Age is one of the proposed main triggers of neuropsychological disease. However, the effect of age is heterogeneous, and the mechanisms behind disease progression are not fully determined. A study in Communications Biology shows that neuroinflammation and white matter disruption have an important role in the progression of delirium in aged mice. When comparing 8- and 25-month-old mice, older mice were more vulnerable to a systemic inflammatory insult, showing increased sickness behavior and inflammation biomarkers. At a regional brain level, older animals subjected to an inflammatory insult exhibited priming of microglia all around, when compared with healthy old animals. Age alone could not explain the cognitive impairment seen in behavioral tests; however, when classifying animals as cognitively resilient or frail, considering their performance in the behavioral tests, frail individuals showed worse performance, increased white matter microgliosis and synaptic loss. These data show that while aging has a role in cognitive vulnerability, factors such as white matter integrity are also relevant for the progression of cognitive impairment and the development of more precise therapies for the prevention of delirium.

Original reference: Healy, D. et al. Commun. Biol. 7, 105 (2024)

年龄是神经心理疾病的主要触发因素之一。然而，年龄的影响是异质的，并且疾病进展背后的机制尚未完全确定。《通讯生物学》的一项研究表明，神经炎症和白质破坏在老年小鼠谵妄的进展中发挥着重要作用。比较 8 个月和 25 个月大的小鼠时，年长的小鼠更容易受到全身炎症损伤，表现出患病行为和炎症生物标志物增加。在大脑区域水平上，与健康的老年动物相比，遭受炎症损伤的老年动物表现出周围小胶质细胞的启动。仅凭年龄无法解释行为测试中发现的认知障碍；然而，当将动物分类为认知弹性或虚弱时，考虑到它们在行为测试中的表现，虚弱的个体表现出较差的表现，白质小胶质细胞增多和突触损失增加。这些数据表明，虽然衰老与认知脆弱性有关，但白质完整性等因素也与认知障碍的进展以及预防谵妄的更精确疗法的开发有关。

原始参考文献： Healy, D. et al. 交流。生物。7 , 105 (2024)