Abstract
Telomere shortening is theorized to accelerate biological aging, however, this has not been tested in the brain and cognitive contexts. We used machine learning age-prediction models to determine brain/cognitive age and quantified the degree of accelerated aging as the discrepancy between brain and/or cognitive and chronological ages (i.e., age gap). We hypothesized these age gaps are associated with telomere length (TL). Using healthy participants from the ADNI-3 cohort (N = 196, Age(mean)=70.7), we trained age-prediction models using 4 modalities of brain features and cognitive scores, as well as a 'stacked' model combining all brain modalities. Then, these 6 age-prediction models were applied to an independent sample diagnosed with mild cognitive impairment (N = 91, Age(mean)=71.3) to determine, for each subject, the model-specific predicted age and age gap. TL was most strongly associated with age gaps from the resting-state functional connectivity model after controlling for confounding variables. Overall, telomere shortening was significantly related to older brain but not cognitive age gaps. In particular, functional relative to structural brain-age gaps, were more strongly implicated in telomere shortening.