INTRODUCTION

Early-onset dementia is a heterogeneous group of neurodegenerative disorders that manifest before the age of 65 years, most commonly including early-onset Alzheimer’s disease (EOAD) and frontotemporal dementia (FTD).[1] Compared with late-onset forms, EOAD is often associated with a stronger genetic contribution and tends to present with atypical clinical phenotypes involving visuospatial, language, or executive dysfunction rather than isolated memory loss. On the other hand, FTD typically occurs at a younger age, often in the fifth or sixth decade of life, and is characterized by prominent behavioral or language disturbances related to frontal and temporal lobe degeneration.

Telomeres are repetitive DNA sequences of TTAGGG located at the ends of chromosomes; these sequences play fundamental roles in DNA replication and repair.[2] Telomeres become shorter with aging owing to end-replication. Accordingly, telomere length (TL), a biomarker of biological aging, has been increasingly recognized as a potential contributor to neurodegenerative processes.[3] Although some previous studies have investigated the association between TL and dementia, such as late-onset Alzheimer’s disease and FTD[4], the results were inconsistent. Some studies have found that shorter TL is associated with cognitive decline[5] and an increased risk of dementia[6], whereas others have suggested that longer TL may also be linked to cognitive decline and a higher likelihood of developing dementia.[7] In addition, the relationship between TL and early-onset dementia has not been comprehensively studied.

In this study, we aim to investigate the distribution of TL across diverse dementia subtypes and genetic variants within the LEAF cohort. In addition, we examined whether there is an association between the disease progression and telomere length in early onset dementia including EOAD and EOFTD.