Predicting cognitive function: Biomarkers and economics in a rural aged cohort

摘要 每九个65岁以上的人中就有一个患有阿尔茨海默病(AD)。在全球范围内，AD和 其他痴呆症患者估计超过6000亿美元。AD的无症状阶段可持续长达20年， 而最有效的治疗将在这段时间内进行。为了有效地解决AD问题，有 迫切需要确定与AD早期阶段相关的生物标记物和风险因素。目标 这项建议的目的是系统地评估正常老年人群的认知功能，并评估 它与视网膜厚度以及社会和经济压力的关系，并量化血管危险因素 缓和这些关联。中心假设是视网膜厚度和压力都能预测认知能力 但这些联系受到体重指数、高血压、吸烟和性别的影响。本研究 将评估100名男性和女性(65岁以上)，这些人是1989年开始的一项研究的子集。我们将测试我们的 有以下三个具体目标的假说：目标1：检验降低视网膜的假说 厚度预示着正常老龄化人群中认知功能的下降。一块60分钟的电池 将使用10种临床神经心理学工具来表征主要认知领域的认知 探测多个大脑区域的区域。一套标准的视网膜神经纤维层厚度测量方法 还将在当地的眼科诊所为每个参与者进行测试，以测试他们预测一系列 个人认知测试。目标2：检验经济和社会压力增加的假设 预测在正常老龄化人口中认知功能下降。我们的标准综合 将再次对每个参与者进行由经济和社会压力指标组成的调查。这个 调查包括对经济状况、情绪困扰和近距离优势或困难的测量。 两性关系。这些经济和社会压力指标将接受测试，以确定它们预测每一套 个人认知测试。目的3.检验血管危险因素和性别适中的假设 认知功能与视网膜神经纤维层厚度(目标1)和 经济和社会压力(目标2)。我们将测试目前的BMI(正常体重与超重/肥胖)， 高血压、吸烟和性别缓和了视网膜厚度、经济压力、 社会压力和认知功能。拟议工作的结果将是对 视网膜厚度、经济和社会压力与认知功能谱之间的关系 老年人群以及性别和血管风险因素如何缓和这些关联。 这项研究具有广泛的公共卫生意义，因为它测试了 适合以最低的成本对数千人进行筛查，以确定最有风险的人 谁将从早期干预措施中获益最多，因为这些干预措施是可用的。

ABSTRACT One in nine individuals older than age 65 has Alzheimer’s disease (AD). Globally the annual cost of AD and other dementias is estimated to exceed $600 billion. The asymptomatic phase of AD can last up to 20 years, and the most effective treatment would be administered during this period. To effectively address AD, there is a critical need to identify biomarkers and risk factors associated with the earliest stages of AD. The goals of this proposal are to systematically evaluate cognitive function in a normative elderly population and assess its association with retinal thickness and social and economic stress, and to quantify how vascular risk factors moderate these associations. The central hypothesis is that both retinal thickness and stress predict cognitive function, but that these associations are moderated by BMI, hypertension, smoking, and gender. This study will assess 100 men and women (65+ years) that are a subset of a study initiated in 1989. We will test our hypothesis with the following three specific aims: Aim 1: To test the hypothesis that reduced retinal thickness predicts decreased cognitive function in a normative aging population. A 60-minute battery of 10 clinical neuropsychological instruments will be used to characterize cognition across the major cognitive domains that probe multiple brain regions. A standard set of retinal nerve fiber layer thickness measurements will also be taken for each participant at a local eye clinic, and tested for their ability to predict a series of individual cognitive tests. Aim 2: To test the hypothesis that increased economic and social stress predicts decreased cognitive function in a normative aging population. Our standard comprehensive survey consisting of economic and social stress indicators will again be measured for each participant. The survey includes measures of economic circumstances, emotional distress, and strengths or difficulties in close relationships. These economic and social stress measures will be tested for their ability to predict each set of individual cognitive tests. Aim 3. To test the hypothesis that vascular risk factors and gender moderate the associations among cognitive function and retinal nerve fiber layer thickness (Aim 1) and economic and social stress (Aim 2). We will test whether current BMI (normal weight vs. overweight/obese), hypertension, smoking, and gender moderate the association between retinal thickness, economic pressure, social stress and cognitive functioning. The outcome of the proposed work will be an understanding of the association between retinal thickness, economic and social stress, and the spectrum of cognitive function in an elderly population and how these associations may be moderated by gender and vascular risk factors. This research has broad public health significance as it tests the effectiveness of assessments that would be appropriate to screen thousands of individuals at minimal cost towards the identification of those most at risk of developing AD, and who would benefit most from early-stage interventions as they become available.