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.

BackgroundInflammatory markers are elevated in patients with dementia. Evidence for an association between inflammation and cognitive function in dementia-free individuals is sparse, inconsistent, and predominantly restricted to the elderly. Assessment of inflammatory markers in young adults as predictors of cognitive function in midlife, well before the onset of overt dementia, is lacking. Furthermore, rarely has the relation with longitudinal change in inflammatory markers been examined.ObjectiveTo examine the association of the inflammatory markers C-reactive protein (CRP), fibrinogen, white blood cell count (WBC) and GlycA, a novel NMR-determined biomarker of systemic inflammation, measured in young adulthood and of GlycA change over 13 years follow-up with cognitive function in midlife.Methods507 participants of the Jerusalem Lipid Research Clinic (LRC) study were assessed at 3 time points over 18–22 years. First, the inflammatory variables GlycA, CRP, fibrinogen, and WBC were measured in blood samples drawn at ages 28–32. Then, in blood samples drawn a mean 13 years later (range, 12–16 years) at ages 41–46, GlycA was again measured (in 484 individuals). Subsequently at ages 48–52, on average 7 years later, global cognitive function and its five specific component domains were assessed with a NeuroTrax computerized test battery. Multiple regression and multivariable logistic models were applied.ResultsInverse unadjusted associations were shown for baseline levels and longitudinal change in inflammatory markers and measures of cognition. Multiple regression models were adjusted for age at cognitive assessment, sex, socio-demographic characteristics, baseline measures of leisure-time vigorous activity, smoking status and body mass index (BMI) at ages 28–32, change in smoking status and BMI between ages 28–32 and 41–46, and depression assessed at the time of cognitive testing. The highest quintile of GlycA change, but not the baseline inflammation measures, was inversely related to global cognition (standardized β = -.109, p = .011) as well as to the information processing speed and memory domains (standardized β = -.124, p = .008 and-.117, p = .014, respectively). The multivariable-adjusted odds ratio for low ranked global cognitive function (lowest fifth) comparing the extreme quintiles of GlycA change was 4.8 (95%CI, 1.7–13.5, p = .003; p for trend = .031).ConclusionsIn this longitudinal study of a novel systemic inflammatory marker in a population-based cohort of young adults, GlycA increase over 13 years, but not baseline measures of inflammation, was associated with poorer cognitive function in midlife.

An adverse association of higher BMI with cognitive function began in adolescence and was restricted to low childhood SEP. Taller stature in both sexes and late growth in women were associated with better midlife cognitive performance.

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A higher FPG in young adults was associated with lower cognitive performance in midlife. Although we cannot dismiss the possibility of reverse causation, hyperglycemia at a young age may be a modifiable risk factor for low-ranked cognitive function in midlife.