Angiotensin-converting enzyme inhibitors and cognitive decline in older adults with hypertension

Results from the cardiovascular health study

Kaycee M. Sink, Xiaoyan Leng, Jeff Williamson, Stephen B. Kritchevsky, Kristine Yaffe, Lewis Kuller, Sevil Yasar, Hal Atkinson, Mike Robbins, Bruce Psaty, David C. Goff

Research output: Contribution to journalArticle

Abstract

Background: Hypertension (HTN) is a risk factor for dementia, and animal studies suggest that centrally active angiotensin-converting enzyme (ACE) inhibitors (those that cross the blood-brain barrier) may protect against dementia beyond HTN control. Methods: Participants in the Cardiovascular Health Study Cognition Substudy with treated HTN and no diagnosis of congestive heart failure (n=1054; mean age, 75 years) were followed up for a median of 6 years to determine whether cumulative exposure to ACE inhibitors (as a class and by central activity), compared with other anti-HTN agents, was associated with a lower risk of incident dementia, cognitive decline (by Modified Mini-Mental State Examination [3MSE]), or incident disability in instrumental activities of daily living (IADLs). Results: Among 414 participants who were exposed to ACEinhibitors and 640 who were not, there were 158 cases of incident dementia. Compared with other anti-HTN drugs, there was no association between exposure to all ACE inhibitors and risk of dementia (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.88-1.15), difference in 3MSE scores (-0.32 points per year; P=.15), or odds of disability in IADLs (odds ratio [OR], 1.06; 95% CI, 0.99-1.14). Adjusted results were similar. However, centrally activeACE inhibitors were associated with 65% less decline in 3MSE scores per year of exposure (P=.01), and noncentrally active ACE inhibitors were associated with a greater risk of incident dementia (adjusted HR, 1.20; 95% CI, 1.00-1.43 per year of exposure) and greater odds of disability in IADLs (adjusted OR, 1.16; 95% CI, 1.03-1.30 per year of exposure) compared with other anti-HTN drugs. Conclusions: While ACE inhibitors as a class do not appear to be independently associated with dementia risk or cognitive decline in older hypertensive adults, there may be within-class differences in regard to these outcomes. These results should be confirmed with a randomized clinical trial of a centrally active ACE inhibitor in the prevention of cognitive decline and dementia.

Original languageEnglish (US)
Pages (from-to)1195-1202
Number of pages8
JournalArchives of Internal Medicine
Volume169
Issue number13
DOIs
StatePublished - Jul 13 2009

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Angiotensin-Converting Enzyme Inhibitors
Dementia
Hypertension
Health
Activities of Daily Living
Confidence Intervals
Odds Ratio
Cognitive Dysfunction
Blood-Brain Barrier
Pharmaceutical Preparations
Cognition
Randomized Controlled Trials
Heart Failure

ASJC Scopus subject areas

  • Internal Medicine

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Angiotensin-converting enzyme inhibitors and cognitive decline in older adults with hypertension : Results from the cardiovascular health study. / Sink, Kaycee M.; Leng, Xiaoyan; Williamson, Jeff; Kritchevsky, Stephen B.; Yaffe, Kristine; Kuller, Lewis; Yasar, Sevil; Atkinson, Hal; Robbins, Mike; Psaty, Bruce; Goff, David C.

In: Archives of Internal Medicine, Vol. 169, No. 13, 13.07.2009, p. 1195-1202.

Research output: Contribution to journalArticle

Sink, KM, Leng, X, Williamson, J, Kritchevsky, SB, Yaffe, K, Kuller, L, Yasar, S, Atkinson, H, Robbins, M, Psaty, B & Goff, DC 2009, 'Angiotensin-converting enzyme inhibitors and cognitive decline in older adults with hypertension: Results from the cardiovascular health study', Archives of Internal Medicine, vol. 169, no. 13, pp. 1195-1202. https://doi.org/10.1001/archinternmed.2009.175
Sink, Kaycee M. ; Leng, Xiaoyan ; Williamson, Jeff ; Kritchevsky, Stephen B. ; Yaffe, Kristine ; Kuller, Lewis ; Yasar, Sevil ; Atkinson, Hal ; Robbins, Mike ; Psaty, Bruce ; Goff, David C. / Angiotensin-converting enzyme inhibitors and cognitive decline in older adults with hypertension : Results from the cardiovascular health study. In: Archives of Internal Medicine. 2009 ; Vol. 169, No. 13. pp. 1195-1202.
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abstract = "Background: Hypertension (HTN) is a risk factor for dementia, and animal studies suggest that centrally active angiotensin-converting enzyme (ACE) inhibitors (those that cross the blood-brain barrier) may protect against dementia beyond HTN control. Methods: Participants in the Cardiovascular Health Study Cognition Substudy with treated HTN and no diagnosis of congestive heart failure (n=1054; mean age, 75 years) were followed up for a median of 6 years to determine whether cumulative exposure to ACE inhibitors (as a class and by central activity), compared with other anti-HTN agents, was associated with a lower risk of incident dementia, cognitive decline (by Modified Mini-Mental State Examination [3MSE]), or incident disability in instrumental activities of daily living (IADLs). Results: Among 414 participants who were exposed to ACEinhibitors and 640 who were not, there were 158 cases of incident dementia. Compared with other anti-HTN drugs, there was no association between exposure to all ACE inhibitors and risk of dementia (hazard ratio [HR], 1.01; 95{\%} confidence interval [CI], 0.88-1.15), difference in 3MSE scores (-0.32 points per year; P=.15), or odds of disability in IADLs (odds ratio [OR], 1.06; 95{\%} CI, 0.99-1.14). Adjusted results were similar. However, centrally activeACE inhibitors were associated with 65{\%} less decline in 3MSE scores per year of exposure (P=.01), and noncentrally active ACE inhibitors were associated with a greater risk of incident dementia (adjusted HR, 1.20; 95{\%} CI, 1.00-1.43 per year of exposure) and greater odds of disability in IADLs (adjusted OR, 1.16; 95{\%} CI, 1.03-1.30 per year of exposure) compared with other anti-HTN drugs. Conclusions: While ACE inhibitors as a class do not appear to be independently associated with dementia risk or cognitive decline in older hypertensive adults, there may be within-class differences in regard to these outcomes. These results should be confirmed with a randomized clinical trial of a centrally active ACE inhibitor in the prevention of cognitive decline and dementia.",
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T2 - Results from the cardiovascular health study

AU - Sink, Kaycee M.

AU - Leng, Xiaoyan

AU - Williamson, Jeff

AU - Kritchevsky, Stephen B.

AU - Yaffe, Kristine

AU - Kuller, Lewis

AU - Yasar, Sevil

AU - Atkinson, Hal

AU - Robbins, Mike

AU - Psaty, Bruce

AU - Goff, David C.

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N2 - Background: Hypertension (HTN) is a risk factor for dementia, and animal studies suggest that centrally active angiotensin-converting enzyme (ACE) inhibitors (those that cross the blood-brain barrier) may protect against dementia beyond HTN control. Methods: Participants in the Cardiovascular Health Study Cognition Substudy with treated HTN and no diagnosis of congestive heart failure (n=1054; mean age, 75 years) were followed up for a median of 6 years to determine whether cumulative exposure to ACE inhibitors (as a class and by central activity), compared with other anti-HTN agents, was associated with a lower risk of incident dementia, cognitive decline (by Modified Mini-Mental State Examination [3MSE]), or incident disability in instrumental activities of daily living (IADLs). Results: Among 414 participants who were exposed to ACEinhibitors and 640 who were not, there were 158 cases of incident dementia. Compared with other anti-HTN drugs, there was no association between exposure to all ACE inhibitors and risk of dementia (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.88-1.15), difference in 3MSE scores (-0.32 points per year; P=.15), or odds of disability in IADLs (odds ratio [OR], 1.06; 95% CI, 0.99-1.14). Adjusted results were similar. However, centrally activeACE inhibitors were associated with 65% less decline in 3MSE scores per year of exposure (P=.01), and noncentrally active ACE inhibitors were associated with a greater risk of incident dementia (adjusted HR, 1.20; 95% CI, 1.00-1.43 per year of exposure) and greater odds of disability in IADLs (adjusted OR, 1.16; 95% CI, 1.03-1.30 per year of exposure) compared with other anti-HTN drugs. Conclusions: While ACE inhibitors as a class do not appear to be independently associated with dementia risk or cognitive decline in older hypertensive adults, there may be within-class differences in regard to these outcomes. These results should be confirmed with a randomized clinical trial of a centrally active ACE inhibitor in the prevention of cognitive decline and dementia.

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