title: Association between circulating hemostatic measures and dementia or cognitive impairment: systematic review and meta-analyzes.
abstract: OBJECTIVE
  Hemostasis and thrombosis may be important contributors to cognitive decline and dementia. Certain blood markers may assist in diagnosis or management.
  
  
  OBJECTIVE
  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.affiliation: Institute Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. Terry.quinn@glasgow.ac.uk
authors.forename: T J
authors.initials: TJ
authors.lastname: Quinn
authors.forename: J
authors.initials: J
authors.lastname: Gallacher
authors.forename: I J
authors.initials: IJ
authors.lastname: Deary
authors.forename: G D O
authors.initials: GD
authors.lastname: Lowe
authors.forename: C
authors.initials: C
authors.lastname: Fenton
authors.forename: D J
authors.initials: DJ
authors.lastname: Stott
mesh_terms: D015415:Biomarkers / Q000097:blood; D003071:Cognition; D003072:Cognition Disorders / Q000097:blood* / Q000175:diagnosis / Q000523:psychology; D003704:Dementia / Q000097:blood* / Q000175:diagnosis / Q000523:psychology; D006487:Hemostasis; D006801:Humans; D009483:Neuropsychological Tests; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D015415:Biomarkers