Cognitive Change during the Life Course and Leukocyte Telomere Length in Late Middle-Aged Men

Abstract

Importance: Cognitive skills are known to decline through the lifespan with large individual differences. The molecular mechanisms for this decline are incompletely understood. Although leukocyte telomere length provides an index of cellular age that predicts the incidence of age-related diseases, it is unclear whether there is an association between cognitive decline and leukocyte telomere length.Objective: To examine the association between changes in cognitive function during adult life and leukocyte telomere length after adjusting for confounding factors such as education, mental health and life style.Design, Setting, and Participants: Two groups of men with negative (n = 97) and positive (n = 93) change in cognitive performance were selected from a birth cohort of 1985 Danish men born in 1953. Cognitive performance of each individual was assessed at age ~20 and 56 years. Leukocyte telomere length at age ~58 was measured using qPCR. Linear regression models were used to investigate the association between cognitive function and leukocyte telomere length.Results: Men with negative change in cognitive performance during adult life had significantly shorter mean leukocyte telomere length than men with positive change in cognitive performance (unadjusted difference β = −0.09, 95% CI −0.16 to −0.02, p = 0.02). This association remained significant after adjusting for smoking, alcohol consumption, leisure time activity, body mass index (BMI) and cholesterol (adjusted difference β = −0.09, 95% CI −0.17 to −0.01, p = 0.02) but was non-significant after adjusting for smoking, alcohol consumption, leisure time activity, BMI, cholesterol, current cognitive function, depression and education (adjusted difference β = −0.07, 95% CI −0.16 to −0.01, p = 0.08).Conclusion and Relevance: Preclinical cognitive changes may be associated with leukocyte telomere length.

Sleep efficiency and neurophysiological patterns in middle‐aged men are associated with cognitive change over their adult life course

“…We considered depressive symptoms and the completed level of formal education as potential covariates; although there was no group difference regarding depression, the participants' education was introduced as a covariate. This is well in accordance with a previous related study that has considered the influence of potential covariates associated with cognitive decline (Rask et al, 2016).…”

Association of telomere length with general cognitive trajectories: a meta-analysis of four prospective cohort studies

“…The strengths of this study include the longitudinal nature, with repeated measurements of general cognitive ability up to seven times in four Swedish and US cohorts. An observed significant association should not be due to the reverse causation in this study because TL was assessed before cognition, although early-life intelligence and cognitive changes have been shown to be predictive of TL in mid-later life (Rask et al, 2016; Schaefer et al, 2016). A further strength is that our combined analytic longitudinal study samples are the largest collection tested thus far and the age periods span from 50 to 100 years and beyond, which is representative of the underlying general aging population.…”

Leukocyte Telomere Length Is Unrelated to Cognitive Performance Among Non-Demented and Demented Persons: An Examination of Long Life Family Study Participants

“…assessment (Mather, Jorm, Parslow, & Christensen, 2011). Further, LTL changes may depend on different factors that vary across the lifespan (Rask et al, 2016). Divergent findings between the Yaffe et al (2011) study and our own investigation may be a consequence of differing study designs and the fact that the former comprises an ethnically diverse population of community residents, while the latter comprises individuals solely of European ancestry, who were selected based on exceptional survival attributes.…”

“…Age-related cognitive decline is caused by oxidative stress triggering neuroinflammation, and subsequent neurodegeneration and cell apoptosis (Ma et al, 2013). In this way, it relates to telomere attrition, which can arise from the cumulative burden of inflammation and oxidative stress through the lifecourse (Ma et al, 2013;Rask et al, 2016). Yet, the extent to which LTL relates to typical and/or pathologic cognitive aging is still largely unknown; it is uncertain whether shortened telomeres are a cause, consequence, or both for deteriorating cognitive ability (Hagg et al, 2017).…”