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: 9762806
• 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 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9762806
• 关键词: African American; Age; Aging; Alleles; Alzheimer' s Disease; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Anterior; Apolipoprotein E; Biological; Biological Factors; Biological Markers; Brain scan; Clinical; Cognitive; Comorbidity; 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); Hispanics; Impaired cognition; Impairment; Individual; Infrastructure; Institutes; Intervention; Knowledge; Magnetic Resonance Imaging; Medial; Medical; Memory impairment; Nerve Degeneration; Neurofibrillary Tangles; Neuropsychology; Odors; Outcome; Parents; Parietal; Participant; Pathology; Pathway interactions; Pennsylvania; Performance; Positron-Emission Tomography; Procedures; Race; Reporting; Resolution; Smell Perception; Standardization; Structure; Sum; Testing; Thinness; Universities; Washington; Work; base; caucasian American; cerebrovascular pathology; cognitive ability; cognitive testing; cohort; cost effective; early detection biomarkers; ethnic difference; follow-up; high risk; indexing; middle age; mild cognitive impairment; mortality; offspring; olfactory bulb; parent project; performance tests; pre-clinical; prevent; racial and ethnic disparities; racial disparity; radiotracer; social; 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12项BSIT，这是40项BSIT的一个简短、标准化、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附加研究中 “阿尔茨海默病种族差异机制的后代研究”(RF1 AG054070)。中年 参加华盛顿高地因伍德哥伦比亚老龄项目的父母的子女(40岁-) (WHICAP)正在进行临床和神经心理学评估(n=3,000)，高分辨率 结构磁共振成像1,000例，Aβ正电子发射计算机体层摄影术15 0例。在2004-2010年期间，超过三分之一(n=1,369)的 经过深入研究的父母队列用完整的40项UPSIT进行了气味识别测试。 气味识别障碍区分痴呆症和认知功能正常的对照组，预测过渡 从轻度认知障碍(MCI)到痴呆症，并预测没有 痴呆症比间歇性言语记忆障碍更好。此外，气味识别损害已经被 即使在控制了老年人的痴呆症和医学合并症后，死亡率也会增加， 在这项子代研究中，如果进行纵向随访，死亡率将成为一个重要的结果 最终会的。在拟议的横断面研究中，我们假设在3000名后代的队列中， BSIT评分(气味识别受损)将与年龄和载脂蛋白Eε4的增加有关 等位基因，并与白人认知能力受损(AD早期病理增加)相关性更大 比非洲裔美国人或西班牙裔美国人更严重(早期脑血管病变增加)。在1000个人中 接受核磁共振脑部扫描的孩子，我们预计BSIT得分较低的人将与较小的孩子相关 白人的海马体体积和皮质变薄，但非裔美国人和西班牙裔美国人没有。在150人中 接受淀粉样蛋白PET扫描的子女，BSIT评分较低预计与淀粉样蛋白较大有关 在白人中接受，但在非裔美国人或西班牙裔美国人中不是。我们还将评估BSIT在 子代与父母的BSIT表现和AD风险的关系。我们已经开始了在 对被研究的第一批300名子女实施BSIT，并期望能够评估所有研究 BSIT的参与者，如果这项提案得到资助，不会丢失任何BSIT数据。我们的首要目标是 在阿尔茨海默病的临床前阶段确定优先干预的生物学或社会因素，并确定 预防阿尔茨海默病的策略是否应该因种族/民族而异。添加气味识别测试剂 现有项目中的这些目标，并允许测试特定的假设，这些假设将增强我们的 了解这一廉价的AD早期生物标记物的相关性和潜在用途。