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<p>Survivors of childhood cancer are prone to neurocognitive impairment and premature aging, raising concerns about early onset dementia. In this cross-sectional study, 1413 survivors of childhood cancer complete a neuropsychological battery. Mean leukocyte telomere length residual (mLTL) and epigenetic age acceleration (EAA) from five different epigenetic clocks, are derived from linear regression of mLTL or epigenetic age on chronological age. Among survivors treated with CNS-directed therapy, higher EAA, measured by PCGrimAge, or DunedinPACE is associated with worse performance on multiple measures of attention, processing speed, and executive functions (p’s &lt; 0.05). Among non-CNS-treated survivors, results are similar for PCGrimAge, however, DunedinPACE is specifically associated with attention variability (p &lt; 0.05). mLTL is not associated with neurocognition. EAA is associated with worse neurocognitive function and may identify survivors at risk for accelerated cognitive aging or serve as an efficacy biomarker for neurocognitive interventions.</p>

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Epigenetic age acceleration, telomere length, and neurocognitive function in long-term survivors of childhood cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月27日

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  • AnnaLynn M. Williams,
  • Nicholas S. Phillips,
  • Qian Dong,
  • Matthew J. Ehrhardt,
  • Nikesha Gilmore,
  • Kah Poh Loh,
  • Xiaoxi Meng,
  • Kirsten K. Ness,
  • Melissa M. Hudson,
  • Leslie L. Robison,
  • Zhaoming Wang,
  • Kevin R. Krull

摘要

Survivors of childhood cancer are prone to neurocognitive impairment and premature aging, raising concerns about early onset dementia. In this cross-sectional study, 1413 survivors of childhood cancer complete a neuropsychological battery. Mean leukocyte telomere length residual (mLTL) and epigenetic age acceleration (EAA) from five different epigenetic clocks, are derived from linear regression of mLTL or epigenetic age on chronological age. Among survivors treated with CNS-directed therapy, higher EAA, measured by PCGrimAge, or DunedinPACE is associated with worse performance on multiple measures of attention, processing speed, and executive functions (p’s < 0.05). Among non-CNS-treated survivors, results are similar for PCGrimAge, however, DunedinPACE is specifically associated with attention variability (p < 0.05). mLTL is not associated with neurocognition. EAA is associated with worse neurocognitive function and may identify survivors at risk for accelerated cognitive aging or serve as an efficacy biomarker for neurocognitive interventions.