Cognitive Abilities of At-Risk Elderly for Dementia

描述：(申请人提供)阿尔茨海默病S病(AD) 最重要和最具挑战性的公共卫生问题将影响 这个国家在未来几十年里，因为它最严重地影响到 我们人口中不断增长的部分：85岁及以上的个人。有能力 确定处于AD Will临床前阶段的非痴呆老年人 对改进早期诊断和使用 抗痴呆症的药物疗法。这类药物治疗旨在减缓 AD的进展(神经保护)如果在以下方面应用将是最有效的 阿尔茨海默病的最早阶段是在发生显著的神经元丢失之前， 这为做出准确的临床前诊断提供了重要的理论基础。 公元一代的。然而，这种努力的剩余障碍之一集中在 难以准确识别早期阿尔茨海默病患者 缺陷在临床上变得明显(即，在认知和 功能衰退)。我们建议招募并跟随一群非痴呆者 AD高危老年人，努力更好地检测和表征 其临床前阶段。 85岁及以上的个人(年龄最大的)，以及具有E4等位基因的个人 在载脂蛋白E基因(ApoE)中，两者都有显著增加的风险 开发AD。然而，仅有高龄或载脂蛋白E4基因型是不够的 决定谁会患上阿尔茨海默病。我们建议进行为期五年的 在纵向研究中，最古老的结合了 将检查神经心理学、神经成像和遗传评估， 相对于年轻人(65-75岁)，努力识别最 阿尔茨海默病的显著临床前标志。因为潜在的神经病理 阿尔茨海默病的变化在年轻的老年人和最年长的老年人之间可能不同，次要的 目标将是确定这些独特的模式和贡献 多模式评估对高龄AD的诊断价值。 这项拟议的研究将(A)检验神经心理学、磁力 磁共振(MR)形态测量和遗传易感标记，以便 确定受损的大脑结构和相关过程的模式 与阿尔茨海默病的临床前阶段在最大的老年人；和(B)进行探索性 分析以确定我们的神经心理测量是否与 早期结构异常(如磁共振成像和神经病理学检测到的 高危个体)。提高我们检测AD的能力 临床前将对年龄最大的老年人至关重要，他们是 增长最快的高危人群。此外，更好地理解 与高危人群早期认知变化相关的脑机制 团体将提高我们针对那些将受益最大的人的能力 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.