LONGITUDINAL STUDIES OF ALZHEIMERS DISEASE AND SIVD

这个项目的目的将是更好地描述AD和SIVD对痴呆的独立和互动贡献。本项目将使用通用的核心数据，这些数据适用于所有注册在总体计划项目拨款(PPG)中的科目。它将侧重于全球和特定的认知能力和独立功能作为因变量，并将纳入纵向随访和神经病理学的数据，以解决AD和SIVD在决定痴呆的表现和进展方面的相加和交互作用的问题。它将制定将在中央协调核心内实施的线性测量程序，并将作为评估AD和SIVD对痴呆症进展的影响的基础。AD和SIVD的认知和功能改变的机制将使用横断面、纵向和病理学数据进行研究。将通过使用来自三个来源的数据执行相同的分析来完成多次重复，以便可以直接比较结果的趋同。神经病理学数据的可获得性将允许一种关键形式的复制。本项目将检验的假说是：1)SIVD和AD的认知和功能损害主要是由于皮质灰质和海马体体积的丧失，1a)腔隙性脑梗塞和异常白质对认知和功能损害的影响主要是由皮质灰质和海马体体积的相关丧失介导的，2)假说1的预测关系将在神经病理学诊断的非AD病例和独立诊断的AD病例中得到支持，3)认知损害和痴呆的进展率将主要由皮质灰质和海马体体积的变化率决定，以及4)特定的认知能力将由局部的脑变化来区分预测。

The purpose of this project will be to better characterize independent and interactive contributions to dementia of AD and SIVD. This project will use common, core data that is available for all subjects enrolled in the overall program project grant (PPG). It will focus on global and specific cognitive abilities and independent functioning as dependent variables and will incorporate date from longitudinal follow-up and neuropathology to address questions about additive and interactive effects of AD and SIVD in determining presentation and progression of dementia. It will develop linear measurement procedures that will be implemented within the Central Coordinating Core and will serve as the basis for evaluating effects of AD and SIVD on progression of dementia. Mechanisms of cognitive and functional change in AD and SIVD will be examined using cross sectional, longitudinal, and pathological data. Multiple replications will be accomplished by performing the same analyses using data from three sources so that convergence of findings can be directly compared. The availability of data from neuropathology will allow for a critical form of replication. Hypotheses to be tested in this project are: 1) Cognitive and functional impairment in SIVD and AD are primarily due to loss of volume of cortical gray matter and hippocampus, 1a) Effects of lacunar infarcts and abnormal white matter on cognitive and functional impairment are primarily mediated by associated loss of volume of cortical gray matter and hippocampus, 2) Predicted relationships from Hypothesis 1 will be supported in neuropathology diagnosed cases without AD and independently in pathology diagnosed cases with AD, 3) Rate of progression of cognitive impairment and dementia will be primarily determined by the rate of change in volume of cortical gray matter and hippocampus and 4) Specific cognitive abilities will be differentially predicted by localized brain changes.