Hemostasis and Vascular Dementia

Abstract

V ascular dementia (VaD) comprises a group of syndromes caused by vascular lesions in the brain. Cognitive impairment may follow a single cortical or lacunar infarct in a strategic area of the brain, multiple infarcts, small-vessel disease (leukoaraiosis), intracerebral hemorrhage, or any of these conditions coexisting with Alzheimer dementia (so-called mixed dementia). Depending on case mix and the type of observational study, 10% of patients already have dementia before their first stroke, 10% develop it soon after their first stroke, and more than 33% have dementia after a recurrent stroke. 1 Typically, dementia develops at a rate of 3% per year after stroke, and it is the stroke, rather than its underlying risk factors, that appears to be the dominant cause of subsequent dementia. 1 See accompanying articles on pages 599 and 605Although VaD, including poststroke dementia, is associated with conventional risk factors, such as hypertension and hypercholesterolemia, 2,3 their relationship with hemostatic factors is less clear. This contrasts with the relationship between hemostatic factors and stroke, which is well established and involves both soluble (eg, fibrinogen 4 ) and cellular (eg, mean platelet volume 5 ) biomarkers. Several hemostatic factors, including fibrinogen and fibrin D-dimer levels, are associated with subsequent cognitive impairment and dementia in observational studies (Table). 6 -10 This issue of Arteriosclerosis, Thrombosis, and Vascular Biology expands on this relationship between "sticky blood" and cognition. 11 Two new studies are described.First, Stott and colleagues 12 report observational data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), which examined lipid lowering 13 : 5699 people (average age, 75 years) not taking warfarin had measurements of hemostatic factors at baseline and annual assessments of cognition over 3.2 years of follow-up. Cognitive measures included speed of information processing (Letter Digit Coding Test and Stroop test) and verbal memory (picture-word naming). The central finding was that increased levels of D-dimer and prothrombin fragment 1ϩ2 (ie, markers of thrombin generation) were associated independently with increased rates of cognitive decline and deterioration in activities of daily living (Table). 12 Interestingly, markers of endothelial dysfunction (eg, tissue plasminogen activator and von Willebrand factor) were not associated with cognitive decline.Second, Gallacher and colleagues 14 present data on 865 men free of vascular disease, with biomarker measurements, who were observed in the Caerphilly community cohort. Hemostasis factors were measured at the age of 45 to 59 years, and cognition and dementia were determined up to the age of 65 to 84 years. During 17 years of follow-up, 59 of the men developed dementia and 112 developed cognitive impairment/no dementia. Increased fibrinogen, factor VIII, and plasminogen activator inhibitor-1 levels were associated independently with VaD (Table). 14 In contrast, increased lev...

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

“…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. 18 Although ABO blood group is a CVD risk factor, we are not aware of studies on its relationship with cognitive impairment.…”

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

“…A dose-dependent relationship between FVIII levels and the occurrence of thrombotic events (including overt ischemic stroke) has also been observed [4][5][6][7][8]. Further studies have linked FVIII, a potential therapeutic target, with dementia risk [9,10] as well as risk for cognitive impairment in a study of men [11]. Previous research in the US-based Cardiovascular Health Study (CHS) found an association between higher FVIII and incident cardiovascular disease, stroke, and death in the older general study population [12], but these studies did not investigate covert WMH or cognitive decline.…”

Vascular Dementia and Crosstalk Between the Complement and Coagulation Systems

“…Although sample size was an issue in all of these studies, the Dutch studies had slightly more robust data due to repeats. Nonetheless, further research is necessary to establish the roles of these inflammatory markers in cognitive decline ( 113 , 114 ).…”