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Background <p>This study aims to investigate the association between leukocyte telomere length (LTL) and the risk of incident NDDs using a large-scale cohort from the UK Biobank.</p> Methods <p>Data from 459,902 subjects were analyzed using Cox proportional hazards models and machine learning (ML) algorithms to assess LTL's association with NDD risk.</p> Results <p>Shorter LTL was associated with an increased risk of NDDs, including Alzheimer's disease (HR: 0.52, 95% CI 0.40–0.67, <i>P</i> &lt; 0.001), dementia in AD (HR: 0.53, 95% CI 0.39–0.73, <i>P</i> &lt; 0.001), unspecified dementia (HR: 0.74, 95% CI 0.58–0.95, <i>P</i> &lt; 0.05), degenerative diseases of the nervous system (including other specified degenerative diseases such as circumscribed brain atrophy and senile degeneration of the brain) (HR: 0.62, 95% CI 0.45–0.84, <i>P</i> &lt; 0.01), extrapyramidal and movement disorders (including other specified extrapyramidal and movement disorders such as a range of tremors, chorea, tics, and other abnormal involuntary movements) (HR: 0.63, 95% CI 0.48–0.82, <i>P</i> &lt; 0.01), and mental and behavioral disorders due to use of alcohol (HR: 0.46, 95% CI 0.38–0.55, <i>P</i> &lt; 0.001). Conversely, longer LTL was associated with a 3.71-fold increased risk of multiple sclerosis (MS) (HR: 3.71, 95% CI 1.91–7.18, <i>P</i> &lt; 0.001). ML models confirmed the predictive value of LTL for NDDs.</p> Conclusion <p>Shorter LTL increased the risk of several NDDs, while longer LTL paradoxically predisposed individuals to MS, especially in younger populations. ML models demonstrated strong potential for predicting NDD risks, enhancing our understanding of the role of telomeres in neurodegeneration.</p>

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Association between leukocyte telomere length and neurodegenerative diseases: a prospective cohort in the UK Biobank

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月11日

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  • Xiangting Chen,
  • Yueqing Huang,
  • Chunhua Zhao,
  • Min Huang

摘要

Background

This study aims to investigate the association between leukocyte telomere length (LTL) and the risk of incident NDDs using a large-scale cohort from the UK Biobank.

Methods

Data from 459,902 subjects were analyzed using Cox proportional hazards models and machine learning (ML) algorithms to assess LTL's association with NDD risk.

Results

Shorter LTL was associated with an increased risk of NDDs, including Alzheimer's disease (HR: 0.52, 95% CI 0.40–0.67, P < 0.001), dementia in AD (HR: 0.53, 95% CI 0.39–0.73, P < 0.001), unspecified dementia (HR: 0.74, 95% CI 0.58–0.95, P < 0.05), degenerative diseases of the nervous system (including other specified degenerative diseases such as circumscribed brain atrophy and senile degeneration of the brain) (HR: 0.62, 95% CI 0.45–0.84, P < 0.01), extrapyramidal and movement disorders (including other specified extrapyramidal and movement disorders such as a range of tremors, chorea, tics, and other abnormal involuntary movements) (HR: 0.63, 95% CI 0.48–0.82, P < 0.01), and mental and behavioral disorders due to use of alcohol (HR: 0.46, 95% CI 0.38–0.55, P < 0.001). Conversely, longer LTL was associated with a 3.71-fold increased risk of multiple sclerosis (MS) (HR: 3.71, 95% CI 1.91–7.18, P < 0.001). ML models confirmed the predictive value of LTL for NDDs.

Conclusion

Shorter LTL increased the risk of several NDDs, while longer LTL paradoxically predisposed individuals to MS, especially in younger populations. ML models demonstrated strong potential for predicting NDD risks, enhancing our understanding of the role of telomeres in neurodegeneration.