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.

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

scholarly journals Effects of L-655,708 on expression changes of GABA, glutamate, and beta-endorphin induced by propofol anesthesia in rats

2018 ◽  
Vol 16 ◽  
pp. 205873921879670
Author(s):  
Jin Wang ◽  
Xinyi Li ◽  
Huisheng Wu ◽  
Jianjuan Ke ◽  
Zongze Zhang ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Cognitive Dysfunction ◽  
Sham Group ◽  
Postoperative Cognitive Dysfunction ◽  
Expression Level ◽  
Control Group ◽  
Beta Endorphin ◽  
Anesthetized Rats ◽  
Significant Difference ◽  
Dentate Gyrus Region

Anesthetics are considered to be one of the important inducing factors of postoperative cognitive dysfunction (POCD). The hippocampal region of the rat is one of the action sites of general anesthesia drugs. L 655,708, a reverse agonist of gamma aminobutyric acid (GABA) receptor, can significantly improve short-term memory dysfunction in mice after anesthetized with isoflurane. So the purpose of this study is to investigate the effects of L-655,708 on expression of GABA, glutamate (GLU), and beta-endorphin (β-EP) in the dentate gyrus region of the hippocampus and cognition of rats anesthetized with propofol. In all, 30 male Sprague–Dawley (SD) rats were randomly allocated into the control group, sham group, and L-655,708 group, with 10 in each group. The cognitive function of rats was measured by Morris water maze before and 1 h after administration. Then the rats were sacrificed for brain tissues. Immunohistochemistry was used to study the expression of GABA, GLU, and β-EP in the hippocampus of anesthetized rats in each group. Compared with the control group, the latency of the sham group and L-655,708 group were significantly prolonged after administration ( P < 0.05). However, L-655,708 could shorten the prolonged latency ( P < 0.05). There was no significant difference in times of accessing original platform area between the three groups before and after medication ( P > 0.05). The expression level of GABA in the dentate gyrus region of hippocampus of rats in the sham group was significantly higher than that in the control group ( P < 0.05), while the expression level in the L-655,708 group was significantly lower than that in the sham group ( P < 0.05). No significant difference was found in the expression of GLU in the dentate gyrus region of hippocampus of rats in each group ( P > 0.05). Compared with the control group, the expression of β-EP was significantly lower in the dentate gyrus region of the hippocampus of sham group rats ( P < 0.05). However, the expression of β-EP in the L-655,708 group was significantly higher than that in the sham group ( P < 0.05). Cognitive dysfunction in rats anesthetized with propofol may be related to high expression of GABA and low expression of β-EP in the hippocampus. The mechanism of L-655,708 in reducing the cognitive impairment in propofol anesthetized rats may be bound up with down-regulating the expression of GABA and increasing the expression of β-EP in the hippocampus.

scholarly journals Does cognitive dysfunction correlate with neurofilament light polypeptide levels in the CSF of patients with multiple sclerosis?

2019 ◽  
Vol 47 (5) ◽  
pp. 2187-2198 ◽  
Author(s):  
Thaleia Kalatha ◽  
Marianthi Arnaoutoglou ◽  
Theodoros Koukoulidis ◽  
Eleni Hatzifilippou ◽  
Emmanouil Bouras ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Dysfunction ◽  
Verbal Learning ◽  
Preliminary Evidence ◽  
Enzyme Linked Immunosorbent Assay ◽  
Neurofilament Light ◽  
Potential Biomarker ◽  
Z Scores ◽  
Learning Test ◽  
Serial Addition

Objective To investigate whether neurofilament light polypeptide (NfL) level in cerebrospinal fluid (CSF), currently a prognostic biomarker of neurodegeneration in patients with multiple sclerosis (MS), may be a potential biomarker of cognitive dysfunction in MS. Methods This observational case–control study included patients with MS. CSF levels of NfL were determined using enzyme-linked immunosorbent assay. Cognitive function was measured with the Brief International Cognitive Assessment for MS (BICAMS) battery and Paced Auditory Serial Addition Test (PASAT3), standardized to the Greek population. Results Of 39 patients enrolled (aged 42.7 ± 13.6 years), 36% were classified as cognitively impaired according to BICAMS z-scores (–0.34 ± 1.13). Relapsing MS was significantly better than progressive forms regarding BICAMS z-score (mean difference [MD] 1.39; 95% confidence interval [CI] 0.54, 2.24), Symbol Digit Modality Test score (MD 1.73; 95% CI 0.46, 3.0) and Greek Verbal Learning Test (MD 1.77; 95% CI 0.82, 2.72). An inversely proportional association between CSF NfL levels and BICAMS z-scores was found in progressive forms of MS (rp = –0.944). Conclusions This study provides preliminary evidence for an association between CSF NfL levels and cognition in progressive forms of MS, which requires validation in larger samples.

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 levels of chitinase 3-like 1 and neurofilament light chain predict multiple sclerosis development and disability after optic neuritis

2015 ◽  
Vol 21 (14) ◽  
pp. 1761-1770 ◽  
Author(s):  
S Modvig ◽  
M Degn ◽  
H Roed ◽  
TL Sørensen ◽  
HBW Larsson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Optic Neuritis ◽  
Light Chain ◽  
Oligoclonal Bands ◽  
Enzyme Linked Immunosorbent Assay ◽  
Csf Biomarkers ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Background: Cerebrospinal fluid (CSF) biomarkers have been suggested to predict multiple sclerosis (MS) after clinically isolated syndromes, but studies investigating long-term prognosis are needed. Objective: To assess the predictive ability of CSF biomarkers with regard to MS development and long-term disability after optic neuritis (ON). Methods: Eighty-six patients with ON as a first demyelinating event were included retrospectively. Magnetic resonance imaging (MRI), CSF leukocytes, immunoglobulin G index and oligoclonal bands were registered. CSF levels of chitinase-3-like-1, osteopontin, neurofilament light-chain, myelin basic protein, CCL2, CXCL10, CXCL13 and matrix metalloproteinase-9 were measured by enzyme-linked immunosorbent assay. Patients were followed up after 13.6 (range 9.6–19.4) years and 81.4% were examined, including Expanded Disability Status Scale and MS functional composite evaluation. 18.6% were interviewed by phone. Cox regression, multiple regression and Spearman correlation analyses were used. Results: Forty-six (53.5%) developed clinically definite MS (CDMS) during follow-up. In a multivariate model MRI ( p=0.0001), chitinase 3-like 1 ( p=0.0033) and age ( p=0.0194) combined predicted CDMS best. Neurofilament light-chain predicted long-term disability by the multiple sclerosis severity scale ( p=0.0111) and nine-hole-peg-test ( p=0.0202). Chitinase-3-like-1 predicted long-term cognitive impairment by the paced auditory serial addition test ( p=0.0150). Conclusion: Neurofilament light-chain and chitinase-3-like-1 were significant predictors of long-term physical and cognitive disability. Furthermore, chitinase-3-like-1 predicted CDMS development. Thus, these molecules hold promise as clinically valuable biomarkers after ON as a first demyelinating event.

scholarly journals Cognitive Dysfunction and Mortality After Carotid Endarterectomy

2021 ◽  
Vol 11 ◽  
Author(s):  
Kristiina Relander ◽  
Marja Hietanen ◽  
Krista Nuotio ◽  
Petra Ijäs ◽  
Irene Tikkala ◽  
...  
Keyword(s):  
Carotid Endarterectomy ◽  
Cognitive Dysfunction ◽  
Prognostic Significance ◽  
Postoperative Cognitive Dysfunction ◽  
Reliable Change Index ◽  
Stable Phase ◽  
Functional Domain ◽  
Cognitive Changes ◽  
Term Survival

Background: Carotid endarterectomy (CEA) has been associated with both postoperative cognitive dysfunction (POCD) and improvement (POCI). However, the prognostic significance of postoperative cognitive changes related to CEA is largely unknown. The aim of this study was to examine the associations between postoperative cognitive changes after CEA and long-term survival.Methods: We studied 43 patients 1 day before CEA as well as 4 days and 3 months after surgery with an extensive neuropsychological test array, and followed them for up to 14 years. POCD and POCI relative to baseline were determined with the reliable change index derived from 17 healthy controls. Associations between POCD/POCI and mortality within the patient group were studied with Cox regression analyses adjusted for confounders.Results: POCD in any functional domain was evident in 28% of patients 4 days after surgery and in 33% of patients 3 months after surgery. POCI was shown in 23% of patients at 4 days and in 44% of patients at 3 months. POCD at 3 months was associated with higher long-term mortality (hazard ratio 5.0, 95% CI 1.8–13.9, p = 0.002) compared with patients with no cognitive decline.Conclusions: Our findings suggest that POCD in a stable phase, 3 months after CEA predicts premature death. Evaluation of postoperative cognitive changes is essential, and POCD in a stable phase after CEA should prompt scrutiny of underlying factors and better adherence to therapies to prevent recurrences and to promote early intervention in imminent deterioration.

scholarly journals The Effect of Dexmedetomidine and Esmolol on Early Postoperative Cognitive Dysfunction After Middle Ear Surgery Under Hypotensive Technique: A Comparative, Randomized, Double-blind Study

2020 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mahmoud Hussein Bahr ◽  
Samaa A Kasem Rashwan ◽  
Doaa Abu Elkassim Rashwan
Keyword(s):  
Cognitive Dysfunction ◽  
Middle Ear ◽  
Postoperative Cognitive Dysfunction ◽  
Adult Patients ◽  
Cerebral Injury ◽  
Middle Ear Surgery ◽  
Double Blind Study ◽  
Arterial Blood ◽  
Hypotensive Anesthesia ◽  
Significant Difference

Objectives: Postoperative cognitive dysfunction (POCD) is multifactorial, which may be caused by anesthetic and surgical causes or cerebral injury. This study aimed to evaluate the effect of dexmedetomidine as a neuroprotective drug compared to esmolol on the prevalence of POCD in adult patients undergoing middle ear surgeries under hypotensive anesthesia. Methods: This study included male and female adult patients, according to American Society of Anesthesiology physical status (ASA) I, the patients who underwent middle ear surgeries under hypotensive anesthesia were randomly assigned to two groups that received esmolol and dexmedetomidine. The demographic data, heart rate, mean arterial blood pressure, duration of the surgery, evaluation of the surgical field, and the Mini-Mental State Examination (MMSE) (preoperatively and at 1, 6 and 24 hours postoperatively) were recorded. Results: There was a significant difference between the numbers of patients who had POCD in MMSE1: 12 cases in the esmolol group (41.37%) compared to three cases in the dexmedetomidine group (10.34%) (P = 0.016), in MMSE6: 10 cases in the esmolol group (34.48%) compared with two cases in the dexmedetomidine group (6.89%) (P = 0.023) and in MMSE24: seven cases in the esmolol group (24.13%) compared with one case in the dexmedetomidine group (3.44%) (P = 0.022), while the median and range of MMSE score were comparable between the two groups (P > 0.05). Conclusions: This study suggests that intraoperative use of dexmedetomidine as an adjuvant to hypotensive anesthesia reduces the incidence of POCD compared to esmolol.

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