Knopman David S, Caselli Richard J
Department of Neurology, College of Medicine, Mayo Clinic Rochester & Mayo Clinic Alzheimer's Disease Research Center, 200 First Street SW, Rochester, MN 55905, USA.
Neurodegener Dis Manag. 2012;2(2):183-195. doi: 10.2217/NMT.12.5.
Biomarker evidence and clinical observations support the hypothesis that there is a diagnosable condition termed preclinical Alzheimer's disease (AD). Recently, a workgroup convened under the auspices of the National Institute on Aging and the Alzheimer's Association proposed a framework for defining preclinical AD. The definition was based on the presence of biomarkers that are indicative of the AD pathophysiological process. In the context of abnormal AD biomarkers, the workgroup postulated that 'subtle cognitive changes' occurred as well. Based on studies of genetically at-risk individuals and those destined to become demented, who were observed while still cognitively normal, low performance on learning and memory functions may be the earliest cognitive manifestations of preclinical AD, at the group level at least. It is not clear whether subtle cognitive decline can be detected reliably on an individual basis. Preclinical AD cognitive changes could be diagnosed by traditional neuropsychological testing, computerized testing, assessments of subjective memory loss, assessments of levels of participation in cognitively stimulating activities and direct measurement of activity using recently developed monitoring technology. Confounding effects of normal aging, test-retest variability, variations in educational attainment, as well as the presence of other brain diseases make diagnosing cognitive decline due to preclinical AD challenging.
生物标志物证据和临床观察结果支持这样一种假说，即存在一种可诊断的疾病状态，称为临床前阿尔茨海默病（AD）。最近，一个在美国国立衰老研究所和阿尔茨海默病协会主持下召集的工作组提出了一个定义临床前AD的框架。该定义基于指示AD病理生理过程的生物标志物的存在。在AD生物标志物异常的背景下，该工作组还假定同时出现了“细微认知变化”。基于对有遗传风险个体以及注定会患痴呆症个体（这些个体在认知仍正常时就被观察）的研究，至少在群体层面上，学习和记忆功能表现低下可能是临床前AD最早的认知表现。目前尚不清楚在个体层面上是否能可靠地检测到细微认知衰退。临床前AD的认知变化可通过传统神经心理学测试、计算机化测试、主观记忆丧失评估、认知刺激活动参与水平评估以及使用最近开发的监测技术直接测量活动来诊断。正常衰老的混杂效应、重测变异性、教育程度差异以及其他脑部疾病的存在使得诊断临床前AD导致的认知衰退具有挑战性。
