Project summary: Early evidence indicates an association between emotional (eudaimonic and hedonic) well- being (EWB) and underlying brain processes, and that those processes change with both normal and pathological brain aging. However, the nature of these associations, the mechanisms by which EWB and its component domains change with brain aging, and how those changes may be associated with common neuropathologies like Alzheimer’s disease and related dementias (ADRD), are largely unexplored. The objective of the Network for Emotional Well-being and Brain Aging (NEW Brain Aging) is to address priority area #2 – mechanistic research on the role of emotional well-being in health – of RFA-AT-20-003, identifying and testing mechanisms by which brain aging influences EWB and how EWB may impact risk for and progression of ADRD. Synthesizing human and animal literature, our premise is that relationships between EWB and ADRD are bidirectional – normal and pathological changes in aging brain influence EWB and EWB contributes to brain health and illness, such as ADRD. Further, we hypothesize that the relationships between EWB and the brain in older adults reflect aging-associated heterogeneity of brain (i.e., resilience, typical aging, or neuropathological changes), and that they are mediated by processes of appraisal and adaptation. To do so we will form a national, transdisciplinary collaborative that includes investigators representing research expertise in human and animal neuroimaging, stress regulation, ADRD research, EWB, and computational/quantitative methods. With direction of an Executive Committee and guided by an External Advisory Committee, NEW Brain Aging will undertake these specific aims: (1) To build an inter-university and transdisciplinary collaborative of senior and junior investigators interested in brain, aging, and EWB research from both human and animal fields; (2) To form a series of time-limited workgroups with relevant experts in the field, each working over 1-2 years, to establish priorities for NEW Brain Aging activities in each of three general areas: (a) brain mechanism research of EWB; (b) research of EWB’s impact on ADRD; and (c) translational animal and cross-species brain research methods; (3) To coalesce and coordinate resources to ensure the rigor and reproducibility of the brain-related EWB research; (4) To provide three types of pilot funding through rigorous peer review: (a) pilot research grants for junior faculty related to brain mechanism studies related to the relationship between EWB and dementia using human or animal models; (b) proof-of-concept grants for established investigators to test aspects related to EWB in their existing studies and cohorts of brain aging; (c) seed collaboration grants for cross-species brain research related to EWB; (5) To evaluate the network by tracking its activities, resource usage, and productivity, and conducting collaborative network density analysis throughout the 4-year gran...