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

冷漠是阿尔茨海默病及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、大脑发育迟缓有关 体积大，淀粉样蛋白β、tau病理和白质高信号负荷较高。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。 中年是干预ADRD危险因素的关键时期，当神经生物学 ADRD下面的底物开始聚集。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。 冷漠是一个多维结构，包括三个主要组成部分：狭隘的情感 反应性、有限的认知努力和好奇心，以及目标导向行为的减少。身份识别 它的认知和大脑的相关性需要一种细粒度的方法，它认为这些不同的 组件。我们将研究冷漠及其成分与认知功能的关系，以及 500例ADRD患者认知无症状中年子代ADRD相关脑标志物分析 以色列预防阿尔茨海默病登记处(IRAP)研究的参与者。IRAP参与者深有体会 认知、行为、健康、生活方式、脑成像和遗传因素的表型。量化 冷漠将基于：(1)参与者和告密者关于冷漠的报告通过VALIDATED 问卷调查；以及(2)冷漠的客观测量--基于自主神经系统(ANS) 以及凝视对情绪和认知刺激的反应。冷漠的情感成分将是 通过ANS和凝视对情绪视觉刺激的反应性进行测量；认知成分将是 通过凝视对认知刺激的反应性和参与者投入认知努力的意愿来衡量 在一项依赖奖赏的认知任务中。参与者关于认知、社交的类型和持续时间 而他们在没有得到提示的情况下进行的身体活动将评估行为部分。 如果我们的假设得到证实，这些创新的、简单易用的、不同的客观衡量标准 冷漠的成分可能有助于诊断的准确性和理清它们在 认知衰退的预测。这项研究将提供关于认知和大脑的新知识 ADRD风险较高的中年人冷漠的相关性，并将为检查 中年冷漠对认知衰退的纵向影响。

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.