Delirium is a complex and multifactorial condition associated with long-term cognitive decline. Due to the strong links between systemic inflammation, delirium and dementia we hypothesized that responses within the brain in patients who develop delirium could show biochemical overlap with patients with Alzheimer's disease (AD). In this observational study we analyzed protein expression signatures in cerebrospinal fluid (CSF) from 15 patients with infectious delirium and compared these to 29 patients with AD, 30 infectious patients without delirium and 15 non-infectious controls free of neurological disease. A proximity extension assay was performed measuring a total of 184 inflammatory and neurology-related proteins. Eight inflammatory proteins (4%), including the key neuron-microglia communication marker CX3CL1 (fractalkine), were significantly upregulated in both delirium and AD, compared to infectious patients without delirium. Likewise, 23 proteins (13%) showed downregulation in both delirium and AD, relative to infectious patients without delirium, which interestingly included CD200R1, another neuron-microglia communication marker, as well as a cluster of proteins related to synapse formation and function. Synaptopathy is an early event in AD and correlates strongly with cognitive dysfunction. These results were partially mediated by aging, which is an important predisposing risk factor among many others for both conditions. Within this study we report the first in vivo human evidence suggesting that synapse pathology and loss of homeostatic microglial control is involved in the pathophysiology of both infectious delirium and AD and thus may provide a link for the association between infections, delirium and long-term cognitive decline.

中文翻译：

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感染性谵妄和阿尔茨海默病患者脑脊液中突触相关蛋白表达的下调和稳态小胶质细胞控制的丧失

谵妄是一种复杂的多因素疾病，与长期认知能力下降有关。由于全身炎症、谵妄和痴呆之间的密切联系，我们假设谵妄患者大脑内的反应可能与阿尔茨海默病 (AD) 患者的生化反应存在重叠。在这项观察性研究中，我们分析了 15 名感染性谵妄患者的脑脊液 (CSF) 中的蛋白质表达特征，并将其与 29 名 AD 患者、30 名无谵妄的感染性患者和 15 名无神经系统疾病的非感染性对照者进行了比较。进行了邻近延伸测定，测量了总共 184 种炎症和神经病学相关蛋白质。八种炎症蛋白 (4%)，包括关键的神经元-小胶质细胞通讯标记物 CX3CL1 (fractalkine)，与没有谵妄的感染性患者相比，谵妄和 AD 中的 同样，相对于没有谵妄的感染性患者，23 种蛋白质 (13%) 在谵妄和 AD 中均表现出下调，有趣的是，其中包括 CD200R1，另一种神经元-小胶质细胞通讯标记物，以及一组与突触形成和功能相关的蛋白质。突触病是 AD 的早期事件，与认知功能障碍密切相关。这些结果部分是由衰老介导的，衰老是这两种情况的一个重要的诱发风险因素。