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7877名欧洲血统的英国老年成年人的端粒长度与认知变化

Telomere length and cognitive changes in 7,877 older UK adults of European ancestry.

作者信息

Packer Amy, Habiballa Leena, Tato-Barcia Esteban, Breen Gerome, Brooker Helen, Corbett Anne, Arathimos Ryan, Ballard Clive, Hampshire Adam, Palmer Abbie, Dima Danai, Aarsland Dag, Creese Byron, Malanchini Margherita, Powell Timothy R

机构信息

Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom.

NIHR Maudsley Biomedical Research Centre, King's College London, London, United Kingdom.

出版信息

Front Aging. 2024 Nov 1;5:1480326. doi: 10.3389/fragi.2024.1480326. eCollection 2024.

Abstract

BACKGROUND

Telomere length (TL) has been linked to cognitive function, decline and dementia. This study aimed to explore whether both measured TL and genetic disposition for TL predict dimensions of cognitive performance in a longitudinal sample of older UK adults.

METHODS

We analysed data from PROTECT study participants aged ≥50 years without a dementia diagnosis, who had completed longitudinal cognitive testing. We calculated polygenic scores for telomere length (PGS-TL) for 7,877 participants and measured relative telomere length (RTL) in a subgroup of 846 participants using DNA extracted from saliva samples collected within 6 months either side of their baseline cognitive testing. Latent growth models were used to examine whether RTL and PGS-TL predict both baseline and longitudinal changes in cognitive performance (4 time-points, annually).

RESULTS

In the whole sample, we did not observe significant associations between either measure of telomere length and initial or longitudinal changes in cognitive performance. Stratifying by median age, in older adults (≥ ∼62 years), longer baseline RTL showed a nominal association with poorer baseline verbal reasoning performance ( = 423, = 47.58, = -1.05, = .011) and PGS-TL was associated with performance over time ( = 3,939; slope factor, = 3.23, = -0.45, = .001; factor, = 0.21, = 0.13, = .002).

CONCLUSION

Our findings suggest either the absence of a significant relationship between telomere length (RTL and PGS-TL) and cognitive performance (baseline and change over time), or possibly a weak age-dependent and domain-specific relationship, in older adults of European ancestry. More research is needed in representative and ancestrally diverse samples over a longer assessment period. Alternative biological ageing indicators may still provide utility in the early detection of individuals at risk for cognitive decline (e.g., pace-of ageing epigenetic clocks).

摘要

背景

端粒长度(TL)与认知功能、衰退及痴呆症相关。本研究旨在探讨在英国老年成年人的纵向样本中,测量得到的端粒长度和端粒长度的遗传倾向是否能预测认知表现的维度。

方法

我们分析了来自PROTECT研究参与者的数据,这些参与者年龄≥50岁,无痴呆症诊断,且完成了纵向认知测试。我们为7877名参与者计算了端粒长度的多基因评分(PGS-TL),并在846名参与者的亚组中使用从其基线认知测试前后6个月内采集的唾液样本中提取的DNA测量相对端粒长度(RTL)。使用潜在增长模型来检验RTL和PGS-TL是否能预测认知表现的基线及纵向变化(每年4个时间点)。

结果

在整个样本中,我们未观察到端粒长度的任何一种测量方法与认知表现的初始或纵向变化之间存在显著关联。按年龄中位数分层后,在老年人(≥约62岁)中,更长的基线RTL与较差的基线语言推理表现存在名义上的关联(=423,=47.58,=-1.05,=0.011),且PGS-TL与随时间的表现相关(=3939;斜率因子,=3.23,=-0.45,=0.001;因子,=0.21,=0.13,=0.002)。

结论

我们的研究结果表明,在欧洲血统的老年人中,要么端粒长度(RTL和PGS-TL)与认知表现(基线及随时间的变化)之间不存在显著关系,要么可能存在一种微弱的年龄依赖性和特定领域的关系。在更长的评估期内,对具有代表性且祖先背景多样的样本进行更多研究是必要的。替代的生物衰老指标可能仍有助于早期检测有认知衰退风险的个体(例如,衰老表观遗传时钟的衰老速度)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a44f/11564160/2b5bb21931c7/fragi-05-1480326-g001.jpg

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