Kimball Tamara N, Prapiadou Savvina, Tack Reinier W P, Yong-Qiang Tan Benjamin, Senff Jasper R, Kourkoulis Christina, Singh Sanjula, Rosand Jonathan, Anderson Christopher D
Brain Care Labs, Mass General Brigham, Boston.
Department of Neurology, Mass General Brigham, Boston.
Neurology. 2025 Jul 8;105(1):e213794. doi: 10.1212/WNL.0000000000213794. Epub 2025 Jun 11.
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.
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.
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.
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.
中风、痴呆和老年期抑郁症（LLD）是与年龄相关的脑部疾病，给公共卫生带来重大挑战并造成高昂成本。白细胞端粒长度（LTL）是一种受遗传和生活方式因素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联。我们进一步调查了使用脑保健评分（BCS）衡量的与年龄相关脑部疾病风险因素的改善是否能减轻LTL的关联。
我们分析了英国生物银行中具有可用LTL和风险因素信息的参与者。我们使用连续测量和三分位数分层，分别以及作为综合结果，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人年的发病率以及调整后的Cox模型评估疾病风险。根据风险因素概况对LTL三分位数之间的风险比较进行分层，高BCS（≥15）表明生活方式选择更健康，低BCS（≤10）反映生活方式选择不太理想。采用孟德尔随机化（MR）来检验因果关联。
该研究纳入了356,173名参与者（中位年龄56岁；53.69%为女性）。较短的LTL与所有结果的较高发病率始终相关。LTL最短三分位数的参与者出现综合结果的风险升高（风险比[HR]1.11；95%置信区间1.08 - 1.15）、中风（HR 1.08；95%置信区间1.02 - 1.15）、痴呆（HR 1.19；95%置信区间1.12 - 1.26）和LLD（HR 1.14；95%置信区间1.09 - 1.18）。LTL较短且BCS较低的个体患与年龄相关脑部疾病的风险显著增加（HR 1.11；95%置信区间1.07 - 1.16），单独来看，中风（HR 1.10；95%置信区间1.02 - 1.19）、痴呆（HR 1.17；95%置信区间1.08 - 1.28）和LLD（HR 1.13；95%置信区间1.07 - 1.19）的风险也增加。相反，在LTL最短组中BCS较高的个体，任何与年龄相关脑部疾病的风险均未显著增加。MR分析未发现LTL与这些结果之间的因果关系。
LTL较短的个体患中风、痴呆和LLD的风险增加。可改善的风险因素概况的改善似乎能减轻LTL对这些疾病的影响。未来的研究应探索生活方式干预在减轻不良生物衰老对脑健康影响方面的有效性。
