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12项BSIT，这是40项BSIT的一个简短的、标准化的、跨文化验证的子集。 宾夕法尼亚大学的身份识别测试（UPSIT），在最近资助的项目的附加研究 “阿尔茨海默病种族差异机制的后代研究”（RF 1 AG 054070）。中年 参加华盛顿高地因伍德哥伦比亚老龄化项目的父母的后代（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Aβ PET（n=150）。在2004-2010年期间，超过三分之一（n= 1，369）的 深入研究的父母队列进行气味识别测试与完整的40项UPSIT。 气味识别障碍区分痴呆与认知完整的对照，预测过渡 从轻度认知障碍（MCI）到痴呆，并预测老年人的认知能力下降， 痴呆症比偶发性言语记忆缺陷更好。此外，气味识别障碍已经被 即使在控制老年人痴呆和医学合并症后， 在这项后代研究中，如果建立纵向随访，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3,000名后代的队列中， BSIT评分（气味识别受损）将与年龄增加和载脂蛋白E ε4 等位基因，并与白人认知能力受损（早期AD病理学增加）相关， 程度高于非洲裔美国人或西班牙裔美国人（早期脑血管病变增加）。在1000 接受MRI脑部扫描的后代，我们预计较低的BSIT分数将与较小的 海马体积和皮质变薄，但非裔美国人或西班牙裔美国人没有。在150 接受淀粉样蛋白PET扫描的后代，较低的BSIT评分预计与较大的淀粉样蛋白相关。 白人中的吸收率，但非裔美国人或西班牙裔中的吸收率却没有。我们还将评估BSIT在 后代与父母BSIT表现和父母AD风险的关系。我们已经开始试点工作， 对前300名正在研究的后代进行BSIT，并期望能够评估所有研究 参与者与BSIT，而不会丢失任何BSIT数据，如果该提案得到资助。我们的首要目标是 确定在AD临床前阶段进行干预的优先生物或社会因素，并确定 预防AD的策略是否应因种族/民族而异。添加气味识别测试进一步 这些目标在现有的项目，并允许测试的具体假设，将提高我们的 了解这种廉价的AD早期生物标志物的相关性和潜在效用。