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

心血管疾病低风险人群中的脑萎缩、认知障碍和阿尔茨海默病

• 批准号: 9552951
• 负责人: CALEB E FINCH
• 金额: $ 13.59万
• 依托单位: CHAPMAN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9552951
• 关键词: Accelerometer; Activities of Daily Living; Adult; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Anatomy; Atherosclerosis; Atrial Fibrillation; Atrophic; Beds; Behavioral; Biomedical Research; Blood; Bolivian; Brain; Calcified; Cardiovascular Diseases; Cardiovascular Physiology; Cerebrospinal Fluid; Classification; Cognitive; Collection; Communicable Diseases; Data; Dementia; Diabetes Mellitus; Diagnostic; Disease; Environment; Epidemiology; Europe; Exhibits; Family member; Genetic; Genotype; Goals; Heart Diseases; Hemorrhage; Horns; Human; Hypertension; Image Analysis; Impaired cognition; Impairment; Incidence; Individual; Industrialization; Infarction; Infection; Inflammation; Inflammatory; Interview; Investigation; Lesion; Life; Life Style; Light; Lobe; Low Prevalence; Measurement; Measures; Medial; Medical; Medical History; Memory; Modernization; Myocardial Infarction; Native Americans; Natural History; Neurologic; Neurologist; Participant; Physical Function; Physical activity; Physicians; Population; Population Heterogeneity; Prevalence; Psychologist; Radial; Radiology Specialty; Recording of previous events; Research; Research Design; Resolution; Role; Sampling; Scanning; Schools; Stroke; Technology; Temporal Lobe; Testing; Thick; Time; Vascular Diseases; Ventricular; Video Recording; Width; X-Ray Computed Tomography; aged; bioimaging; brain tissue; calcification; cardiovascular disorder risk; cerebral atrophy; cognitive function; cognitive performance; cognitive reserve; cognitive testing; experience; gray matter; indexing; insight; interdisciplinary approach; multidisciplinary; neuroimaging; novel; radiologist; rate of change; regional atrophy; resilience

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.

项目摘要/摘要 关于阿尔茨海默氏病的发病率，患病率和预测因素知之甚少 （AD）在人口中生活的传统前工业前生活方式类似于经历的生活方式 人类的史前。此信息对于确定AD是否是现代的副产品至关重要 环境。与年龄匹配的工业化人群相比，TSIMANE展示：A） 延迟了动脉粥样硬化的一生发展； b）糖尿病患病率低和 高血压; c）几乎没有心房颤动，中风和心肌梗塞。在 同时，Tsimane一生都经历了高感染和炎症的速度。这 该提案的两个主要目标是：1）脑萎缩和认知的衡量率 与动脉粥样硬化和炎症负担相关的下降， APOE基因型 和 教育，以及2）产生全因痴呆症的患病率和发病率的估计 广告。我们的中心假设是与西方人相比，动脉粥样硬化率低 在tsimane中，将与大脑萎缩速度较慢，并降低与年龄有关 认知障碍。我们将测试替代假设，即感染和炎症是 与大脑萎缩和认知障碍的加速率有关。 为了测试这些预测，我们提出以下特定目标，利用小组研究 设计，最先进的生物成像技术和1,310个Tsimane的代表性样本 40岁以上的成年人，占该年龄段的约85％的人口：目标1是 通过测量 评估之间的体育活动； AIM 2是进行大脑的解剖神经影像学 与认知障碍，AD和其他痴呆症有关；目标3是调查 大脑萎缩，认知障碍，AD和其他痴呆症的流行病学。 这项研究对时间敏感，因为Tsimane正在以加速速度进行现代化。它 可能是我们研究AD，大脑萎缩和认知的自然历史的最后机会 在生活中生活方式的人群中有大量样本的损害，类似于前 历史悠久的人群，CVD率低，传染病率很高。多 纪律方法将利用14年的TSIMANE研究，包括有关 四个动脉床，心脏病，感染和炎症的动脉粥样硬化，体育活动 水平和认知表现。如果脑萎缩和认知障碍率较低 在老化的tsimane中，尽管有严重的全身性炎症和有限的教育，但 调查结果将对我们对美国的AD理解具有重要意义。