Telomere length and brain imaging phenotypes in UK Biobank

• Published in: PloS one 2023-03, Vol.18 (3), p.e0282363
• Main Authors: Topiwala, Anya, Nichols, Thomas E, Williams, Logan Z J, Robinson, Emma C, Alfaro-Almagro, Fidel, Taschler, Bernd, Wang, Chaoyue, Nelson, Christopher P, Miller, Karla L, Codd, Veryan, Samani, Nilesh J, Smith, Stephen M
• Format: Article
• Language: English
• Subjects: Aging; Alzheimer's disease; Alzheimers disease; Analysis; Basal ganglia; Biobanks; Biological Specimen Banks; Biology and Life Sciences; Blood; Brain; Brain - diagnostic imaging; Care and treatment; Cell division; Cells; Chromosomes; Corpus callosum; Dementia; Dementia - diagnostic imaging; Dementia - genetics; Dementia disorders; Diagnosis; Executive function; Fibers; Functional anatomy; Ganglia; Health aspects; Humans; Leukocytes; Magnetic resonance imaging; Measurement; Medical examination; Medical imaging; Medicine and Health Sciences; Memory; Mental disorders; Mental illness; Movement disorders; Neurodegenerative Diseases; Neuroimaging; Neurological diseases; Parkinson's disease; Parkinsons disease; Phenotype; Phenotypes; Registration; Research and Analysis Methods; Risk factors; Structure-function relationships; Substantia alba; Substantia grisea; Telomere - genetics; Telomeres; United Kingdom
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0282363

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.