This study aimed to investigate the relationship between hypertension and Alzheimer's disease (AD) and demonstrate the key role of stroke in this relationship using mediating Mendelian randomization. AD, a neurodegenerative disease characterized by memory loss, cognitive impairment, and behavioral abnormalities, severely affects the quality of life of patients. Hypertension is an important risk factor for AD. However, the precise mechanism underlying this relationship is unclear. To investigate the relationship between hypertension and AD, we used a mediated Mendelian randomization method and screened for mediating variables between hypertension and AD by setting instrumental variables. The results of the mediated analysis showed that stroke, as a mediating variable, plays an important role in the causal relationship between hypertension and AD. Specifically, the mediated indirect effect value for stroke obtained using multivariate mediated MR analysis was 54.9%. This implies that approximately 55% of the risk of AD owing to hypertension can be attributed to stroke. The results suggest that the increased risk of AD owing to hypertension is mediated through stroke. The finding not only sheds light on the relationship between hypertension and AD but also indicates novel methods for the prevention and treatment of AD. By identifying the critical role of stroke in the link between hypertension and AD, this study provides insights into potential interventions that could mitigate the impact of hypertension on AD. This could help develop personalized treatments and help improve the quality of life of patients with AD who suffer from hypertension.
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