OLFACTORY IMPAIRMENT IN OFFSPRING STUDY OF RACIAL DISPARITIES IN ALZHEIMER'S DISEASE

阿尔茨海默病种族差异的后代嗅觉障碍研究

• 批准号: 10439609
• 负责人: DAVANGERE P DEVANAND
• 金额: $ 35.32万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10439609
• 关键词: African American population; Age; Aging; Alleles; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Anterior; Apolipoprotein E; Biological Factors; Biological Markers; Brain scan; Clinical; Cognitive; Cross-Sectional Studies; Data; Dementia; Diagnosis; Elderly; Ethnic Origin; Evaluation; Family history of; First Degree Relative; Funding; Funding Agency; Future; Gender; Goals; Health; Hippocampus (Brain); Hispanic Populations; Impaired cognition; Impairment; Individual; Infrastructure; Institutes; Intervention; Knowledge; Magnetic Resonance Imaging; Medial; Medical; Memory impairment; Nerve Degeneration; Neurofibrillary Tangles; Neuropsychology; Odors; Olfactory dysfunction; Outcome; Parents; Parietal; Participant; Pathway interactions; Pennsylvania; Performance; Positron-Emission Tomography; Procedures; Race; Reporting; Resolution; Smell Perception; Standardization; Sum; Testing; Thinness; Universities; Washington; Work; base; brain magnetic resonance imaging; caucasian American; cerebrovascular pathology; cognitive ability; cognitive testing; cohort; comorbidity; cost effective; early detection biomarkers; ethnic difference; follow-up; high risk; indexing; middle age; mild cognitive impairment; mortality; multi-ethnic; offspring; olfactory bulb; parent project; performance tests; pre-clinical; prevent; racial and ethnic disparities; racial disparity; radiotracer; social factors; uptake

We plan to test the 12-item BSIT, a short, standardized, cross-culturally validated subset of the 40-item University of Pennsylvania Smell Identification Test (UPSIT), in an add-on study to the recently funded project “Offspring study of mechanisms for racial disparities in Alzheimer's disease” (RF1 AG054070). Middle-aged offspring (age 40-64) of parents who participated in the Washington Heights Inwood Columbia Aging Project (WHICAP) are being studied with clinical and neuropsychological evaluation (n=3,000), high-resolution structural MRI (n=1,000), and Aβ PET (n=150). In the years 2004-2010, over one-third (n=1,369) of the intensively studied parent cohort had odor identification testing with the full 40-item UPSIT. Odor identification impairment distinguishes dementia from cognitively intact controls, predicts transition from mild cognitive impairment (MCI) to dementia, and predicts cognitive decline in older adults without dementia better than episodic verbal memory deficits. Further, odor identification impairment has been associated with increased mortality even after controlling for dementia and medical comorbidity in older adults, and in this offspring study, mortality will become an important outcome if longitudinal follow-up is instituted eventually. In the proposed cross-sectional study, we hypothesize that in the cohort of 3,000 offspring, lower BSIT scores (impaired odor identification) will be associated with increased age and the apolipoprotein E ε4 allele, and correlate with impaired cognitive ability in Whites (increased incipient AD pathology) to a greater extent than in African Americans or Hispanics (increased incipient cerebrovascular pathology). In the 1,000 offspring that get MRI brain scans, we expect that lower BSIT scores will be associated with smaller hippocampal volume and cortical thinning in Whites but not African Americans or Hispanics. In the 150 offspring that get amyloid PET scans, lower BSIT scores are anticipated to be associated with greater amyloid uptake among Whites, but not among African Americans or Hispanics. We will also evaluate BSIT in the offspring in relation to parental BSIT performance and risk of AD in the parents. We have begun pilot work in administering the BSIT to the first 300 offspring being studied, and expect to be able to assess all study participants with the BSIT, without loss of any BSIT data, if this proposal is funded. Our overarching goal is to identify priority biological or social factors for intervention during the preclinical stage of AD, and determine whether strategies to prevent AD should differ across race/ethnicity. Adding odor identification testing furthers these goals in the existing project and allows for the testing of specific hypotheses that will enhance our understanding of the associations and potential utility of this inexpensive early biomarker of AD.

我们计划测试40个项目的12项BSIT，这是一个简短的，标准化的，跨文化验证的子集 宾夕法尼亚大学气味识别测试（UPSIT），在最近资助的项目的一项附加研究中 “阿尔茨海默氏病种族差异机制的后代研究”（RF1 AG054070）。中年 参加华盛顿高地的父母的后代（40-64岁） （WHICAP）正在研究临床和神经心理学评估（n = 3,000），高分辨率 结构MRI（n = 1,000）和AβPET（n = 150）。在2004 - 2010年，超过三分之一（n = 1,369） 经过深入研究的家长队列具有与完整的40个项目UPSIT的气味识别测试。 气味识别障碍与认知完整控制的痴呆症不同，预测过渡 从轻度认知障碍（MCI）到痴呆，预测老年人的认知能力下降 痴呆症比情节性言语记忆缺陷更好。此外，气味识别障碍已经 即使在控制老年人的痴呆症和医疗合并症之后，与死亡率提高有关， 在这项后代研究中，如果进行纵向随访，死亡率将成为重要的结果 最终。在拟议的横断面研究中，我们假设在3,000个后代的队列中，较低 BSIT评分（气味鉴定受损）将与年龄增加和载脂蛋白Eε4有关 等位基因，与白人的认知能力受损（增加的AD病理学）与更大的认知能力相关 范围比非洲裔美国人或西班牙裔（增加起始脑血管病理学）。在1,000中 获得MRI脑扫描的后代，我们预计BSIT分数较低会与较小 海马体积和皮质稀疏在白人中，而不是非裔美国人或西班牙裔。在150中 获得淀粉样蛋白PET扫描的后代，预计BSIT分数较低与较大的淀粉样蛋白有关 白人的吸收，但不在非裔美国人或西班牙裔中。我们还将评估BSIT 与父母BSIT表现和父母的AD风险有关的后代。我们已经开始进行飞行员的工作 对研究的前300个后代进行管理，并希望能够评估所有研究 如果此提案获得资助，则具有BSIT的参与者，不会丢失任何BSIT数据。我们的总体目标是 在AD的临床前阶段确定优先生物或社会因素进行干预，并确定 防止广告的策略是否应在种族/种族中有所不同。添加气味识别测试进一步 现有项目中的这些目标，并允许测试特定的假设，以增强我们的 理解这种廉价的AD早期生物标志物的关联和潜在效用。