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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
[+] Article and Author 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.


Ann Intern Med. 2004;140(4):237-247. doi:10.7326/0003-4819-140-4-200402170-00005
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We found that carotid artery disease was associated with cognitive impairment and decline. The association between high-grade stenosis of the left internal carotid artery and cognitive impairment was particularly strong and persisted after adjustment for contralateral disease and risk factors for vascular disease, even though only 32 patients had high-grade left-sided stenosis. High-grade stenosis of the right internal carotid artery, which was present in 29 participants, was not associated with cognitive impairment. Cognitive decline also tended to be more frequent in participants with left-sided stenosis but not in those with right-sided stenosis; the magnitude of these effects was smaller than for cognitive impairment, probably because the duration of follow-up was relatively short. The different patterns observed between left-sided and right-sided disease argue against the hypothesis that high-grade stenosis of the internal carotid artery is simply a marker for vascular disease and its risk factors. Rather, it is consistent with a direct link between stenosis of the internal carotid artery and brain dysfunction that results in cognitive impairment. By extension, we expect that high-grade stenosis of the right internal carotid artery would be associated with impairment in measures of right hemispheric function.

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Figures

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Figure 1.
Mean Modified Mini-Mental State Examination scores.

Top. Scores by degree of stenosis of the left internal carotid artery or right internal carotid artery. Bottom. Scores by quartile of intima–media thickness (IMT) of the left common carotid artery or right common carotid artery. Error bars represent upper limits of 95% CIs.

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Grahic Jump Location
Figure 2.
Odds ratios and 95% CIs for cognitive impairment associated with high-grade (≥ 75%) stenosis of the left or right internal carotid artery compared with no stenosis adjusted for contralateral stenosis, demographic characteristics, and risk factors for vascular disease.

The asterisk indicates that no participant had high-grade right-sided stenosis, the apolipoprotein E (ApoE) ε4 genotype, and score less than 80 on the Modified Mini-Mental State Examination. MRI = magnetic resonance imaging.

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Summary for Patients

Cognitive Function and Carotid Artery Disease

The summary below is from the full report titled “Cognitive Impairment and Decline Are Associated with Carotid Artery Disease in Patients without Clinically Evident Cerebrovascular Disease.” It is in the 17 February 2004 issue of Annals of Internal Medicine (volume 140, pages 237-247). The authors are S.C. Johnston, E.S. O'Meara, T.A. Manolio, D. Lefkowitz, D.H. O'Leary, S. Goldstein, M.C. Carlson, L.P. Fried, and W.T. Longstreth Jr.

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