Levey Allan, Lah James, Goldstein Felicia, Steenland Kyle, Bliwise Donald
Department of Neurology and Alzheimer's Disease Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
Clin Ther. 2006 Jul;28(7):991-1001. doi: 10.1016/j.clinthera.2006.07.006.
There is increasing evidence that subtle losses in cognitive function may be symptomatic of a transition to early Alzheimer's disease (AD). Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to AD. Of the MCI subtypes, patients with amnestic MCI (a-MCI) are at greatest risk.
The objectives of this article were to review the relationship between MCI, normal aging, and AD, and to summarize recent research on the diagnosis and potential treatment of MCI.
Relevant articles were identified through searches of MEDLINE and EMBASE using the terms mild cognitive impairment; cognitive impairment, no dementia; and dementia prodrome, with no restrictions as to year. Additional papers of interest were identified from the reference lists of the identified articles. The search was current as of February 2006.
Guidelines and recommendations are being developed to assist physicians in diagnosing MCI, identifying its subtype and etiology, understanding the risks for conversion to AD, and managing disease progression. Given the existence of a subset of individuals with a-MCI, who are at greatest risk for progression to AD but still have high levels of cognition and function, the ability to improve symptoms and delay progression to AD would be particularly beneficial. In a 3-year, randomized, double-blind, placebo-controlled study in 769 patients with a-MCI, treatment with the cholinesterase inhibitor donepezil was associated with a significantly lower rate of progression to AD compared with placebo during the first 12 months of treatment (hazard ratio=0.42; 95% CI, 0.24-0.76; P=0.004) but not at later time points. Of other types of agents that have been investigated (antioxidants, estrogen replacement therapy, cyclooxygenase-2-selective inhibitors), none have shown significant beneficial effects in delaying cognitive decline or progression to AD. New drugs such as secretase inhibitors, small molecules that disrupt amyloid aggregation, and immunotherapies are in preclinical development.
MCI involves more substantial cognitive and memory decline than normal aging and represents a significant risk factor for the development of dementia. Further research is needed into treatments to delay the conversion from MCI to AD.
越来越多的证据表明，认知功能的细微丧失可能是向早期阿尔茨海默病（AD）转变的症状。正在进行的研究集中于识别那些最有可能转变为AD的轻度认知障碍（MCI）个体。在MCI亚型中，遗忘型MCI（a-MCI）患者风险最高。
本文的目的是回顾MCI、正常衰老和AD之间的关系，并总结近期关于MCI诊断和潜在治疗的研究。
通过检索MEDLINE和EMBASE，使用术语“轻度认知障碍”、“无痴呆的认知障碍”和“痴呆前驱期”来识别相关文章，对年份无限制。从已识别文章的参考文献列表中识别出其他感兴趣的论文。检索截至2006年2月。
正在制定指南和建议，以帮助医生诊断MCI、识别其亚型和病因、了解转变为AD的风险以及管理疾病进展。鉴于存在一部分a-MCI个体，他们进展为AD的风险最高，但认知和功能水平仍较高，改善症状并延迟进展为AD的能力将特别有益。在一项针对769例a-MCI患者的为期3年的随机、双盲、安慰剂对照研究中，与安慰剂相比，在治疗的前12个月使用胆碱酯酶抑制剂多奈哌齐治疗使进展为AD的发生率显著降低（风险比=0.42；95%CI，0.24-0.76；P=0.004），但在后期时间点则不然。在已研究的其他类型药物（抗氧化剂、雌激素替代疗法、环氧化酶-2选择性抑制剂）中，没有一种在延迟认知衰退或进展为AD方面显示出显著的有益效果。诸如分泌酶抑制剂、破坏淀粉样蛋白聚集的小分子以及免疫疗法等新药正处于临床前开发阶段。
MCI涉及比正常衰老更严重的认知和记忆衰退，是痴呆发生的一个重要风险因素。需要进一步研究延缓从MCI转变为AD的治疗方法。
