Evaluating the association between genetically proxied ACE inhibition and dementias

Author:

Nassan Malik1,Daghlas Iyas2,Piras Ignazio S.3,Rogalski Emily1,Reus Lianne M45,Pijnenburg Yolande5,Cuddy Leah K.6,Saxena Richa7,Mesulam M‐Marsel1,Huentelman Matt3

Affiliation:

1. Mesulam Center for Cognitive Neurology and Alzheimer's Disease Northwestern University Chicago Illinois USA

2. Department of Neurology University of California San Francisco San Francisco California USA

3. Neurogenomics Division Translational Genomics Research Institute, Tgen Phoenix Arizona USA

4. Center for Neurobehavioral Genetics University of California, Los Angeles California USA

5. Alzheimer Center Amsterdam, Neurology Vrije Universiteit Amsterdam Amsterdam the Netherlands

6. Ken and Ruth Davee Department of Neurology Northwestern University Feinberg School of Medicine Chicago Illinois USA

7. Center for Genomic Medicine, Massachusetts General Hospital Harvard Medical School Boston Massachusetts USA

Abstract

AbstractIntroductionAngiotensin‐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.MethodsWe examined the causal association of genetically proxied ACE inhibition with four types of dementias using a two‐sample Mendelian randomization (MR) approach.ResultsGenetically 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.DiscussionThis 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.

Publisher

Wiley

Subject

Psychiatry and Mental health,Cellular and Molecular Neuroscience,Geriatrics and Gerontology,Neurology (clinical),Developmental Neuroscience,Health Policy,Epidemiology

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