Is sticky blood bad for the brain?: Hemostatic and inflammatory systems and dementia in the Caerphilly Prospective Study.

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 [HR], 1.68; 95% confidence interval [CI], 1.02-2.76), factor VIII (HR, 1.79; 95% CI, 1.09-3.00), and plasminogen activator inhibitor 1 (HR, 3.13; 95% CI, 1.73-5.70). For vascular dementia, the HR risk from high levels of all three hemostatic variables (fibrinogen, factor VIII, and plasminogen activator inhibitor 1) was 2.97 (P<0.001). Inflammatory factors were not associated with vascular dementia. CONCLUSIONS: The associations of these hemostatic markers with vascular dementia may implicate clot formation as the primary mechanism and are consistent with a microinfarct model of vascular dementia.