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

项目摘要/摘要 人们对阿尔茨海默病的发病率、患病率和预测因素知之甚少 (AD)生活在传统的工业化前生活方式的人口中， 人类的史前时期。这一信息对于确定AD是否是现代 环境。与年龄匹配的工业化人口相比，Tsimane展示了：a) 延缓他们一生中的动脉粥样硬化进展；b)糖尿病的低患病率和 高血压；(C)几乎没有心房颤动、中风和心肌梗死。在… 与此同时，齐曼在一生中经历了高感染率和炎症。这个 这项建议的两个主要目标是：1)测量大脑萎缩和认知能力的比率 与动脉粥样硬化和炎症负担相关的下降， 载脂蛋白E基因 和 学校教育，以及2)估计各种原因引起的痴呆症的患病率和发病率，以及 广告。我们的中心假设是，与西方人相比，动脉粥样硬化的低发生率 在齐曼人中，大脑萎缩的速度较慢，与年龄相关的减少也会伴随而来 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1310只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 对认知障碍和痴呆症进行纵向评估 两次评估之间的体力活动；目标2是对大脑进行解剖神经成像 与认知障碍、阿尔茨海默病和其他痴呆症有关；目标3是调查 脑萎缩、认知障碍、阿尔茨海默病和其他痴呆的流行病学。 这项研究是对时间敏感的，因为齐曼正在加速现代化。它 可能是我们研究阿尔茨海默病、脑萎缩和认知障碍自然病史的最后机会 在生活在自给自足生活方式的人群中，具有大样本的损害，类似于 历史悠久的人口，心血管疾病发病率低，传染病发病率高。多种多样- 纪律方法将利用Tsimane 14年的研究，包括以下数据 四条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。如果大脑萎缩和认知障碍的比率较低 在年迈的齐曼人中，尽管他们的全身炎症程度很高，受教育程度有限，但那些 这一发现将对我们理解美国的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.