Angiotensin converting enzyme (ACE) inhibitors modulate the rate of progression of amnestic mild cognitive impairment

Rozzini, Luca; Chilovi, Barbara Vicini; Bertoletti, Erik; Conti, Marta Zaffira; Rio, Ilenia Del; Trabucchi, Marco; Padovani, Alessandro

doi:10.1002/gps.1523

Cited by 82 publications

(59 citation statements)

References 43 publications

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“…Cumulative exposure of enalapril plus lisinopril and captopril (results not showed) compared with (A) those who were exposed to other antihypertensive drugs or (B) those with untreated hypertension a Model 1: partially adjusted models for age and gender b Model 2: fully adjusted models for age, gender, education, pack-years (0 for smokers and 1 for ever smokers), type 2 diabetes, coronary artery disease, serum creatinine level, and apolipoprotein B to apolipoprotein A1 ratio at baseline as well as history of stroke, history of hypertension, and other hypertension drug use at each wave evaluation. Patients with congestive heart failure exposed to ACE-Is were excluded from statistical evaluation A few small observational and case-control studies of individuals with MCI have suggested that ACE-Is slowed cognitive decline and reduced progression to AD (Hajjar et al 2005;He et al 2006;Rozzini et al 2006Rozzini et al , 2008. The present findings also support some suggestions from secondary analyses in two large stroke-prevention trials Syst-Eur (Forette et al 2002) and PROGRESS (Tzourio et al 2003), where a significant reduction in the incidence of dementia was found with antihypertensive therapies also including ACE-Is.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, large-scale clinical trials of ACE-Is in AD and cognitive decline are lacking (Weiner et al 1992;Sudilovsky et al 1993;Louis et al 1999;Ohrui et al 2004b). In other small observational studies of individuals with MCI, ACE-Is slowed cognitive decline and reduced progression to AD (Hajjar et al 2005;He et al 2006;Rozzini et al 2006Rozzini et al , 2008. ACE-Is are described collectively as a "class" of drugs, but in reality, this classification is one of convenience based solely on their biological function which is the inhibition of ACE.…”

Section: Introductionmentioning

confidence: 99%

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

Solfrizzi

Scafato

Frisardi

et al. 2011

AGE

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Midlife elevated blood pressure and hypertension contribute to the development of Alzheimer's disease (AD) and overall dementia. We sought to estimate whether angiotensin-converting enzyme AGE (2013) inhibitors (ACE-Is) reduced the risk of developing mild cognitive impairment (MCI) in cognitively normal individuals. In the Italian Longitudinal Study on Aging, we evaluated 1,445 cognitively normal individuals treated for hypertension but without congestive heart failure from a population-based sample from eight Italian municipalities with a 3.5-year follow-up. MCI was diagnosed with current clinical criteria. Dementia, AD, and vascular dementia were diagnosed based on DSM-IIIR criteria, NINCDS-ADRDA criteria, and ICD-10 codes. Among 873 hypertensiontreated cognitively normal subjects, there was no significant association between continuous exposure to all ACE-Is and risk of incident MCI compared with other antihypertensive drugs [hazard ratio (HR), 0.45, 95% confidence interval (CI), 0.16-1.28]. Captopril exposure alone did not significantly modify the risk of incident MCI (HR, 1.80, 95% CI,). However, the enalapril sub-group alone (HR, 0.17, 95% CI, 0.04 -0.84) or combined with the lisinopril sub-group (HR, 0.27, 95% CI, 0.08-0.96), another ACE-I structurally related to enalapril and with similar potency, were associated with a reduced risk of incident MCI. Study duration exposure to ACE-Is as a "class" was not associated with incident MCI in older hypertensive adults. However, within-class differences linked to different chemical structures and/or drug potencies may exist, with a possible effect of the enalapril and lisinopril sub-groups in reducing the risk of incident MCI.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Solfrizzi

Scafato

Frisardi

et al. 2011

AGE

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“…Previous non-randomized controlled studies on treatment of nephropathy by inhibiting the renin-angiotensin system (by angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) showed protective effects on cognitive decline and reduced progression to dementia in patients with mild cognitive impairment [11,17] . However, in a population-based study the use of angiotensinconverting enzyme inhibitors was not associated with incident Alzheimer's disease [18] .…”

Section: Discussionmentioning

confidence: 99%

Microvascular Determinants of Cognitive Decline and Brain Volume Change in Elderly Patients with Type 2 Diabetes

Bresser

Reijmer²,

Berg³

et al. 2010

Dement Geriatr Cogn Disord

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Background/Aims: The present study examined the relationship between microvascular complications and cognitive decline and the development of structural brain abnormalities over a period of 4 years in patients with type 2 diabetes mellitus (T2DM). Methods: Sixty-eight elderly patients with T2DM had 2 cognitive assessments with a 4-year interval. Two MRI scans, performed at the same time as the cognitive assessments, were available from 55 patients. Changes in cognitive performance over time were expressed as a regression-based index (RBI). Automated volumetric measurements of total brain, lateral ventricles and white matter hyperintensities were performed. The relationship between baseline microvascular complications [diabetic retinopathy, peripheral neuropathy or albuminuria (micro- or macroalbuminuria)] and cognition and brain volumes was examined with linear regression analyses adjusted for age and sex (for cognition also for IQ). Results: At baseline, diabetic retinopathy was present in 18% of patients, peripheral neuropathy in 36%, albuminuria in 15%. Retinopathy or neuropathy were not significantly associated with baseline cognition or brain volumes, or changes in these measures over time. Albuminuria was associated with a lower composite RBI score, indicating accelerated cognitive decline (adjusted mean difference between patients with or without albuminuria: –0.58, 95% CI –0.85 to –0.31, p < 0.001). Conclusion: Albuminuria predicted accelerated cognitive decline in patients with T2DM, but other microvascular complications were unrelated to accelerated cognitive decline or brain MRI abnormalities.

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“…Blood pressure lowering has been shown to be effective in preventing stroke-related dementia, but the data on Alzheimer's disease are conflicting (24). The use of ACEIs was associated with reduced progression to dementia in patients with mild cognitive impairment (25) but not incident Alzheimer's disease in a population-based study (26).…”

Section: Predictors From Fds Recruitment (1993-1996)mentioning

confidence: 99%

Predictors of Cognitive Decline in Older Individuals With Diabetes

Bruce¹,

Davis²,

Casey³

et al. 2008

Diabetes Care

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OBJECTIVE -The purpose of this study was to determine longitudinal predictors of cognitive decline in older individuals with diabetes who did not have dementia.RESEARCH DESIGN AND METHODS -Cognitive assessments were performed in 205 subjects with diabetes (mean age 75.3 years) and repeated a median 1.6 years later. The sample was drawn from an existing cohort study, and data on diabetes, cardiovascular risk factors, and complications were collected 7.6 Ϯ 1.1 years before and at the time of the initial cognitive assessment. Cognitive status was defined using the Clinical Dementia Rating (CDR) scale, and cognitive decline was defined by change in CDR.RESULTS -The sample included 164 subjects with normal cognition (CDR 0) and 41 with cognitive impairment without dementia (CDR 0.5). At follow-up, 33 (16.1%) had experienced cognitive decline (4 new cases of dementia and 29 cognitive impairment without dementia). Only educational attainment predicted cognitive decline from the data collected 7.6 years before cognitive assessment. Univariate predictors of cognitive decline at the time of the first cognitive assessment included age, education, urinary albumin-to-creatinine ratio (ACR), and treatment with either ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). With multiple logistic regression controlling for age and education, cognitive decline was predicted by natural logarithm ACR (odds ratio 1.37 [95% CI 1.05-1.78], P ϭ 0.021), whereas treatment with either ACEIs or ARBs was protective (0.28 [0.12-0.65], P ϭ 0.003).CONCLUSIONS -In this sample of older patients with diabetes, microalbuminuria was a risk factor for cognitive decline, whereas drugs that inhibit the renin-angiotensin system were protective. These observations require confirmation because of their considerable potential clinical implications.

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Angiotensin converting enzyme (ACE) inhibitors modulate the rate of progression of amnestic mild cognitive impairment

Abstract: Older age, higher education, poor global cognitive performance, higher levels of plasma total homocysteine are independently associated with the progression of memory decline while the prescription of ACE Inhibitors is a protective factor for cognitive deterioration.

Cited by 82 publications

References 43 publications

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

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

Microvascular Determinants of Cognitive Decline and Brain Volume Change in Elderly Patients with Type 2 Diabetes

Predictors of Cognitive Decline in Older Individuals With Diabetes

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