddy ◽  
Kathleen Patterson ◽  
Anthony G. Hudetz ◽  
David C. Warltier
Keyword(s):  
Cognitive Dysfunction ◽  
Postoperative Cognitive Dysfunction

Postoperative cognitive dysfunction: progress mechanisms and clinical characteristics

2019 ◽  
Vol 2 (19) ◽  
pp. 29-33
Author(s):  
K. B. Manysheva ◽  
M. A. Akhmedov ◽  
A. A. Rakhmanova ◽  
S. M. Khutalieva
Keyword(s):  
Cognitive Dysfunction ◽  
Clinical Characteristics ◽  
Cognitive Deficit ◽  
Neuropsychological Testing ◽  
Postoperative Cognitive Dysfunction ◽  
Clinical Manifestations ◽  
Postoperative Recovery ◽  
Neuropsychological Rehabilitation ◽  
Brain Barrier Permeability ◽  
The Central Nervous System

The article is devoted to the study of postoperative cognitive dysfunction — a syndrome that is often found in the postoperative period and does not depend on the volume of surgeon. Based on the analysis of the results of modern studies, the authors cite the most likely etiological causes of the syndrome, grouped according to different categories of risk factors. The pathogenetic algorithm for cognitive dysfunction includes the appearance of systemic inflammation, improving blood-brain barrier permeability with the endothelial dysfunction, the migration of inflammatory agents into the central nervous system, and the formation of oxidative stress. The clinical manifestations of cognitive deficit in the outcome of surgeon performed under general anesthesia, the authors illustrate with their own observations of patients with a neurosurgical profile with spinal pathology operated on with the use of propofol anesthesia, comparing the results of neuropsychological testing with an assessment of the level of anxiety. In conclusion, the authors outline a strategy for the prevention of postoperative cognitive dysfunction and recommend conducting neuropsychological rehabilitation as an important component of postoperative recovery for all patients with a diagnosed cognitive deficit that occurred after surgery.

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