• Joon Hyung Jung, Min Soo Byun, Dahyun Yi, Hyejin Ahn, LeeJun HoJHDepartment of Neuropsychiatry, Seoul National University Hospital, Seoul, Korea (the Republic of)., Jang-Seok Lee, Hyun-Seob Lee, Jun-Young Lee, Yu Kyeong Kim, Yun-Sang Lee, Koung Mi Kang, Chul-Ho Sohn, Dong Young Lee, and KBASE Research Group.
• Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea (the Republic of).
• J. Neurol. Neurosurg. Psychiatr. 2024 Dec 12.

BackgroundWhether 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.MethodsA 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.ResultsOverall, 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.ConclusionOur 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.© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.

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