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. 2025 May 14;96(6):558-565.
doi: 10.1136/jnnp-2024-334314.

Telomere length, in vivo Alzheimer's disease pathologies and cognitive decline in older adults

Joon Hyung Jung  1   2 , Min Soo Byun  3   4   5 , Dahyun Yi  6 , Hyejin Ahn  7 , Jun Ho Lee  4 , Jang-Seok Lee  8 , Hyun-Seob Lee  8 , Jun-Young Lee  1   9 , Yu Kyeong Kim  10   11 , Yun-Sang Lee  11 , Koung Mi Kang  12   13 , Chul-Ho Sohn  12   13 , Dong Young Lee  1   4   5   6   7 ; KBASE Research Group
Collaborators, Affiliations

Telomere length, in vivo Alzheimer's disease pathologies and cognitive decline in older adults

Joon Hyung Jung et al. J Neurol Neurosurg Psychiatry. .

Abstract

Background: Whether telomere length (TL), an indicator of biological ageing, reflects Alzheimer's disease (AD)-related neuropathological change remains unclear. We investigated the relationships between TL, in vivo AD pathologies, including cerebral beta-amyloid and tau deposition, and cognitive outcomes in older adults.

Methods: A total of 458 older adults were included, encompassing both cognitively normal (CN) individuals and those cognitively impaired (CI), with the CI group consisting of individuals with mild cognitive impairment or AD dementia. All participants underwent clinical and neuropsychological assessments, amyloid positron emission tomography (PET) scan and DNA extraction for measuring TL at baseline. A subset of participants (n=140) underwent tau PET scan. At follow-up, the participants underwent neuropsychological assessments annually for up to 4 years.

Results: Overall, longer TL was associated with greater brain tau deposition (B=0.139, 95% CI 0.040, 0.238) and a faster decline in global cognition (B = - 0.371, 95% CI - 0.720, -0.023). In the subgroup analysis, the association between longer TL and greater in vivo AD pathologies, as well as faster cognitive decline, was observed particularly in the CI group. Mediation analysis suggested that longer TL was associated with cognitive decline through increased tau deposition in the CI group.

Conclusion: Our finding suggests that older adults with relatively longer TL, particularly in the CI group, may have greater in vivo AD pathologies and experience more rapid cognitive decline, potentially mediated by brain tau deposition. Further studies are necessary to elucidate the biological links underlying these associations.

Keywords: ALZHEIMER'S DISEASE; IMAGE ANALYSIS; NEUROBIOLOGY; NEUROPATHOLOGY; PET.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Association between telomere length and in vivo AD pathologies. Linear regression plots with 95% CIs. AD, Alzheimer’s disease.
Figure 2
Figure 2
Association of telomere length at baseline with longitudinal global cognition changes. Predicted cognitive function at standardised telomere lengths of −1.5, 0 and 1.5 derived from linear mixed models with 95% CIs. The first row is figures of cognitively normal (A) and cognitively impaired (B) subjects, and the row below is beta-amyloid-negative (C) and beta-amyloid-positive (D) subjects.
Figure 3
Figure 3
Mediation effects of global tau deposition on the association between telomere length and cognitive changes in cognitively impaired participants. CERAD-TS, Consortium to Establish a Registry for Alzheimer’s Disease total score. The bold lines indicate p values of <0.05.
See this image and copyright information in PMC

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