Association between circulating hemostatic measures and dementia or cognitive impairment: systematic review and meta‐analyzes

Quinn, Terence J.; Gallacher, John; Deary, Ian J.; Lowe, G. D. O.; Fenton, Candida; Stott, David J.

doi:10.1111/j.1538-7836.2011.04403.x

Cited by 67 publications

(73 citation statements)

References 46 publications

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“…Similarly, little is currently known about the relationship between FVIII and cognitive impairment, although it was prospectively associated with risk of vascular dementia in one study of men. 6 Other hemostatic factors, including FVII, fibrinogen, D-dimer, and vWF, are associated with dementia and cognitive impairment, 8 highlighting the role of coagulation in the pathogenesis of these disorders.…”

Section: Resultsmentioning

confidence: 99%

“…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%

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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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Section: Resultsmentioning

confidence: 99%

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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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“…Results are presented as adjusted unstandardized regression coefficients with 95% confidence intervals (CIs can be caused by many of the risk factors that predispose to atherosclerosis. 20 Because individuals with elevated serum markers of endothelial dysfunction are at higher risk for developing cognitive impairment, 21 possibly through changes in cerebral blood flow, 22,23 increased LDL-C variability might lead to cognitive impairment. In line with this hypothesis, we observed that higher LDL-C variability was associated with lower cerebral blood flow but also with greater white matter hyperintensity load, which has been linked to endothelial (dys)function.…”

Section: Discussionmentioning

confidence: 99%

Higher Visit-to-Visit Low-Density Lipoprotein Cholesterol Variability Is Associated With Lower Cognitive Performance, Lower Cerebral Blood Flow, and Greater White Matter Hyperintensity Load in Older Subjects

et al. 2016

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Background: Recently, it was shown that intraindividual variation in low-density lipoprotein cholesterol (LDL-C) predicts both cerebrovascular and cardiovascular events. We aimed to examine whether this extends to cognitive function and examined possible pathways using a magnetic resonance imaging substudy. Methods: We investigated the association between LDL-C variability and 4 cognitive domains at month 30 in 4428 participants of PROSPER (PROspective Study of Pravastatin in the Elderly at Risk). Additionally, we assessed the association of LDL-C variability with neuroimaging outcomes in a subset of 535 participants. LDL-C variability was defined as the intraindividual standard deviation over 4 postbaseline LDL-C measurements, and all analyses were adjusted for mean LDL-C levels and cardiovascular risk factors. Results: Higher LDL-C variability was associated with lower cognitive function in both the placebo and pravastatin treatment arms. Associations were present for selective attention ( P =0.017 and P =0.11, respectively), processing speed ( P =0.20 and P =0.029), and memory (immediate recall, P =0.002 and P =0.006; delayed recall, P =0.001 and P ≤0.001). Furthermore, higher LDL-C variability was associated with lower cerebral blood flow in both trial arms ( P =0.031 and P =0.050) and with greater white matter hyperintensity load in the pravastatin arm ( P =0.046). No evidence was found for interaction between LDL-C variability and pravastatin treatment for both cognitive and magnetic resonance imaging outcomes. Conclusions: We found that higher visit-to-visit variability in LDL-C, independently of mean LDL-C levels and statin treatment, is associated with lower cognitive performance, lower cerebral blood flow, and greater white matter hyperintensity load.

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“…Recent systematic review and meta-analysis have confirmed this link with blood markers; observed associations were strongest for Bvascular^dementia but also apparent for Ballcause^(undifferentiated) dementias (Quinn et al 2011). The summary data on strength of associations were modest with wide confidence intervals but were consistent across the available data.…”

Section: Introductionmentioning

confidence: 61%

“…We used a hypothesis-driven gene-centric analysis informed by systematic review of available published data (Quinn et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Association between cognition and gene polymorphisms involved in thrombosis and haemostasis

Quinn

Alghamdi

Padmanabhan

et al. 2015

AGE

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An association between blood markers of thrombosis and haemostasis and cognitive decline has been described. These results may be confounded by lifestyle and environmental factors. We used a Mendelian randomisation approach to describe the association between thrombosis/haemostasis genotypes and cognition. We studied the genetic variants (single nucleotide polymorphisms) of circulating markers of thrombosis and haemostasis. Our chosen blood factors and associated polymorphisms were D-dimer [rs12029080], fibrinogen [rs1800789], plasminogen activator inhibitor [rs2227631], and von Willebrand factor [rs1063857]. We described association with multidomain cognitive test scores using data from the Scottish Family Health Study. Cognitive data were analysed for individual tests and combined to give a general cognitive factor. In 20,288 subjects, we found no evidence of association between cognitive function (individual tests and combined scores) and any of the above-mentioned single nucleotide polymorphisms. Lower scores on cognitive measures were associated with increasing age, socioeconomic deprivation, blood pressure, waist-hip ratio, smoking, and vascular comorbidity (all p < 0.001). In a post hoc sensitivity analysis restricted to those aged over 50 years, there was still no signal of association. Our data add to our understanding of determinants of cognition but are not definitive; the variation in blood levels explained by SNPs was modest and our sample size may have been insufficient to detect a modest association.

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Association between circulating hemostatic measures and dementia or cognitive impairment: systematic review and meta‐analyzes

Cited by 67 publications

References 46 publications

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

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

Higher Visit-to-Visit Low-Density Lipoprotein Cholesterol Variability Is Associated With Lower Cognitive Performance, Lower Cerebral Blood Flow, and Greater White Matter Hyperintensity Load in Older Subjects

Association between cognition and gene polymorphisms involved in thrombosis and haemostasis

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