BACKGROUND AND OBJECTIVES: 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.
BACKGROUND AND OBJECTIVES: 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.
Authors: Renske Uiterwijk; Marjolein Huijts; Julie Staals; Rob P W Rouhl; Peter W De Leeuw; Abraham A Kroon; Robert J Van Oostenbrugge Journal: Am J Hypertens Date: 2015-08-12 Impact factor: 2.689
Authors: S R Gillett; L A McClure; P W Callas; E L Thacker; F W Unverzagt; V G Wadley; A J Letter; M Cushman Journal: J Thromb Haemost Date: 2018-06-06 Impact factor: 5.824
Authors: James R Hall; Leigh A Johnson; Robert C Barber; Hoa T Vo; A Scott Winter; Sid E O'Bryant Journal: J Alzheimers Dis Date: 2012 Impact factor: 4.472
Authors: Terence J Quinn; Jahad Alghamdi; Sandosh Padmanabhan; David J Porteous; Blair H Smith; Lynne Hocking; Ian J Deary; John Gallacher; Martina Messow; David J Stott Journal: Age (Dordr) Date: 2015-08-01
Authors: Kristine S Alexander; Neil A Zakai; Sarah Gillett; Leslie A McClure; Virginia Wadley; Fred Unverzagt; Mary Cushman Journal: Neurology Date: 2014-09-10 Impact factor: 9.910