Angiotensin-converting enzyme inhibitors and incidence of mild cognitive impairment. The Italian Longitudinal Study on Aging

Solfrizzi, Vincenzo; Scafato, Emanuele; Frisardi, Vincenza; Seripa, Davide; Logroscino, Giancarlo; Kehoe, Patrick Gavin; Imbimbo, Bruno P.; Baldereschi, Marzia; Crepaldi, Gaetano; Carlo, Antonio Di; Galluzzo, Lucia; Gandin, Claudia; Inzitari, Domenico; Maggi, Stefania

doi:10.1007/s11357-011-9360-z

Cited by 35 publications

(30 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The similar pharmacologic effects of the ACE inhibitors on cognitive function were also found in recent clinical trials [9][10][11] and in animal models [12,13]. It is noteworthy that some studies denoted that the direct effects of the ACE inhibitors to lower the risk of developing dementia could be independent from the controlling of cardiovascular disease and blood pressure control [2,4,14].…”

supporting

confidence: 68%

Pharmarcogenetic Mechanism of ACE I/D Polymorphism Adversely Responding to ACE Inhibitors in Regulating the ACE Promoter Activity in Neurons

Yang¹,

Chang²,

Chang³

et al. 2016

JPP

View full text Add to dashboard Cite

Abstract:The ACE (angiotensin converting enzyme) inhibitors are not only drugs widely prescribed drugs in cardiovascular diseases, but also potentially therapeutic agents in dementia. Based on the findings that the ACE inhibitors could activate the c-Jun N-terminal kinase signal to increase the ACE gene expression and that the Alu element of the human ACE gene involved in regulating ACE promoter activity, we aimed to investigate whether there are different pharmacogenetic responses of ACE I/D polymorphism to the ACE inhibitors in neurons. The three reporter vectors, pACEpro(f)-SEAP, p-I-ACEpro-SEAP, and p-D-ACEpro-SEAP were used to examine the transcriptional activity of the vectors responding to the lisinopril treatment using a transient-transfection method in SH-SY5Y cells. Our results showed that lisinopril increased the promoter activity of an ACE gene by 16.7%. Additionally, we found the lisinopril enhanced the ACE promoter activity of the I-form vector by 17.2%, but adversely reduced that of the D-form vector by 16.8%, as compared with the respective control without the lisinopril treatment. Firstly, our findings had proved that the I/D polymorphism of ACE gene contrarily responds to the ACE inhibitors in regulating the ACE expression in neurons, which provide a novel insight suggesting genetic testing to tailor the treatment regimens in AD (Alzheimer's disease) patients.

show abstract

supporting

confidence: 68%

Pharmarcogenetic Mechanism of ACE I/D Polymorphism Adversely Responding to ACE Inhibitors in Regulating the ACE Promoter Activity in Neurons

Yang¹,

Chang²,

Chang³

et al. 2016

JPP

View full text Add to dashboard Cite

show abstract

“…6 We were unable to reproduce their findings of superiority of ARB over ACE-I in decreasing AD dementia risk, which could be attributable to either the smaller number of participants using ARB or a drug-specific effect, because their ACE-I group consisted only of lisinopril users, which according to a recent study showed that enalapril, but not lisinopril, was associated with decreased risk of developing MCI. 28 Previous studies have shown associations between elevated blood pressure and incidence of AD dementia 1 ; thus, blood pressure control should result in decreased incidence of AD dementia. However, studies have also suggested that antihypertensive medications may have protective effects in addition and or independently of blood pressure control and that the effects may be specific to the class of drugs to which they belong.…”

Section: 21mentioning

confidence: 98%

Antihypertensive drugs decrease risk of Alzheimer disease

et al. 2013

View full text Add to dashboard Cite

Objectives: The aim of this study was to determine whether use of diuretics, angiotensin-1 receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), or b-blockers (BB) was associated with a reduced risk of Alzheimer disease (AD) dementia in participants with normal cognition or mild cognitive impairment (MCI).Methods: Secondary longitudinal data analysis of the Ginkgo Evaluation of Memory Study in older adults at least 75 years of age with normal cognition (n 5 1,928) or MCI (n 5 320) over a median 6.1-year period using Cox proportional hazard models after adjusting for confounders.Results: Diuretic use was reported by 15.6%, ARB 6.1%, ACE-I 15.1%, CCB 14.8%, and BB 20.5%. Of the 2,248 participants, 290 (13%) developed AD dementia. Hazard ratio for incident AD dementia among participants with normal cognition was 0.51 in diuretic (95% confidence interval [CI] 0.31-0.82), 0.31 in ARB (95% CI 0.14-0.68), 0.50 in ACE-I (95% CI 0.29-0.83), 0.62 in CCB (95% CI 0.35-1.09), and 0.58 in BB (95% CI 0.36-0.93) users and was not significantly altered when mean systolic blood pressure was above 140 mm Hg. In participants with MCI, only diuretic use was associated with decreased risk (hazard ratio 5 0.38, 95% CI 0.20-0.73).Conclusions: Diuretic, ARB, and ACE-I use was, in addition to and/or independently of mean systolic blood pressure, associated with reduced risk of AD dementia in participants with normal cognition, while only diuretic use was associated with reduced risk in participants with MCI. Observational studies suggest protective effects of antihypertensive medications on risk of dementia 1-6 independently or in addition to their ability to control blood pressure, and that these effects may be specific to the class of drugs to which they belong. A postmortem study of subjects with Alzheimer disease (AD) dementia showed that treated hypertensive subjects had less AD dementia neuropathology than untreated hypertensive and normotensive subjects, 7 while imaging studies showed preserved hippocampus in normotensive and treated hypertensive subjects. 8,9 However, clinical trials evaluating antihypertensive medications for dementia prevention found no risk reduction, 10-12 which could be explained by dementia being a secondary outcome and therefore insufficiently powered. Additionally, the majority of these studies were confounded by combined antihypertensive medication use 11,13-16 to achieve acceptable blood pressure. There are few studies with equivocal evidence regarding the role of hypertension (HTN) and no randomized clinical trials evaluating the effects of antihypertensive medications on progression of mild cognitive impairment (MCI) to dementia.

show abstract

“…A total of 37 potentially eligible studies were selected. After detailed evaluations, 10 prospective cohort studies were selected for the final meta-analysis [12–21]. A manual search of the reference lists of these studies did not yield any new eligible studies.…”

Section: Resultsmentioning

confidence: 99%

“…The findings of this study are in contrast with the findings of subgroup analysis in the previous meta-analysis and also indicate that antihypertensive drug use has a beneficial effect on dementia, but not on Alzheimer's disease, cognitive impairment, and cognitive decline. The reason for this could be that several studies with similar results on cognitive decline and dementia [13, 17, 18, 21] were published after the previous meta-analysis. The limitation of the previous meta-analysis was that it combined randomized controlled trials and prospective cohort studies, while the treatment effects of antihypertensive drugs in participants with specific characteristics were not examined.…”

Section: Discussionmentioning

confidence: 99%

Association between Antihypertensive Drug Use and the Incidence of Cognitive Decline and Dementia: A Meta-Analysis of Prospective Cohort Studies

Bai

Lin

et al. 2017

BioMed Research International

View full text Add to dashboard Cite

Background Antihypertensive drug use is inconsistently associated with the risk of dementia, Alzheimer's disease, cognitive impairment, and cognitive decline. Therefore, we conducted a meta-analysis of available prospective cohort studies to summarize the evidence on the strength of these relationships. Methods Three electronic databases including MedLine, Embase, and the Cochrane Library were searched to identify studies from inception to April 2017. Only prospective cohort studies that reported effect estimates with corresponding 95% confidence intervals (CIs) of dementia, Alzheimer's disease, cognitive impairment, and cognitive decline for antihypertensive drug use versus not using antihypertensive drugs were included. Results We included 10 prospective cohort studies reporting data on 30,895 individuals. Overall, participants who received antihypertensive drugs had lower incidence of dementia (relative risk [RR]: 0.86; 95% CI: 0.75–0.99; p = 0.033), while there was no significant effect on the incidence of Alzheimer's disease (RR: 0.83; 95% CI: 0.64–1.09; p = 0.154), cognitive impairment (RR: 0.89; 95% CI: 0.57–1.38; p = 0.596), and cognitive decline (RR: 1.11; 95% CI: 0.86–1.43; p = 0.415). Further, the incidence of Alzheimer's disease might be affected by antihypertensive drug use in participants with specific characteristics. Conclusions Antihypertensive drug use was associated with a significantly reduced risk of dementia, but not with the risk of Alzheimer's disease, cognitive impairment, and cognitive decline.

show abstract

Angiotensin-converting enzyme inhibitors and incidence of mild cognitive impairment. The Italian Longitudinal Study on Aging

Cited by 35 publications

References 52 publications

Pharmarcogenetic Mechanism of ACE I/D Polymorphism Adversely Responding to ACE Inhibitors in Regulating the ACE Promoter Activity in Neurons

Pharmarcogenetic Mechanism of ACE I/D Polymorphism Adversely Responding to ACE Inhibitors in Regulating the ACE Promoter Activity in Neurons

Antihypertensive drugs decrease risk of Alzheimer disease

Association between Antihypertensive Drug Use and the Incidence of Cognitive Decline and Dementia: A Meta-Analysis of Prospective Cohort Studies

Contact Info

Product

Resources

About