Unlocking the future of dementia: Your telomere length could predict your risk

By Dr. Liji Thomas, MDSep 12 2023Reviewed by Benedette Cuffari, M.Sc.

The overall age of the world population is increasing due to advances in medical technology and reduced birth rates in many countries. This has led to a significant increase in the number of older adults who lose partial or complete independence due to dementia and, as a result, require care for the rest of their lives.

A recent paper in General Psychiatry explores the value of leukocyte chromosomal changes called telomere shortening for predicting dementia in aging populations.

Study: Leucocyte telomere length, brain volume and risk of dementia: a prospective cohort study. Image Credit: peterschreiber.media / Shutterstock.com

Introduction

Leukocyte telomere length (LTL) may be associated with brain health, thus offering an approach to predict dementia before its clinical onset; however, evidence supporting this hypothesis is lacking.

Chronological age remains the primary predictor of dementia risk. Leukocyte telomeres are the protein-bound ends of every chromosome that prevent the loss of DNA. Telomeres shorten with every cell division, thus causing older people to have significantly shorter telomeres.

Both chronological and biological age can be assessed using telomere length, which could help predict the risk of age-related diseases like dementia. Nevertheless, large-scale population-level screening for diseases using LTL is inefficient and not cost-effective.

Previous studies have suggested that decreasing LTL is associated with age-related diseases, including dementia; however, the evidence is inconsistent. Brain shrinkage on magnetic resonance imaging (MRI) has been used to diagnose dementia and mild cognitive impairment; however, many of these studies examined specific brain regions or included small sample sizes.

The United Kingdom Biobank provides prospective data from a large cohort of over 500,000 patients, many of whom have contributed to LTL data using quantitative polymerase chain reaction (PCR) testing.

The current study used LTL data from over 430,000 individuals who entered the study between 2006 and 2010 and were monitored until 2020. The incidence of dementia, including Alzheimer’s disease (AD) and vascular dementia (VD), was determined using electronic health records (EHR). Brain volume was also assessed in almost 39,000 individuals using magnetic resonance imaging (MRI).

This study aimed to identify any association between these measures. Several confounding factors were considered in the analysis, including social and demographic attributes and chronic diseases, as well as lifestyle characteristics.

What did the study show?

The median follow-up period was approximately 12 years, in which 1.3% of the population, or 5,820 people, developed dementia. AD and VD were detected in 0.4% and 0.2% of the study cohort, respectively.

LTL was significantly associated with the risk of overall dementia, particularly AD, whereas VD was not found to have this association. After adjusting for multiple confounding factors, including age and sex, the lowest LTL tertile was 14% for an increased risk of dementia as compared to those in the highest tertile. For AD, the risk was increased by 28%.

The association remained robust to self-reported cardiovascular or depressive disease or cancer at the beginning of the study or after excluding cases that developed during the first two years of the study. However, the effects were stronger at younger ages and in people without a family history of dementia.

Shortening of the leukocyte telomere was associated with shrinking of the brain, with total brain volume and various specific parts of the brain associated with smaller values as compared to those in individuals with longer telomeres. The shrinkage was observed for total white matter, hippocampus, thalamus, and nucleus accumbens.

There was no difference in this association after adjusting for sex differences or the presence of apolipoprotein E (APOE) ε4, which is a risk factor for dementia. The associations remained consistent after excluding those who already had dementia at the beginning of the study.

The inclusion of LTL into a model to predict dementia risk slightly improved the discrimination of the model. When multiple brain volumes were considered in the model, its predictive value increased to about 85% of the area under the curve.

What are the implications?

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.”

LTL is largely inherited; therefore, shorter LTL may help provide a basis for lifestyle counseling, as it indicates poor neuropsychological condition. Glial cell telomere measurements might have been better for the purpose but were unavailable in any large-scale study.