Brain and Behavioral Mechanisms Linking Loneliness and Social Isolation with Accelerated Cognitive Aging and Alzheimer's Disease and Related Dementias

Brain and Behavioral Mechanisms Linking Loneliness and Social Isolation with Accelerated Cognitive Aging and Alzheimer’s Disease and Related Dementias Loneliness and social isolation (SIL) increase risk for all ten leading causes of death in the U.S. and are strongly linked to cognitive decline and Alzheimer’s Disease and Related Dementias (ADRD). Reducing SIL

can foster healthy aging, improve mental and physical health, optimize quality of life, and prevent cognitive decline and ADRD. However, healthcare has not capitalized on promoting social connection as preventive medicine: it is not routinely assessed nor treated, in part because current data do not allow for definitive

conclusions about evidence-based approaches. Dr. Van Orden’s research aims to identify evidence-based strategies for SIL—grounded in the study of mechanisms—to promote healthy aging and increase quality of life for older adults. In line with NIA priorities of increasing understanding of the aging brain and ADRD; developing

interventions to address ADRD and promote healthy brain aging; and understanding mechanisms underlying effective interventions, the objective of this mid-career K24 award in patient-oriented research (POR) is to incorporate the study of cognition and healthy brain aging into Dr. Van Orden’s research on SIL interventions

to understand benefits for brain aging (and preventing ADRD) as well as identifying intervention targets to optimize interventions. This K24 will allow her to develop capacity in interdisciplinary science in healthy brain aging by co-mentoring clinical scientists who study ADRD as well as basic scientists in neuroscience (and

related disciplines) to foster development of a program of research on the translational science of SIL and its role in brain aging. Dr. Van Orden’s long-term objective in POR is to identify and disseminate evidence-based interventions for SIL in later life, including determining the mechanisms that account for improved health

outcomes—mental health, cognitive health, and physical health outcomes. The research project component of this proposal is designed to advance the translational science of SIL and brain aging while producing an optimal training laboratory for mentees. The scientific premise is that SIL and brain aging have reciprocal

associations that can result in a downward spiral towards unhealthy brain aging and ADRD, or with intervention, an upward spiral towards healthy brain aging and social connection. To produce efficient training for mentees, the project relies on published data (meta-analysis) and secondary analyses of completed trials

(from the PI’s laboratory and NIA-funded Roybal ADRD caregiving research center). The first aim is to examine whether behavioral interventions for SIL improve cognitive functioning. The second aim it to examine baseline cognitive impairment as a prognostic indicator for improvement in SIL. The third aim is to examine potential

mechanisms for non-compliance to SIL interventions. We will integrate findings with the published literature on social and affective processing in SIL and the published literature on experimental studies with animal models of SIL to develop a testable model of brain and behavioral mechanisms that simultaneously maintain SIL and

accelerate cognitive aging and that could serve as intervention targets to optimize interventions.