MILD PARKINSONIAN SIGNS AND THE RISK OF ALZHEIMER'S DISEASE

轻度帕金森病症状和阿尔茨海默病风险

• 批准号: 6827805
• 负责人: ELAN D LOUIS
• 金额: $ 12.69万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6827805
• 关键词: Alzheimer' s disease; Parkinson' s disease; aging; apolipoprotein E; basal ganglia; clinical research; dementia; disease /disorder proneness /risk; human subject; longitudinal human study; magnetic resonance imaging; neuroanatomy; sign /symptom

Cardiovascular risk factors (diabetes, hyperinsutinemia, hypertension, hyperlipidemia), cerebrovascular disease, and Alzheimer's disease (AD) are some of the most common problems in the elderly and represent an important public health burden. These problems often coexist, but it is unclear if the relation between these problems is coincidental or causal. Given the public health importance of cardiovascular and cerebrovascular disease as well as AD, it is important to clarify their relation to one another. We propose to conduct longitudinal and cross-sectional studies of cardiovascular and cerebrovascular disease in relation to AD in the WHICAP II cohort, which began recruitment in 1999 of over 2,000 individuals to complement those still followed from WtllCAP I. We will use data from the baseline examinations in 1999 and from subsequent follow-up assessments. In addition, we propose to conduct a brain imaging in 1,000 individuals without dementia from WHICAP II at the second follow-up assessment that will include quantitative assessment of cerebrovascular disease and of imaging biomarkers of AD, namely hippocampal basal metabolism and hippocampal volumes. We also intend to study the association between the recently discovered haplotype of the phosphodiesterase gene (PDE4D) related to stroke in relation to the outcomes in this project. The assessment of cardiovascular risk factors will include the measurement of hyperinsulinemia, a potentially important risk factor for AD at baseline and the second, third, and fourth follow-ups. The following is a brief description of the aims of this project. AIMI: to conduct longitudinal studies of the associations between cardiovascular risk factors (including insulin and c-peptide) and mild cognitive impairment (MCI), AD, and cognitive decline. AIM 2: to conduct longitudinal studies of the associations between clinical stroke, white matter hyperintensities (WMH) and silent infarcts to MCI, AD, and cognitive decline. AIM 3: to conduct cross-sectional studies of the associations between cardiovascular risk factors and measures of hippocampal volume and basal metabolism. AIM 4: to conduct cross-sectional studies of the associations between clinical stroke, WMH and silent infarcts to imaging measures of hippocampal volume and basal metabolism. AIM 5: to conduct longitudinal studies of the associations between the gene encoding PDE4D and MCI, AD, cognitive decline, and measures of hippocampal volume and metabolism. This proposal provides a unique opportunity to study cardiovascular risk factors and eerebrovascular disease with great detail and in relation to several levels of AD related outcomes: imaging biomarkers, clinical precursors, and changes in specific neuropsychologieal profiles. In addition it is likely to advance the clarification of the mechanisms relating cardiovascular risk factors and cerebrovascular disease to MCI, AD and cognitive decline in the elderly.

心血管危险因素（糖尿病、高胰岛素血症、高血压、高脂血症）、脑血管疾病和 阿尔茨海默病（AD）是老年人最常见的问题之一，也是重要的公共卫生负担。这些问题常常同时存在，但尚不清楚这些问题之间的关系是巧合还是因果关系。鉴于心脑血管疾病以及 AD 对公共卫生的重要性，澄清它们之间的相互关系非常重要。我们建议在 WHICAP II 队列中开展与 AD 相关的心脑血管疾病的纵向和横断面研究，该队列于 1999 年开始招募 2,000 多名个体，以补充 WtllCAP I 中仍在跟踪的人员。我们将使用 1999 年基线检查和后续随访评估的数据。此外，我们建议在第二次后续评估中对 1,000 名未患痴呆症的 WHICAP II 个体进行脑成像，其中包括脑血管疾病和 AD 成像生物标志物（即海马基础代谢和海马体积）的定量评估。我们还打算研究最近发现的与中风相关的磷酸二酯酶基因（PDE4D）单倍型与本项目结果之间的关联。心血管危险因素的评估将包括高胰岛素血症的测量，高胰岛素血症是基线和第二次、第三次和第四次随访时 AD 的潜在重要危险因素。以下是该项目目标的简要描述。 AIMI：对心血管危险因素（包括胰岛素和c肽）与轻度认知障碍（MCI）、AD和认知能力下降之间的关联进行纵向研究。目标 2：对临床卒中、白质高信号 (WMH) 和无症状梗塞与 MCI、AD 和认知能力下降之间的关联进行纵向研究。目标 3：对心血管危险因素与海马体积和基础代谢测量之间的关联进行横断面研究。目标 4：对临床卒中、WMH 和无症状梗塞与海马体积和基础代谢的影像学测量之间的关联进行横断面研究。目标 5：对 PDE4D 编码基因与 MCI、AD、认知能力下降以及海马体积和代谢测量之间的关联进行纵向研究。该提案提供了一个独特的学习机会 心血管危险因素和脑血管疾病非常详细，并且与 AD 相关结果的多个水平相关：成像生物标志物、临床前兆和特定神经心理学特征的变化。此外，它还可能促进心血管危险因素和脑血管疾病与 MCI、AD 和老年人认知能力下降的相关机制的阐明。