Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan ; Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan.
Curr Neuropharmacol. 2012 Sep;10(3):272-85. doi: 10.2174/157015912803217288.
Dementia has become an all-important disease because the population is aging rapidly and the cost of health care associated with dementia is ever increasing. In addition to cognitive function impairment, associated behavioral and psychological symptoms of dementia (BPSD) worsen patient's quality of life and increase caregiver's burden. Alzheimer's disease is the most common type of dementia and both behavioral disturbance and cognitive impairment of Alzheimer's disease are thought to be associated with the N-methyl-D-aspartate (NMDA) dysfunction as increasing evidence of dysfunctional glutamatergic neurotransmission had been reported in behavioral changes and cognitive decline in Alzheimer's disease. We review the literature regarding dementia (especially Alzheimer's disease), BPSD and relevant findings on glutamatergic and NMDA neurotransmission, including the effects of memantine, a NMDA receptor antagonist, and NMDA-enhancing agents, such as D-serine and D-cycloserine. Literatures suggest that behavioral disturbance and cognitive impairment of Alzheimer's disease may be associated with excitatory neurotoxic effects which result in impairment of neuronal plasticity and degenerative processes. Memantine shows benefits in improving cognition, function, agitation/aggression and delusion in Alzheimer's disease. On the other hand, some NMDA modulators which enhance NMDA function through the co-agonist binding site can also improve cognitive function and psychotic symptoms. We propose that modulating NMDA neurotransmission is effective in treating behavioral and psychological symptoms of Alzheimer's disease. Prospective study using NMDA enhancers in patients with Alzheimer's disease and associated behavioral disturbance is needed to verify this hypothesis.
痴呆症已成为一种至关重要的疾病，原因是人口老龄化迅速，与痴呆症相关的医疗保健成本不断增加。除了认知功能障碍外，痴呆症相关的行为和心理症状（BPSD）还会降低患者的生活质量并增加照顾者的负担。阿尔茨海默病是最常见的痴呆症类型，阿尔茨海默病的行为障碍和认知障碍都被认为与 N-甲基-D-天冬氨酸（NMDA）功能障碍有关，因为越来越多的证据表明，在阿尔茨海默病的行为改变和认知能力下降中，谷氨酸能神经传递功能失调。我们回顾了有关痴呆症（尤其是阿尔茨海默病）、BPSD 以及谷氨酸能和 NMDA 神经传递相关的研究文献，包括 NMDA 受体拮抗剂美金刚以及 NMDA 增强剂如 D-丝氨酸和 D-环丝氨酸的作用。文献表明，阿尔茨海默病的行为障碍和认知障碍可能与兴奋性神经毒性作用有关，从而导致神经元可塑性和退行性过程受损。美金刚可改善阿尔茨海默病患者的认知、功能、激越/攻击和妄想。另一方面，一些通过共同激动剂结合位点增强 NMDA 功能的 NMDA 调节剂也可以改善认知功能和精神病症状。我们提出，调节 NMDA 神经传递对治疗阿尔茨海默病的行为和心理症状有效。需要对阿尔茨海默病患者和相关行为障碍使用 NMDA 增强剂进行前瞻性研究，以验证这一假设。
