Brain atrophy, cognitive impairment and Alzheimer's in a low CVD-risk population

项目概要/摘要 关于阿尔茨海默病的发病率、患病率和预测因素知之甚少 (AD)生活在传统的前工业化生活方式的人群中， 人类史前史这些信息对于确定AD是否是现代医学的副产品至关重要。 环境.与年龄匹配的工业化人口相比，Tsimane表现出： 在其一生中动脉粥样硬化进展延迟; B）糖尿病的低患病率， 高血压;和c）几乎没有心房纤颤、中风和心肌梗塞。在 与此同时，Tsimane一生中感染和炎症的几率很高。的 该提案的两个主要目标是：1）测量脑萎缩和认知功能障碍的发生率。 与动脉粥样硬化和炎症负荷相关的下降， apoe基因型 和 学校教育，和2）产生的患病率和发病率的估计全因痴呆症， ad.我们的中心假设是，与西方人相比， 在Tsimane之间，脑萎缩的速度会减慢， 认知障碍我们将检验另一种假设，即感染和炎症是 与大脑萎缩和认知障碍的加速率有关。 为了验证这些预测，我们提出了以下具体目标，利用小组研究 设计，最先进的生物成像技术，以及1，310 Tsimane的代表性样本 40岁以上的成年人，占该年龄段人口的约85%：目标1是 对认知障碍和痴呆进行纵向评估， 评估之间的身体活动;目标2是进行大脑的解剖神经成像 与认知障碍、AD和其他痴呆相关;目的3是研究 脑萎缩、认知障碍、AD和其他痴呆的流行病学。 这项研究是时间敏感的，因为Tsimane正在加速现代化。它 这可能是我们研究AD自然史、脑萎缩和认知功能障碍的最后机会。 在一个过着温饱生活方式的人群中进行大样本的损害，类似于 历史上的人口，心血管疾病的发病率低，传染病的发病率高。多- 学科方法将利用Tsimane 14年的研究，包括数据， 四个动脉床的动脉粥样硬化，心脏病，感染和炎症，体力活动 水平和认知表现。如果脑萎缩和认知障碍的发生率较低 在年老的Tsimane中，尽管他们的全身炎症很高，学校教育有限， 这些发现将对我们了解美国的AD有重要意义。

PROJECT SUMMARY/ABSTRACT Little is known about the incidence, prevalence, and predictors of Alzheimer's disease (AD) in populations living traditional pre-industrial lifestyles similar to those experienced over human pre-history. This information is critical to determine whether AD is a byproduct of modern environments. Compared to age-matched industrialized populations, Tsimane exhibit: a) delayed atherosclerosis progression over their lifetime; b) low prevalence of diabetes and hypertension; and c) a near absence of atrial fibrillation, stroke and myocardial infarctions. At the same time Tsimane experience high rates of infection and inflammation throughout life. The two major goals of this proposal are to: 1) measure rates of cerebral atrophy and cognitive decline in association with atherosclerotic and inflammatory burden, APOE genotype and schooling, and 2) generate estimates of the prevalence and incidence of all-cause dementia and AD. Our central hypothesis is that compared to Westerners, the low rate of atherosclerosis among Tsimane will be paralleled by a slower rate of cerebral atrophy, and reduced age-related cognitive impairment. We will test the alternative hypothesis that infection and inflammation are associated with accelerated rates of cerebral atrophy and cognitive impairment. To test these predictions we propose the following specific aims, utilizing a panel study design, state-of-the-art bioimaging technology, and a representative sample of 1,310 Tsimane adults aged 40+, which comprises ~85% of the population in that age range: Aim 1 is to conduct longitudinal assessment of cognitive impairment and dementia with measurement of physical activity between assessments; Aim 2 is to conduct anatomic neuroimaging of the brain related to cognitive impairment, AD and other dementias; and Aim 3 is to investigate the epidemiology of brain atrophy, cognitive impairment, AD and other dementias. This research is time-sensitive, as Tsimane are modernizing at an accelerating rate. It may be our last chance to study the natural history of AD, cerebral atrophy and cognitive impairment with a large sample in a population living a subsistence lifestyle, similar to pre- historic populations, with low rates of CVD and high rates of infectious disease. The multi- disciplinary approach will leverage 14 years of Tsimane research, including data on atherosclerosis in four arterial beds, heart disease, infection and inflammation, physical activity level, and cognitive performance. If rates of cerebral atrophy and cognitive impairment are lower among aging Tsimane, despite their high systemic inflammation and limited schooling, those findings will have important implications for our understanding of AD in the US.