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

在成像或尸检中具有类似数量的阿尔茨海默氏症或血管性脑病理的人可能有 非常不同的临床和功能体验。一个可能的原因可能是不同数量的 认知储备或大脑健康，保护他们免受临床表现的影响。因此，就像健康的骨骼一样， 通过生活质量保护骨质疏松症和骨折，在65-85岁时拥有健康的大脑， 遗传倾向和终身环境，行为和疾病相关因素的影响， AD、痴呆和中风的发展。我们如何定义一个健康的大脑表型？大脑健康通常是 其特征在于使用定量测量MRI和PET脑成像，认知测试和尸检。 在认知之前，大脑健康的其他方面通常在衰老中改变，包括视网膜结构和视网膜结构。 血管系统、嗅觉、视觉、听觉、触觉和感官知觉以及运动能力。感觉运动 这些指标是有希望的AD早期生物标志物，可能在AD的发展或进展中发挥因果作用。 老年痴呆症一个名为“衰老和AD中的感觉和运动功能障碍”的NIA研讨会得出结论， 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。我们 我提议在最近资助的1874年第10次考试中纳入多种这样的感觉运动测量 心脏研究（FHS）后代和Omni 1队列参与者，并制定多维度 感觉运动脑健康指数（smBHI），以及复合BHI（cBHI），另外包括脑 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 风险因素分析，脑结构和功能的重复测量，MCI、痴呆（AD）的信息 和VCID）和FHS中已有的卒中结局。将在另外3个群体样本中进行验证， 200名非裔美国人在杰克逊，MS，400名西班牙裔参与者在圣安东尼奥，得克萨斯州和1650名欧洲 意大利巴里大时代研究的祖先参与者（仅限LOS）将收集和分析意大利语数据， 经费目标1：使用多维感觉-运动“脑健康”来表征个人的脑健康 通过评估嗅觉、视网膜、视觉、听觉功能、前庭功能、触觉、运动 功能，并检查其与（i）横断面MRI，PET和认知功能和（ii）事件 轻度认知功能障碍（MCI）、痴呆（包括AD）、VCID、TIA、卒中和全因死亡率超过3-5 目的2：研究终身（20-40岁以上）社会、行为、 和血管/代谢因素，以前对这些参与者进行测量，对个体感觉运动 功能、smBHI和cBHI以及脑储备（BH年龄与实足年龄之间的差异）目的3： 检查（1）遗传，（2）推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：在我们的三个重复样本中重复目标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.