Jung Joon Hyung, Byun Min Soo, Yi Dahyun, Ahn Hyejin, Lee Jun Ho, Lee Jang-Seok, Lee Hyun-Seob, Lee Jun-Young, Kim Yu Kyeong, Lee Yun-Sang, Kang Koung Mi, Sohn Chul-Ho, Lee Dong Young
Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea (the Republic of).
Department of Psychiatry, Chungbuk National University Hospital, Cheongju, Korea (the Republic of).
J Neurol Neurosurg Psychiatry. 2025 May 14;96(6):558-565. doi: 10.1136/jnnp-2024-334314.
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.
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.
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.
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.
端粒长度（TL）作为生物衰老的一个指标，是否能反映阿尔茨海默病（AD）相关的神经病理变化仍不清楚。我们研究了老年人的TL、体内AD病理（包括脑β-淀粉样蛋白和tau蛋白沉积）与认知结果之间的关系。
共纳入458名老年人，包括认知正常（CN）个体和认知受损（CI）个体，CI组由轻度认知障碍或AD痴呆个体组成。所有参与者在基线时均接受了临床和神经心理学评估、淀粉样蛋白正电子发射断层扫描（PET）以及用于测量TL的DNA提取。一部分参与者（n = 140）接受了tau PET扫描。在随访期间，参与者每年接受神经心理学评估，为期4年。
总体而言，较长的TL与更大的脑tau蛋白沉积相关（B = 0.139，95%置信区间0.040，0.238）以及整体认知功能的更快下降（B = - 0.371，95%置信区间 - 0.720，-0.023）。在亚组分析中，较长的TL与更大的体内AD病理以及更快的认知下降之间的关联尤其在CI组中观察到。中介分析表明，在CI组中，较长的TL通过增加tau蛋白沉积与认知下降相关。
我们的研究结果表明，TL相对较长的老年人，特别是在CI组中，可能具有更大的体内AD病理，并经历更快的认知下降，这可能由脑tau蛋白沉积介导。需要进一步研究以阐明这些关联背后的生物学联系。
