Coagulation factor VIII, white matter hyperintensities and cognitive function: Results from the Cardiovascular Health Study

PLoS One. 2020 Nov 16;15(11):e0242062. doi: 10.1371/journal.pone.0242062. eCollection 2020.


Objective: To investigate the relationship between high FVIII clotting activity (FVIII:C), MRI-defined white matter hyperintensities (WMH) and cognitive function over time.

Methods: Data from the population-based Cardiovascular Health Study (n = 5,888, aged ≥65) were used. FVIII:C was measured in blood samples taken at baseline. WMH burden was assessed on two cranial MRI scans taken roughly 5 years apart. Cognitive function was assessed annually using the Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Test (DSST). We used ordinal logistic regression models adjusted for demographic and cardiovascular factors in cross-sectional and longitudinal WMH analyses, and adjusted linear regression and linear mixed models in the analyses of cognitive function.

Results: After adjustment for confounding, higher levels of FVIII:C were not strongly associated with the burden of WMH on the initial MRI scan (OR>p75 = 1.20, 95% CI 0.99-1.45; N = 2,735) nor with WMH burden worsening over time (OR>p75 = 1.18, 95% CI 0.87-1.59; N = 1,527). High FVIII:C showed no strong association with cognitive scores cross-sectionally (3MSE>p75 β = -0.06, 95%CI -0.45 to 0.32, N = 4,005; DSST>p75 β = -0.69, 95%CI -1.52 to 0.13, N = 3,954) or over time (3MSE>p75 β = -0.07,95% CI -0.58 to 0.44, N = 2,764; DSST>p75 β = -0.22, 95% CI -0.97 to 0.53, N = 2,306) after confounding adjustment.

Interpretation: The results from this cohort study of older adult participants indicate no strong relationships between higher FVIII:C levels and WMH burden or cognitive function in cross-sectional and longitudinal analyses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Coagulation
  • Cognition / physiology*
  • Cross-Sectional Studies
  • Factor VIII / metabolism*
  • Female
  • Humans
  • Logistic Models
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Mental Status and Dementia Tests
  • Up-Regulation*
  • White Matter / diagnostic imaging
  • White Matter / pathology*


  • F8 protein, human
  • Factor VIII