ADRD spousal caregivers, loneliness, & immune dysregulation: Real-Time, real-world intervention targets - Caregiving for a spouse with Alzheimer's disease or related dementias (ADRD) is among life’s most stressful experiences and is characterized by caregiver burden, grief, and higher rates of morbidity and premature mortality. Yet, there is considerable unexplained variability in ADRD spousal caregivers' mental and physical health patterns. ADRD spousal caregivers are prone to social isolation and loneliness, two separate but related constructs thought to fuel physical and mental health problems in ADRD spousal caregivers. Very little is known about how loneliness, social isolation, and their temporal dynamics and interactions play out in real-time in the real-world. This is unfortunate because dementia spousal caregivers’ experiences of objective social isolation and loneliness, and their concurrent physiological state, are constantly changing in real-time based on a constellation of temporal dynamics, proximal momentary factors (e.g., location, time, tasks/stressors, quality and type of recent social interaction), and trait-like patterns of relational expectations, emotions, and behaviors (e.g., attachment orientations). A cohort of 300 ADRD spousal caregivers will answer questions about their mental wellbeing (caregiver burden, depression & grief) and provide blood to evaluate proinflammatory cytokine and two related determinants of inflammatory phenotypes, cellular aging, and disease (i.e., mitochondrial, and glycolytic function) at baseline, and during two follow-up visits (2 weeks and 6 months after baseline). They will also provide intrapersonal and contextual data by self-report. During a 2-week gap between visits 1 and 2, a 14- day ecological assessment will provide momentary data on loneliness, depressive affect, momentary context (e.g., current location, social context, daily activities, caregiving and non-caregiving stressors). Using a sophisticated smartwatch we successfully piloted in ADRD spousal caregivers, we will continuously evaluate vagally mediated heart rate variability (vmHRV). Aim 1 models the momentary associations between loneliness, depressive affect, and vagally mediated heart rate variability; Aim 1 will also model the impact of loneliness (both severity and variability) on indices of ADRD spousal caregiver mental wellbeing (caregiver burden, depression & grief), and physical health (inflammation, mitochondrial and glycolytic function) over time. Aim 2 investigates whether associations between momentary loneliness, spousal caregiver mental well-being, and physical health indices are modified by momentary context and by relatively stable indices of intrapersonal factors (i.e., attachment orientation). Aim 3 (exploratory) models the impact of vmHRV on indices of ADRD spousal caregiver mental wellbeing (caregiver burden, depression & grief), and physical health (inflammation, mitochondrial and glycolytic function) over time.