Genetic Influence of Telomere Reverse Transcriptase on Cognition and Cortical Thickness in Aging

Poster Session F - Tuesday, April 16, 2024, 8:00 – 10:00 am EDT, Sheraton Hall ABC

Anna Thompson¹ (act200004@utdallas.edu), Chen Gonen¹, Karen Rodrigue¹, Kristen Kennedy¹; ¹University of Texas at Dallas

Telomeres are the protective endings on chromosomes that degrade with age. Telomere length (TL) is associated with length of lifespan and Alzheimer’s disease risk, with both longer and shorter telomere linked to poorer outcomes. Here we investigate whether differences in a single-nucleotide polymorphism (SNP), telomere reverse transcriptase (TERT), a proxy for TL, influences cognitive aging and cortical thinning in healthy adults. Cognitive assessments and MRI were collected for N=183 adults ages 20-89. We predicted that genetic predisposition to longer (G/G carriers) and shorter (T/T carriers) TL may differentially impact cognition and associated brain regions with aging. Analysis of overall cognition, comprised of executive function (EF), working memory (WM), processing speed, and episodic memory using a general linear model (GLM) revealed a significant TERT by Age interaction (p<.05) on cognition. EF and WM were independently significant (p<.05) and showed TERT by Age interactions, where older adult T/G carriers had better performance. Nine frontal and parietal regions, integral to EF and WM processes, were examined in participants with MRI (n=161). GLM analyses revealed a significant TERT by Posterior Cingulate (PCG) thickness interaction on EF (p < .05), suggesting that PCG’s association with EF depends on TERT genotype. Specifically, G/G homozygotes experience less of a benefit of thicker PCG on cognition than T/G or T/T carriers. In sum, moderate telomere disposition may be beneficial to older adults' cognition, whereas across the lifespan longer telomere carriers show weaker association between brain and cognition. Future research will examine TERT influence on longitudinal change.

Topic Area: EXECUTIVE PROCESSES: Development &aging