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

在成像或尸检中有相似数量的阿尔茨海默氏症或血管脑病理的人可能有 在生活中有非常不同的临床和功能体验。一个可能的原因是不同数量的 认知储备，或大脑健康，保护他们免受临床症状的影响。因此，就像一块健康的骨骼 一生中的大量活动可以防止骨质疏松症和骨折，结果是在65-85岁时拥有健康的大脑 遗传倾向以及终生环境、行为和疾病相关因素，将保护人们免受 阿尔茨海默病、痴呆症和中风的发展。我们如何定义健康的大脑表型？大脑健康通常是 通过定量测量MRI和PET脑成像、认知测试和尸检来表征。 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 血管、嗅觉、视觉、听觉、触觉和感官知觉和运动能力。感觉运动 措施是有希望的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的一个名为“衰老和AD中的感觉和运动功能障碍”的研讨会得出结论： 全面的感觉运动测试将为AD的发病机制提供关键的机制洞察。我们 建议在最近资助的1874年第10次考试中纳入多种这样的感觉-运动测试 弗雷明翰心脏研究(FHS)后代和OMNI 1队列参与者并开发多维 感觉-运动脑健康指数(SmBHI)，以及另外包括大脑的综合BHI(CBHI) 核磁共振和认知测量。与BHI相关的预测因素和结果将使用广泛的 描述危险因素，重复测量大脑结构和功能，关于MCI，痴呆(AD)的信息 和VCID)和中风预后已经在FHS中提供。它将在另外3个总体样本中得到验证， 马萨诸塞州杰克逊市的200名非裔美国人，德克萨斯州圣安东尼奥的400名西班牙裔参与者和1650名欧洲人 意大利巴里大时代研究的祖先参与者(仅限洛杉矶，将与意大利人一起收集和分析数据 资金问题。目的1：用多维感觉运动‘脑健康’来表征个体的脑健康 通过评估嗅觉、视网膜、视力、听觉功能、前庭功能、触觉、运动 功能，并检查其与(I)横断面MRI、PET和认知功能以及(Ii)事件的关系 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 年和随后的随访目标2：调查终生(20-40年)社会、行为的影响 以及先前在这些参与者身上测量的血管/代谢因素对个体感觉-运动的影响 功能、smBHI和cBHI和脑储备(BH年龄和实际年龄的差异)目标3： 检查(1)遗传的，(2)假定的循环生物标志物和(3)表观遗传老化和 “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。

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.