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Interaction of atherosclerosis and inflammation in elderly subjects with poor cognitive function

E. van Exel, MD PhD, A. J.M. de Craen, PhD, E. J. Remarque, PhD, J. Gussekloo, MD PhD, P. Houx, PhD, A. Bootsma–van der Wiel, MD PhD, M. Frölich, PhD, P. W. Macfarlane, DSc FESC, G. J. Blauw, MD PhD and R. G.J. Westendorp, MD PhD

From the Section of Gerontology and Geriatrics (Drs. van Exel, de Craen, Remarque, Gussekloo, Bootsma–van der Wiel, Blauw, and Westendorp), Department of General Internal Medicine, and Department of Clinical Chemistry (Dr. Frölich), Leiden University Medical Center, and University Department of Psychiatry and Neuropsychology (Dr. Houx), University of Limburg, the Netherlands; and Section of Cardiology (Dr. Macfarlane), University of Glasgow Division of Cardiovascular and Medical Sciences, Royal Infirmary, Scotland.

Address correspondence and reprint requests to Dr. A.J.M. de Craen, Section of Gerontology and Geriatrics, Leiden University Medical Center, C2-R, PO Box 9600, 2300 RC Leiden, the Netherlands; e-mail: craen{at}lumc.nl

Objective: To test the hypothesis that a pro-inflammatory response is associated with cognitive impairment among individuals with cardiovascular disease.

Method: All 85-year-old inhabitants of Leiden (n = 599) were visited at their place of residence. A history of cardiovascular disease and an EKG were used as indicators of atherosclerosis. Production of the pro-inflammatory cytokine tumor necrosis factor- and the anti-inflammatory cytokine interleukin-10 was assessed in a whole-blood assay using lipopolysaccharide as a stimulus. Global cognitive functioning was determined with the Mini-Mental State Examination (MMSE); attention, cognitive speed, and memory were determined with four neuropsychological tests; and a history of dementia was obtained.

Results: In subjects with cardiovascular disease, median MMSE scores were lower in those with a pro-inflammatory response when compared with those with an anti-inflammatory response (p = 0.02). Similar associations were found for the Stroop Test, measuring attention (p < 0.01), the Coding Test measuring cognitive speed (p = 0.02), the Word Learning Test measuring memory (p < 0.01), and the presence of dementia (p = 0.04). The associations remained unaltered after adjustments for possible confounders such as gender, level of education, use of nonsteroidal anti-inflammatory drugs, use of cardiovascular drugs, and cardiovascular risk factors. In contrast, outcomes of the cognitive tests and presence of dementia were not dependent on the inflammatory response when cardiovascular disease was absent.

Conclusion: The combination of cardiovascular disease and a pro-inflammatory cytokine response may be associated with cognitive impairment and dementia.

Received February 12, 2003. Accepted in final form August 20, 2003.

Deceased.

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