Leucocyte telomere length, brain volume and risk of dementia: a prospective cohort study.

Background: The evidence regarding the association between leucocyte telomere length (LTL) and brain health is sparse and inconclusive. Aims: To investigate the associations of LTL with brain structure and the risk of dementia based on a large-scale prospective study. Methods: LTL in the peripheral blood was measured by the quantitative polymerase chain reaction (qPCR) assay from 439 961 individuals in the UK Biobank recruited between 2006 and 2010 and followed up until 2020. Electronic health records were used to record the incidence of dementia, including Alzheimer's disease (AD) and vascular dementia (VD). The brain structure, including total and regional brain volume, of 38 740 participants was then assessed by magnetic resonance imaging (MRI). Results: During a median follow-up of 11.6 years, a total of 5 820 (1.3%) dementia cases were documented. The restricted cubic spline model showed significant overall associations between LTL and the risk of dementia and AD (p for overall <0.05). The multivariable adjusted hazard ratios (HRs) for the lowest LTL tertile compared with the highest LTL tertile were 1.14 (95% confidence interval (CI): 1.06 to 1.21) for dementia, 1.28 (95% CI: 1.12 to 1.46) for AD and 1.18 (95% CI: 0.98 to 1.42) for VD. Furthermore, we found that shorter LTL was associated with smaller total brain volume (β=-0.012 8, p=0.003), white matter volume (β=-0.022 4, p<0.001), hippocampus volume (β=-0.017 2, p<0.001), thalamus volume (β=-0.023 9, p<0.001) and accumbens (β=-0.015 5, p=0.001). Conclusions: Shorter LTL is associated with total and regional brain structure and a higher risk of incident dementia and AD, implying the potential of telomere length as a predictive biomarker of brain health.