War Related Illness and Injury Study Center, VA Palo Alto Health Care System and Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA.
J Alzheimers Dis. 2019;67(3):923-930. doi: 10.3233/JAD-181106.
In this issue, an article by La et al. provides evidence that trazodone delayed cognitive decline in 25 participants with Alzheimer's disease (AD), mild cognitive impairment, or normal cognition. For participants considered to have AD pathology, trazodone non-users declined at a rate 2.4 times greater than those taking trazodone for sleep over a 4-year period. In the analysis of sleep complaints, the relationship between trazodone, a widely used medication for sleep problems in the elderly, and cognition was associated with subjective improvement of sleep disruption. Due to the design of the study, it was not possible to prove that the benefit of slowing cognitive decline was due specifically to the improvement in sleep. However, trazodone uniquely improves the deeper phases of slow-wave sleep. Other sedative medications are generally associated with worse cognitive function over time, and they do not improve sleep characteristics as does trazodone. Trazodone has a variety of effects on several monoaminergic mechanisms: a potent serotonin 5-HT2A and α1-adrenergic receptor antagonist, a weak serotonin reuptake inhibitor, and a weak antihistamine or histamine H1 receptor inverse agonist. Because of the potential importance of this finding, further discussion is provided on the roles that trazodone may play in the modulation of monoamines, cognition, and the development of AD. If trazodone really does provide such a dramatic slowing in the development of dementia associated with AD, a great deal more research on trazodone is needed, including environmental and behavioral factors related to improvement of sleep, energy management, and neuroplasticity.
在本期中，La 等人的一篇文章提供了证据，表明曲唑酮可延缓 25 名阿尔茨海默病（AD）、轻度认知障碍或认知正常患者的认知能力下降。对于被认为具有 AD 病理的参与者，在 4 年的时间里，未使用曲唑酮治疗睡眠的患者的下降速度是使用曲唑酮治疗睡眠的患者的 2.4 倍。在对睡眠抱怨的分析中，曲唑酮（一种广泛用于老年人群睡眠问题的药物）与认知之间的关系与睡眠障碍的主观改善有关。由于研究的设计，无法证明减缓认知能力下降的益处是否专门归因于睡眠的改善。然而，曲唑酮独特地改善了慢波睡眠的更深阶段。其他镇静药物通常会随着时间的推移导致认知功能恶化，而不像曲唑酮那样改善睡眠特征。曲唑酮对几种单胺能机制有多种影响：一种强效的 5-羟色胺 5-HT2A 和 α1-肾上腺素能受体拮抗剂、一种弱的 5-羟色胺再摄取抑制剂、一种弱的抗组胺药或组胺 H1 受体反向激动剂。由于这一发现的潜在重要性，进一步讨论了曲唑酮在调节单胺、认知和 AD 发展方面可能发挥的作用。如果曲唑酮确实对与 AD 相关的痴呆发展产生如此显著的减缓作用，那么还需要对曲唑酮进行更多的研究，包括与改善睡眠、能量管理和神经可塑性相关的环境和行为因素。
