Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
Neuropharmacology. 2010 Sep-Oct;59(4-5):221-9. doi: 10.1016/j.neuropharm.2010.02.010. Epub 2010 Feb 13.
Neuron and synapse loss together with neurotransmitter dysfunction have, along with Abeta deposition and neurofibrillary tangles, been recognized as hallmarks of Alzheimer's disease (AD). Furthermore, clinical and preclinical studies point to neuronal loss and associated neurochemical alterations of several transmitter systems as a main factor underlying both cognitive and neuropsychiatric symptoms. Treatment for the cognitive decline in AD, based on early findings of a cholinergic deficit, has been in the clinic for more than a decade but provides only modest benefit in most patients. Therefore there is still considerable scope for new treatments that demonstrate greater efficacy against cognitive dysfunction in spite of the fact that the mainstays of current treatments, the cholinesterase inhibitors Aricept, Exelon and Reminyl (Razadyne) will become generic over the next few years. However, the most important area for drug development is for the treatment of behavioural disturbance in AD since many existing treatments have limited efficacy and have potentially life-threatening side effects. This review examines the neurochemical underpinning of both cognitive and neuropsychiatric symptoms in dementia and provides some basis for rational drug development.
神经元和突触的丢失以及神经递质功能障碍，与 Abeta 沉积和神经纤维缠结一起，被认为是阿尔茨海默病（AD）的标志。此外，临床和临床前研究表明，神经元丢失和几个递质系统的相关神经化学改变是导致认知和神经精神症状的主要因素。基于早期胆碱能缺乏的发现，针对 AD 认知能力下降的治疗已经在临床上应用了十多年，但在大多数患者中仅提供适度的益处。因此，尽管目前的主要治疗方法——胆碱酯酶抑制剂安理申、艾斯能和艾斯能（雷美隆）——将在未来几年内成为通用药物，但仍有很大的空间开发新的治疗方法，以证明其在认知功能障碍方面的疗效更强。然而，药物开发最重要的领域是治疗 AD 中的行为障碍，因为许多现有治疗方法的疗效有限，并且具有潜在的危及生命的副作用。这篇综述检查了痴呆症中认知和神经精神症状的神经化学基础，并为合理的药物开发提供了一些依据。
