Alzheimers Disease in Mild Cognitive Impairment

本研究的目的是确定罹患AD风险最高的个体。为了实现这一目标，我们将对基于轻度认知损害(MCI)的高危个体进行纵向研究。这些受试者是心血管健康研究(CHS)痴呆症研究匹兹堡队列的一部分。CHS痴呆症研究于1999年结束，本研究将跟踪那些被确定为MCI或正常对照的参与者。具体地说，我们研究了142名MCI受试者和218名对照，进行了详细的神经行为、神经成像和神经学检查。这些前CHS参与者中的每一位都在1992-93和1997-98年间进行了临床和神经心理学检查、核磁共振研究和血液样本。在1998-1999年间，这些参与者中的每一个都进行了详细的神经心理学、精神病学和神经学测试，这使我们能够确定MCI和正常老年人的明确和特征鲜明的队列。因此，我们处于独特的地位，可以在以人口为基础的样本中审查AD发展的自然历史。这项研究将使用前瞻性的结构和灌注MRI扫描、遗传因素(例如载脂蛋白E epsilon4等位基因)、生物标记物(例如炎症标记物[IL-6、C反应蛋白和肿瘤坏死因子α]和血浆β淀粉样蛋白水平[Abeta1-40和Abeta1-40])，以及特定的神经心理指标作为AD发生的标记物。我们认为有两种类型的MCI：1)MCI遗忘型，代表一个独特的实体，发生AD的风险显著增加(每年10%)。2)MCI多认知缺陷型，它代表了从老年到AD正常过渡的时间延伸。因此，这些参与者患AD的风险将降低(每年5%)。

The purpose of this study is to identify the individuals with the highest risk to develop AD. To accomplish this goal we will conduct a longitudinal study on at-risk individuals who have been identified based on the presence of mild cognitive impairment (MCI). The subjects were part of the Pittsburgh cohort of the Dementia Study of the Cardiovascular Health Study (CHS). The CHS Dementia study ended in 1999, and the present study will follow those participants identified as MCI or normal control. Specifically, we study 142 MCI subjects and 218 controls with detailed neurobehavioral, neuroimaging, and neurological examinations. Each of these former CHS participants had clinical and neuropsychological exams, MRI studies, and blood samples in 1992-93 and 1997-98. In 1998-1999, each of these participants had detailed neuropsychological, psychiatric, and neurological testing that allowed us to identify a clear and well- characterized cohort of MCI and normal elderly individuals. Consequently, we are in the unique position to examine the natural history of the development of AD in a population-based sample. The study will make use of prospective structural and perfusion MRI- scans, genetic factors (e.g., apolipoprotein E epsilon4 allele), biological markers (e.g., inflamation markers [Inter-leukin-6, C- reactive protein, and Tumor necrosis factor alpha) and plasma beta amyloid level [Abeta1-40 and Abeta 1-40]), and specific neuropsychological measures as markers for the development of AD. We propose that there are two types of MCI: 1) The MCI amnestic- type, which represents a distinct entity, with a significantly increased risk to develop AD (10 percent per year). 2) the MCI multiple cognitive deficit-type, which represents a temporal elongation of the normal transition from aged to AD. Consequently, these participants will have a reduced risk to develop AD (5 percent per year).