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Interleukin-6 Covaries Inversely With Cognitive Performance Among Middle-Aged Community Volunteers

From the Behavioral Immunology Laboratory (A.L.M., R.S.) and the Behavioral Physiology Laboratory (K.L.P., S.A.N., J.D.F., S.B.M.), Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania; the Center for Clinical Pharmacology (M.F.M.) and the Department of Psychiatry (C.R.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and the Department of Psychiatry (J.D.F.), Mount Sinai School of Medicine, New York, New York.

Address correspondence and reprint requests to Anna L. Marsland, PhD, RN, Behavioral Immunology Laboratory, Department of Psychology, 3943 O'Hara Street, Pittsburgh, PA 15260. E-mail: marsland{at}pitt.edu

Objective: Recent evidence suggests that higher peripheral levels of interleukin 6 (IL-6) are associated with poorer cognitive function and predict future cognitive decline among the elderly. The current investigation extends the study of relationships between plasma IL-6 and cognitive performance to healthy middle-aged adults and to an examination of more specific cognitive domains.

Methods: Five hundred relatively healthy community volunteers aged 30 to 54 had blood drawn for the determination of plasma IL-6 levels and completed a battery of neuropsychological tests evaluating memory and executive function.

Results: After controlling for age, gender, race, and education, hierarchical regression analyses revealed an inverse relationship between circulating levels of IL-6 and performance on clusters of tests assessing auditory recognition memory, attention/working memory, and executive function. In contrast, there was no association between IL-6 and performance on tests of general memory. Secondary analyses demonstrated that relationships between IL-6 and auditory recognition and working memory and executive function were independent of a number of health factors, including body mass index, smoking, and hypertension.

Conclusions: These findings contribute to a growing body of evidence linking chronic inflammation to poorer cognitive functioning and extend these findings to a midlife community sample, raising the possibility that IL-6 may represent a biomarker for risk of future cognitive decline.

Key Words: interleukin-6 • cognitive performance • memory • executive function • middle age

Abbreviations: IL = interleukin; CNS = central nervous system; BMI = body mass index; WMS = Wechsler Memory Scale; BP = blood pressure.

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