Cognitive impact of COVID-19: looking beyond the short term.
Cognitive impact of COVID-19: looking beyond the short term.
复制标题
DOI：
10.1186/s13195-020-00744-w
复制
发表时间：
2020-12-30
期刊：
影响因子：
--
通讯作者：
Love S
中科院分区：
文献类型：
--
作者：
Miners S;Kehoe PG;Love S
COVID-19主要是一种呼吸道疾病，但多达三分之二的住院患者显示中枢神经系统（CNS）损伤的证据，主要是缺血性，在某些情况下出血，偶尔出现脑炎。目前尚不清楚有多少缺血性损伤是由病毒对CNS血管系统的直接或炎症作用介导的，有多少是继发于颅外心肺疾病。有限的数据表明，致病SARS-CoV-2病毒可能通过鼻粘膜和嗅纤维或通过血行传播进入CNS，并且能够感染内皮细胞、周细胞和可能的神经元。在颅外，SARS-CoV-2靶向内皮细胞和周细胞，导致内皮细胞功能障碍、血管渗漏和免疫激活，有时导致弥散性血管内凝血。脑血管系统中的内皮细胞和周细胞是否也被类似地靶向，仍有待证实。COVID-19的几个方面可能会影响认知。大脑白色物质特别容易受到COVID-19的缺血性损伤，对认知功能也至关重要。有越来越多的证据表明，脑灌注不足加速淀粉样蛋白-β（Aβ）蓄积，并与tau和TDP-43病理学相关，并且通过诱导α-突触核蛋白丝氨酸-129磷酸化，缺血也可能增加路易体病发生的风险。可以理解的是，目前COVID-19的治疗集中在支持呼吸功能、预防血栓形成和减少免疫激活上。由于血管紧张素转换酶（ACE）-2是SARS-CoV-2的受体，预计ACE抑制剂和血管紧张素受体阻滞剂会增加ACE-2的表达，因此最初担心它们的使用可能会加剧COVID-19。最近的荟萃分析表明，这些药物是保护性的。这可能是因为SARS-CoV-2进入可能耗尽ACE-2，使平衡向血管紧张素II-ACE-1介导的经典RAS激活倾斜：加重灌注不足并促进炎症。可能相关的是，APOE ε4个体似乎具有增加的COVID-19风险，也具有最低的ACE-2活性。COVID-19可能会在大量幸存者中留下长期神经系统并发症的意外遗产。COVID-19患者的认知随访将非常重要，特别是在急性疾病期间发生脑血管和神经系统并发症的患者。
COVID-19 is primarily a respiratory disease but up to two thirds of hospitalised patients show evidence of central nervous system (CNS) damage, predominantly ischaemic, in some cases haemorrhagic and occasionally encephalitic. It is unclear how much of the ischaemic damage is mediated by direct or inflammatory effects of virus on the CNS vasculature and how much is secondary to extracranial cardiorespiratory disease. Limited data suggest that the causative SARS-CoV-2 virus may enter the CNS via the nasal mucosa and olfactory fibres, or by haematogenous spread, and is capable of infecting endothelial cells, pericytes and probably neurons. Extracranially, SARS-CoV-2 targets endothelial cells and pericytes, causing endothelial cell dysfunction, vascular leakage and immune activation, sometimes leading to disseminated intravascular coagulation. It remains to be confirmed whether endothelial cells and pericytes in the cerebral vasculature are similarly targeted. Several aspects of COVID-19 are likely to impact on cognition. Cerebral white matter is particularly vulnerable to ischaemic damage in COVID-19 and is also critically important for cognitive function. There is accumulating evidence that cerebral hypoperfusion accelerates amyloid-β (Aβ) accumulation and is linked to tau and TDP-43 pathology, and by inducing phosphorylation of α-synuclein at serine-129, ischaemia may also increase the risk of development of Lewy body disease. Current therapies for COVID-19 are understandably focused on supporting respiratory function, preventing thrombosis and reducing immune activation. Since angiotensin-converting enzyme (ACE)-2 is a receptor for SARS-CoV-2, and ACE inhibitors and angiotensin receptor blockers are predicted to increase ACE-2 expression, it was initially feared that their use might exacerbate COVID-19. Recent meta-analyses have instead suggested that these medications are protective. This is perhaps because SARS-CoV-2 entry may deplete ACE-2, tipping the balance towards angiotensin II-ACE-1-mediated classical RAS activation: exacerbating hypoperfusion and promoting inflammation. It may be relevant that APOE ε4 individuals, who seem to be at increased risk of COVID-19, also have lowest ACE-2 activity. COVID-19 is likely to leave an unexpected legacy of long-term neurological complications in a significant number of survivors. Cognitive follow-up of COVID-19 patients will be important, especially in patients who develop cerebrovascular and neurological complications during the acute illness.
登录
查看更多内容
影响因子：
3.7
作者：
Biron KE;Dickstein DL;Gopaul R;Jefferies WA
通讯作者：
Jefferies WA
影响因子：
39.3
作者：
Abd El-Aziz TM;Al-Sabi A;Stockand JD
通讯作者：
Stockand JD
影响因子：
5.3
作者：
Burkhart, KK;Beard, DC;Billingsley, ML
通讯作者：
Billingsley, ML
DOI：
10.1152/ajpheart.00247.2015
发表时间：
2016-02-01
影响因子：
4.8
作者：
Biancardi, Vinicia Campana;Stranahan, Alexis M.;Stern, Javier E.
通讯作者：
Stern, Javier E.
阿尔茨海默氏病的顶叶皮层中的脑壁细胞损失与认知能力下降和TDP-43病理相关。
影响因子：
5
作者：
Bourassa P;Tremblay C;Schneider JA;Bennett DA;Calon F
通讯作者：
Calon F