Tamara N Kimball, Savvina Prapiadou, Reinier W P Tack, Benjamin Yong-Qiang Tan, Jasper R Senff, Christina Kourkoulis, Sanjula Singh, Jonathan Rosand, Christopher D Anderson
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引用次数: 0
Abstract
Background and objectives: Stroke, dementia, and late-life depression (LLD) are age-related brain diseases that pose significant public health challenges and costs. Leucocyte telomere length (LTL) is a biological aging marker influenced by both genetic and lifestyle factors. The aim of our study was to determine the association between LTL and these diseases. We further investigated whether modifying risk factors of age-related brain disease, as measured using the Brain Care Score (BCS), mitigates LTL associations.
Methods: We analyzed participants from the UK Biobank with available LTL and risk factor information. We examined LTL's associations with stroke, dementia, and LLD, individually and as a composite outcome, using continuous measures and tertile stratification. Disease risks were evaluated through cumulative incidence curves, incidence rates per 1,000 person-years, and adjusted Cox models. Risk comparisons across LTL tertiles were stratified by risk factor profiles, with high BCS (≥15) indicating healthier lifestyle choices and low BCS (≤10) reflecting less optimal lifestyle choices. Mendelian randomization (MR) was used to test causal associations.
Results: The study included 356,173 participants (median age 56 years; 53.69% female). Shorter LTL was consistently associated with higher incidence rates across all outcomes. Participants in the shortest LTL tertile had elevated risks of the composite outcome (hazard ratio [HR] 1.11; 95% CI 1.08-1.15), stroke (HR 1.08; 95% CI 1.02-1.15), dementia (HR 1.19; 95% CI 1.12-1.26), and LLD (HR 1.14; 95% CI 1.09-1.18). Individuals with both shorter LTL and lower BCS faced significantly increased risks of age-related brain diseases (HR 1.11; 95% CI 1.07-1.16) and individually for stroke (HR 1.10; 95% CI 1.02-1.19), dementia (HR 1.17; 95% CI 1.08-1.28), and LLD (HR 1.13; 95% CI 1.07-1.19). Conversely, individuals with higher BCS within the shortest LTL group did not show a significant increase in risk of any age-related brain diseases. MR analyses did not identify causal relationships between LTL and these outcomes.
Discussion: Individuals with shorter LTL are at increased risk of stroke, dementia, and LLD. Improved modifiable risk factor profiles seem to mitigate the impact of LTL on these diseases. Future research should explore the effectiveness of lifestyle interventions in mitigating adverse biological aging effects on brain health.
背景和目的：脑卒中、痴呆和晚年抑郁症（LLD）是与年龄相关的脑部疾病，对公共卫生构成重大挑战和成本。白细胞端粒长度（LTL）是一种受遗传和生活方式影响的生物衰老标志物。我们研究的目的是确定LTL与这些疾病之间的关系。我们进一步研究了使用脑保健评分（BCS）测量的改变与年龄相关的脑部疾病的危险因素是否可以减轻LTL的关联。方法：我们分析了来自英国生物银行的参与者，他们有可用的LTL和危险因素信息。我们使用连续测量和分值分层，分别和作为综合结果，研究了LTL与中风、痴呆和LLD的关联。通过累积发病率曲线、每1000人年发病率和调整后的Cox模型评估疾病风险。LTL各分位的风险比较按风险因素进行分层，高BCS（≥15）表明选择了更健康的生活方式，低BCS（≤10）表明选择的生活方式不理想。孟德尔随机化（MR）用于检验因果关系。结果：该研究包括356173名参与者(中位年龄56岁；53.69%的女性)。在所有结果中，较短的LTL始终与较高的发病率相关。最短LTL组的参与者出现复合结局的风险较高(风险比[HR] 1.11；95% CI 1.08-1.15)，卒中(HR 1.08；95% CI 1.02-1.15)，痴呆(HR 1.19；95% CI 1.12-1.26), LLD (HR 1.14；95% ci 1.09-1.18)。LTL较短和BCS较低的个体面临与年龄相关的脑部疾病的风险显著增加(HR 1.11；95% CI 1.07-1.16)和单独的卒中(HR 1.10；95% CI 1.02-1.19)，痴呆(HR 1.17；95% CI 1.08-1.28)和LLD (HR 1.13；95% ci 1.07-1.19)。相反，在最短LTL组中BCS较高的个体没有显示出任何与年龄相关的脑部疾病的风险显着增加。MR分析没有确定LTL和这些结果之间的因果关系。讨论：LTL较短的个体中风、痴呆和LLD的风险增加。改进的可修改风险因素概况似乎减轻了LTL对这些疾病的影响。未来的研究应该探索生活方式干预在减轻不利的生物衰老对大脑健康的影响方面的有效性。
期刊介绍：
Neurology, the official journal of the American Academy of Neurology, aspires to be the premier peer-reviewed journal for clinical neurology research. Its mission is to publish exceptional peer-reviewed original research articles, editorials, and reviews to improve patient care, education, clinical research, and professionalism in neurology.
As the leading clinical neurology journal worldwide, Neurology targets physicians specializing in nervous system diseases and conditions. It aims to advance the field by presenting new basic and clinical research that influences neurological practice. The journal is a leading source of cutting-edge, peer-reviewed information for the neurology community worldwide. Editorial content includes Research, Clinical/Scientific Notes, Views, Historical Neurology, NeuroImages, Humanities, Letters, and position papers from the American Academy of Neurology. The online version is considered the definitive version, encompassing all available content.
Neurology is indexed in prestigious databases such as MEDLINE/PubMed, Embase, Scopus, Biological Abstracts®, PsycINFO®, Current Contents®, Web of Science®, CrossRef, and Google Scholar.
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