Lin Chieh-Hsin, Lane Hsien-Yuan
Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
School of Medicine, Chang Gung University, Taoyuan, Taiwan.
Front Pharmacol. 2019 May 22;10:540. doi: 10.3389/fphar.2019.00540. eCollection 2019.
While the world's population is aging, the prevalence of dementia and the associated behavioral and psychological symptoms of dementia (BPSD) rises rapidly. BPSD are associated with worsening of cognitive function and poorer prognosis. No pharmacological treatment has been approved to be beneficial for BPSD to date. Dysfunction of the N-methyl-D-aspartate receptor (NMDAR)-related neurotransmission leads to cognitive impairment and behavioral changes, both of which are core symptoms of BPSD. Memantine, an NMDAR partial antagonist, is used to treat moderate to severe Alzheimer's disease (AD). On the other hand, a D-amino acid oxidase inhibitor improved early-phase AD. Whether to enhance or to attenuate the NMDAR may depend on the phases of dementia. It will be valuable to develop biomarkers indicating the activity of NMDAR, particularly in BPSD. In addition, recent reports suggest that gender difference exists in the treatment of dementia. Selecting subpopulations of patients with BPSD who are prone to improvement with treatment would be important. We reviewed literatures regarding the treatment of BPSD, focusing on the NMDAR-related modulation and precision medicine. Future studies examining the NMDAR modulators with the aid of potential biomarkers to tailor the treatment for individualized patients with BPSD are warranted.
随着世界人口老龄化，痴呆症以及相关的痴呆行为和心理症状（BPSD）的患病率迅速上升。BPSD与认知功能恶化和预后较差有关。迄今为止，尚无药物治疗被批准对BPSD有益。N-甲基-D-天冬氨酸受体（NMDAR）相关神经传递功能障碍会导致认知障碍和行为改变，这两者都是BPSD的核心症状。美金刚，一种NMDAR部分拮抗剂，用于治疗中度至重度阿尔茨海默病（AD）。另一方面，一种D-氨基酸氧化酶抑制剂改善了早期AD。增强还是减弱NMDAR可能取决于痴呆的阶段。开发指示NMDAR活性的生物标志物将很有价值，尤其是在BPSD中。此外，最近的报告表明，痴呆症治疗中存在性别差异。选择易于通过治疗改善的BPSD患者亚群很重要。我们回顾了关于BPSD治疗的文献，重点是与NMDAR相关的调节和精准医学。未来有必要借助潜在的生物标志物研究NMDAR调节剂，为个体化的BPSD患者量身定制治疗方案。
