Leukocyte Telomere Length and Cross-Sectional and Longitudinal Variations in Gray Matter Volume and Cortical...

Telomere length (TL) has emerged as a candidate predictor for biological aging and age-associated conditions, yet its relationship with structural brain changes remains incompletely characterized. This study aimed to investigate the cross-sectional and longitudinal associations between TL, brain gray matter volume (GMV), white matter volume, and cortical thickness (CT) and to examine individual variability in age-related brain changes.

The study included 196 cognitively healthy individuals aged ≥50 years. All participants underwent baseline MRI and TL measurement from leukocytes. Among them, 46 individuals had a second MRI scan after an average of 4.7 years. Associations between TL and brain structural measures were assessed using multivariate models adjusting for demographic and imaging confounders. Longitudinal volumetric changes were modeled using region-of-interest analyses, whereas regional CT changes were examined using surface-based methods in FreeSurfer.

The mean age of the cohort was 65.9 ± 8.6 years; 60.9% were women. Median TL was 7.0 kB (interquartile range [IQR]: 6.0-8.4). No significant associations were found between TL and global brain measures in the cross-sectional analysis. However, longitudinal analysis revealed a significant inverse correlation between TL and GMV decline over time (r = -0.370, p = 0.012), which remained robust after adjusting for age, sex, follow-up duration, and baseline GMV (standardized β = -0.32). No significant association was found between TL and overall cortical thinning; however, at the regional level, shorter TL was significantly associated with cortical thinning in the left superior parietal lobule.

TL may serve as a predictor of age-dependent structural brain changes, with the left superior parietal cortex appearing particularly susceptible within this telomere-brain aging interaction.