Cognitive and brain imaging correlates of apathy- components in asymptomatic middle aged individuals at high ADRD- risk

认知和脑成像与 ADRD 高风险无症状中年个体的冷漠成分相关

• 批准号: 10875019
• 负责人: Ramit Ravona
• 金额: $ 21.01万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10875019
• 关键词: Adult; Affect; Age; Alzheimer disease prevention; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amyloid; Autonomic nervous system; Behavior; Behavior assessment; Behavioral; Behavioral Symptoms; Biological; Brain; Brain imaging; Brain region; Cerebrovascular Disorders; Characteristics; Cognition; Cognitive; Collaborations; Curiosities; Data; Dementia; Development; Devices; Dimensions; Disease; Elderly; Emotional; Eye; Functional Magnetic Resonance Imaging; Genetic; Goals; Health; Health Services; Impaired cognition; Individual; Intervention; Investments; Israel; Knowledge; Life; Life Style; Link; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Medical center; Mental Depression; Neurobiology; PET/CT scan; Parietal; Participant; Pathology; Patients; Personality; Phenotype; Photic Stimulation; Physical activity; Questionnaires; Recording of previous events; Registries; Reporting; Rewards; Risk; Role; Screening procedure; Signal Transduction; Stimulus; Testing; Time; White Matter Hyperintensity; age group; behavioral impairment; brain magnetic resonance imaging; brain volume; cerebral atrophy; cognitive function; cognitive task; critical period; diagnostic accuracy; disorder risk; frontal lobe; gaze; high risk; human old age (65+); imaging biomarker; informant; innovation; longitudinal design; medical schools; middle age; offspring; preventive intervention; smartphone application; social; tau Proteins; visual stimulus; willingness; young adult; β-amyloid burden

Apathy is the most prevalent behavioral symptom in Alzheimer’s disease and related disorders (ADRD). In older adults, presence of apathy is associated with faster cognitive decline, lower brain volumes and with a higher burden of Amyloid β, tau pathology and white matter hyperintensities. Thus, in old age, apathy is an important behavioral marker of incipient dementia and its underlying pathology. Midlife is a critical period for intervening against risk factors for ADRD and when the neurobiological substrates underlying ADRD begin to aggregate. However, the cognitive and ADRD-related brain correlates of apathy in midlife are essentially unknown. Apathy is a multidimensional construct encompassing three main components: narrowed emotional reactivity, limited cognitive effort and curiosity and reduced goal- directed behavior. The identification of its cognitive and brain correlates requires a granular approach, which considers these distinct components. We will study the relationship of apathy and its components with cognitive function and ADRD-related brain markers in 500 cognitively asymptomatic middle aged offspring of ADRD patients, participants of the Israel Registry for Alzheimer’s Prevention (IRAP) study. IRAP participants are deeply phenotyped for cognitive, behavioral, health, lifestyle, brain imaging and genetic factors. Quantification of apathy will be based on: (1) Participants' and informants' report on apathy via validated questionnaires; and (2) Objective measurement of apathy- based on autonomic nervous system (ANS) and gaze reactivity to emotional and cognitive stimuli. The emotional component of apathy will be measured via ANS and gaze reactivity to emotional visual stimuli; The cognitive component will be measured via gaze reactivity to cognitive stimuli and by participants' willingness to invest cognitive effort in a reward-dependent cognitive task. Participants' report on the type and duration of cognitive, social and physical activities they performed without being prompted will assess the behavioral component. If our hypotheses are corroborated, these innovative, simple to use, objective measures of different components of apathy may facilitate diagnostic accuracy and disentangling their unique value in the prediction of cognitive decline. The study will provide new knowledge on the cognitive and brain correlates of apathy in middle aged individuals at high ADRD risk and will set the basis for examining the longitudinal consequences of midlife apathy on cognitive decline.

冷漠是阿尔茨海默病和相关疾病中最常见的行为症状 （ADRD）。在老年人中，冷漠的存在与认知能力下降更快、大脑功能较低有关。 体积和β淀粉样蛋白、tau蛋白病理学和白质高信号的负担更高。因此， 在老年，冷漠是早期痴呆及其潜在病理的重要行为标志。 中年是针对 ADRD 危险因素进行干预的关键时期，并且当神经生物学 ADRD 下的底物开始聚集。然而，认知和 ADRD 相关的大脑 中年冷漠的相关因素基本上是未知的。 冷漠是一种多维结构，包含三个主要组成部分： 反应性、认知努力和好奇心有限以及目标导向行为减少。鉴定 其认知和大脑的相关性需要一种细粒度的方法，该方法考虑到这些不同的 成分。我们将研究冷漠及其组成部分与认知功能和认知功能的关系 500 名无认知症状的 ADRD 患者中年后代的 ADRD 相关脑标志物， 以色列阿尔茨海默病预防登记处 (IRAP) 研究的参与者。 IRAP 参与者深感 针对认知、行为、健康、生活方式、大脑成像和遗传因素进行表型分析。量化 冷漠程度的评估将基于： (1) 参与者和知情者通过经过验证的冷漠情况报告 问卷调查； （2）基于自主神经系统（ANS）的冷漠客观测量 以及凝视对情感和认知刺激的反应。冷漠的情感成分是 通过 ANS 和凝视对情感视觉刺激的反应来测量；认知部分将是 通过对认知刺激的凝视反应以及参与者投入认知努力的意愿来衡量 在依赖奖励的认知任务中。参与者关于认知、社交的类型和持续时间的报告 他们在没有提示的情况下进行的身体活动将评估行为成分。 如果我们的假设得到证实，这些创新的、易于使用的、客观的不同测量方法 冷漠的组成部分可能会提高诊断的准确性并阐明其在诊断中的独特价值 认知能力下降的预测。该研究将提供有关认知和大脑的新知识 ADRD 高风险中年人冷漠的相关性，并将为检查奠定基础 中年冷漠对认知能力下降的纵向影响。