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，冷漠的存在与更快的认知能力下降， 体积和淀粉样蛋白β、tau病理学和白色高信号负荷较高。因此，在本发明中， 在老年，冷漠是早期痴呆症及其潜在病理学重要行为标志。 中年是干预ADRD风险因素的关键时期， ADRD的底物开始聚集。然而，认知和ADRD相关的大脑 中年冷漠的相关性基本上是未知的。 冷漠是一个多维的结构，包括三个主要组成部分： 反应性、有限的认知努力和好奇心以及减少的目标导向行为。识别 它的认知和大脑相关性需要一个粒度的方法，考虑这些不同的 件.我们将研究冷漠及其成分与认知功能的关系， 500例ADRD患者无认知症状中年后代的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、脑成像和遗传因素进行表型分析。定量 冷漠的评估将基于：（1）参与者和被调查者通过验证的方式对冷漠的报告 问卷调查;（2）冷漠的客观测量-基于自主神经系统（ANS） 以及对情绪和认知刺激的凝视反应。冷漠的情感成分将是 通过ANS和对情绪视觉刺激的凝视反应来测量;认知部分将是 通过对认知刺激的凝视反应和参与者投入认知努力的意愿来测量 在一个奖励依赖的认知任务中。参与者关于认知、社会和心理障碍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，简单易用的，客观的措施， 冷漠的组成部分可能有助于诊断的准确性，并解开他们在治疗中的独特价值。 预测认知能力下降。这项研究将为认知和大脑提供新的知识 在ADRD高风险的中年人冷漠的相关性，并将为检查 中年冷漠对认知能力下降的纵向影响。

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.