@article {1112, title = {Angiotensin-converting enzyme inhibitors and cognitive decline in older adults with hypertension: results from the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {169}, year = {2009}, month = {2009 Jul 13}, pages = {1195-202}, 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 ACE inhibitors 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 active ACE 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.

}, keywords = {Aged, Angiotensin-Converting Enzyme Inhibitors, Blood-Brain Barrier, Cognition, Dementia, Female, Follow-Up Studies, Humans, Hypertension, Incidence, Male, Prospective Studies, Risk Factors}, issn = {1538-3679}, doi = {10.1001/archinternmed.2009.175}, author = {Sink, Kaycee M and Leng, Xiaoyan and Williamson, Jeff and Kritchevsky, Stephen B and Yaffe, Kristine and Kuller, Lewis and Yasar, Sevil and Atkinson, Hal and Robbins, Mike and Psaty, Bruce and Goff, David C} }