LONGITUDINAL STUDIES OF ALZHEIMERS DISEASE AND SIVD

该项目的目的将是更好地描述AD和SIVD痴呆的独立和相互作用的贡献。本项目将使用总体计划项目拨款（PPG）中所有受试者可用的通用核心数据。它将重点关注整体和特定的认知能力以及作为因变量的独立功能，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中的附加和相互作用的问题。它将制定将在中央协调核心内实施的线性测量程序，并将作为评估阿尔茨海默病和SIVD对痴呆症进展影响的基础。AD和SIVD的认知和功能改变机制将使用横断面、纵向和病理数据进行检查。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收敛性。神经病理学数据的可用性将允许一种关键的复制形式。本项目需要检验的假设有：1) SIVD和AD的认知和功能障碍主要是由于皮质灰质和海马体积的损失，1a)腔隙性梗死和白质异常对认知和功能障碍的影响主要是由皮质灰质和海马体积的相关损失介导的，2)假设1的预测关系在非AD的神经病理学诊断病例中得到支持，在AD的病理诊断病例中独立存在。3)认知障碍和痴呆的进展速度主要由皮质灰质和海马体积的变化率决定；4)特定的认知能力将由局部脑变化差异预测。

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.