 |
|
Angiotensin-Converting Enzyme Inhibitors and Cognitive Decline in Older Adults With HypertensionResults From the Cardiovascular Health Study
Kaycee M. Sink, MD, MAS;
Xiaoyan Leng, PhD;
Jeff Williamson, MD, MHS;
Stephen B. Kritchevsky, PhD;
Kristine Yaffe, MD;
Lewis Kuller, MD;
Sevil Yasar, MD, PhD;
Hal Atkinson, MD;
Mike Robbins, PhD;
Bruce Psaty, MD, PhD;
David C. Goff Jr, MD, PhD
Arch Intern Med. 2009;169(13):1195-1202. doi:10.1001/archinternmed.2009.175
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.
Author Affiliations: Sticht Center on Aging, Wake Forest University, Winston-Salem, North Carolina (Drs Sink, Leng, Williamson, Kritchevsky, Atkinson, Robbins, and Goff); Departments of Neurology and Psychiatry, University of California, San Francisco (Dr Yaffe); Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Kuller); Division of Geriatric Medicine, The Johns Hopkins University, Baltimore, Maryland (Dr Yasar); and Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle (Dr Psaty).
Group Information: A list of the principal investigators and institutions of the Cardiovascular Health Study can be found at http://www.chs-nhlbi.org/pi.htm.
 CiteULike  Connotea  Delicious  Digg  Facebook  Reddit  Technorati  Twitter
What's this?
RELATED LETTERS
Designing Appropriate Clinical Trials to Assess ACEI Use and Cognitive Decline in Older Adults With Hypertension
Stephen Todd, Bernadette McGuinness, and A. Peter Passmore
Arch Intern Med. 2010;170(1):107.
EXTRACT
| FULL TEXT
Centrally Active ACEIs and Cognitive Decline
Takaaki Asamura, Takashi Ohrui, Kaori Une, Katsutoshi Furukawa, and Hiroyuki Arai
Arch Intern Med. 2010;170(1):107-108.
EXTRACT
| FULL TEXT
Centrally Active ACEIs and Cognitive Decline—Reply
Kaycee M. Sink and David C. Goff, Jr
Arch Intern Med. 2010;170(1):108.
EXTRACT
| FULL TEXT
RELATED ARTICLE
In This Issue of Archives of Internal Medicine
Arch Intern Med. 2009;169(13):1179.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Perindopril, a centrally active angiotensin-converting enzyme inhibitor, prevents cognitive impairment in mouse models of Alzheimer's disease
Dong et al.
FASEB J. 2011;25:2911-2920.
ABSTRACT
| FULL TEXT
Albuminuria and Decline in Cognitive Function: The ONTARGET/TRANSCEND Studies
Barzilay et al.
Arch Intern Med 2011;171:142-150.
ABSTRACT
| FULL TEXT
Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals
Corneveaux et al.
Hum Mol Genet 2010;19:3295-3301.
ABSTRACT
| FULL TEXT
Cognitive decline: the relevance of diabetes, hyperlipidaemia and hypertension
Etgen et al.
British Journal of Diabetes & Vascular Disease 2010;10:115-122.
ABSTRACT
Advances in Vascular Cognitive Impairment
Gorelick and Bowler
Stroke 2010;41:e93-e98.
FULL TEXT
Designing Appropriate Clinical Trials to Assess ACEI Use and Cognitive Decline in Older Adults With Hypertension
Todd et al.
Arch Intern Med 2010;170:107-107.
FULL TEXT
Centrally Active ACEIs and Cognitive Decline--Reply
Sink and Goff
Arch Intern Med 2010;170:108-108.
FULL TEXT
Centrally Active ACEIs and Cognitive Decline
Asamura et al.
Arch Intern Med 2010;170:107-108.
FULL TEXT
A{beta}42-to-A{beta}40- and Angiotensin-converting Activities in Different Domains of Angiotensin-converting Enzyme
Zou et al.
J. Biol. Chem. 2009;284:31914-31920.
ABSTRACT
| FULL TEXT
|
