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Short telomere length is associated with impaired cognitive performance in European ancestry cohorts
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2017 (English)In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 7, article id e1100Article in journal (Refereed) Published
Abstract [en]

The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N = 17 052; mean age = 59.2 +/- 8.8 years) provided results for associations between qPCR-measuredTL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (beta = 0.051 per s. d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P = 0.0002), and MMSE (beta = 0.025; 95% CI: 0.002, 0.047; P = 0.03), and faster STROOP (beta = -0.053; 95% CI: -0.087, -0.018; P = 0.003). Effects for DSST were stronger in APOE epsilon 4 non-carriers (beta = 0.081; 95% CI: 0.045, 0.117; P = 1.0 x 10(-5)), whereas carriers performed better in STROOP (beta = -0.074; 95% CI: -0.140, -0.009; P = 0.03). Causal associations were found for STROOP only (beta = -0.598 per s. d.-increase of TL; 95% CI: -1.125, -0.072; P = 0.026), with a larger effect in epsilon 4-carriers (beta = -0.699; 95% CI: -1.330, -0.069; P = 0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE epsilon 4-carriers might be at differential risk.

Place, publisher, year, edition, pages
2017. Vol. 7, article id e1100
National Category
Psychology (excluding Applied Psychology)
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URN: urn:nbn:se:umu:diva-136343DOI: 10.1038/tp.2017.73ISI: 000402330500008PubMedID: 28418400OAI: oai:DiVA.org:umu-136343DiVA, id: diva2:1110627
Available from: 2017-06-16 Created: 2017-06-16 Last updated: 2019-05-09Bibliographically approved

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Lundquist, AndersDegerman, SofieAdolfsson, Annelie N.Nyberg, LarsAdolfsson, Rolf

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Lundquist, AndersDegerman, SofieAdolfsson, Annelie N.Nyberg, LarsAdolfsson, Rolf
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StatisticsPathologyPsychiatryDepartment of Radiation SciencesDepartment of Integrative Medical Biology (IMB)Umeå Centre for Functional Brain Imaging (UFBI)
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Translational Psychiatry
Psychology (excluding Applied Psychology)

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