This will be an administrative supplement project prepared in response to NOT-AG-21-018 which seeks to expand existing NIH awards that are not currently focused on Alzheimer’s disease and its related dementias (ADRD) to collect data to guide and support a future competitive application from promising leads found through the supplement. This administrative supplement request is directly relevant to Aim 2 as well as the exploratory Aim of the parent grant (R01MH120201). These Aims are focused on determining the association of persistent loneliness with biological markers of health, medical comorbidity, cognitive dysfunction, functional capacity, and well-being, as well as examining the short-term stability and temporal relationships among loneliness, social motivation, social activity, and mood/affect in real-time using EMA (Ecological Momentary Assessment), and their association with “gold standard” lab-based measures. The parent grant is focused on these questions in the context of aging with schizophrenia, but these issues also have direct relevance to ADRD. Specifically, chronic loneliness is a known risk factor for cognitive decline and ADRD, but there is little known about the mediators of this association. The latter may have key applied relevance in the development of interventions to prevent or delay progression from Mild Cognitive Impairment (MCI) to ADRD. As in the parent study, we will examine both biological markers (inflammatory, lipid, and metabolic) and psychosocial factors (negative and positive health behaviors) and their association with loneliness. As part of that effort, we will also use the EMA data to identify the temporal boundaries of acute “adaptive” vs. chronic “maladaptive” loneliness. Identification of adaptive responses to acute loneliness among persons with MCI may reveal modifiable targets that can be taught to others with presently maladaptive responses to loneliness. To evaluate these issues, this supplement study will enroll 40 adults ages 51-90 years with MCI but no history of serious mental illness. Participants will receive targeted relevant measures from the parent study, including loneliness, social isolation, social motivation, depression, objective cognitive functioning, functional capacity, positive and negative health behaviors, blood-based inflammatory markers, a lipid panel, as well as blood pressure and body mass index. In a slight modification of the time pattern, EMA surveys of loneliness, social motivation, social interaction, and affect will be measured once per day for 60 days to enable real-time assessment of persistent loneliness, and the temporal relationships with social motivation, social interaction, and positive and negative affect. The data from this supplement study will be used to inform/guide and support our plans for a more definitive R01-level project to be submitted to the NIA. It will also enrich the data from the parent study in enabling examination of the specificity of observed r...