Department of Brain Sciences, Imperial College London, London, UK.
Department of Brain Sciences, Imperial College London, London, UK
J Neurol Neurosurg Psychiatry. 2024 May 14;95(6):581-589. doi: 10.1136/jnnp-2023-332661.
A growing body of evidence suggests that cardiometabolic risk factors play a significant role in Alzheimer's disease (AD). Diabetes, obesity and hypertension are highly prevalent and can accelerate neurodegeneration and perpetuate the burden of AD. Insulin resistance and enzymes including insulin degrading enzymes are implicated in AD where breakdown of insulin is prioritised over amyloid-β. Leptin resistance and inflammation demonstrated by higher plasma and central nervous system levels of interleukin-6 (IL-6), IL-1β and tumour necrosis factor-α, are mechanisms connecting obesity and diabetes with AD. Leptin has been shown to ameliorate AD pathology and enhance long-term potentiation and hippocampal-dependent cognitive function. The renin-aldosterone angiotensin system, involved in hypertension, has been associated with AD pathology and neurotoxic reactive oxygen species, where angiotensin binds to specific angiotensin-1 receptors in the hippocampus and cerebral cortex. This review aims to consolidate the evidence behind putative processes stimulated by obesity, diabetes and hypertension, which leads to increased AD risk. We focus on how novel knowledge can be applied clinically to facilitate recognition of efficacious treatment strategies for AD.
越来越多的证据表明，心脏代谢风险因素在阿尔茨海默病（AD）中起着重要作用。糖尿病、肥胖症和高血压的患病率很高，会加速神经退行性变并使 AD 的负担持久存在。胰岛素抵抗和包括胰岛素降解酶在内的酶与 AD 有关，在 AD 中，胰岛素的分解优先于淀粉样蛋白-β。肥胖症和糖尿病与 AD 相关的机制是血浆和中枢神经系统中白细胞介素-6 (IL-6)、IL-1β 和肿瘤坏死因子-α 水平升高表明存在瘦素抵抗和炎症。瘦素已被证明可以改善 AD 病理，并增强长时程增强和海马依赖性认知功能。参与高血压的肾素-血管紧张素-醛固酮系统与 AD 病理和神经毒性活性氧有关，其中血管紧张素与海马和大脑皮层中的特定血管紧张素-1 受体结合。本综述旨在整合肥胖症、糖尿病和高血压刺激的潜在过程的证据，这些过程会增加 AD 风险。我们专注于如何将新的知识应用于临床，以促进识别 AD 的有效治疗策略。
