Integrative Pathways to Cognitive, Affective, and Brain Health

认知、情感和大脑健康的综合途径

• 批准号: 10707362
• 负责人: Sterling C Johnson
• 金额: $ 346.64万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10707362
• 关键词: Acute; Adult; Affective; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Atrophic; Axon; Behavioral; Biological; Biological Assay; Biological Markers; Blood Vessels; Brain; Buffers; COVID-19 pandemic; Cardiovascular Diseases; Chronic; Classification; Clinical assessments; Cognition; Cognitive; Cognitive aging; Collaborations; Collection; Data; Dementia; Dendrites; Development; Discrimination; Disease; Disease Outcome; Distal; Emotional; Emotions; Event; Exhibits; Family; Functional Magnetic Resonance Imaging; Health; Image; Impaired cognition; Impairment; Independent Living; Individual; Intervention; Knowledge; Life; Life Experience; Light; Link; Magnetic Resonance Imaging; Measures; Memory; Molecular; Nerve Degeneration; Neuropathy; Neuropsychology; Neurosciences; Neurotic Disorders; Participant; Pathway interactions; Patient Self-Report; Perfusion; Persons; Plasma; Positron-Emission Tomography; Prevention; Process; Psychophysiology; Quality of life; Recording of previous events; Recovery; Resources; Risk; Risk Factors; Risk Marker; Sampling; Science; Speed; Stimulus; Stress; Symptoms; Telephone Interviews; Testing; Time; Tissues; Vascular Diseases; Work; affective neuroscience; aged; aging brain; amyloid imaging; apolipoprotein E-4; biomarker identification; biopsychosocial; brain health; burden of illness; cognitive change; cognitive interview; cognitive testing; dementia risk; executive function; genetic risk factor; insight; lifestyle factors; longitudinal analysis; multimodal neuroimaging; multimodality; neurofilament; neuroimaging; neurovascular; novel; peer; perceived discrimination; prevent; protective factors; psychologic; psychosocial; psychosocial resources; racial disparity; resilience; response; social; socioeconomic disparity; stem; symptomatology; tau Proteins; therapy development; trend; white matter

ABSTRACT MIDUS has unprecedented opportunities to advance knowledge of risk and protective factors for cognitive decline as well as for Alzheimer’s Disease (AD) and Related Dementias (ADRD). Such potential stems from its comprehensive assessments from two national samples (Core, Refresher) of behavioral, social, psychological, and biological assessments from prior decades in the participants’ lives. Identifying markers of risk before disease symptomatology is foremost to AD/ADRD prevention science. Key aims are to: (1) Conduct additional waves of cognitive assessments on both national samples and obtain new measures focused on cognitive impairment. The Brief Test of Adult Cognition will be re-administered to ~ 4,000 adults (Core n = 2,062; Refresher n = 1,935), ages 25 to 95 at the last wave with key neuropsychological assessments of memory, speed, fluency, reasoning, and executive functioning. Global cognitive status will be assessed with the Telephone Interview for Cognitive Status and self-reported symptoms. (2) Conduct additional waves of emotion-related functional neuroimaging and psychophysiological assessments on Core and Refresher Neuroscience subsamples and obtain comprehensive measures of brain aging. Multimodal neuroimaging and psychophysiological data will be collected on ~ 450 adults (Core n = 215 longitudinal + 60 new; Refresher n = 115 longitudinal + 60 new). Longitudinal analyses will examine changes in affective chronometry of emotional processes, computed brain age, atrophy, white matter structural integrity and hyperintensities, microstructural complexity of dendrites and axons, and network connectivity and modularity. (3) Quantify AD and neurovascular disease burden and collect new ADRD-related plasma and neuropsychological measures and clinical assessments in the Biomarker subsamples. Conduct advanced molecular amyloid PET to identify individuals exhibiting amyloid accumulation indicative of AD neuropathic change, and neurovascular MRI to identify vascular diseases including vessel stiffness and oligemic tissue perfusion. Cross-validate plasma markers of amyloid beta (42/40) against amyloid imaging in participants who have both, and in conjunction with the MIDUS U19 collect aβ42/aβ40, p-tau181, ptau217, total tau, and neurofilament light (NFL) on the full biomarker samples (~ 1280 participants; Core n = 630; Refresher n = 647), thereby extending the reach of MIDUS to include ADRD biomarkers. In conjunction with the U19 application, these new measures will be used to test hypotheses regarding cognitive decline and the precursors of AD/ADRD and neurovascular disease via cumulative stress over 30 years and consider socioeconomic and race disparities and resilience. The protective influence of biopsychosocial resources, affective style, and lifestyle factors assessed over multiple prior waves of MIDUS will be examined in relation to early indicators to gain a better understanding of the relations of these factors to cognitive impairment and dementia. These new assessments and analyses offer ground-breaking science on mechanisms to advance prevention, including development of interventions and treatments for aging declines and dementia.

摘要 MIDUS拥有前所未有的机会来提高对认知风险和保护因素的认识 阿尔茨海默病(AD)和相关痴呆症(ADRD)的发病率也有所下降。这种潜力源于它的 来自两个国家样本(核心样本、复习样本)的全面评估， 以及参与者生活中前几十年的生物学评估。在此之前确定风险标记 疾病症状学是AD/ADRD预防科学的首要任务。主要目标是：(1)开展其他 对两个国家的样本进行了一波又一波的认知评估，并获得了专注于认知的新措施 减损。成人认知简明测试将对约4,000名成年人重新进行(核心n=2,062；复习 N=1,935)，最后一波的年龄在25岁至95岁之间，对记忆力、速度、流利性、 推理和执行功能。全球认知状况将通过电话采访进行评估 认知状态和自我报告的症状。(2)进行额外的情绪相关功能波 核心和更新神经科学亚样本的神经成像和心理生理学评估 获得全面的脑老化指标。多模式神经成像和心理生理学数据将 收集了约450名成年人(核心n=215个纵向+60个新；更新n=115个纵向+60个新)。 纵向分析将检查情绪过程的情感计时器的变化，计算大脑 年龄、萎缩、白质结构完整性和高信号、树突和 轴突，以及网络连接性和模块化。(3)量化AD和神经血管疾病负担，收集 生物标记物中与ADRD相关的新的血浆和神经心理测量及临床评估 子样本。进行先进的分子淀粉样蛋白PET以识别表现出淀粉样蛋白积聚的个体 提示阿尔茨海默病的神经病变，神经血管磁共振成像识别包括血管在内的血管疾病 僵硬，组织灌注量少。淀粉样β蛋白血浆标志物(42/40)与淀粉样蛋白的交叉验证 两者都有的参与者的成像，并结合MIDUS U19收集aβ42/aβ40，p-tau181， Ptau217、总tau和神经丝光(NFL)在全部生物标记物样本上(约1280名参与者；核心n=630； 更新者n=647)，从而将MIDUS的覆盖范围扩大到包括ADRD生物标志物。与 U19应用，这些新的测量将被用来测试关于认知下降和 AD/ADRD和神经血管疾病的先兆通过30年的累积应激和考虑 社会经济和种族差距和韧性。生物心理社会的保护性影响 资源，情感风格和生活方式因素评估的多个以前的MIDUS浪潮将被检查 关于早期指标，以更好地了解这些因素与认知的关系 损伤和痴呆症。这些新的评估和分析为机构学提供了开创性的科学 推进预防，包括制定针对衰老衰退和痴呆症的干预和治疗措施。