@article {8706, title = {Hemostatic factor levels and cognitive decline in older adults: The Cardiovascular Health Study.}, journal = {J Thromb Haemost}, year = {2021}, month = {2021 Mar 16}, abstract = {

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-α -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 β~=~-0.65, 95\% confidence interval [CI]: -1.08 to -0.21; TFPI β~=~-0.55, 95\% CI: -0.90 to -0.19; FXc β~=~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.

}, issn = {1538-7836}, doi = {10.1111/jth.15300}, author = {Harrington, Laura B and Ehlert, Alexa N and Thacker, Evan L and Jenny, Nancy S and Lopez, Oscar and Cushman, Mary and Fitzpatrick, Annette and Mukamal, Kenneth J and Jensen, Majken K} } @article {9613, title = {Levels of procoagulant factors and peak thrombin generation in relation to dementia risk in older adults: The Cardiovascular Health Study.}, journal = {Thromb Res}, volume = {235}, year = {2024}, month = {2024 Mar}, pages = {148-154}, abstract = {

INTRODUCTION: Markers of hemostasis such as procoagulant factors and peak thrombin generation are associated with cardiovascular outcomes, but their associations with dementia risk are unclear. We aimed to evaluate prospective associations of selected procoagulant factors and peak thrombin generation with dementia risk.

METHODS: We measured levels of 7 hemostatic factors (fibrinogen, factor VII coagulant activity [FVIIc], activated factor VII [FVIIa], factor VIIa-antithrombin [FVIIa-AT], factor XI antigen [FXI], peak thrombin generation, and platelet count) among participants in the Cardiovascular Health Study, a cohort of older adults free of dementia in 1992/1993 (n~=~3185). Dementia was adjudicated and classified by DSM-IV criteria through 1998/1999. Cox proportional hazards models estimated hazard ratios (HRs) for any dementia associated with 1-standard deviation (SD) differences, adjusting for sociodemographic and clinical factors and APOE genotype. Secondary analyses separately evaluated the risk of vascular dementia, Alzheimer{\textquoteright}s disease, and mixed dementia.

RESULTS: At baseline, participants had a median age of 73~years. Over 5.4~years of follow-up, we identified 448 dementia cases. There was no evidence of linear associations between levels of these hemostatic factors with any dementia risk (HRs per 1-SD difference ranged from 1.0 to 1.1; 95~\% confidence intervals included 1.0). Results of secondary analyses by dementia subtype were similar.

CONCLUSIONS: In this prospective study, there was no strong evidence of linear associations between levels of fibrinogen, FVIIc, FVIIa, FVIIa-AT, FXI, peak thrombin generation, or platelet count with dementia risk. Despite their associations with cardiovascular disease, higher levels of these biomarkers measured among older adults may not reflect dementia risk.

}, keywords = {Aged, Anticoagulants, Antithrombin III, Antithrombins, Dementia, Factor VIIa, Fibrinogen, Hemostatics, Humans, Prospective Studies, Thrombin}, issn = {1879-2472}, doi = {10.1016/j.thromres.2024.01.024}, author = {Harrington, Laura B and Ehlert, Alexa N and Thacker, Evan L and Jenny, Nancy S and Lopez, Oscar and Cushman, Mary and Olson, Nels C and Fitzpatrick, Annette and Mukamal, Kenneth J and Jensen, Majken K} }