Institute of Experimental Medicine, Almazov National Medical Research Center, Saint Petersburg, Russian Federation.
Department of Faculty Therapy, Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russian Federation.
Life Sci. 2019 Nov 15;237:116932. doi: 10.1016/j.lfs.2019.116932. Epub 2019 Oct 10.
The prevalence of dementia worldwide is growing at an alarming rate. A number of studies and meta-analyses have provided evidence for increased risk of dementia in patients with metabolic syndrome (MS) as compared to persons without MS. However, there are some reports demonstrating a lack of association between MS and increased dementia risk. In this review, taking into account the potential role of individual MS components in the pathogenesis of MS-related cognitive dysfunction, we considered the underlying mechanisms in arterial hypertension, diabetes mellitus, dyslipidemia, and obesity. The pathogenesis of dementia in MS is multifactorial, involving both vascular injury and non-ischemic neuronal death due to neurodegeneration. Neurodegenerative and ischemic lesions do not simply coexist in the brain due to independent evolution, but rather exacerbate each other, leading to more severe consequences for cognition than would either pathology alone. In addition to universal mechanisms of cognitive dysfunction shared by all MS components, other pathogenetic pathways leading to cognitive deficits and dementia, which are specific for each component, also play a role. Examples of such component-specific pathogenetic pathways include central insulin resistance and hypoglycemia in diabetes, neuroinflammation and adipokine imbalance in obesity, as well as arteriolosclerosis and lipohyalinosis in arterial hypertension. A more detailed understanding of cognitive disorders based on the recognition of underlying molecular mechanisms will aid in the development of new methods for prevention and treatment of devastating cognitive problems in MS.
全球痴呆症的患病率正在以惊人的速度增长。许多研究和荟萃分析都提供了证据，表明与没有代谢综合征（MS）的人相比，代谢综合征患者发生痴呆的风险增加。然而，也有一些报告表明 MS 与痴呆风险增加之间缺乏关联。在这篇综述中，考虑到 MS 个体成分在 MS 相关认知功能障碍发病机制中的潜在作用，我们考虑了动脉高血压、糖尿病、血脂异常和肥胖症中的潜在机制。MS 中的痴呆发病机制是多因素的，涉及血管损伤和非缺血性神经元死亡导致的神经退行性变。神经退行性和缺血性病变并非由于独立的演变而简单地共存于大脑中，而是相互加剧，导致认知后果比任何一种病变单独发生时更为严重。除了所有 MS 成分共同具有的认知功能障碍的普遍机制外，其他导致认知缺陷和痴呆的特定于每个成分的发病机制途径也起作用。这种特定于成分的发病机制途径的例子包括糖尿病中的中枢胰岛素抵抗和低血糖、肥胖症中的神经炎症和脂肪因子失衡，以及动脉高血压中的小动脉硬化和脂透明蛋白病。基于对潜在分子机制的认识，更详细地了解认知障碍将有助于开发预防和治疗 MS 破坏性认知问题的新方法。
