Longer Telomere Length in Leukocytes May Decrease Dementia Incidence

Leukocyte telomere length is associated with multiple MRI phenotypes and dementia incidence.

Leukocyte telomere length (LTL) may be a biomarker for multiple magnetic resonance imaging (MRI) endophenotypes of neurodegenerative disease. Longer LTL is associated with a larger volume of global and subcortical grey matter, a larger hippocampus, and reduced dementia incidence. These are the findings of a study published in PLoS One.

Telomeres shorten with each cell division and are markers for biological aging and susceptibility for age-related diseases. Despite this relationship, the mechanism by which shorter telomeres accelerate cellular aging and thereby increase the risk for neuropsychiatric diseases remains unclear.

In this study, researchers from University of Oxford in the United Kingdom sourced data from the UK Biobank to perform this analysis relating LTL with brain structure and function. Individuals (N=31,661) aged 40-69 years who underwent MRI between 2006 and 2010 were included in this analysis. Telomere lengths in leukocytes were measured from samples collected at baseline using a quantitative polymerase chain reaction assay.

The study population comprised individuals mean age, 55.30±7.50 years; 53.08% were women; 49.46% had a higher education degree; 5.99% were smokers; they consumed 17.48±15.71 units of alcohol per week; and the Townsend Deprivation Index was 1.92±2.71.

Associations between LTL and brain structure provide a mechanism explaining the protective association of longer LTL on dementia incidence we observed.

The LTL was found to have multiple positive relationships, such as with global grey matter and cerebrospinal fluid (CSF) volumes and global white matter volume as well as negative relationships, such as with global and periventricular white matter hyperintensity volumes.

In individual analyses, LTL explained 5% of the variance in peripheral grey matter volume. Longer LTL associated with decreased fractional anisotropy, intracellular volume fraction, and mode as well as increased L1-3, mean diffusivity, and isotropic volume fraction in multiple regions, such as the corpus callosum, sagittal stratum, and fasciculus.

Longer LTL was also strongly related with greater cortical thickness in the right hemisphere regions and greater connectivity between motor, central, and cerebellar networks. Conversely LTL was negatively related with functional connectivity within the visual network and corpus callosum.

During a median follow-up of 12.82 years, in the entire UK Biobank sample, 1.65% had a stroke, 1.42% were diagnosed with dementia, and 0.61% with Parkinson disease. In this subgroup, 53 individuals developed dementia.

Overall, longer LTL was associated with decreased risk for dementia (hazard ratio [HR], 0.930; 95% CI, 0.910-0.960) and tended to associate with decreased stroke risk (HR, 0.980; 95% CI, 0.950-1.000). No relationship between LTL and Parkinson was observed (HR, 1.010; 95% CI, 0.960-1.060).

This study may have been limited by healthy subject bias and the fact that the length of telomeres was only measured in leukocytes, which may not be generalizable for other organs.

Researchers concluded, “LTL associated with several MRI endophenotypes for neurodegenerative disease. These include: larger global and subcortical grey matter volumes, lower volume of white matter hyperintensities, lower basal ganglia iron deposition, and grey-white matter contrast of sensory cortices. Associations between LTL and brain structure provide a mechanism explaining the protective association of longer LTL on dementia incidence we observed.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Topiwala A, Nichols TE, Williams LZJ, et al. Telomere length and brain imaging phenotypes in UK Biobank. PLoS One. Published online March 22, 2023. doi:10.1371/journal.pone.0282363