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

Hemostasis and thrombosis may be important contributors to cognitive decline and dementia. Certain blood markers may assist in diagnosis or management. Objectives: To collate evidence for the association of circulating hemostatic variables and dementia or cognitive impairment. Methods: A systematic review of studies describing blood markers of hemostatic function and cognition/dementia. Abstracts were reviewed by two independent assessors and studies selected based on pre-specified criteria. We described methodological quality and performed meta-analyzes where data allowed. Results: From 7103 titles, 485 abstracts and included 21 studies (n = 32 773) were assessed. In two longitudinal studies, the incident of vascular dementia risk was greater for higher D-dimer [hazard ratio (HR): 1.50, 95% confidence interval (CI): 1.15–1.96]. For case–control data, we calculated standardized mean differences (SMD) and 95% CI. Higher levels of: factor (F)VII (SMD: 0.93; 95% CI: 0.60–1.26), fibrinogen (SMD: 1.53; 95% CI: 1.17–1.87), prothrombin fragment 1 and 2 (SMD: 0.64; 95% CI: 0.32–0.96), plasminogen activator inhibitor (SMD: 0.68; 95% CI: 0.26–1.10), D-dimer (SMD: 2.00; 95% CI: 1.59–2.40) and von Willebrand factor (VWF) (SMD: 1.68; 95% CI: 1.30–2.06) showed modest but significant associations with vascular dementia. For patients with any dementia diagnosis, associations were with higher D-dimer (SMD: 0.36; 95% CI: 0.15–0.56) and VWF (SMD: 0.31; 95% CI: 0.11–0.51). For specific cognitive domains, significant (P < 0.001) positive correlations were fibrinogen and speed of processing (0.76; 95% CI: 0.67–0.84), verbal memory (0.69; 95% CI: 0.59–0.79) and non-verbal reasoning (0.57; 95% CI: 0.49–0.65). Conclusions: The present results suggest a modest association between hemostasis and vascular dementia including increased levels of thrombin generation markers (D-dimer and prothrombin fragment 1 + 2) and endothelial dysfunction (VWF and plasminogen activator inhibitor). Associations are weaker for specific cognitive tests and when all dementias are combined