Effects of Centrally Acting Angiotensin Converting Enzyme Inhibitors on Functional Decline in Patients with Alzheimer's Disease

Ó’Caoimh, Rónán; Healy, Liam O.; Gao, Yang; Svendrovski, Anton; Kerins, David M.; Eustace, Joseph A.; Kehoe, Patrick Gavin; Guyatt, Gordon; Molloy, D. William

doi:10.3233/jad-131694

Cited by 72 publications

(56 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Antagonists of the renin–angiotensin–aldosterone system, such as angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, have recently gained interest in the dementia field, because the renin–angiotensin–aldosterone system is involved in several major processes such as regulation of cerebral blood flow, inflammation or memory consolidation [16-18]. Centrally active angiotensin-converting enzyme inhibitors have been shown to protect against brain injury and to slow down cognitive decline [6,19-21]. Angiotensin II receptor blockers have been associated with a significant reduction in the incidence and progression of dementia compared with other CV drugs in a prospective cohort analysis [22].…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular medication burden in dementia disorders: a nationwide study of 19,743 dementia patients in the Swedish Dementia Registry

et al. 2014

View full text Add to dashboard Cite

IntroductionAdministration of several cardiovascular drugs has an effect on dementia. We aimed to investigate whether there are differences in the use of cardiovascular medication between different dementia disorders.MethodsWe obtained information about dementia patients from the Swedish Dementia Registry. Patients were diagnosed with one of these dementia disorders: Alzheimer’s disease (n = 8,139), mixed dementia (n = 5,203), vascular dementia (n = 4,982), Lewy body dementia (n = 605), frontotemporal dementia (n = 409) and Parkinson’s disease dementia (n = 405). Multivariate logistic regression analysis was performed to investigate the association between use of cardiovascular medication and dementia disorders, after adjustment for age, gender, living alone, cognitive status and total number of drugs (a proxy for overall co-morbidity).ResultsSeventy percent of all the dementia patients used cardiovascular medication. Use of cardiovascular drugs is common in patients with vascular and mixed dementia. Male gender, higher age, slightly better cognitive status and living with another person was associated with use of cardiovascular medication.ConclusionsCardiovascular medication is used extensively across dementia disorders and particularly in vascular and mixed dementia. Future research should investigate the tolerability and effectiveness of these drugs in the different dementia disorders.

show abstract

Section: Introductionmentioning

confidence: 99%

Cardiovascular medication burden in dementia disorders: a nationwide study of 19,743 dementia patients in the Swedish Dementia Registry

et al. 2014

View full text Add to dashboard Cite

show abstract

“…[69] Medications to control high blood pressure during advanced aging, particularly calcium channel blockers and centrally acting ACE inhibitors may have a protective role in slowing down cognitive decline but the evidence remains far from clear due to the difficulty of assessing their effects on a heterogenous population in adequately powered, randomized controlled clinical trials. [70] Hypotension As the pendulum swings back from drugs treating hypertension during advanced aging, the paradoxical phenomenon of inducing hypotension and low diastolic blood pressure becomes a real possibility that may usher an increased risk of AD. Thus, diastolic pressures of <65 mm Hg appear to be associated with a greater chance of developing AD.…”

mentioning

confidence: 99%

Cerebral Perfusion Enhancing Interventions: A New Strategy for the Prevention of Alzheimer Dementia

Torre

2016

Brain Pathology

View full text Add to dashboard Cite

Cardiovascular and cerebrovascular diseases are major risk factors in the development of cognitive impairment and Alzheimer's disease (AD). These cardio-cerebral disorders promote a variety of vascular risk factors which in the presence of advancing age are prone to markedly reduce cerebral perfusion and create a neuronal energy crisis. Long-term hypoperfusion of the brain evolves mainly from cardiac structural pathology and brain vascular insufficiency. Brain hypoperfusion in the elderly is strongly associated with the development of mild cognitive impairment (MCI) and both conditions are presumed to be precursors of Alzheimer dementia. A therapeutic target to prevent or treat MCI and consequently reduce the incidence of AD aims to elevate cerebral perfusion using novel pharmacological agents. As reviewed here, the experimental pharmaca include the use of Rho kinase inhibitors, neurometabolic energy boosters, sirtuins and vascular growth factors. In addition, a compelling new technique in laser medicine called photobiomodulation is reviewed. Photobiomodulation is based on the use of low level laser therapy to stimulate mitochondrial energy production non-invasively in nerve cells. The use of novel pharmaca and photobiomodulation may become important tools in the treatment or prevention of cognitive decline that can lead to dementia.

show abstract

“…In view of these pleotropic actions of Ang II, that are associated with a number of AD pathological processes, and the recent observations in animal models of AD treated with losartan, AT1Rs have come under scrutiny as a potential therapeutic option for AD. Data from large retrospective clinical studies (Li et al, 2010; Davies et al, 2011) and secondary explorations of clinical trial studies (Gao et al, 2013; O'Caoimh et al, 2014) suggest that use of ARBs may be protective against the development and progression of AD (reviewed in Ashby and Kehoe, 2013). The finding in some studies that the reduction in risk is associated with ARBs but not (or not to the same extent) with ACE inhibitors (Kehoe et al, 2013) may reflect a beneficial effect of maintaining ACE-mediated Aβ degradation.…”

Section: The Renin-angiotensin System In Alzheimer's Diseasementioning

confidence: 99%

AÎ² degradation or cerebral perfusion? Divergent effects of multifunctional enzymes

Miners

Palmer

Tayler

et al. 2014

Front. Aging Neurosci.

View full text Add to dashboard Cite

There is increasing evidence that deficient clearance of β-amyloid (Aβ) contributes to its accumulation in late-onset Alzheimer disease (AD). Several Aβ-degrading enzymes, including neprilysin (NEP), endothelin-converting enzyme (ECE), and angiotensin-converting enzyme (ACE) reduce Aβ levels and protect against cognitive impairment in mouse models of AD. In post-mortem human brain tissue we have found that the activity of these Aβ-degrading enzymes rise with age and increases still further in AD, perhaps as a physiological response that helps to minimize the build-up of Aβ. ECE-1/-2 and ACE are also rate-limiting enzymes in the production of endothelin-1 (ET-1) and angiotensin II (Ang II), two potent vasoconstrictors, increases in the levels of which are likely to contribute to reduced blood flow in AD. This review considers the possible interdependence between Aβ-degrading enzymes, ischemia and Aβ in AD: ischemia has been shown to increase Aβ production both in vitro and in vivo, whereas increased Aβ probably enhances ischemia by vasoconstriction, mediated at least in part by increased ECE and ACE activity. In contrast, NEP activity may help to maintain cerebral perfusion, by reducing the accumulation of Aβ in cerebral blood vessels and lessening its toxicity to vascular smooth muscle cells. In assessing the role of Aβ-degrading proteases in the pathogenesis of AD and, particularly, their potential as therapeutic agents, it is important to bear in mind the multifunctional nature of these enzymes and to consider their effects on other substrates and pathways.

show abstract

Effects of Centrally Acting Angiotensin Converting Enzyme Inhibitors on Functional Decline in Patients with Alzheimer's Disease

Abstract: This observational study suggests that CACE-Is, and potentially perindopril in particular, are associated with a reduced rate of functional decline in patients with AD, without an association with mood or behavior. This suggests that CACE-Is may slow disease progression in AD.

Cited by 72 publications

References 79 publications

Cardiovascular medication burden in dementia disorders: a nationwide study of 19,743 dementia patients in the Swedish Dementia Registry

Cardiovascular medication burden in dementia disorders: a nationwide study of 19,743 dementia patients in the Swedish Dementia Registry

Cerebral Perfusion Enhancing Interventions: A New Strategy for the Prevention of Alzheimer Dementia

AÎ² degradation or cerebral perfusion? Divergent effects of multifunctional enzymes

Contact Info

Product

Resources

About