Effect of the angiotensin I-converting enzyme I/D polymorphism on cognitive decline☆

Richard, Florence; Berr, Claudine; Amant, Carole; Helbecque, Nicole; Amouyel, Philippe; Alpérovitch, Annick

doi:10.1016/s0197-4580(99)00102-5

Cited by 41 publications

(40 citation statements)

References 39 publications

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“…Prior studies had also suggested that the ACE gene might contribute to complications of cerebrovascular disease, such as vascular dementia, 29 and the ACE gene has been associated with both cognitive decline 30 and Alzheimer's disease. 31 In the PROGRESS study, careful assessment of cognitive function 12 identified several hundred patients who developed dementia and more with cognitive decline.…”

Section: Discussionmentioning

confidence: 99%

The ACE Gene I/D Polymorphism Is Not Associated With the Blood Pressure and Cardiovascular Benefits of ACE Inhibition

et al. 2003

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Abstract-The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene might have consequences for the risks of vascular diseases. We examined the ACE genotype and the effects of a perindopril-based blood pressure-lowering regimen on macrovascular events, dementia, and cognitive decline among hypertensive and nonhypertensive patients with a history of cerebrovascular disease. ACE I/D genotypes were measured in 5688 of 6105 individuals with previous stroke or transient ischemic attack who participated in the PROGRESS trial. The DD genotype was significantly (PϽ0.0001) less frequent in Asian subjects (Chinese and Japanese, 14.7%) than in non-Asian subjects (32.0%). Controlling for racial background, there were no associations between ACE genotypes and cerebrovascular disease history or cardiovascular risk factors, including baseline blood pressure. The ACE genotype was not associated with the long-term risks of stroke, cardiac events, mortality, dementia, or cognitive decline; neither did the ACE genotype predict the blood pressure reduction associated with the use of the ACE inhibitor perindopril. Similarly, there was no evidence that the ACE genotype modified the relative benefits of ACE inhibitor-based therapy over placebo. This study provides no evidence that in patients with cerebrovascular disease, knowledge of ACE genotype is useful for predicting either the risk of disease or the benefits of perindopril-based blood pressure-lowering treatment.

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Section: Discussionmentioning

confidence: 99%

The ACE Gene I/D Polymorphism Is Not Associated With the Blood Pressure and Cardiovascular Benefits of ACE Inhibition

et al. 2003

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“…Richard et al reported a synergistic negative effect of the ACE-DD genotype in combination with the APOE-4 allele on cognitive decline in a large community-dwelling elderly cohort, whereas Gustafsen et al reported a relationship between the ACE-II genotype, the presence of an APOE-4 allele and age having a negative effect on cognition [22,65] .…”

Section: Discussionmentioning

confidence: 99%

“…Patients carrying the ACE-DD genotype have higher rates of ACE in their plasma and more often suffer from myocardial infarction, hypertension, diabetes mellitus, leukoaraiosis and stroke [19,20] . Furthermore, the ACE-D allele has been associated with cognitive decline in older persons, and Richard et al report an increased negative effect of an ACE-DD genotype in combination with the presence of APOE-4 on cognitive decline [21,22] . Purandare et al report a higher load of white matter hyperintensities in the presence of an ACE-DD homozygosity [23] .…”

Section: Introductionmentioning

confidence: 99%

The Effect of the APOE-ε4 Allele and ACE-I/D Polymorphism on Cognition during a Two-Year Follow-Up in First-Ever Stroke Patients

Bour

Rasquin²,

Baars³

et al. 2010

Dement Geriatr Cogn Disord

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Background: Cognitive impairment is commonly observed after stroke and has a negative impact on survival and rehabilitation. Some stroke patients deteriorate in cognitive functioning whereas others do not. Environmental and demographic risk factors cannot fully explain this. There is growing evidence that a genetic predisposition plays a role in the pathogenesis of post-stroke cognitive decline. Objective: To study the influence of the APOE-Ε4 allele and the ACE-I/D polymorphism on cognitive functioning after stroke. Methods: We included 194 first-ever stroke patients of whom information about APOE genotyping and ACE-I/D polymorphism was available in 92 and 129 patients, respectively. Patients were cognitively assessed at 1, 6, 12 and 24 months after the event. Linear mixed models with slope estimates were used to study the influence of the APOE-Ε4 allele and the ACE-I/D polymorphism on the MMSE score, CAMCOG, executive functioning, psychomotor speed, and verbal memory function during follow-up. Results: Patients carrying the APOE-Ε4 allele more often suffered a lacunar infarction than non-carriers. The APOE-Ε4 allele had no effect on cognitive functioning during the follow-up. ACE-DD homozygosity was associated with a worse performance in executive functioning compared to patients with neither an APOE-Ε4 allele nor the ACE-DD genotype. There was no interaction between the APOE-Ε4 allele and the ACE-DD phenotype in the prediction of cognitive decline. Conclusion: The ACE-DD genotype may be associated with post-stroke cognitive decline while the APOE-Ε4 allele is not. Further research is needed to examine the role of genetic risk factors for post-stroke cognitive decline and to determine why some patients deteriorate cognitively after stroke but others do not.

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“…Variants in the ACE gene have been considered as risk factor for a number of diseases such as Alzheimer's disease, diabethic nephropathy, coronary heart disease and stroke [39]. There are reports of a possible role for ACE gene in the risk of cognitive impairment and AD [40][41][42]. In a study conducted by Edwards et al in 2008, a significant association between ACE haplotype and susceptibility for AD was shown in family-based and case-control samples [43].…”

Section: Acementioning

confidence: 99%

Genetic and Blood Biomarkers of Alzheimer`s Disease

Momeni¹,

Ferrari²

2010

TONMEDJ

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Alzheimer's disease (AD) is the most prevalent form of dementia. AD is highly heritable, with a complex pattern. Although clinical diagnosis is based on accurate and well defined diagnostic criteria (NINCDS-ADRDA), the definite diagnosis relies on the postmortem pathological findings. The need for measures for the early detection of AD, as well as the need to distinguish between AD and other forms of dementia, has put great emphasis on the discovery of biomarkers for Alzheimer's disease. In clinical practice, there is need for non-invasive, accurate methods for the early detection and differential diagnosis of AD. The successful identification and development of the biomarkers, depends completely on the understanding of pathology, genetic and molecular mechanisms involved in the disease. As blood is a circulating dynamic tissue and transcription reflects the ongoing changes in the system, it makes the transcriptional profiling of the blood cells, potentially, the most sensitive source for transcriptional biomarkers. A systematic comparison of the genetic and proteomic blood biomarkers in patients and healthy controls can reveal additional potential candidates for AD. In the first part of this review, we would like to discuss the most recent genetic findings and their possible involvement in the pathogenesis of AD. In the second part, we review the blood biomarkers which can be derived from peripheral blood mononuclear cells (PBMC), serum, and plasma. We discus three main category of bio-molecules, namely DNA, RNA (miRNA and mRNA), and protein as well as their possible role in the hypothetical mechanisms involved in pathogenesis of AD. A dynamic interaction between the genetic findings through the whole genome association studies and biomarkers discovery can advance our knowledge of AD pathogenesis beyond the scope of each field independently.

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Effect of the angiotensin I-converting enzyme I/D polymorphism on cognitive decline☆

Cited by 41 publications

References 39 publications

The ACE Gene I/D Polymorphism Is Not Associated With the Blood Pressure and Cardiovascular Benefits of ACE Inhibition

The ACE Gene I/D Polymorphism Is Not Associated With the Blood Pressure and Cardiovascular Benefits of ACE Inhibition

The Effect of the APOE-ε4 Allele and ACE-I/D Polymorphism on Cognition during a Two-Year Follow-Up in First-Ever Stroke Patients

Genetic and Blood Biomarkers of Alzheimer`s Disease

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Effect of the angiotensin I-converting enzyme I/D polymorphism on cognitive decline☆

Cited by 41 publications

References 39 publications

The ACE Gene I/D Polymorphism Is Not Associated With the Blood Pressure and Cardiovascular Benefits of ACE Inhibition

The ACE Gene I/D Polymorphism Is Not Associated With the Blood Pressure and Cardiovascular Benefits of ACE Inhibition

The Effect of the APOE-&#949;4 Allele and ACE-I/D Polymorphism on Cognition during a Two-Year Follow-Up in First-Ever Stroke Patients

Genetic and Blood Biomarkers of Alzheimer`s Disease

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Resources

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The Effect of the APOE-ε4 Allele and ACE-I/D Polymorphism on Cognition during a Two-Year Follow-Up in First-Ever Stroke Patients