Multidimensional Assessment of Brain Health as A Marker of Dementia Risk and Resilience

大脑健康的多维评估作为痴呆症风险和复原力的标志

• 批准号: 10451624
• 负责人: Amir H Kashani
• 金额: $ 192.46万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10451624
• 关键词: African American population; Age; Aging; Alzheimer' s Disease; Alzheimer’s disease biomarker; Amyloid; Anisotropy; Auditory; Autopsy; Behavioral; Biological Markers; Biology; Blood; Blood Glucose; Blood Vessels; Brain; Brain Pathology; Brain imaging; Brain-Derived Neurotrophic Factor; Chronology; Clinic; Clinical; Clinical Trials; Cognition; Cognitive; Cohort Studies; DNA Methylation; Data; Dementia; Development; Diet; Diffuse; Dimensions; Disease; Early Diagnosis; Education; Educational workshop; Elderly; Epigenetic Process; Equilibrium; European; Evaluation; Event; Fracture; Framingham Heart Study; Funding; Gait; Genetic; Genomics; Grant; Hearing; Heart; Hippocampus (Brain); Hispanic; Hispanic ancestry; IGF1 gene; Image; Impaired cognition; Individual; Injury; Italy; Life; Life Style; Lipids; Magnetic Resonance Imaging; Marital Status; Measurement; Measures; Memory; Metabolic; Mexican Americans; Motor; Neurologic; Neurological status; Occupations; Osteoporosis; Outcome; Participant; Pathogenesis; Pathology; Pattern; Perception; Persons; Phase; Phenotype; Physical activity; Play; Population; Positron-Emission Tomography; Proteins; Proteomics; Research; Resistance; Retina; Risk; Risk Factors; Risk Marker; Role; Sampling; Sensory; Skeleton; Sleep; Smell Perception; Social Network; Stroke; Structure; Tactile; Testing; Texas; Therapeutic Intervention; Touch sensation; Transient Ischemic Attack; Vascular Endothelial Growth Factors; Vision; Visual; Water; White Matter Hyperintensity; aging brain; base; blood-based biomarker; bone mass; brain health; brain magnetic resonance imaging; cerebral atrophy; circulating biomarkers; cognitive function; cognitive reserve; cognitive testing; cohort; dementia risk; early detection biomarkers; endophenotype; epidemiology study; executive function; experience; follow-up; genetic predictors; genetic variant; gray matter; human old age (65+); indexing; insight; mild cognitive impairment; mortality; motor disorder; nervous system disorder; normal aging; offspring; outcome prediction; personalized risk prediction; pre-clinical; predictive marker; prevent; resilience; risk stratification; sensorimotor system; social; stroke outcome; sulfated glycoprotein 2; tau Proteins; vascular cognitive impairment and dementia; vascular factor

Persons with similar amount of Alzheimer's or vascular brain pathology on imaging or autopsy may have had very different clinical and functional experiences during life. One possible reason could be varying amounts of cognitive reserve, or brain health which protects them from clinical manifestations. Thus, just as a healthy bone mass through life protects from osteoporosis and fractures, having a healthy brain at age 65-85, a consequence of genetic propensity and lifelong environmental, behavioral and disease-related factors, will protect from development of AD, dementia and stroke. How do we define a healthy brain phenotype? Brain health is typically characterized using quantitative measurements MRI and PET brain imaging, cognitive testing and at autopsy. Other dimensions of brain health, often altered in aging, prior to cognition, include retinal structure and vasculature, olfactory, visual, auditory, tactile and sensory perception and motor abilities. Sensory-motor measures are promising early biomarkers of AD and may play a causal role in the development or progression of dementia. An NIA workshop titled “Sensory and Motor dysfunctions in Aging and AD” concluded that comprehensive sensory motor testing would provide key mechanistic insights into AD pathogenesis. We propose to incorporate multiple such sensory-motor measures in the recently funded 10th exam for 1874 Framingham Heart Study (FHS) Offspring and Omni 1 cohort participants and develop a multi-dimensional sensory-motor Brain Health Index (smBHI), as well as a composite BHI (cBHI) that additionally includes brain MRI and cognitive measures. Predictors and outcomes related to the BHI will be identified using the extensive profiling of risk factors, repeated measures of brain structure and function, information on MCI, dementia (AD and VCID) and stroke outcomes already available in FHS. It will be validated in 3 additional population samples, 200 African- Americans in Jackson, MS, 400 Hispanic participants in San Antonio, Texas and 1650 European ancestry participants in the Great Age Study in Barri, Italy (LOS only, will collect and analyze data with Italian funding. Aim 1: To characterize individual brain health using a multidimensional sensory-motor `Brain Health Index' by assessing olfaction, retina, vision, auditory function, vestibular function, touch sensation, motor function, and examine its association with (i) cross-sectional MRI, PET and cognitive function and (ii) incident mild cognitive impairment (MCI), dementia including AD, VCID, TIA, stroke and all-cause mortality over 3-5 years and subsequent follow-up Aim 2: To investigate the effect of lifelong (20-40+ years) social, behavioral and vascular/metabolic factors, measured previously on these participants, on individual sensory-motor functions, smBHI and cBHI and brain reserve (difference between BH age and chronological age) Aim 3: To examine the association between (1) genetic, (2) putative circulating biomarkers and (3) epigenetic aging and `brain health' Aim 4: To replicate the associations observed in Aims 1, 2 and 3 in our three replication samples.

在影像学或尸检中具有相似程度的阿尔茨海默氏症或血管脑病理学的人可能患有 一生中非常不同的临床和功能经历可能是不同数量的原因。 认知储备，或保护他们免受临床表现影响的大脑健康，就像健康的骨骼一样。 终生保持体重可以预防骨质疏松症和骨折，在 65-85 岁时拥有健康的大脑，其结果是 遗传倾向和终生环境、行为和疾病相关因素的影响，将防止 AD、痴呆和中风的发展 我们如何定义健康的大脑表型？ 使用定量测量 MRI 和 PET 脑成像、认知测试和尸检进行表征。 大脑健康的其他方面通常在认知之前随着年龄的增长而改变，包括视网膜结构和 脉管系统、嗅觉、视觉、听觉、触觉和感觉运动能力。 这些措施是有前景的 AD 早期生物标志物，可能在 AD 的发生或进展中发挥因果作用 NIA 题为“衰老和 AD 中的感觉和运动功能障碍”的研讨会得出的结论是： 全面的感觉运动测试将为 AD 发病机制提供关键的机制见解。 建议在最近资助的 1874 年第十次考试中纳入多种此类感觉运动测量 弗雷明汉心脏研究 (FHS) 后代和 Omni 1 队列参与者并开发了多维 感觉运动大脑健康指数 (smBHI)，以及另外包括大脑在内的复合 BHI (cBHI) 将使用广泛的数据来确定与 BHI 相关的 MRI 和认知测量。 风险因素分析、大脑结构和功能的重复测量、MCI 信息、痴呆症 (AD 和 VCID）以及 FHS 中已有的卒中结果将在另外 3 个人群样本中进行验证， 密西西比州杰克逊市有 200 名非裔美国人参加，得克萨斯州圣安东尼奥有 400 名西班牙裔参加者，还有 1650 名欧洲人参加 意大利巴里伟大时代研究（仅LOS）的祖先参与者将与意大利人一起收集和分析数据 目标 1：利用多维感觉运动“大脑健康”来表征个体大脑健康。 通过评估嗅觉、视网膜、视觉、听觉功能、前庭功能、触觉、运动的指数 功能，并检查其与 (i) 横断面 MRI、PET 和认知功能以及 (ii) 事件的关联 轻度认知障碍 (MCI)、痴呆（包括 AD、VCID、TIA）、中风和 3-5 岁以上的全因死亡率 目标 2：调查终生（20-40 岁以上）社交、行为的影响 以及血管/代谢因素（之前在这些参与者身上测量）对个体感觉运动的影响 功能、smBHI 和 cBHI 以及大脑储备（BH 年龄和实际年龄之间的差异） 目标 3： 检查 (1) 遗传、(2) 假定的循环生物标志物和 (3) 表观遗传衰老之间的关联 “大脑健康”目标 4：在我们的三个复制样本中复制目标 1、2 和 3 中观察到的关联。