Hypertension linked to Alzheimer's disease via stroke: Mendelian randomization
Chao Tang1, Yayu Ma1, Xiaoyang Lei1
1Department of Neurology, Affiliated Hospital of Guizhou Medical University, No. 28, Guiyi Street, Yunyan District, Guiyang, 550004, Guizhou Province, China.
Insights
Hypertension increases Alzheimer's disease (AD) risk, with stroke acting as a key mediator. Approximately 55% of hypertension-related AD risk is linked to stroke, suggesting stroke as a therapeutic target.
Area of Science:
- Neuroscience
- Cardiovascular Science
- Genetics
Background:
- Alzheimer's disease (AD) is a neurodegenerative disorder impacting cognition and quality of life.
- Hypertension is a known risk factor for AD, but the underlying mechanisms remain unclear.
- Understanding the hypertension-AD link is crucial for developing effective interventions.
Purpose of the Study:
- To investigate the causal relationship between hypertension and Alzheimer's disease (AD).
- To identify mediating factors, specifically stroke, in the hypertension-AD pathway.
- To quantify the indirect effect of hypertension on AD risk via stroke.
Main Methods:
- Utilized a mediated Mendelian randomization (MR) approach.
- Screened for mediating variables between hypertension and AD using instrumental variables.
- Employed multivariate mediated MR analysis to determine the indirect effect of stroke.
Main Results:
- Stroke was identified as a significant mediating variable in the hypertension-AD relationship.
- The mediated indirect effect of stroke accounted for 54.9% of the risk.
- Approximately 55% of AD risk associated with hypertension is attributable to stroke.
Conclusions:
- The increased risk of AD associated with hypertension is significantly mediated through stroke.
- Stroke plays a critical role in the causal pathway linking hypertension to Alzheimer's disease.
- Findings suggest stroke prevention and management as potential strategies to mitigate AD risk in hypertensive individuals.
Abstract:
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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