Genetic priming of a proinflammatory profile predicts low IQ in octogenarians

Krabbe, K.S.; Mortensen, E.L.; Avlund, K.; Pilegaard, H.; Christiansen, L.; Pedersen, A.N.; Schroll, M.; Jørgensen, T.; Pedersen, B.K.; Bruunsgaard, H.

doi:10.1016/j.neurobiolaging.2007.08.013

« Previous Next »Neurobiology of Aging
Volume 30, Issue 5 , Pages 769-781, May 2009

Genetic priming of a proinflammatory profile predicts low IQ in octogenarians

K.S. Krabbe
- The Centre of Inflammation and Metabolism, Department of Infectious Diseases and CMRC, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark
- Corresponding author at: Centre of Inflammation and Metabolism, Rigshospitalet, Section 7641, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Tel.: +45 35 45 73 77; fax: +45 35 45 76 44.
E.L. Mortensen
- Institute of Public Health, University of Copenhagen, Denmark
- Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
- Present address: Institute of Public Health, Faculty of Health Sciences, University of Copenhagen, Øster Farimagsgade 5, opg Z, 1 sal, DK-1014 Copenhagen, Denmark.
K. Avlund
- Institute of Public Health, University of Copenhagen, Denmark
- Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
- Present address: Institute of Public Health, Faculty of Health Sciences, University of Copenhagen, Øster Farimagsgade 5, Building 9, Post Box 2099, DK-1014 Copenhagen, Denmark.
H. Pilegaard
- The August Krogh Building, Institute of Molecular Biology, University of Copenhagen, Denmark
- Present address: The August Krogh Building, Room 431, Institute of Molecular Biology, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen, Denmark.
L. Christiansen
- Department of Epidemiology, Institute of Public Health, University of Southern Denmark, Denmark
- Present address: Institute of Public Health, Department of Epidemiology, University of Southern Denmark, J.B. Winsløws Vej 9, DK-5000 Odense C, Denmark.
A.N. Pedersen
- National Food Institute, Technical University of Denmark, Denmark
- Present address: National Food Institute, Technical University of Denmark, Anker Engelundsvej 1, 101 A, DK-2800 Kgs. Lyngby, Denmark.
M. Schroll
- Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
- Present address: Research Centre for Prevention and Health, Building 84/85, Glostrup University Hospital, DK-2600 Glostrup, Denmark.
T. Jørgensen
- Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
- Present address: Research Centre for Prevention and Health, Building 84/85, Glostrup University Hospital, DK-2600 Glostrup, Denmark.
B.K. Pedersen
- The Centre of Inflammation and Metabolism, Department of Infectious Diseases and CMRC, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark
- Present address: Centre of Inflammation and Metabolism, Rigshospitalet, Section 7641, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
H. Bruunsgaard
- The Centre of Inflammation and Metabolism, Department of Infectious Diseases and CMRC, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark
- Present address: Centre of Inflammation and Metabolism, Rigshospitalet, Section 7641, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.

Received 8 May 2007; received in revised form 11 July 2007; accepted 21 August 2007. published online 04 October 2007.

Abstract

The purpose of the study was to test the hypothesis that single nucleotide polymorphisms (SNPs) within interleukin (IL)-18, TNF-α, IL-6 and IL-10 gene promoter regions are risk factors for cognitive decline in healthy octogenarians, and to isolate the strongest inflammatory biomarkers of cognitive function in the peripheral blood. The Wechsler Adult Intelligence Scale was administered to 112 individuals at ages 80 and 85. An IL-18 haplotype was an independent risk factor of poor Performance IQ. The TNF-308GA genotype was related to individual declines in Verbal IQ, and the IL-10-592 CC genotype was related to better Verbal IQ at the age of 80. Circulating levels of TNF-α, sTNFRs, and IL-6 were negatively correlated with IQ at age 85 and less strongly to IQ at age 80 with activation of the TNF system as the strongest biomarker. In conclusion, SNPs related to high proinflammatory or low anti-inflammatory activity are independent risk factors of reduced cognitive function in octogenarians. Only the IL-18 haplotype was associated with inflammation in the peripheral blood and only with regard to circulating TNF-α.

Keywords: Intelligence, Brain, Aging, Cognitive aging, Inflammation, Single nucleotide polymorphisms, Cytokine, Interleukin, TNF-α, sTNFR, IL-6, IL-18, IL-10