Genetic priming of a proinflammatory profile predicts low IQ in octogenarians

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

doi:10.1016/j.neurobiolaging.2007.08.013

Genetic priming of a proinflammatory profile predicts low IQ in octogenarians

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

27 Citationer (Scopus)

Abstract

The purpose of the study was to test the hypothesis that single nucleotide polymorphisms (SNPs) within interleukin (IL)-18, TNF-alpha, 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-alpha, 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-alpha.

Originalsprog	Engelsk
Tidsskrift	Neurobiology of Aging
Vol/bind	30
Udgave nummer	5
Sider (fra-til)	769-81
Antal sider	13
ISSN	0197-4580
DOI	https://doi.org/10.1016/j.neurobiolaging.2007.08.013
Status	Udgivet - maj 2009
Udgivet eksternt	Ja

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10.1016/j.neurobiolaging.2007.08.013

Citationsformater

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title = "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-alpha, 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-alpha, 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-alpha.",

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author = "Krabbe, {K S} and Mortensen, {E L} and K Avlund and H Pilegaard and L Christiansen and Pedersen, {A N} and M Schroll and T J{\o}rgensen and Pedersen, {B K} and H Bruunsgaard",

year = "2009",

month = may,

doi = "10.1016/j.neurobiolaging.2007.08.013",

language = "English",

volume = "30",

pages = "769--81",

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T1 - Genetic priming of a proinflammatory profile predicts low IQ in octogenarians

AU - Krabbe, K S

AU - Mortensen, E L

AU - Avlund, K

AU - Pilegaard, H

AU - Christiansen, L

AU - Pedersen, A N

AU - Schroll, M

AU - Jørgensen, T

AU - Pedersen, B K

AU - Bruunsgaard, H

PY - 2009/5

Y1 - 2009/5

N2 - The purpose of the study was to test the hypothesis that single nucleotide polymorphisms (SNPs) within interleukin (IL)-18, TNF-alpha, 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-alpha, 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-alpha.

AB - The purpose of the study was to test the hypothesis that single nucleotide polymorphisms (SNPs) within interleukin (IL)-18, TNF-alpha, 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-alpha, 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-alpha.

KW - Aged, 80 and over

KW - Aging/genetics

KW - Biomarkers/analysis

KW - Cognition Disorders/genetics

KW - Cytokines/analysis

KW - DNA Mutational Analysis

KW - Encephalitis/genetics

KW - Female

KW - Genetic Predisposition to Disease/genetics

KW - Genetic Testing

KW - Genotype

KW - Haplotypes

KW - Humans

KW - Intelligence/genetics

KW - Intelligence Tests

KW - Interleukin-10/analysis

KW - Interleukin-18/analysis

KW - Interleukin-6/analysis

KW - Male

KW - Polymorphism, Single Nucleotide/genetics

KW - Receptors, Tumor Necrosis Factor/analysis

KW - Risk Factors

KW - Tumor Necrosis Factor-alpha/analysis

U2 - 10.1016/j.neurobiolaging.2007.08.013

DO - 10.1016/j.neurobiolaging.2007.08.013

M3 - Journal article

C2 - 17913303

SN - 0197-4580

VL - 30

SP - 769

EP - 781

JO - Neurobiology of Aging

JF - Neurobiology of Aging

IS - 5

ER -

Genetic priming of a proinflammatory profile predicts low IQ in octogenarians

Abstract

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