Fibrinolysis and von Willebrand factor in Alzheimer's disease and vascular dementia – a case-referent study

Hagnelius, Nils-Olof; Boman, Kurt; Nilsson, Torbjörn

doi:10.1016/j.thromres.2009.10.001

Cited by 12 publications

(11 citation statements)

References 35 publications

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“…No differences were observed in activated partial thromboplastin time, 28,30 30,31 thrombin-antithrombin complex, 30,31 PAI-1, 30-34 t-PA, 30,31,33 activated protein C activity, 30,31 and platelet counts 28,35 between VD and controls. An increase in levels of fibrinogen (►Fig.…”

Section: Mild Cognitive Impairmentmentioning

confidence: 89%

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

Loures

Duarte

Silva

et al. 2019

Semin Thromb Hemost

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Alzheimer's disease (AD) is considered the most frequent cause of dementia. It is known that vascular risk factors play an important role in the development and progression of this condition. Alterations in vascular walls represent documented findings in patients with AD and other dementias affecting elderly people. The authors performed a systematic review and meta-analysis, aiming to synthesize observational studies that evaluated how the hemostatic system may contribute to cognitive decline in the elderly, using papers published until April 2018 and as indexed in Medline (PubMed), Scopus, Web of Science, ScienceDirect, Lilacs, Cinahl, PsycINFO, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. Among 5,278 studies identified, 32 were included in the final synthesis, and these included 485 patients with mild cognitive impairment, 568 with vascular dementia (VD), 1,781 with AD, and 2,855 participants without dementia. AD patients had increased plasma von Willebrand factor (VWF) (standardized mean difference [SMD]: 2.53; 95% confidence interval [CI]: 0.10–4.95), D-dimer (SMD: 0.50; 95% CI: 0.35–0.66), plasminogen activator inhibitor-1 (SMD: 3.34; 95% CI: 1.01–5.67), thrombomodulin (SMD: 1.08; 95% CI: 0.53–1.62), and homocysteine levels (SMD: 0.65; 95% CI: 0.15–1.15). In contrast, the VD group showed increased fibrinogen levels (SMD: 0.77; 95% CI: 0.13–1.41), activated factor VII (SMD: 0.36; 95% CI: 0.05–0.67), factor VIII (SMD: 0.57; 95% CI: 0.22–0.91), VWF (SMD: 2.34; 95% CI: 0.38–4.29), D-dimer (SMD: 1.14; 95% CI: 0.51–1.78), and homocysteine (SMD: 2.17; 95% CI: 1.67–2.68). AD showed an elevation in some markers of endothelial dysfunction, whereas VD presented mostly an involvement of coagulation cascade components.

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Section: Mild Cognitive Impairmentmentioning

confidence: 89%

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

Loures

Duarte

Silva

et al. 2019

Semin Thromb Hemost

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“…Future studies might benefit from including two vascular markers to generate a capillary mask and reduce the bias resulting from missing vessels because protein expression of many capillary markers is reported to change in AD. 18,28…”

Section: Discussionmentioning

confidence: 99%

An automated method measures variability in P-glycoprotein and ABCG2 densities across brain regions and brain matter

Kannan

Schain

Kretzschmar

et al. 2016

J Cereb Blood Flow Metab

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Changes in P-glycoprotein and ABCG2 densities may play a role in amyloid-beta accumulation in Alzheimer's disease. However, previous studies report conflicting results from different brain regions, without correcting for changes in vessel density. We developed an automated method to measure transporter density exclusively within the vascular space, thereby correcting for vessel density. We then examined variability in transporter density across brain regions, matter, and disease using two cohorts of post-mortem brains from Alzheimer's disease patients and age-matched controls. Changes in transporter density were also investigated in capillaries near plaques and on the mRNA level. P-glycoprotein density varied with brain region and matter, whereas ABCG2 density varied with brain matter. In temporal cortex, P-glycoprotein density was 53% lower in Alzheimer's disease samples than in controls, and was reduced by 35% in capillaries near plaque deposits within Alzheimer's disease samples. ABCG2 density was unaffected in Alzheimer's disease. No differences were detected at the transcript level. Our study indicates that region-specific changes in transporter densities can occur globally and locally near amyloid-beta deposits in Alzheimer's disease, providing an explanation for conflicting results in the literature. When differences in region and matter are accounted for, changes in density can be reproducibly measured using our automated method.

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“…Higher levels of the hemostatic markers von Willebrand factor (vWF), coagulation factor VIII (FVIII), and D-dimer have also been related to risk of cognitive impairment and dementia. [6][7][8][9] ABO blood group is associated with many forms of CVD, including coronary heart disease (CHD), stroke, and venous thromboembolism. [10][11][12] In general, individuals with blood group O have a reduced risk of CVD.…”

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confidence: 99%

ABO blood type, factor VIII, and incident cognitive impairment in the REGARDS cohort

et al. 2014

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Objective: To assess the relationships among ABO group, factor VIII (FVIII), and incident cognitive impairment in a large, prospective cohort study of black and white adults in the United States using a nested case-control design.Methods: Incident cognitive impairment was defined using cognitive domain tests over a mean follow-up of 3.4 years. ABO blood group was measured by genotyping in a nested case-control sample of 495 cases with cognitive impairment and 587 controls.Results: Those with blood group AB and those with higher FVIII had an increased risk of cognitive impairment, adjusting for age, race, region, and sex (respective odds ratios 1.82, 95% confidence interval [CI] 1.15-2.90; and 1.24, 95% CI 1.10-1.38 for 40 IU/dL higher FVIII). Mean FVIII was higher in those with blood type AB (142 IU/dL; 95% CI 119-165) compared with O (104 IU/dL; 95% CI 101-107), and FVIII mediated 18% of the association between AB group and incident cognitive impairment (95% CI for mediation 230% to 68%).Conclusions: Blood group AB and higher FVIII were associated with increased incidence of cognitive impairment in this prospective study. The association of blood group AB with incident cognitive impairment was not significantly mediated by FVIII levels. There is a growing understanding that cardiovascular disease (CVD) and cognitive impairment share many common risk factors. Hypertension, 1,2 elevated cholesterol, 3 hyperglycemia, 2,4 and obesity 4,5 are all associated with longitudinal declines in cognitive function and dementia. Higher levels of the hemostatic markers von Willebrand factor (vWF), coagulation factor VIII (FVIII), and D-dimer have also been related to risk of cognitive impairment and dementia. [6][7][8][9] ABO blood group is associated with many forms of CVD, including coronary heart disease (CHD), stroke, and venous thromboembolism. [10][11][12] In general, individuals with blood group O have a reduced risk of CVD.13,14 Non-O blood types are associated with higher levels of vWF and FVIII, procoagulant proteins that circulate as a complex in blood, 11,12 because the ABO antigen affects clearance of vWF.15 Levels of both vWF and FVIII are associated with thrombosis, 16 and were recently linked to dementia risk. 17 A recent report demonstrating an association between blood type AB and stroke risk found that 60% of that association was mediated by differences in FVIII level. 18Although ABO blood group is a CVD risk factor, we are not aware of studies on its relationship with cognitive impairment. In this study, we examined the relationships among ABO group, FVIII, and incident cognitive impairment in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. We hypothesized that blood group A, B, or AB would be associated with an increased risk of cognitive impairment relative to group O.

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Fibrinolysis and von Willebrand factor in Alzheimer's disease and vascular dementia – a case-referent study

Cited by 12 publications

References 35 publications

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

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

An automated method measures variability in P-glycoprotein and ABCG2 densities across brain regions and brain matter

ABO blood type, factor VIII, and incident cognitive impairment in the REGARDS cohort

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