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衰老和痴呆症中大脑病理学与认知功能的关系。随着年龄的增长，个体的心理能力发生了显着的变化。有些人的变化很小（如果有的话），而另一些人的变化则很大，使人衰弱。为什么，不得而知。一种解释是阿尔茨海默病 (AD) 和梗塞（中风）等脑部病变。 AD 是痴呆症的主要原因，它发展缓慢，实际上可能在出现明显症状之前几十年就开始出现在大脑中。大多数老年人都存在一定程度的 AD 变化和血管疾病。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。或者，大脑病理学无论测量得多么精确，都可能永远无法充分解释认知丧失，因为存在调节病理学影响的因素。这种解释是在“储备”概念中发展起来的，即一些先天和后天的特征形成缓冲，提供一定程度的保护，防止大脑病理的影响。这个概念对公共卫生具有巨大的潜在重要性，因为它表明，在这些因素可以改变的范围内，人们可以采取措施来充分保护自己免受各种常见和衰弱性大脑疾病的影响。我们建议比以前更好地测量脑病理学，模拟病理学对认知功能的影响，然后使用这些改进的模型更好地理解储备作为脑病理学影响的调节器的作用。先前研究的一个主要障碍是无法测量一生中阿尔茨海默病的存在情况。最近开发的β淀粉样蛋白（一种对AD至关重要的异常蛋白片段）示踪剂改变了这一点。我们将使用 PET 和示踪剂 Pittsburgh B (PIB) 来量化脑淀粉样蛋白的程度，并获得结构性脑病理学（萎缩、梗死和白质病变）的 MRI 测量结果，从而模拟这两种主要的与年龄相关的病理学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。我们将在具有广泛教育背景的种族多元化样本中进行此操作，这通常被认为是储备的标志，并将使用具有卓越测量特性的神经心理学测试。因此，我们将能够比以前更好地描述一生中的大脑病理水平，并将这些发现与认知功能联系起来，认知功能在广泛的假定储备中得到了特别好的测量。公共健康相关性：该项目重点关注病理学如何影响心理功能以及“储备”可以缓冲这些影响的概念。储备是一个对公共卫生具有巨大潜在重要性的概念，因为储备是基于一生经历（例如认知刺激活动）的，它表明人们可以采取措施保护自己免受各种常见和使人衰弱的大脑疾病的侵害。

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.