Department of Epidemiology and Biostatistics, University of South Florida, 13201 Bruce B. Downs Blvd., MDC-56, Tampa, FL 33612-3805, USA.
Curr Alzheimer Res. 2012 Jul;9(6):621-7. doi: 10.2174/156720512801322546.
The Nun Study was the first cohort study to enroll and follow a large, well-defined population that included demented and non-demented participants, all of whom agreed to donate their brains for research. The inclusion of systematic neuropathologic analysis in this study has resulted in a greater understanding of the role of Alzheimer and vascular pathology in the expression of memory deficits and dementia and has provided data showing that biomarkers for the pathology may be evident many decades earlier in adult life. Findings related to neuropathology in this study have included the following: (1) Although clinical outcomes were strongly correlated with Alzheimer neuropathology, about one-third of the participants fulfilling criteria for neuropathologic Alzheimer's disease (AD) were not demented at the time of death. (2) Brain infarcts by themselves had little effect on cognitive status, but played an important role in increasing the risk of dementia associated with Alzheimer pathology. (3) Hippocampal volume was strongly correlated with Braak neurofibrillary stage even in participants with normal cognitive function. (4) A linguistic characteristic of essays written in early adult life, idea density, had a strong association with not only clinical outcomes in late life, but the severity of Alzheimer neuropathology as well. (5) The effect of apolipoprotein E-e4 on dementia was mediated through Alzheimer, but not vascular pathology.
《修女研究》是第一项招募并随访大量明确界定人群的队列研究，该人群包括痴呆和非痴呆参与者，所有参与者均同意捐献大脑用于研究。这项研究纳入了系统的神经病理学分析，从而使人们更深入地了解阿尔茨海默病和血管病理学在记忆缺陷和痴呆表现中的作用，并提供了数据表明，该病理学的生物标志物可能在成年早期就已经明显存在。这项研究中与神经病理学相关的发现包括以下几点：（1）尽管临床结局与阿尔茨海默病神经病理学密切相关，但在死亡时符合阿尔茨海默病神经病理学诊断标准的参与者中，约有三分之一并未出现痴呆。（2）单纯的脑梗死本身对认知状态影响不大，但在增加与阿尔茨海默病病理学相关的痴呆风险方面起着重要作用。（3）即使在认知功能正常的参与者中，海马体积也与 Braak 神经纤维缠结阶段高度相关。（4）成年早期写作的散文的语言特征——思想密度，不仅与晚年的临床结局密切相关，而且与阿尔茨海默病神经病理学的严重程度也密切相关。（5）载脂蛋白 E-e4 对痴呆的影响是通过阿尔茨海默病介导的，而不是通过血管病理学。
