Hemostatic Abnormalities in Dementia: A Systematic Review and Meta-Analysis

Loures, Cristina de Mello Gomide; Duarte, Rita Carolina Figueiredo; Silva, Marcos Vinícius Ferreira; Cicarini, Walter Batista; Souza, Leonardo Cruz de; Caramelli, Paulo; Borges, Karina Braga Gomes; Carvalho, Maria das Graças

doi:10.1055/s-0039-1688444

Cited by 17 publications

(11 citation statements)

References 65 publications

(82 reference statements)

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“…It was suggested that these components increased VaD risk by altering fibrin clot formation and lysis activity through the FVIII / von Willebrand factor complex and elevated plasminogen activator inhibitor-1 (impaired fibrinolytic activity), which lead to hypercoagulability and microinfarction ( 104 ). Further systematic reviews and meta-analyses support associations between fibrinogen, FVIII, D-dimer, FVIIa, and von Willebrand factor in VaD patients ( 105 , 106 ).…”

Section: Coagulation and Complement Systems In Vascular Dementiamentioning

confidence: 81%

Vascular Dementia and Crosstalk Between the Complement and Coagulation Systems

Parsi

Duval

Ariëns

2021

Front. Cardiovasc. Med.

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Vascular Dementia (VaD) is a neurocognitive disorder caused by reduced blood flow to the brain tissue, resulting in infarction, and is the second most common type of dementia. The complement and coagulation systems are evolutionary host defence mechanisms activated by acute tissue injury to induce inflammation, clot formation and lysis; recent studies have revealed that these systems are closely interlinked. Overactivation of these systems has been recognised to play a key role in the pathogenesis of neurological disorders such as Alzheimer's disease and multiple sclerosis, however their role in VaD has not yet been extensively reviewed. This review aims to bridge the gap in knowledge by collating current understanding of VaD to enable identification of complement and coagulation components involved in the pathogenesis of this disorder that may have their effects amplified or supressed by crosstalk. Exploration of these mechanisms may unveil novel therapeutic targets or biomarkers that would improve current treatment strategies for VaD.

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Section: Coagulation and Complement Systems In Vascular Dementiamentioning

confidence: 81%

Vascular Dementia and Crosstalk Between the Complement and Coagulation Systems

Parsi

Duval

Ariëns

2021

Front. Cardiovasc. Med.

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“…The DEGs obtained were remarkably enriched in GO terms and pathway under defense response, whole membrane, molecular transducer activity, neutrophil degranulation, ion transport, integral component of plasma membrane, transporter activity and neuronal system. Defense response [Licastro and Chiappelli, 2003], cell activation [Schubert and Rudolphi, 1998], whole membrane [Paonessa et al 2019], intrinsic component of plasma membrane [Verdier et al 2004], neutrophil degranulation [Licastro et al 1994], innate immune system [van der Willik et al 2019], hemostasis [Loures et al 2019], ion transport [Benos et al 1994], neuron projection [Bondareff et al 1982], transporter activity [Jellinger et al 2020], neuronal system [Seeley, 2008] and axon guidance [Zhou et al 2012] were responsible for progression of dementia. HGF (hepatocyte growth factor) [Sharma, 2010], HLA-DRB1 [Lu et al 2017], CHI3L1 [Lananna et al 2020], S100A8 [Lodeiro et al 2017 [Halks-Miller et al 2003], ALOX5AP [Manev and Manev, 2006], FPR2 [Iribarren et al 2005], CR1 [Mahmoudi et al 2018], CFI (complement factor I) [Lashkari et al 2018], AQP4 [Zeppenfeld et al 2017], SLC11A1 [Jamieson et al 2005], CTSS (cathepsin S) [Lemere et al 1995 [Matsumura et al 2015], CD74 [Kiyota et al 2015], LTF (lactotransferrin) [Wang et al 2010], LYZ (lysozyme) [Sandin et al 2016], S100A10 [King et al 2020], AQP1 [Nikpour et al 2020], GPR84 [Audoy-Rémus et al 2015], HPSE (heparanase) [García et al 2017], NGFR (nerve growth factor receptor) [Cheng et al 2012], RHOQ (ras homolog family member Q) [Tian et al 2021], EGF (epidermal...…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis

Vastrad¹,

Vastrad²

2021

Preprint

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To provide a better understanding of dementia at the molecular level, this study aimed to identify the genes and key pathways associated with dementia by using integrated bioinformatics analysis. Based on the expression profiling by high throughput sequencing dataset GSE153960 derived from the Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) between patients with dementia and healthy controls were identified. With DEGs, we performed a series of functional enrichment analyses. Then, a protein protein interaction (PPI) network, modules, miRNA hub gene regulatory network and TF hub gene regulatory network was constructed, analyzed and visualized, with which the hub genes miRNAs and TFs nodes were screened out. Finally, validation of hub genes was performed by using receiver operating characteristic curve (ROC) analysis and RT PCR. A total of 948 DEGs were screened out, among which 475 genes were up regulated; while 473 were down regulated. Functional enrichment analyses indicated that DEGs were mainly involved in defense response, ion transport, neutrophil degranulation and neuronal system. The hub genes (CDK1, TOP2A, MAD2L1, RSL24D1, CDKN1A, NOTCH3, MYB, PWP2, WNT7B and HSPA12B) were identified from PPI network, modules, miRNA hub gene regulatory network and TF hub gene regulatory network. We identified a series of key genes along with the pathways that were most closely related with dementia initiation and progression. Our results provide a more detailed molecular mechanism for the advancement of dementia, shedding light on the potential biomarkers and therapeutic targets.

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“…More recently, a systematic review and metaanalysis synthesized findings from 32 identified studies on the role of the hemostatic system (including some coagulation factors) in cognitive decline in older persons. Among individuals with vascular dementia, higher levels of FVIII were observed together with other coagulation factors [35].…”

Section: Plos Onementioning

confidence: 98%

Coagulation factor VIII, white matter hyperintensities and cognitive function: Results from the Cardiovascular Health Study

et al. 2020

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Objective To investigate the relationship between high FVIII clotting activity (FVIII:C), MRI-defined white matter hyperintensities (WMH) and cognitive function over time. Methods Data from the population-based Cardiovascular Health Study (n = 5,888, aged ≥65) were used. FVIII:C was measured in blood samples taken at baseline. WMH burden was assessed on two cranial MRI scans taken roughly 5 years apart. Cognitive function was assessed annually using the Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Test (DSST). We used ordinal logistic regression models adjusted for demographic and cardiovascular factors in cross-sectional and longitudinal WMH analyses, and adjusted linear regression and linear mixed models in the analyses of cognitive function. Results After adjustment for confounding, higher levels of FVIII:C were not strongly associated with the burden of WMH on the initial MRI scan (OR>p75 = 1.20, 95% CI 0.99–1.45; N = 2,735) nor with WMH burden worsening over time (OR>p75 = 1.18, 95% CI 0.87–1.59; N = 1,527). High FVIII:C showed no strong association with cognitive scores cross-sectionally (3MSE>p75 β = -0.06, 95%CI -0.45 to 0.32, N = 4,005; DSST>p75 β = -0.69, 95%CI -1.52 to 0.13, N = 3,954) or over time (3MSE>p75 β = -0.07,95% CI -0.58 to 0.44, N = 2,764; DSST>p75 β = -0.22, 95% CI -0.97 to 0.53, N = 2,306) after confounding adjustment. Interpretation The results from this cohort study of older adult participants indicate no strong relationships between higher FVIII:C levels and WMH burden or cognitive function in cross-sectional and longitudinal analyses.

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Hemostatic Abnormalities in Dementia: A Systematic Review and Meta-Analysis

Cited by 17 publications

References 65 publications

Vascular Dementia and Crosstalk Between the Complement and Coagulation Systems

Vascular Dementia and Crosstalk Between the Complement and Coagulation Systems

Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis

Coagulation factor VIII, white matter hyperintensities and cognitive function: Results from the Cardiovascular Health Study

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