Is Sticky Blood Bad for the Brain?

Abstract

Objective-Hemostasis and inflammation have been implicated in dementia. This study investigates the role of specific hemostatic and inflammatory pathways with incident vascular and nonvascular dementia. Methods and Results-This was a prospective study of a population sample of men aged 65 to 84 years, with baseline assessment of hemostatic and inflammatory factors and cognition measured 17 years later. The sample included 865 men (59 had dementia and 112 had cognitive impairment, not dementia), free of vascular disease at baseline and for whom hemostatic and inflammatory marker data were available and cognitive status was known. A total of 15 hemostatic and 6 inflammatory markers were assessed. Factor analysis was used to identify hemostatic subsystems. The National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurologie criteria were used to identify vascular dementia. By using standardized (z) scores for hemostatic and inflammatory markers, and after adjustment for age and risk factors, vascular dementia was associated with fibrinogen (hazard ratio Key Words: dementia Ⅲ hemostasis Ⅲ inflammation Ⅲ cognition Ⅲ aging H emostasis and the inflammatory response are complex and interrelated processes that are associated with a variety of phenotypes, including cardiovascular diseases. 1 There is limited case-control evidence associating markers of hemostasis and inflammation with dementia. [2][3][4][5][6] Limited prospective data come from the Rotterdam Study, which found that fibrinogen, but not C-reactive protein (CRP), was associated with incident dementia at the age of 6 years. 7 Therefore, further studies of hemostatic and inflammatory markers and risk of dementia (both vascular and nonvascular) are required. See accompanying article on page 461Hemostasis involves a delicate balance of several closely related subsystems or pathways. It is possible, therefore, that associations with these responses reflect the impact of specific pathways rather than of individual biomarkers. One area of interest is whether hemostatic markers can be analyzed within the context of the coagulation pathways that they represent and whether these pathways can be used to identify more closely the mechanisms associated with cognitive impairment. In the Caerphilly Prospective Study, a wide range of available hemostatic markers allows the comparative influence of several pathways to be assessed. 8 Methods The Study PopulationBetween 1979 and 1983, all men aged 45 to 59 years within the locality of Caerphilly in South Wales, England, were invited to participate. Of the 2818 men found eligible, 2512 (89.1%) were recruited. For the second examination (1985), the original cohort was supplemented with all men of a similar age who had moved into the

Microinfarcts in an older population‐representative brain donor cohort (MRC CFAS): Prevalence, relation to dementia and mobility, and implications for the evaluation of cerebral Small Vessel Disease

“…These findings potentially imply a role for artery‐to‐artery microembolization as a significant pathogenetic event 7. There is further supportive evidence based on an increase in haemostatic biomarkers in people with microinfarction 19. There are significant limitations on the utility of human post‐mortem‐based observations in determining the underlying mechanisms that give rise to WMLs, lacunes, microbleeds and microinfarcts so that the development of preclinical models is an urgent priority to accelerate effective translational research towards therapies with the potential to modify these different types of tissue injury.…”

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

“…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.…”

“…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.…”

Hemostasis and Vascular Dementia

“…Increased fibrinogen, factor VIII, and plasminogen activator inhibitor-1 levels were associated independently with VaD (Table). 14 In contrast, increased levels of these factors were not related to non-VaD; however, there were few cases of this occurrence. By using factor analysis and structural equation modeling, VaD appeared to be related to certain coagulation "pathways," in particular accentuated clot formation (increased fibrinogen and/or D-dimer level), platelet and fibrin plug formation (factor VIII/von Willebrand factor), and possibly impaired fibrinolytic activity (plasminogen activator inhibitor 1); in contrast, increased thrombin generation (thrombin-antithrombin complex and prothrombin fragment 1ϩ2) did not appear to be relevant.…”