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: 10096721
• 负责人: CALEB E FINCH
• 金额: $ 38.23万
• 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/10096721
• 关键词: Accelerometer; Activities of Daily Living; Adult; Agatston Score; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Anatomy; Atherosclerosis; Atrial Fibrillation; Atrophic; Beds; Behavioral; Biomedical Research; Blood; Bolivian; Brain; 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; 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; infection rate; 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.

项目总结/文摘