Background Many common neurological disorders are associated with advancing chronological age, but their association with biological age (BA) remains poorly understood. Methods We studied 325 870 participants in the UK Biobank without a diagnosed neurological condition at baseline and generated three previously-described measures of BA based on 18 routinely measured clinical biomarkers (PhenoAge, Klemera-Doubal method age (KDMAge), homeostatic dysregulation age). Using survival models, we assessed the effect of advanced BA on incident neurological diagnoses, including all-cause and cause-specific dementia, ischaemic stroke, Parkinson’s disease and motor neuron disease. Results During a mean follow-up of 9.0 years, there were 1397 incident cases of dementia and 2515 of ischaemic stroke, with smaller case numbers of other diagnoses. The strongest associations with a 1 SD in BA residual were seen for all-cause dementia (KDMAge HR=1.19, 95% CI=1.11 to 1.26), vascular dementia (1.41, 1.25 to 1.60) and ischaemic stroke (1.39, 1.34 to 1.46). Weaker associations were seen for Alzheimer’s disease and motor neuron disease, while, in contrast, HRs for Parkinson’s disease tended to be <1. Results were largely consistent after adjustment for disease-specific covariates including common cardiometabolic risk factors. Conclusions Advanced BA calculated from routine clinical biomarker results increases the risk of subsequent neurological diagnoses including all-cause dementia and ischaemic stroke.

中文翻译：

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英国生物银行基于临床生物标志物的生物衰老和神经系统疾病的未来风险

背景 许多常见的神经系统疾病与实际年龄的增加有关，但它们与生物年龄 (BA) 的关系仍知之甚少。方法 我们研究了英国生物库中的 325 870 名基线时未诊断出神经系统疾病的参与者，并根据 18 种常规测量的临床生物标志物（PhenoAge、Klemera-Doubal 方法年龄 (KDMAge)、稳态失调年龄）生成了三种先前描述的 BA 测量值。使用生存模型，我们评估了高级 BA 对神经系统诊断的影响，包括全因和特异性痴呆、缺血性中风、帕金森病和运动神经元疾病。结果 在平均 9.0 年的随访期间，有 1397 例痴呆病例和 2515 例缺血性中风病例，其他诊断病例数较少。 BA 残差与 1 SD 的最强相关性见于全因痴呆（KDMAge HR=1.19，95% CI=1.11 至 1.26）、血管性痴呆（1.41、1.25 至 1.60）和缺血性中风（1.39、1.34 至 1.46） ）。阿尔茨海默病和运动神经元疾病的相关性较弱，而相比之下，帕金森病的 HR 往往<1。对疾病特异性协变量（包括常见的心脏代谢危险因素）进行调整后，结果基本一致。结论 根据常规临床生物标志物结果计算出的高级 BA 会增加后续神经系统诊断的风险，包括全因痴呆和缺血性中风。