Inflammation as a mediator of the relationship between cortical thickness and metabolic syndrome
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Metabolic Syndrome (MetS), the clustering of obesity, high blood pressure, and disordered glucose and lipid/lipoprotein metabolism within a single individual, is associated with poorer cognitive function. It has been hypothesized that cognitive impairment in MetS occurs primarily within the context of inflammation. MetS risk factors are also associated with thinning of the cerebral cortex. However, the mechanisms by which MetS and inflammation affect the brain are poorly understood. The present study used statistical mediation to examine the relationship between MetS risk factors, cortical thickness in a priori regions of interest (ROIs) and inflammation. ROIs were chosen from the previous literature. Forty-three adults between the ages of 40 and 60 years underwent a health screen, neuropsychological testing and structural magnetic resonance imaging. Serum levels of pro-inflammatory markers (interleukin 1, interleukin 2, interleukin 6 and C-Reactive Protein) were measured using enzyme-linked immunosorbent assays. A higher number of MetS risk factors were associated with thinning in the inferior frontal ROI (β = −0.35, p = 0.019) as well as higher levels of serum interleukin 2 (β = 0.31, p = 0.04). A higher level of serum interleukin 2 was also associated with reduced thickness in the inferior frontal gyrus (β = −0.41, p = 0.013). After accounting for the effects of interleukin 2, the number of MetS risk factors was no longer associated with cortical thickness in the inferior frontal gyrus indicating successful statistical mediation. The results indicate a potentially important role for inflammation in linking MetS to cortical thinning and cognitive vulnerability.
KeywordsInflammation Cortical thickness Metabolic syndrome
S.S.K wrote the manuscript and conducted all data analyses. D.E.E and M.M.G assisted with data collection, imaging data analyses, and data interpretation. K.G contributed to data collection and manuscript review and discussion. H.T. contributed to project conceptualization and funding, supervision of data collection, data interpretation and manuscript review. A.P.H was the principal investigator for the project; she contributed to project conceptualization and funding, supervision of data collection, data analysis and interpretation, and manuscript review.
This work was made possible by funding provided by the American Heart Association (09BGIA2060722), the National Institute of Neurological Disorders and Stroke (R01 NS075565), the National Institute on Aging (F31AG040890, MMG), and the University of Texas at Austin.
Conflicts of interest
Sonya S. Kaur, Mitzi M. Gonzales, Danielle E. Eagan, Katyoon Goudarzi, Hirofumi Tanaka, and Andreana P. Haley report no conflicts of interest.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.
- Alberti, K. G. M. M., Eckel, R. H., Grundy, S. M., Zimmet, P. Z., Cleeman, J. I., Donato, K. A., et al. (2009). Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; american heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. Circulation, 120, 1640–1645.CrossRefPubMedGoogle Scholar
- Dickerson, B. C., Bakkour, A., Salat, D. H., Feczko, E., Pacheco, J., Greve, D. N., et al. (2009). The Cortical signature of Alzheimer’s disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals. Cereb Cortex, 19, 497–510.PubMedCentralCrossRefPubMedGoogle Scholar
- Eagan, DE, Gonzales, MM, Tarumi, T, Tanaka, H, Stautberg, S, Haley, AP (2012) Elevated C-Reactive Protein relates to increased cerebral myo-inositol levels in middle-aged adults, Cardiovascular Psychiatry and Neurology Google Scholar
- Leritz, E. C., Salat, D. H., Williams, V. J., Schnyer, D. M., Rudolph, J. L., Lipsitz, L., et al. (2011). Thickness of the human cerebral cortex is associated with metrics of cerebrovascular health in a normative sample of community dwelling older adults. Neuroimage, 54, 2659–2671.PubMedCentralCrossRefPubMedGoogle Scholar
- McGeer EG, McGeer PL (1999) Brain inflammation in Alzheimer disease and the therapeutic implications. Curr Pharm Des, 5821–5836Google Scholar
- Sidak, Z. (1967). Rectangular confidence region for the means of multivariate normal distributions. J Am Stat Assoc, 62, 626–633.Google Scholar
- Yaffe, K., Weston, A. L., Blackwell, T., & Krueger, K. A. (2009). The metabolic syndrome and the development of cognitive impairment among older women. Clin Neurol, 72, A99.Google Scholar