Center for Neurosciences of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
J Alzheimers Dis. 2010;20 Suppl 1:S95-116. doi: 10.3233/JAD-2010-1408.
Caffeine, the most widely consumed psychoactive drug, enhances attention/vigilance, stabilizes mood, and might also independently enhance cognitive performance. Notably, caffeine displays clearer and more robust beneficial effects on memory performance when memory is perturbed by stressful or noxious stimuli either in human or animal studies. Thus, caffeine restores memory performance in sleep-deprived or aged human individuals, a finding replicated in rodent animal models. Likewise, in animal models of Alzheimer's disease (AD), caffeine alleviates memory dysfunction, which is in accordance with the tentative inverse correlation between caffeine intake and the incidence of AD in different (but not all) cohorts. Caffeine also affords beneficial effects in animal models of conditions expected to impair memory performance such as Parkinson's disease, chronic stress, type 2 diabetes, attention deficit and hyperactivity disorder, early life convulsions, or alcohol-induced amnesia. Thus, caffeine should not be viewed as a cognitive enhancer but instead as a cognitive normalizer. Interestingly, these beneficial effects of caffeine on stress-induced memory disturbance are mimicked by antagonists of adenosine A2A receptors. This prominent role of A2A receptors in preventing memory deterioration is probably related to the synaptic localization of this receptor in limbic areas and its ability to control glutamatergic transmission, especially NMDA receptor-dependent plasticity, and to control apoptosis, brain metabolism, and the burden of neuroinflammation. This opens the real and exciting possibility that caffeine consumption might be a prophylactic strategy and A2A receptor antagonists may be a novel therapeutic option to manage memory dysfunction both in AD and in other chronic neurodegenerative disorders where memory deficits occur.
咖啡因是最广泛使用的精神活性药物，可增强注意力/警觉性，稳定情绪，并且还可能独立地增强认知表现。值得注意的是，在人类或动物研究中，当记忆受到应激或有害刺激干扰时，咖啡因对记忆表现显示出更清晰和更强大的有益作用。因此，咖啡因可以恢复睡眠剥夺或衰老的人类个体的记忆表现，这在啮齿动物动物模型中得到了复制。同样，在阿尔茨海默病（AD）的动物模型中，咖啡因可缓解记忆功能障碍，这与不同（但不是全部）队列中咖啡因摄入量与 AD 发生率之间的暂定负相关一致。咖啡因还可在预期会损害记忆表现的动物模型中提供有益作用，如帕金森病、慢性应激、2 型糖尿病、注意力缺陷多动障碍、早期癫痫发作或酒精引起的健忘症。因此，不应将咖啡因视为认知增强剂，而应将其视为认知正常化剂。有趣的是，咖啡因对应激诱导的记忆障碍的这些有益作用可被腺苷 A2A 受体拮抗剂模拟。A2A 受体在防止记忆恶化中的这种突出作用可能与该受体在边缘区域的突触定位及其控制谷氨酸能传递的能力有关，特别是 NMDA 受体依赖性可塑性，以及控制细胞凋亡、大脑代谢和神经炎症负担。这为一个真正令人兴奋的可能性开辟了道路，即咖啡因的消耗可能是一种预防策略，而 A2A 受体拮抗剂可能是一种新的治疗选择，可以管理 AD 以及其他发生记忆障碍的慢性神经退行性疾病中的记忆功能障碍。
