Emine Berrin Yüksel

Objective: Thrombophilic and cardiovascular genetic variants are known contributors to venous and arterial thrombotic disease. However, their combined effect on neurovascular and neurodegenerative outcomes is less understood. This study explores the independent and combined links of these genetic factors with neurovascular events and cognition using a multivariate approach. Methods: This retrospective clinical-genetic study involved 91 adult patients evaluated between January 2022 and February 2025. Genetic analyses were performed using a standardized thrombophilia panel focusing on MTHFR C677T, PAI-1 4G/5G, Factor V Leiden (G1691A), and Prothrombin G20210A polymorphisms. Clinical endpoints included ischemic stroke, transient ischemic attack, venous thrombosis, vascular dementia, and cognitive impairment assessed by Mini-Mental State Examination. Results: MTHFR C677T homozygosity was independently associated with vascular dementia (OR 3.2; 95% CI 1.1–8.9; p=0.027) and showed clustering with cognitive impairment. Factor V Leiden (OR 2.6; 95% CI 1.1–6.3; p=0.031) and Prothrombin G20210A carriage (OR 2.1; 95% CI 1.0–4.2; p=0.049) were independently associated with stroke and thrombotic events. Individuals carrying multiple mutations demonstrated higher rates of stroke (up to 40%), thrombosis (up to 40%), and cognitive impairment compared with single-mutation carriers or genetically negative individuals, supporting a cumulative polygenic risk effect. Biochemical correlations were concordant with genotype–phenotype patterns, including elevated homocysteine levels among MTHFR carriers and increased fibrinogen tendency among β-fibrinogen polymorphism carriers. Conclusion: Thrombophilic and cardiovascular genetic variants are associated not only with classical thrombotic phenotypes but also with neurovascular and cognitive outcomes.