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: 9217135
• 负责人: CALEB E FINCH
• 金额: $ 19.26万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 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 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9217135
• 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.

项目概要/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）在传统的工业化前生活方式的人群中，与过去经历过的人群相似 人类史前时期。这些信息对于确定 AD 是否是现代社会的副产品至关重要。 环境。与年龄匹配的工业化人口相比，Tsimane 表现出：a) 在一生中延缓动脉粥样硬化的进展； b) 糖尿病患病率低 高血压; c) 几乎没有心房颤动、中风和心肌梗塞。在 与此同时，提斯曼一生中感染和炎症的发生率很高。这 该提案的两个主要目标是：1）测量脑萎缩和认知能力的发生率 与动脉粥样硬化和炎症负担相关的下降， APOE基因型 和 学校教育，2) 对全因痴呆的患病率和发病率进行估计， 广告。我们的中心假设是，与西方人相比，动脉粥样硬化发生率较低 Tsimane 中的脑萎缩速度会减慢，并且与年龄相关的疾病也会减少 认知障碍。我们将检验另一种假设：感染和炎症是 与脑萎缩和认知障碍的加速发生有关。 为了测试这些预测，我们利用小组研究提出以下具体目标 设计、最先进的生物成像技术以及 1,310 个 Tsimane 的代表性样本 40 岁以上的成年人，约占该年龄段人口的 85%：目标 1 是 对认知障碍和痴呆症进行纵向评估，测量 评估之间的体力活动；目标 2 是进行大脑的解剖神经成像 与认知障碍、AD 和其他痴呆症相关；目标 3 是调查 脑萎缩、认知障碍、AD 和其他痴呆症的流行病学。 这项研究具有时间敏感性，因为提斯曼正在加速现代化。它 可能是我们研究 AD、脑萎缩和认知自然史的最后机会 过着自给自足生活方式的人群中的大样本的损害，类似于前 历史悠久的人群，心血管疾病发病率低，传染病发病率高。多 学科方法将利用 Tsimane 14 年的研究，包括 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 在老龄化的 Tsimane 中，尽管全身炎症严重且受教育程度有限，但 研究结果将对我们对美国 AD 的理解产生重要影响。