Genetic priming of a proinflammatory profile predicts low IQ in octogenarians

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 co...

Full description

Saved in:
Bibliographic Details
Published in:Neurobiology of aging 2009-05, Vol.30 (5), p.769-781
Main Authors: Krabbe, K.S, Mortensen, E.L, Avlund, K, Pilegaard, H, Christiansen, L, Pedersen, A.N, Schroll, M, Jørgensen, T, Pedersen, B.K, Bruunsgaard, H
Format: Article
Language:English
Subjects:
Aged, 80 and over
Aging
Aging - genetics
Aging - immunology
Biological and medical sciences
Biomarkers - analysis
Brain
Cognition Disorders - genetics
Cognition Disorders - immunology
Cognitive aging
Cytokine
Cytokines - analysis
Cytokines - genetics
Development. Senescence. Regeneration. Transplantation
DNA Mutational Analysis
Encephalitis - genetics
Encephalitis - immunology
Female
Fundamental and applied biological sciences. Psychology
Genetic Predisposition to Disease - genetics
Genetic Testing
Genotype
Haplotypes
Humans
IL-10
IL-18
IL-6
Inflammation
Intelligence
Intelligence - genetics
Intelligence Tests
Interleukin
Interleukin-10 - analysis
Interleukin-10 - genetics
Interleukin-18 - analysis
Interleukin-18 - genetics
Interleukin-6 - analysis
Interleukin-6 - genetics
Internal Medicine
Male
Neurology
Polymorphism, Single Nucleotide - genetics
Receptors, Tumor Necrosis Factor - analysis
Receptors, Tumor Necrosis Factor - genetics
Risk Factors
Single nucleotide polymorphisms
sTNFR
TNF-α
Tumor Necrosis Factor-alpha - analysis
Tumor Necrosis Factor-alpha - genetics
Vertebrates: nervous system and sense organs
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2007.08.013