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.

在成像或尸检时具有相似数量的阿尔茨海默氏症或血管脑病理学的人 生活中的临床和功能经历截然不同。一个可能的原因可能是不同的 认知储备或大脑健康，可以保护它们免受临床表现。就像健康的骨头一样 通过生命的质量可防止骨质疏松和骨折，在65-85岁时具有健康的大脑，结果是 遗传倾向和终身环境，行为和疾病相关的因素将保护 AD，痴呆和中风的发展。我们如何定义健康的大脑表型？大脑健康通常是 使用定量测量值MRI和PET脑成像，认知测试和尸检表征。 在认知之前，脑部健康的其他方面通常会改变，包括残留结构和 脉管系统，嗅觉，视觉，听觉，触觉和感官感知和运动能力。感觉运动 承诺措施是AD的早期生物标志物，并可能在发展或进展中起因果作用 痴呆症。 NIA讲习班标题为“衰老和广告中的感觉和运动功能障碍”得出结论 全面的感觉运动测试将为AD发病机理提供关键的机械见解。我们 提议将多种此类感官运动量度纳入1874年最近资助的第10次考试 Framingham心脏研究（FHS）后代和Omni 1队列参与者并发展多维 感觉运动脑健康指数（SMBHI）以及还包括大脑的复合BHI（CBHI） MRI和认知测量值。与BHI相关的预测因素和结果将使用广泛的 危险因素的分析，大脑结构和功能的重复度量，有关MCI的信息，痴呆症（AD） 和VCID）和中风成果已在FHS中提供。它将在另外3个人口样本中进行验证， 200名非裔美国人在杰克逊，MS，400名西班牙裔参与者，得克萨斯州圣安东尼奥和1650年欧洲人 意大利巴里（Barri）的伟大年龄研究的祖先参与者（仅LOS，将与意大利语收集和分析数据 资金。目的1：使用多维感觉运动``` 索引'通过评估嗅觉，视网膜，视觉，听觉功能，前庭功能，触摸感，电动机 功能，并检查其与（i）横截面MRI，PET和认知功能以及（II）事件的关联 轻度认知障碍（MCI），痴呆症，包括AD，VCID，TIA，中风和全因死亡率以上3-5 年和随后的后续目标2：研究终身（20-40岁以上）社会，行为的影响 和血管/代谢因素，先前在这些参与者上，在单个感觉运动上测量 功能，SMBHI和CBHI和大脑储备（BH年龄和年代年龄之间的差异）目标3： 检查（1）遗传，（2）假定的循环生物标志物与（3）表观遗传衰老和 “大脑健康”目标4：复制在我们的三个复制样本中目标1、2和3中观察到的关联。