Pastena Paola, Campagnoli Gabriele, Rahmani Ali Reza, Kalogeropoulos Andreas P
Division of Cardiology, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA.
Faculty of Medicine and Surgery, University of Milan, 20122 Milan, Italy.
J Pers Med. 2025 Jan 30;15(2):57. doi: 10.3390/jpm15020057.
Cognitive impairment is a debilitating comorbidity affecting diverse patient populations, yet the cognitive effects of therapies like mineralocorticoid receptor antagonists (MRAs) remain underexplored. Preclinical evidence suggests that MRAs, particularly spironolactone, may reduce cognitive decline by modulating aldosterone-dependent pathways and targeting hippocampal receptors. However, evidence in humans is fragmented, and no systematic review has consolidated these findings. This review evaluates the cognitive effects of MRAs, synthesizes current data, and identifies research gaps. A literature search using terms related to MRAs and cognitive outcomes was performed in PubMed and Web of Science from 1979 to 2023. A total of 143 articles were identified and 85 were screened after removing duplicates. Ultimately, 44 studies were included and were classified based on study design and population focus (preclinical, healthy controls, patients with psychiatric disorders, and cardiovascular patients). Spironolactone demonstrated mixed effects on cognition. In healthy participants, it improved spatial memory under stress and prevented stress-related suppression of medial temporal activity, but impaired working memory and selective attention. In patients with psychiatric conditions, spironolactone reduced cognitive empathy deficits in major depressive disorder and improved working memory in bipolar I disorder. In cardiovascular patients, spironolactone improved cognitive scores and hippocampal memory but had no effect on non-hippocampal memory. Spironolactone exhibits potential cognitive benefits across diverse populations. However, its effects on cognition are mixed, highlighting the need for further research to understand its mechanisms and therapeutic potential, particularly in patients with heart failure and other related conditions.
认知障碍是一种影响多种患者群体的使人衰弱的合并症，然而盐皮质激素受体拮抗剂（MRAs）等疗法对认知的影响仍未得到充分研究。临床前证据表明，MRAs，尤其是螺内酯，可能通过调节醛固酮依赖性途径和靶向海马体受体来减少认知衰退。然而，人类研究证据零散，尚无系统性综述整合这些发现。本综述评估了MRAs的认知效应，综合了现有数据，并确定了研究空白。在PubMed和Web of Science数据库中，使用与MRAs和认知结果相关的术语进行了文献检索，检索时间范围为1979年至2023年。共识别出143篇文章，去除重复项后筛选出85篇。最终纳入44项研究，并根据研究设计和人群重点（临床前、健康对照、精神疾病患者和心血管疾病患者）进行分类。螺内酯对认知的影响呈现出混合效应。在健康参与者中，它改善了应激状态下的空间记忆，并防止了与应激相关的内侧颞叶活动抑制，但损害了工作记忆和选择性注意力。在患有精神疾病的患者中，螺内酯减少了重度抑郁症患者的认知共情缺陷，并改善了双相I型障碍患者的工作记忆。在心血管疾病患者中，螺内酯提高了认知得分和海马体记忆，但对非海马体记忆没有影响。螺内酯在不同人群中展现出潜在的认知益处。然而，其对认知的影响是复杂的，这凸显了进一步研究以了解其机制和治疗潜力的必要性，特别是在心力衰竭和其他相关疾病患者中。
