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

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.

Leukocyte Telomere Length Is Related to Brain Parenchymal Fraction and Attention/Speed in the Elderly: Results of the Austrian Stroke Prevention Study

“…In the first pathway, we hypothesize that those inheriting longer telomeres or loosing less of their telomere during growth, develop a larger brain translating to higher brain reserve. Indeed, faster LTL attrition in younger life was associated with poorer global cognitive function as well as worse performance in domains including processing speed in midlife (24). We further hypothesize that the effect modulators acting already early in life such as female sex, lower education, and ApoE4 non-carrier status, mainly act on this developmental pathway (Modulators I).…”

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

“…Other studies have found no correlation between LTL and cognitive function (Harris et al, 2006; Bendix et al, 2011, 2014a; Cohen-Manheim et al, 2016). Furthermore, two cohort studies have found that short LTL predicts cognitive decline (Martin-Ruiz et al, 2006; Yaffe et al, 2011).…”

“…A recent study based on the Jerusalem Lipid Research Clinic study has examined longitudinal LTL data and association with cognitive ability (Cohen-Manheim et al, 2016). The LTL dynamics was measured over 13 years in young adults (measured at ages 28–32 and 41–46 years) and compared with cognitive function at ages 48–52.…”

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

“…Some studies have also found relationships between LTL with neuropsychiatric disorders such as depression, anxietyrelated disorders, schizophrenia, and other psychotic disorders, as well as bipolar disorder (Richard, Reitz, Honig, Schupf, & Tamg, 2013;Chang et al, 2018;Czepielewski et al, 2018;Nieratschker et al, 2013, Powell, Dima, Frangou, & Breen, 2018Vasconcelos-Moreno et al, 2017;Wang et al, 2017;Colpo, Leffa, Quevedo, & Carvalho, 2015;Lindqvist et al, 2015). Such aging-, metabolic-, psychiatric-, and inflammation-related conditions have all been associated with cognitive outcomes (Cohen-Manheim 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). The literature is limited and inconsistent in that some studies have observed LTL being associated with cognitive decline, whereas others have not (Cohen-Manheim et al, 2016;Devore, Prescott, De Vivo, & Grodstein, 2011;Hagg et al, 2017;Harris et al, 2012;Honig et al, 2006;Martin-Ruiz et al, 2006;Mather et al, 2010;Moverare-Skrtic et al, 2012;Valdes et al, 2010;Yaffe et al, 2011;Zekry et al, 2010). Differences in study findings may be attributed to methodological differences in the measurement of LTL, use of varying cognitive assessment tools, diverse sociodemographic and clinical characteristics, and distinct study designs (e.g., cross-sectional vs. cohort).…”