Cognitive Impairment and Decline Are Associated with Carotid Artery Disease in Patients without Clinically Evident Cerebrovascular Disease

S. Claiborne Johnston, MD, PhD; Ellen S. O'Meara, PhD; Teri A. Manolio, MD, PhD; David Lefkowitz, MD; Daniel H. O'Leary, MD; Steven Goldstein, MD; Michelle C. Carlson, PhD; Linda P. Fried, MD, MPH; and W. T. Longstreth, Jr., MD, MPH

17 February 2004 | Volume 140 Issue 4 | Pages 237-247

Background: Whether carotid artery disease is a cause of cognitive impairment in persons who have not had stroke is unknown. If this is the case, diminished performance on the Modified Mini-Mental State Examination should be more common in persons with left carotid artery disease than in those with right carotid artery disease.

Objective: To determine whether left carotid artery disease is associated with cognitive impairment.

Design: Cross-sectional and cohort study.

Setting: Four U.S. communities participating in the Cardiovascular Health Study.

Patients: 4006 right-handed men and women 65 years of age or older without history of stroke, transient ischemic attack, or carotid endarterectomy.

Measurements: Internal carotid artery stenosis and intima–media thickness of the common carotid artery were assessed by using duplex ultrasonography. Cognitive impairment was defined as a score less than 80 on the Modified Mini-Mental State Examination, and cognitive decline was defined as an average decrease of more than 1 point annually in Modified Mini-Mental State Examination score during up to 5 years of follow-up. Multivariate logistic regression models were used to estimate the risk for cognitive impairment and decline associated with left internal carotid artery stenosis and intima–media thickness, after adjustment for measures of right-sided disease and risk factors for vascular disease.

Results: After adjustment for right-sided stenosis, high-grade ( 75% narrowing of diameter) stenosis of the left internal carotid artery (32 patients) was associated with cognitive impairment (odds ratio, 6.7 [95% CI, 2.4 to 18.1] compared with no stenosis) and cognitive decline (odds ratio, 2.6 [CI, 1.1 to 6.3]). Intima–media thickness of the left common carotid artery was associated with cognitive impairment and decline in univariate analysis, but this effect did not persist after adjustment.

Conclusions: Cognitive impairment and decline are associated with asymptomatic high-grade stenosis of the left internal carotid artery. The persistence of the association after adjustment for right-sided stenosis indicates that the association is not due to underlying vascular risk factors or atherosclerosis in general.

Editors' Notes Context While stroke is a known cause of cognitive impairment, the relationship between carotid artery stenosis and cognitive function in people without a history of stroke is unclear. Contribution In this study of 4006 right-handed individuals 65 years of age and older, left-sided carotid artery stenosis of at least 75% was associated with cognitive impairment at baseline and cognitive decline over 5 years. This association persisted after right-sided carotid stenosis and cardiovascular risk factors were taken into account, which means that left-sided stenosis is more than simply an indicator of cardiovascular disease. Cautions This observational study does not constitute evidence that treatment of left-sided stenosis would benefit cognition. –The Editors

 

Author and Article Information

From University of California, San Francisco, San Francisco, California; University of Washington, Seattle, Washington; National Heart, Lung, and Blood Institute, Bethesda, and Johns Hopkins University, Baltimore, Maryland; Wake Forest University, Winston-Salem, North Carolina; Tufts-New England Medical Center, Boston, Massachusetts; and University of Pittsburgh, Pittsburgh, Pennsylvania.

Deceased.

A full list of investigators and institutions that participated in the Cardiovascular Health Study can be found at http://www.chs-nhlbi.org.

Grant Support: The research reported in this article was supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, and N01-HC-15103 from the National Heart, Lung, and Blood Institute. Dr. Johnston was supported by National Institute of Neurological Disorders and Stroke (grant no. NS02254).

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: S. Claiborne Johnston, MD, PhD, Department of Neurology, Box 0114, University of California, San Francisco, 505 Parnassus Avenue, M-798, San Francisco, CA 94143-0114.

Current Author Addresses: Dr. Johnston: Department of Neurology, Box 0114, University of California, San Francisco, 505 Parnassus Avenue, M-798, San Francisco, CA 94143-0114.

Dr. O'Meara: Department of Biostatistics, Box 354922, University of Washington, Seattle, WA 98115.

Dr. Manolio: National Lung, Heart and Blood Institute, National Institutes of Health, Two Rockledge Centre, 6701 Rockledge Drive, Room 8160, Mail Station 7934, Bethesda, MD 20892-7934.

Dr. Lefkowitz: Department of Neurology, Wake Forest University, Medical Center Boulevard, Winston-Salem, NC 27157.

Dr. O'Leary: Department of Radiology, Box 380, New England Medical Center, 750 Washington Street, Boston, MA 02111.

Drs. Carlson and Fried: Bloomberg School of Public Health, Johns Hopkins University, 2024 East Monument Street, Baltimore, MD 21205.

Dr. Longstreth: Department of Neurology, Box 359775, Harborview Medical Center, 325 9th Avenue, Seattle, WA 98104.

Author Contributions: Conception and design: S.C. Johnston.

Analysis and interpretation of the data: S.C. Johnston, E.S. O'Meara, D. Lefkowitz, D.H. O'Leary, M.C. Carlson, W.T. Longstreth.

Drafting of the article: S.C. Johnston.

Critical revision of the article for important intellectual content: T.A. Manolio, D. Lefkowitz, D.H. O'Leary, W.T. Longstreth.

Final approval of the article: S.C. Johnston, E.S. O'Meara, T.A. Manolio, D.H. O'Leary, M.C. Carlson, W.T. Longstreth.

Provision of study materials or patients: D.H. O'Leary, L.P. Fried.

Statistical expertise: S.C. Johnston, E.S. O'Meara.

Administrative, technical, or logistic support: S.C. Johnston, W.T. Longstreth.

Collection and assembly of data: D.H. O'Leary.