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

点击翻译按钮获取中文摘要

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.