Brain pathologies, reserve and cognition in aging and dementia

描述（由申请人提供）：本研究旨在更好地了解大脑病理学与衰老和痴呆症中认知功能的关系。个体的心智能力随年龄的变化有着惊人的差异;有些人变化很小，如果有的话，其他人则有重大的，使人衰弱的下降。为什么，是未知的。一种解释是大脑病理学，如阿尔茨海默病（AD）和梗塞（中风）。AD是痴呆症的主要原因，发展缓慢，实际上可能在明显症状出现之前开始就出现在大脑中。某些程度的AD变化和血管疾病存在于大多数非常老的人中。然而，将病理学与认知功能联系起来的研究通常无法解释大部分差异。一个潜在的原因可能是病理学测量不充分。另一种可能是，大脑病理学，无论测量得多么精确，都永远无法充分解释认知丧失，因为有一些因素会减轻病理学的影响。这种解释是在“储备”的概念中发展起来的，这种概念认为一些先天和后天的特征形成了一种缓冲，提供了一定程度的保护，免受大脑病理学的影响。这是一个对公共卫生具有巨大潜在重要性的概念，因为它表明，在这些因素可以改变的程度上，人们可以采取措施，充分保护自己免受一系列常见和使人衰弱的大脑疾病的影响。我们建议测量大脑病理学比以前做的更好，对认知功能的病理学的影响建模，然后使用这些改进的模型，以更好地了解储备的作用，作为一个调解人的影响，大脑病理学。以前研究的一个主要障碍是无法测量生活中阿尔茨海默病的存在。最近开发的β淀粉样蛋白（一种在AD中至关重要的异常蛋白质片段）示踪剂改变了这一点。我们将使用PET和示踪剂匹兹堡B（PI B）来量化脑淀粉样蛋白的程度，并将获得结构性脑病理（萎缩、梗死和白色病变）的MRI测量结果，从而模拟两种主要年龄相关病理对认知功能的联合影响。然后，我们将利用这一努力的结果来研究储备。我们将在一个种族多样的样本中进行研究，该样本具有广泛的教育背景，这通常被认为是储备的标志，并将使用具有上级测量特性的神经心理学测试。因此，我们将能够比以往任何时候都更好地描述生活中的大脑病理水平，并将这些发现与认知功能联系起来，这些认知功能在广泛的假定储备中得到了很好的测量。公共卫生相关性：该项目侧重于病理学如何影响心理功能，以及“储备”可能缓冲这些影响的概念。储备是一个对公共健康具有巨大潜在重要性的概念，因为储备是基于一生的经验，例如认知刺激活动，它表明人们可以采取措施保护自己免受广泛的常见和衰弱的大脑疾病的影响。

DESCRIPTION (provided by applicant): This study seeks to better understand the relationship of brain pathology to cognitive function in aging and dementia. There is striking variability in how individuals' mental abilities change with age; some people change little, if any, others have major, debilitating drops. Why, is unknown. One explanation is brain pathologies such as Alzheimer's disease (AD) and infarcts (strokes). AD, which is the predominant cause of dementia, develops slowly and may actually begin to appear in brain decades before overt symptoms are appear. Some degree of AD changes and vascular disease is present in most very old people. However, studies that relate pathology to cognitive function generally fail to explain most of the variance. One potential reason may be that the pathology has been inadequately measured. Alternatively, it may be that brain pathology, no matter how exquisitely measured, will never explain cognitive losses adequately because of factors that moderate the impact of pathology. This explanation has been developed in the concept of "reserve", the idea that some set of innate and acquired characteristics form a buffer that provides a degree of protection against the impact of brain pathology. It is a concept that holds enormous potential importance for public health because it suggests that, to the degree these factors are modifiable, people can take steps to substantially protect themselves against a broad array of common and debilitating brain conditions. We propose to measure cerebral pathology better than has been done previously, to model the effects of pathology on cognitive function, and then to use these improved models to better understand the role of reserve as a moderator of the impact of brain pathology. A major barrier to previous investigation has been the inability to measure the presence of Alzheimer's disease during life. The recent development of tracers for beta amyloid (an abnormal protein fragment critical in AD) changes this. We will use PET with the tracer Pittsburgh B (PIB) to quantify the extent of cerebral amyloid, and will obtain MRI measures of structural brain pathology (atrophy, infarcts and white matter lesions) and thus model the joint effects of the two major age- associated pathologies on cognitive function. We will then use the results of that effort to study reserve. We will do so in an ethnically diverse sample that has a wide range of education, which is generally thought to be a marker for reserve, and will use neuropsychological tests with superior measurement properties. Thus we will be able to characterize brain pathology levels during life better than has ever been done before and relate those findings to cognitive function that is measured especially well across a broad spectrum of putative reserve. PUBLIC HEALTH RELEVANCE: This project focuses on how pathology affects mental function and on the notion that "reserve" may buffer these effects. Reserve is a concept that holds enormous potential importance for public health because, to the extent reserve is based in lifetime experiences-cognitively stimulating activities, for example-- it suggests that people can take steps to protect themselves against a broad array of common and debilitating brain disorders.