Cognitive Abilities of At-Risk Elderly for Dementia

描述：（由申请人提供）阿尔茨海默病（AD）代表一种 最重要和最具挑战性的公共卫生问题， 这个国家在未来几十年，因为它最严重的影响最快的 我们人口中不断增长的部分：85岁及以上的个人。的能力 识别处于AD临床前阶段的非痴呆老年人将 对改善早期诊断和使用 抗痴呆药物治疗。这些药物治疗旨在减缓 AD的进展（“神经保护”）将是最有效的，如果应用于 在发生显著神经元损失之前的AD的最早阶段， 这为进行准确的临床前诊断提供了重要的理论基础 的AD。然而，这种努力的剩余障碍之一集中在 难以准确识别患有早期AD的个体， 缺陷在临床上变得明显（即，在认知和 功能衰退）。我们打算招募一群非痴呆的 老年人在AD的高风险，以努力更好地检测和表征 其临床前阶段。 85岁及以上的个体（最年长者），以及具有E4等位基因的个体 载脂蛋白E基因（ApoE），两者都有显着增加的风险， 发展AD。然而，高龄或ApoF E4基因型本身不足以 决定谁会患上AD我们建议进行一项为期五年的 最年长者的纵向研究， 将检查神经心理学、神经影像学和遗传评估， 相对于65-75岁的老年人， AD的显著临床前标志物。因为潜在的神经病理学 老年痴呆症的变化可能在老年人和最老的老年人之间有所不同， 目标将是确定这些独特的模式和贡献， 多模式评估对高龄老年人AD的诊断。 拟议的研究将（a）检查神经心理学，磁 共振（MR）形态测量和遗传易感性标记，以 确定受损的大脑结构和相关过程的模式 与最年长者中的AD的临床前阶段;和（B）进行探索性研究 分析以确定我们的神经心理学测量是否与 早期结构异常（如通过MR成像和神经病理学检测） 指数）中的风险个体。提高我们检测AD的能力 临床前将是至关重要的最古老的老人，谁是 增长最快的高危人群。此外，更好地了解 与高危人群最早期认知变化相关的大脑机制 团体将提高我们的能力，以针对那些谁站在受益最多， 早期药物干预。

DESCRIPTION: (provided by applicant) Alzheimer' s disease (AD) represents one of the most important and challenging public health concerns that will affect this country in the coming decades, since it most severely affects the fastest growing segment of our population: individuals age 85 and older. The ability to identify nondemented older adults who are in a preclinical phase of AD will have far-reaching implications for both improved early diagnosis and use of anti-dementia pharmacologic therapies. Such drugs treatments aimed at slowing the progression of AD ('neuroprotection') will be most effective if applied at the earliest stages of AD before significant neuronal losses have occurred, which provides an important rationale for making accurate preclinical diagnoses of AD. However, one of the remaining obstacles to such efforts centers on the difficulty in accurately identifying individuals with incipient AD before their deficits become clinically apparent (i.e., prior to both cognitive and functional decline). We propose to recruit and follow a group of nondemented older adults at high risk for AD in an effort to better detect and characterize its preclinical stage. Individuals age 85 and older (oldest-old), and individuals with the E4 allele of the apolipoprotein E gene (ApoE), both have significantly elevated risks of developing AD. However, advanced age or ApoF E4 genotype alone are insufficient in determining who will develop AD. We propose to conduct a five-year longitudinal study of the oldest-old in which the combination of neuropsychologic, neuroimaging, and genetic assessments will be examined, relative to the young-old (ages 65-75), in an effort to identify the most salient preclinical markers of AD. Because the underlying neuropathologic changes in AD may differ between the young-old and the oldest-old, a secondary goal will be to determine the unique patterns and contributions of these multi-modal assessments to the diagnosis of AD in the oldest-old. The proposed study will (a) examine the utility of neuropsychologic, magnetic resonance (MR) morphometric, and genetic susceptibility markers in order to determine the pattern of impaired brain structures and processes associated with the preclinical phase of AD in the oldest-old; and (b) conduct exploratory analyses to determine whether our neuropsychologic measures are associated with early structural abnormalities (as detected by MR imaging and neuropathologic indices) in at-risk individuals. Improving our ability to detect AD preclinically will be of critical importance for the oldest-old, who are the fastest growing high-risk population. Furthermore, an improved understanding of the brain mechanisms associated with the earliest cognitive changes in at-risk groups will advance our ability to target those who stand to benefit most from early pharmacologic intervention.