TY - JOUR

T1 - Hemostatic factor levels and cognitive decline in older adults

T2 - The Cardiovascular Health Study

AU - Harrington, Laura B.

AU - Ehlert, Alexa N.

AU - Thacker, Evan L.

AU - Jenny, Nancy S.

AU - Lopez, Oscar

AU - Cushman, Mary

AU - Fitzpatrick, Annette

AU - Mukamal, Kenneth J.

AU - Jensen, Majken K.

PY - 2021

Y1 - 2021

N2 - Background Hemostasis is a key factor in cerebrovascular disease, but the association of hemostatic factors with cognitive decline is unclear.Objective To prospectively evaluate associations of 20 hemostatic factor levels with changes in cognition during >= 8 years of follow-up in the Cardiovascular Health Study (CHS) of older adults.Methods We included participants of an existing CHS cross-sectional substudy (n = 400) with hemostatic factors measured in 1989-1990. Between 1989-1990 and 1998-1999, cognitive function was measured using the Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Tests. Mixed-effects linear regression models estimated change in cognitive function over time, adjusting for sociodemographic and clinical factors and APOE genotype, using Bonferroni adjustment. We also derived principal components to account for the interrelationship among factors.Results Of 20 factors evaluated individually, only higher levels of plasmin-alpha(2)-antiplasmin complex (PAP), tissue factor pathway inhibitor (TFPI), and lower factor X (FXc) levels were associated with faster cognitive decline, estimated by annual change in 3MSE points (1 standard deviation PAP beta = -0.65, 95% confidence interval [CI]: -1.08 to -0.21; TFPI beta = -0.55, 95% CI: -0.90 to -0.19; FXc beta = 0.52, 95% CI: 0.21-0.84). One of four principal components, loading positively on D-dimer, prothrombin fragment 1.2 (F1.2), and PAP was significantly associated with change in 3MSE.Conclusions Levels of PAP, TPFI, and FXc and a combination of factors driven by PAP, D-dimer, and F1.2 were associated with cognitive decline. Whether these findings can be used to improve dementia prevention or prediction requires further study.

AB - Background Hemostasis is a key factor in cerebrovascular disease, but the association of hemostatic factors with cognitive decline is unclear.Objective To prospectively evaluate associations of 20 hemostatic factor levels with changes in cognition during >= 8 years of follow-up in the Cardiovascular Health Study (CHS) of older adults.Methods We included participants of an existing CHS cross-sectional substudy (n = 400) with hemostatic factors measured in 1989-1990. Between 1989-1990 and 1998-1999, cognitive function was measured using the Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Tests. Mixed-effects linear regression models estimated change in cognitive function over time, adjusting for sociodemographic and clinical factors and APOE genotype, using Bonferroni adjustment. We also derived principal components to account for the interrelationship among factors.Results Of 20 factors evaluated individually, only higher levels of plasmin-alpha(2)-antiplasmin complex (PAP), tissue factor pathway inhibitor (TFPI), and lower factor X (FXc) levels were associated with faster cognitive decline, estimated by annual change in 3MSE points (1 standard deviation PAP beta = -0.65, 95% confidence interval [CI]: -1.08 to -0.21; TFPI beta = -0.55, 95% CI: -0.90 to -0.19; FXc beta = 0.52, 95% CI: 0.21-0.84). One of four principal components, loading positively on D-dimer, prothrombin fragment 1.2 (F1.2), and PAP was significantly associated with change in 3MSE.Conclusions Levels of PAP, TPFI, and FXc and a combination of factors driven by PAP, D-dimer, and F1.2 were associated with cognitive decline. Whether these findings can be used to improve dementia prevention or prediction requires further study.

KW - aged

KW - blood coagulation

KW - cognition

KW - fibrinolysis

KW - hemostasis

U2 - 10.1111/jth.15300

DO - 10.1111/jth.15300

M3 - Journal article

C2 - 33725412

VL - 19

SP - 1219

EP - 1227

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

SN - 1538-7933

IS - 5

ER -