Increased attrition of leukocyte telomere length in young adults is associated with poorer cognitive function in midlife.

Irit Cohen-Manheim,Ely Samuel Simon,Glen Michael Doniger,Abraham Aviv,Ronit Pinchas,Jeremy David Kark,Ronit Sinnreich

doi:10.1007/s10654-015-0051-4

Abstract

Evidence for an association of leukocyte telomere length (LTL) with cognitive function, predominantly in older adults, is inconsistent. No report has examined the association of LTL dynamics (age-specific LTL and its attrition rate) with cognitive function. We aimed to examine the association of LTL dynamics over 13 years in young adulthood with cognitive function in midlife. 497 individuals who had LTL measured at ages 28–32 and 41–46 years were assessed at ages 48–52 for global cognitive function and its five specific component domains with a NeuroTrax computerized test battery. Multivariable regression and logistic models were applied for cognition treated as a continuous and categorical variable, respectively. We found that LTL attrition (adjusted for sex, baseline LTL and potential confounders including socioeconomic variables) was inversely associated with global cognition (standardized β = −.119, p = .004) and its component domains: information processing speed (β = −.102, p = .024), visual-spatial function (β = −.102, p = .017) and memory (β = −.093, p = .045), but less so for the attention and executive domains. The multivariable-adjusted odds ratio for low global cognition comparing the upper versus lower thirds of LTL attrition was 2.12 (95 % CI 1.11–4.08, p for trend = .023). There was no association of baseline or follow-up LTL with cognition. No effect modification was evident for sex, smoking or inflammatory markers. In conclusion, faster LTL attrition in young adulthood was associated with poorer global and domain-specific cognitive function in midlife, suggesting that more rapid LTL attrition may be predictive of cognitive aging in healthy young adults.Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-015-0051-4) contains supplementary material, which is available to authorized users.

Highlights

Telomeres, DNA–protein complexes with tandem repeats of 50-TTAGGG-30 capping the chromosomal ends, shorten progressively with each somatic cell division, owing to the inability of DNA polymerase to fully replicate the 30 end of the DNA strand
We aimed to examine the association of leukocyte telomere length (LTL) dynamics over 13 years in young adulthood with cognitive function in midlife. 497 individuals who had LTL measured at ages 28–32 and 41–46 years were assessed at ages 48–52 for global cognitive function and its five specific component domains with a NeuroTrax computerized test battery
Notably global cognition and domainspecific information processing speed, visual spatial function and memory, among cognitively intact middle-aged adults were associated with the rate of change of LTL over the young adult life course

Summary

Introduction

DNA–protein complexes with tandem repeats of 50-TTAGGG-30 capping the chromosomal ends, shorten progressively with each somatic cell division, owing to the inability of DNA polymerase to fully replicate the 30 end of the DNA strand. Telomere length (TL) attrition is enhanced by elevated oxidative stress and, by extrapolation, by inflammation. TL may eventually reach a critical threshold at which a DNA damage signal is generated, resulting in cellular senescence or apoptosis [1]. TL has been proposed as a marker of replicative ageing in cultured somatic cells in vitro and presumably in vivo. Growing epidemiological evidence has linked shorter leukocyte TL (LTL) to reduced longevity

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