Dataset Information

Fibrinogen Levels and Cognitive Profile Differences in Patients with Mild Cognitive Impairment.

ABSTRACT:

Background

Fibrinogen is considered a marker of vascular pathology, indicating a weakened blood-brain barrier, and has a causative role in neuroinflammation and neurodegeneration. Little is known about the relationship between fibrinogen levels and cognitive function in patients with mild cognitive impairment (MCI). We aimed to investigate differences in cognitive profiles according to plasma fibrinogen levels in patients with MCI and the influence of plasma fibrinogen levels on cognitive decline.

Methods

This retrospective cohort study included 643 patients with MCI: 323 patients in the high fibrinogen (high fib) group and 320 patients in the low fibrinogen (low fib) group. A multiple linear regression model was performed to compare cognitive test performance between groups. The Cox proportional hazard model was used to analyze the hazard ratio of fibrinogen level for disease progression.

Results

The high fib group demonstrated poorer performance in attention, executive function, and confrontation naming than the low fib group. After adjustment for APOE genotype, the high fib group was associated with poor attention and executive function. After adjustment for vascular risk factors including body mass index, hypertension, diabetes mellitus, dyslipidemia, and smoking history, the high fib group showed declined attention and confrontation naming ability. High fibrinogen levels did not predict disease progression to CDR 1.

Conclusion

High plasma fibrinogen levels were associated with poor performance in attention in patients with MCI, regardless of APOE genotype or vascular risk factors.

SUBMITTER: Pyun JM

PROVIDER: S-EPMC7949208 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Fibrinogen Levels and Cognitive Profile Differences in Patients with Mild Cognitive Impairment.

Pyun Jung-Min JM Ryoo Nayoung N Park Young Ho YH Kim SangYun S

Dementia and geriatric cognitive disorders 20201103 5

<h4>Background</h4>Fibrinogen is considered a marker of vascular pathology, indicating a weakened blood-brain barrier, and has a causative role in neuroinflammation and neurodegeneration. Little is known about the relationship between fibrinogen levels and cognitive function in patients with mild cognitive impairment (MCI). We aimed to investigate differences in cognitive profiles according to plasma fibrinogen levels in patients with MCI and the influence of plasma fibrinogen levels on cognitiv ...[more]

PMID: 33142286

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Project description:Background Cognitive impairment is the main manifestation of diabetes central neuropathy. Currently, there is no effective dementia treatment; early diagnosis and treatment are particularly crucial. Inflammation index fibrinogen-to-albumin ratio (FAR) has been shown to predict complications of type 2 diabetes (diabetic kidney disease and diabetes-related arteriosclerosis), but its relationship with mild cognitive impairment (MCI) in type 2 diabetes (T2D) is undetermined. In this study, we examined the association between the FAR and mild cognitive impairment in type 2 diabetes. Methods This is a retrospective and cross-sectional study. From January 2022 to December 2022, we have retrieved 328 inpatient medical records for T2D patients hospitalized at the First Hospital of Harbin Medical University from the hospital’s electronic system. Subjects’ cognitive function was assessed and grouped by the MoCA scales. Subjects’ demographic and various laboratory indicators were collected. Using Spearman’s bivariate correlation analysis, the FAR and other clinical variables were analyzed for association strength. A multiple linear regression analysis was conducted to determine the independent relationship between FAR and MoCA scores. Multivariate logistic regression was used to analyze the independent relationship between FAR and MCI. The capacity of the FAR to detect MCI was carried using receiver operating characteristic (ROC) analysis. Results The included participants’ (n = 328; 61.9% male) mean age was 52.62 ± 10.92 years. MoCA scores and MCI prevalence significantly differed (p < 0.05) between the four subgroups of FAR quartiles. The FAR and the MoCA score were significantly negatively correlated in the entire population (p < 0.05). Based on the multiple linear regression analysis, lnFAR and lnMoCA are significantly correlated (β = −0.449, t = −8.21, p < 0.05, R2 = 0.469). In multivariate logistic regression analysis, FAR and MCI were independently correlated after adjusting for covariates (OR 95% CI 34.70 [13.90–86.66]). Finally, the analysis of receptor working characteristics shows that the optimal FAR cut-off value was 0.08 (sensitivity: 95.81%, specificity: 84.47%) for detecting MCI in type 2 diabetes. Conclusion In type 2 diabetes, the FAR was positive associations with MCI and negative associations with MoCA score. The high FAR was associated with an increased risk of MCI. FAR maybe a appropriate indicator of MCI risk for type 2 diabetes.

Project description:IntroductionWhile Alzheimer's disease (AD) is divided into severity stages, mild cognitive impairment (MCI) remains a solitary construct despite clinical and prognostic heterogeneity. This study aimed to characterize differences in genetic, cerebrospinal fluid (CSF), neuroimaging, and neuropsychological markers across clinician-derived MCI stages.MethodsVanderbilt Memory & Aging Project participants with MCI were categorized into 3 severity subtypes at screening based on neuropsychological assessment, functional assessment, and Clinical Dementia Rating interview, including mild (n = 18, 75 ± 8 years), moderate (n = 89 72 ± 7 years), and severe subtypes (n = 18, 78 ± 8 years). At enrollment, participants underwent neuropsychological testing, 3T brain magnetic resonance imaging (MRI), and optional fasting lumbar puncture to obtain CSF. Neuropsychological testing and MRI were repeated at 18-months, 3-years, and 5-years with a mean follow-up time of 3.3 years. Ordinary least square regressions examined cross-sectional associations between MCI severity and apolipoprotein E (APOE)-ε4 status, CSF biomarkers of amyloid beta (Aβ), phosphorylated tau, total tau, and synaptic dysfunction (neurogranin), baseline neuroimaging biomarkers, and baseline neuropsychological performance. Longitudinal associations between baseline MCI severity and neuroimaging and neuropsychological trajectory were assessed using linear mixed effects models with random intercepts and slopes and a follow-up time interaction. Analyses adjusted for baseline age, sex, race/ethnicity, education, and intracranial volume for MRI models.ResultsStages differed at baseline on APOE-ε4 status (early < middle = late; p-values < 0.03) and CSF Aβ (early > middle = late), phosphorylated and total tau (early = middle < late; p-values < 0.05), and neurogranin concentrations (early = middle < late; p-values < 0.05). MCI stage related to greater longitudinal cognitive decline, hippocampal atrophy, and inferior lateral ventricle dilation (early < late; p-values < 0.03).DiscussionClinician staging of MCI severity yielded longitudinal cognitive trajectory and structural neuroimaging differences in regions susceptible to AD neuropathology and neurodegeneration. As expected, participants with more severe MCI symptoms at study entry had greater cognitive decline and gray matter atrophy over time. Differences are likely attributable to baseline differences in amyloidosis, tau, and synaptic dysfunction. MCI staging may provide insight into underlying pathology, prognosis, and therapeutic targets.

Project description:BackgroundLow levels of plasma apolipoprotein E (apoE) and presence of the APOE ε4 allele are associated with an increased risk of Alzheimer's disease (AD). Although the increased risk of AD in APOE ε4-carriers is well-established, the protein levels have received limited attention.MethodsWe here report the total plasma apoE and apoE isoform levels at baseline from a longitudinally (24 months) followed cohort including controls (n = 39), patients with stable amnestic mild cognitive impairment during 24 months follow up (MCI-MCI, n = 30), patients with amnestic MCI (aMCI) that during follow-up were clinically diagnosed with AD with dementia (ADD) (MCI-ADD, n = 28), and patients with AD with dementia (ADD) at baseline (ADD, n = 28). We furthermore assessed associations between plasma apoE levels with cerebrospinal fluid (CSF) AD biomarkers and α-synuclein, as well as both CSF and plasma neurofilament light chain (NfL), YKL-40 and kallikrein 6.ResultsIrrespective of clinical diagnosis, the highest versus the lowest apoE levels were found in APOE ε2/ε3 versus APOE ε4/ε4 subjects, with the most prominent differences exhibited in females. Total plasma apoE levels were 32% and 21% higher in the controls versus MCI-ADD and ADD patients, respectively. Interestingly, MCI-ADD patients exhibited a 30% reduction in plasma apoE compared to MCI-MCI patients. This decrease appeared to be associated with brain amyloid-β (Aβ42) pathology regardless of disease status as assessed using the Amyloid, Tau, and Neurodegeneration (A/T/N) classification. In addition to the association between low plasma apoE and low levels of CSF Aβ42, lower apoE levels were also related to higher levels of CSF total tau (t-tau) and tau phosphorylated at Threonine 181 residue (p-tau) and NfL as well as a worse performance on the mini-mental-state-examination. In MCI-ADD patients, low levels of plasma apoE were associated with higher levels of CSF α-synuclein and kallikrein 6. No significant correlations between plasma apoE and the astrocytic inflammatory marker YKL40 were observed.ConclusionsOur results demonstrate important associations between low plasma apoE levels, Aβ pathology, and progression from aMCI to a clinical ADD diagnosis.

Dataset Information

Fibrinogen Levels and Cognitive Profile Differences in Patients with Mild Cognitive Impairment.

Background

Methods

Results

Conclusion

Publications

Fibrinogen Levels and Cognitive Profile Differences in Patients with Mild Cognitive Impairment.

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