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; 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.

抽象的 MIDUS有前所未有的机会来提高对认知风险和保护因素的了解 下降以及阿尔茨海默氏病（AD）和相关痴呆症（ADRD）。从它的潜在步骤 对行为，社会，心理学的两个国家样本（核心，复习）的全面评估， 以及参与者生活前几十年的生物评估。识别风险标记之前 疾病症状学是AD/ADRD预防科学的最重要的。关键目的是：（1）进行额外 在两个国家样本上的认知评估波浪波浪，并获得着针对认知的新措施 损害。成人认知的简短测试将重新管理为约4,000名成年人（核心n = 2,062；复习 n = 1,935），在最后一波中，年龄在25至95岁之间，对记忆，速度，流利性的关键神经心理学评估， 推理和执行功能。全球认知状况将通过电话采访评估 认知状况和自我报告的症状。 （2）进行额外的情绪相关功能波 核心和复习神经科学子样本的神经影像学和心理生理评估 获得脑老化的综合措施。多模式的神经影像学和心理生理数据将是 收集在〜450名成年人（核心n = 215纵向 + 60新的新;复习n = 115纵向 + 60新的）上。 纵向分析将检查情绪过程的情感时间表的变化，计算的大脑 年龄，萎缩，白质结构完整性和超强度，树突的微结构复杂性和 轴突以及网络连接性和模块化。 （3）量化AD和神经血管疾病伯恩伯恩并收集 新的与ADRD相关的血浆和神经心理学测量和生物标志物中的临床评估 子样本。进行晚期分子淀粉样蛋白PET以识别表现出淀粉样蛋白积累的个体 指示AD神经性变化和神经血管MRI，以鉴定包括血管在内的血管疾病 刚度和寡聚组织灌注。淀粉样蛋白β（42/40）的跨效率等离子体标志物针对淀粉样蛋白 具有两者兼会的参与者的成像，并与Midus U19收集Aβ42/Aβ40，P-TAU181， 完整生物标志物样品上的PTAU217，Total Tau和Neurofament Light（NFL）（〜1280名参与者；核心n = 630; 复习n = 647），从而扩展了Midus的覆盖范围，以包括ADRD生物标志物。与 U19应用，这些新措施将用于检验有关认知能力下降和 AD/ADRD和神经血管疾病的前体在30年内通过累积应激，并考虑 社会经济和种族差异和韧性。生物心理社会的受保护影响 将检查资源，情感风格和对MIDUS多个先前浪潮评估的生活方式因素 关于早期指标，以更好地了解这些因素与认知的关系 障碍和痴呆症。这些新的评估和分析提供了有关机制的开创性科学 提高预防，包括开发衰老下降和痴呆症的干预措施和治疗方法。