Buckley Jacob S, Salpeter Shelley R
Brown University, Providence, RI, USA.
Drugs Aging. 2015 Jun;32(6):453-67. doi: 10.1007/s40266-015-0266-9.
There is no cure for dementia, and no treatments exist to halt or reverse the course of the disease. Treatments are aimed at improving cognitive and functional outcomes.
Our objective was to review the basis of pharmacological treatments for dementia and to summarize the benefits and risks of dementia treatments.
We performed a systematic literature search of MEDLINE through November 2014, for English-language trials and observational studies on treatment of dementia and mild cognitive impairment. Additional references were identified by searching bibliographies of relevant publications. Whenever possible, pooled data from meta-analyses or systematic reviews were obtained. Studies were included for review if they were randomized trials or observational studies on dementia or mild cognitive impairment that evaluated efficacy outcomes or adverse outcomes associated with treatment. Studies were excluded if they evaluated non-FDA approved treatments, or if they evaluated treatment in disorders other than dementia and mild cognitive impairment.
The literature search found 540 potentially relevant studies, of which 257 were included in the systematic review. In pooled trial data, cholinesterase inhibitors (ChEIs) produce small improvements in cognitive, functional, and global benefits in patients with mild to moderate Alzheimer's and Lewy body dementia, but the clinical significance of these effects are unclear. There is no significant benefit seen for vascular dementia. The efficacy of ChEI treatment appears to wane over time, with minimal benefit seen after 1 year. There is no evidence for benefit for those with advanced disease or those aged over 85 years. Adverse effects are significantly increased with ChEIs, in a dose-dependent manner. A two- to fivefold increased risk for gastrointestinal, neurological, and cardiovascular side effects is related to cholinergic stimulation, the most serious being weight loss, debility, and syncope. Those aged over 85 years have double the risk of adverse events compared with younger patients. Memantine monotherapy may provide some cognitive benefit for patients with moderate to severe Alzheimer's and vascular dementia, but the benefit is small and may wane over the course of several months. Memantine exhibits no significant benefit in mild dementia or Lewy body dementia or as an add-on treatment with ChEIs. Memantine has a relatively favorable side-effect profile, at least under controlled trial conditions.
ChEIs produce small, short-lived improvements in cognitive function in mild to moderate dementia, which may not translate into clinically meaningful effects. Marginal benefits are seen with severe disease, long-term treatment, and advanced age. Cholinergic side effects, including weight loss, debility, and syncope, are clinically significant and could be especially detrimental in the frail elderly population, in which the risks of treatment outweigh the benefits. Memantine monotherapy may have minimal benefits in moderate to severe dementia, balanced by minimal adverse effects.
痴呆症无法治愈，也不存在能够阻止或逆转该疾病病程的治疗方法。治疗旨在改善认知和功能结果。
我们的目的是回顾痴呆症药物治疗的基础，并总结痴呆症治疗的益处和风险。
我们对截至2014年11月的MEDLINE进行了系统的文献检索，以查找关于痴呆症和轻度认知障碍治疗的英文试验和观察性研究。通过搜索相关出版物的参考文献来识别其他参考文献。只要有可能，就获取来自荟萃分析或系统评价的汇总数据。如果研究是关于痴呆症或轻度认知障碍的随机试验或观察性研究，评估了与治疗相关的疗效结果或不良结果，则纳入综述。如果研究评估的是非FDA批准的治疗方法，或者评估的是痴呆症和轻度认知障碍以外疾病的治疗，则排除该研究。
文献检索发现540项可能相关的研究，其中257项纳入了系统评价。在汇总的试验数据中，胆碱酯酶抑制剂（ChEIs）在轻度至中度阿尔茨海默病和路易体痴呆患者的认知、功能和整体益处方面有小幅改善，但这些效果的临床意义尚不清楚。血管性痴呆未见明显益处。ChEI治疗的疗效似乎会随着时间减弱，1年后益处甚微。对于晚期疾病患者或85岁以上的患者，没有证据表明有益处。ChEIs的不良反应显著增加，且呈剂量依赖性。胃肠道、神经和心血管副作用的风险增加了两到五倍与胆碱能刺激有关，最严重的是体重减轻、身体虚弱和晕厥。85岁以上的患者发生不良事件的风险是年轻患者的两倍。美金刚单药治疗可能对中度至重度阿尔茨海默病和血管性痴呆患者有一些认知益处，但益处较小，且可能在几个月内减弱。美金刚在轻度痴呆或路易体痴呆或作为ChEIs的联合治疗中未见明显益处。至少在对照试验条件下，美金刚的副作用相对较小。
ChEIs在轻度至中度痴呆症中对认知功能有小幅、短暂的改善，这可能不会转化为临床上有意义的效果。在严重疾病、长期治疗和高龄患者中可见边际益处。胆碱能副作用，包括体重减轻、身体虚弱和晕厥，具有临床意义，在体弱的老年人群中可能尤其有害，因为治疗风险超过了益处。美金刚单药治疗在中度至重度痴呆症中可能益处最小，但其副作用也最小。
