Evaluating the association between genetically proxied ACE inhibition and dementias

失智症 痴呆 孟德尔随机化 优势比 阿尔茨海默病 血管紧张素转换酶 血管性痴呆 医学 内科学 疾病 肿瘤科 心理学 遗传学 生物 基因型 遗传变异 血压 基因
作者
Malik Nassan,Iyas Daghlas,Ignazio S. Piras,Emily Rogalskı,Lianne M. Reus,Yolande A.L. Pijnenburg,Leah K. Cuddy,Richa Saxena,M‐Marsel Mesulam,Matt Huentelman
出处
期刊:Alzheimers & Dementia [Wiley]
卷期号:19 (9): 3894-3901 被引量:9
标识
DOI:10.1002/alz.13062
摘要

Abstract Introduction Angiotensin‐converting enzyme (ACE) has been implicated in the metabolism of amyloid beta; however, the causal effect of ACE inhibition on risk of Alzheimer's disease (AD) dementia and other common dementias is largely unknown. Methods We examined the causal association of genetically proxied ACE inhibition with four types of dementias using a two‐sample Mendelian randomization (MR) approach. Results Genetically proxied ACE inhibition was associated with increased risk of AD dementia (odds ratio per one standard deviation reduction in serum ACE [95% confidence interval]; 1.07 [1.04–1.10], P = 5 × 10 −07 ) and frontotemporal dementia (1.16 [1.04–1.29], P = 0.01) but not with Lewy body dementia or vascular dementia ( P > 0.05). These findings were independently replicated and remained consistent in sensitivity analyses. Discussion This comprehensive MR study provided genetic evidence for an association between ACE inhibition and the risk for AD and frontotemporal dementias. These results should encourage further studies of the neurocognitive effects of ACE inhibition. HIGHLIGHTS This study evaluated genetically proxied angiotensin‐converting enzyme (ACE) inhibition association with dementias. The results suggest an association between ACE inhibition and Alzheimer's disease. The results suggest an association between ACE inhibition and frontotemporal dementia. Those associations can be interpreted as potentially causal.
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