Longitudinal Study of MRI, Clinical, and Genetic Biomarkers of Cognitive Impairment and Alzheimer's Disease in Elderly American Indians

美国印第安人老年认知障碍和阿尔茨海默病的 MRI、临床和遗传生物标志物的纵向研究

• 批准号: 10164621
• 负责人: DEDRA S BUCHWALD
• 金额: $ 36.48万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10164621
• 关键词: 3-Dimensional; Activities of Daily Living; Address; Adverse effects; Advisory Committees; Affect; Alaska Native; Alleles; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer' s disease risk; Alzheimer’s disease biomarker; American Indians; Amyloid Proteins; Apolipoprotein E; Asians; Atrophic; Behavioral; Biological Markers; Brain; Brain region; Cause of Death; Cerebrovascular Disorders; Cerebrovascular Trauma; Cessation of life; Choctaw; Clinical; Clinical Data; Cognitive; Communities; Computer software; Data; Data Collection; Dementia; Detection; Development; Disease; Dose; Elderly; Elements; Enrollment; Ethnic Origin; Exhibits; Genes; Genetic; Genetic Markers; Genetic Risk; Health Personnel; Heart; Hippocampus (Brain); Hyperlipidemia; Hypertension; Impaired cognition; Latino; Link; Longitudinal Studies; Magnetic Resonance Imaging; Maps; Measures; Medial; National Institute on Aging; Neurodegenerative Disorders; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Parietal; Participant; Pathologic; Patients; Pattern; Phase; Physical Function; Population; Prevalence; Prevention; Process; Prognosis; Protocols documentation; Race; Reporting; Research; Risk Assessment; Risk Factors; Sampling; Sampling Studies; Structure; Synapses; Therapeutic Intervention; Time; Tribes; Variant; Work; abeta accumulation; aged; base; cerebral atrophy; cingulate cortex; clinical biomarkers; clinical risk; cognitive function; cognitive testing; cohort; disorder risk; early experience; early onset; effective therapy; ethnic minority population; follow-up; functional loss; functional outcomes; health disparity; high risk; imaging biomarker; improved; low socioeconomic status; magnetic resonance imaging biomarker; member; mild cognitive impairment; neuron loss; northern plains; patient subsets; performance tests; population based; pre-clinical; precision medicine; predict clinical outcome; racial minority; recruit; regional atrophy; response; sociodemographics; tailored health care; tau aggregation; treatment response

ABSTRACT Precision medicine is the emerging practice of delivering healthcare tailored to patients on the basis of specific factors that contribute to disease risk, prognosis, and treatment response. The prospect of applying precision medicine to neurodegenerative disorders such as Alzheimer's disease (AD) is especially promising. Genetic markers, most notably variation in the apolipoprotein E gene, and measures of vascular brain injury and cerebral atrophy assessed by MRI have emerged as useful biomarkers of preclinical AD and risk of clinical disease. More than 3 million American Indians (AIs), Alaska Natives, Blacks, Latinos, and Asians suffer from AD, and experience earlier onset of cognitive impairment and AD than Whites. The few studies of AD in AIs are limited by small, single-community samples. We will use data from the Strong Heart Study (SHS) and ancillary Cerebrovascular Disease and its Consequences in American Indians (CDCAI) study to evaluate cognitive function, AD risk factors, and MRI-defined biomarkers of AD in older AIs. The SHS collected data from 4,549 AIs aged 45-74 years from tribes in the Southwest, Southern Plains, and Northern Plains in 3 phases from 1988 to 2000. The CDCAI study assessed cognitive function and MRI-defined vascular brain injury in 818 surviving SHS participants in 2010-2013 and is reassessing surviving participants with the same MRI and cognitive tests. We will use statistical mapping software to reprocess MRIs from both the original and follow-up CDCAI examinations and will create 3-dimensional brain maps for older AIs. We will quantify cerebral atrophy in brain regions preferentially affected by AD such as the hippocampus, parahippocampal, medial temporal, and parietal regions, and the posterior cingulate cortex. We will compare structural patterns on MRI at both CDCAI time points with normative data on AD patients from other populations. We will define probable AD cases by assessing change in MRI-defined loss in regions selectively affected by AD, in combination with AD-related cognitive test performance and activities of daily living; and examine associations of probable AD with risk factors and functional outcomes. Our Specific Aims are to: 1) establish AI-specific normative values of MRI atrophy in brain regions selectively affected by AD, and evaluate AD-related regional atrophy in combination with cognitive and behavioral changes to calculate prevalence of probable AD; 2) use genetic, sociodemographic, and clinical data on risk factors for AD observed in other populations to identify correlates of probable AD in elderly AIs; and 3) estimate associations of MRI markers of probable AD with measures of cognitive and physical function, independent of the effects of vascular brain injury. AD is the leading cause of dementia and of death in the US. The CDCAI sample is the only population-based cohort of AIs with MRI data and genetic biomarkers relevant to AD. We will leverage these unique data to address key elements of PM, namely, risk assessment and detection of preclinical pathophysiologic processes of AD among AIs.

摘要