Nuffield Department Population Health, Big Data Institute, University of Oxford, Oxford, United Kingdom.
Nuffield Department of Clinical Neurosciences, Wellcome Centre for Integrative Neuroimaging, FMRIB, University of Oxford, Oxford, United Kingdom.
PLoS One. 2023 Mar 22;18(3):e0282363. doi: 10.1371/journal.pone.0282363. eCollection 2023.
Telomeres form protective caps at the ends of chromosomes, and their attrition is a marker of biological aging. Short telomeres are associated with an increased risk of neurological and psychiatric disorders including dementia. The mechanism underlying this risk is unclear, and may involve brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized. Here we show that leucocyte telomere length (LTL) is associated with multi-modal MRI phenotypes in 31,661 UK Biobank participants. Longer LTL is associated with: i) larger global and subcortical grey matter volumes including the hippocampus, ii) lower T1-weighted grey-white tissue contrast in sensory cortices, iii) white-matter microstructure measures in corpus callosum and association fibres, iv) lower volume of white matter hyperintensities, and v) lower basal ganglia iron. Longer LTL was protective against certain related clinical manifestations, namely all-cause dementia (HR 0.93, 95% CI: 0.91-0.96), but not stroke or Parkinson's disease. LTL is associated with multiple MRI endophenotypes of neurodegenerative disease, suggesting a pathway by which longer LTL may confer protective against dementia.
端粒形成染色体末端的保护性帽子，其损耗是生物衰老的标志。端粒较短与神经和精神障碍（包括痴呆）的风险增加有关。这种风险的机制尚不清楚，可能涉及大脑结构和功能。然而，端粒长度与神经影像学标志物之间的关系尚未得到充分描述。在这里，我们在 31661 名英国生物银行参与者中显示白细胞端粒长度 (LTL) 与多模态 MRI 表型相关。较长的 LTL 与：i）更大的全球和皮质下灰质体积，包括海马体，ii）感觉皮层中 T1 加权灰质-白质组织对比度降低，iii）胼胝体和联合纤维的白质微观结构测量值降低，iv）白质高信号体积降低，v）基底节铁含量降低。较长的 LTL 对某些相关临床表现具有保护作用，即全因痴呆（HR 0.93，95%CI：0.91-0.96），但对中风或帕金森病没有保护作用。LTL 与神经退行性疾病的多种 MRI 表型相关，这表明较长的 LTL 可能通过某种途径对痴呆具有保护作用。
