Short telomere length is associated with impaired cognitive performance in European ancestry cohorts
Year: 2017
Type: article
Abstract: 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-measured TL (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 (β=0.051 per s.d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE (β=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (β=−0.053; 95% CI: −0.087, −0.018; P=0.003). Effects for DSST were stronger in APOE ɛ4 non-carriers (β=0.081; 95% CI: 0.045, 0.117; P=1.0 × 10−5), whereas carriers performed better in STROOP (β=−0.074; 95% CI: −0.140, −0.009; P=0.03). Causal associations were found for STROOP only (β=−0.598 per s.d.-increase of TL; 95% CI: −1.125, −0.072; P=0.026), with a larger effect in ɛ4-carriers (β=−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 ɛ4-carriers might be at differential risk.
Source: Translational Psychiatry
DOI: 10.1038/tp.2017.73
Authors: S Hägg, Y Zhan, R Karlsson, L Gerritsen, A Ploner, S J van der Lee, L Broer, J Deelen, R E Marioni, A Wong, A Lundquist, G Zhu, N K Hansell, E Sillanpää, I O Fedko, N A Amin, M Beekman, A J M de Craen, S Degerman, S E Harris, K-J Kan, C M Martin-Ruiz, G W Montgomery, NeuroCHARGE Cognitive Working Group, A N Adolfsson, C A Reynolds, N J Samani, H E D Suchiman, A Viljanen, T von Zglinicki, M J Wright, J-J Hottenga, D I Boomsma, T Rantanen, J A Kaprio, D R Nyholt, N G Martin, L Nyberg, R Adolfsson, D Kuh, J M Starr, I J Deary, P E Slagboom, C M van Duijn, V Codd, N L Pedersen
Institutions: Karolinska Institutet, Erasmus MC, Leiden University Medical Center, Max Planck Institute for Biology of Ageing, The University of Queensland, University of Edinburgh, MRC Unit for Lifelong Health and Ageing, University College London, Umeå University, QIMR Berghofer Medical Research Institute, University of Jyväskylä, Vrije Universiteit Amsterdam, NIHR Newcastle Biomedical Research Centre, Newcastle University, University of California, Riverside, University of Leicester, Glenfield Hospital, National Institute for Health and Care Research, NIHR Leicester Cardiovascular Biomedical Research Unit, University of Helsinki, Finnish Institute for Health and Welfare, Institute for Molecular Medicine Finland, Queensland University of Technology, Alzheimer Scotland
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,290
OpenAlex ID: W2607464515