Department of Neurology, Qingdao Municipal Hospital, Qingdao University, No.5 Donghai Middle Road, Qingdao, China.
Department of Thoracic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
Alzheimers Res Ther. 2024 Feb 6;16(1):28. doi: 10.1186/s13195-024-01396-w.
Cardiometabolic multimorbidity is associated with an increased risk of dementia, but the pathogenic mechanisms linking them remain largely undefined. We aimed to assess the associations of cardiometabolic multimorbidity with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathology to enhance our understanding of the underlying mechanisms linking cardiometabolic multimorbidity and AD.
This study included 1464 cognitively intact participants from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database. Cardiometabolic diseases (CMD) are a group of interrelated disorders such as hypertension, diabetes, heart diseases (HD), and stroke. Based on the CMD status, participants were categorized as CMD-free, single CMD, or CMD multimorbidity. CMD multimorbidity is defined as the coexistence of two or more CMDs. The associations of cardiometabolic multimorbidity and CSF biomarkers were examined using multivariable linear regression models with demographic characteristics, the APOE ε4 allele, and lifestyle factors as covariates. Subgroup analyses stratified by age, sex, and APOE ε4 status were also performed.
A total of 1464 individuals (mean age, 61.80 years; age range, 40-89 years) were included. The markers of phosphorylated tau-related processes (CSF P-tau181: β = 0.165, P = 0.037) and neuronal injury (CSF T-tau: β = 0.065, P = 0.033) were significantly increased in subjects with CMD multimorbidity (versus CMD-free), but not in those with single CMD. The association between CMD multimorbidity with CSF T-tau levels remained significant after controlling for Aβ42 levels. Additionally, significantly elevated tau-related biomarkers were observed in patients with specific CMD combinations (i.e., hypertension and diabetes, hypertension and HD), especially in long disease courses.
The presence of cardiometabolic multimorbidity was associated with tau phosphorylation and neuronal injury in cognitively normal populations. CMD multimorbidity might be a potential independent target to alleviate tau-related pathologies that can cause cognitive impairment.
心脏代谢性多种疾病与痴呆风险增加相关，但将它们联系起来的发病机制在很大程度上仍未得到明确。我们旨在评估心脏代谢性多种疾病与阿尔茨海默病（AD）病理的脑脊液（CSF）生物标志物之间的关联，以增强我们对将心脏代谢性多种疾病与 AD 联系起来的潜在机制的理解。
本研究纳入了来自中国阿尔茨海默病生物标志物和生活方式（CABLE）数据库的 1464 名认知正常的参与者。心脏代谢疾病（CMD）是一组相互关联的疾病，如高血压、糖尿病、心脏病（HD）和中风。根据 CMD 状态，参与者分为无 CMD、单一 CMD 或 CMD 多种疾病。CMD 多种疾病定义为两种或多种 CMD 的共存。使用多变量线性回归模型，以人口统计学特征、APOE ε4 等位基因和生活方式因素为协变量，检查心脏代谢多种疾病与 CSF 生物标志物之间的关联。还进行了按年龄、性别和 APOE ε4 状态分层的亚组分析。
共纳入 1464 名个体（平均年龄 61.80 岁；年龄范围 40-89 岁）。磷酸化 tau 相关过程标志物（CSF P-tau181：β=0.165，P=0.037）和神经元损伤标志物（CSF T-tau：β=0.065，P=0.033）在 CMD 多种疾病（与 CMD 无疾病）患者中显著增加，但在单一 CMD 患者中未增加。在校正 Aβ42 水平后，CMD 多种疾病与 CSF T-tau 水平之间的关联仍然显著。此外，在具有特定 CMD 组合（即高血压和糖尿病、高血压和 HD）的患者中观察到明显升高的 tau 相关生物标志物，尤其是在疾病病程较长的患者中。
心脏代谢性多种疾病的存在与认知正常人群中的 tau 磷酸化和神经元损伤有关。CMD 多种疾病可能是减轻可导致认知障碍的 tau 相关病理的一个潜在独立靶点。
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