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: 10558956
• 负责人: Sterling C Johnson
• 金额: $ 370.81万
• 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/10558956
• 关键词: Acute; Adult; Affective; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Amyloid; Amyloid beta-42; 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; 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; biopsychosocial; brain health; burden of illness; cognitive change; cognitive development; 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 拥有前所未有的机会来增进对认知风险和保护因素的了解 以及阿尔茨海默病（AD）和相关痴呆症（ADRD）的潜力源于其。 对行为、社会、心理、 以及参与者过去几十年生活中的生物评估，识别风险标记。 疾病症状学对于 AD/ADRD 预防科学至关重要。 主要目标是： (1) 开展额外的研究。 对两个国家样本进行一系列的认知评估，并获得侧重于认知的新措施 将对大约 4,000 名成年人重新进行成人认知简短测试（核心 n = 2,062；复习） n = 1,935），最后一波年龄为 25 至 95 岁，对记忆、速度、流畅性进行关键神经心理学评估， 推理和执行功能将通过电话访谈进行评估。 (2) 进行额外的情绪相关功能波 对核心神经科学子样本和复习神经科学子样本进行神经影像学和心理生理学评估 获得大脑衰老的多模式神经影像和心理生理学数据的综合测量。 收集约 450 名成人（核心 n = 215 纵向 + 60 新；复习 n = 115 纵向 + 60 新）。 纵向分析将检查情绪过程、计算机大脑的情感计时的变化 年龄、萎缩、白质结构完整性和高强度、树突微观结构的复杂性和 轴突、网络连接性和模块化 (3) 量化 AD 和神经血管疾病负担并收集。 生物标志物中新的 ADRD 相关血浆和神经心理学测量和临床评估 进行先进的分子淀粉样蛋白 PET 来识别表现出淀粉样蛋白积累的个体。 指示 AD 神经病变，以及神经血管 MRI 来识别血管疾病，包括血管 交叉验证淀粉样蛋白 (42/40) 与淀粉样蛋白的血浆标记物。 对同时患有这两种疾病的参与者进行成像，并与 MIDUS U19 结合收集 aβ42/aβ40、p-tau181、 完整生物标志物样本上的 ptau217、总 tau 和神经丝光 (NFL)（约 1280 名参与者；核心 n = 630； 复习 n = 647)，从而扩大了 MIDUS 的范围，将 ADRD 生物标志物纳入其中。 U19 应用程序中，这些新措施将用于测试有关认知衰退和 AD/ADRD 和神经血管疾病的前兆是通过 30 年来的累积压力造成的，并考虑 失业和种族差异以及复原力的保护性影响。 将检查之前多次 MIDUS 评估的资源、情感风格和生活方式因素 与早期指标相关，以更好地理解这些因素与认知的关系 这些新的评估和分析提供了有关机制的突破性科学。 促进预防，包括制定针对衰老衰退和痴呆症的干预措施和治疗方法。