LONGITUDINAL STUDIES OF ALZHEIMERS DISEASE AND SIVD

该项目的目的是更好地描述AD和SIVD对痴呆的独立和互动贡献。该项目将使用通用的核心数据，这些数据适用于所有参加总体项目资助（PPG）的受试者。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，以解决有关AD和SIVD在确定痴呆的表现和进展方面的叠加和交互作用的问题。它将开发线性测量程序，该程序将在中央协调核心内实施，并将作为评估AD和SIVD对痴呆症进展影响的基础。AD和SIVD的认知和功能变化的机制将使用横截面，纵向和病理学数据进行检查。将通过使用三个来源的数据进行相同的分析来完成多次重复，以便可以直接比较结果的一致性。神经病理学数据的可用性将允许复制的关键形式。本项目中要检验的假设是：1）SIVD和AD中的认知和功能损害主要是由于皮质灰质和海马体积的损失，1a）腔隙性梗死和异常白色物质对认知和功能损害的影响主要由皮质灰质和海马体积的相关损失介导，2）来自假设1的预测关系将在无AD的神经病理学诊断病例中得到支持，并且独立地在具有AD的病理学诊断病例中得到支持，3）认知障碍和痴呆的进展速率将主要由皮质灰质和海马体积的变化速率决定，以及特定的认知能力将通过局部大脑变化进行差异预测。

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.