and relevance to parent announcement Our ongoing research (K01MH112683) aims to better understand the risk architecture of depression in dementia caregivers (dCGs). We propose this supplemental study to develop a new line of research focused on understanding why dCGs also have higher dementia risk1-7. Literature suggests cognitive impairment may be more common in dCGs due to caregiving-related stressor exposure 3-5. But, of the myriad of exposures related to caregiving, there is not yet systematic evidence regarding which have toxic effects on the brain and cognition. In addition, it is not known which biological pathways to dementia are exacerbated by the stresses of dementia caregiving. To begin building evidence that can support risk stratification and prevention approaches, we propose a supplemental study in 60 dCGs who are experiencing stress. Building on our ongoing study and local Alzheimer-research infrastructure, we propose to add a comprehensive neuropsychological battery, measure dementia-related circulating markers, and store blood for future assays. Adding these measures will allow us to generate initial evidence regarding: (1) the caregiving-related exposures (i.e., psychosocial and/or sleep-wake risk factors) associated with cognitive function in dCGs; and (2) the biomarkers (blood- and brain- based) that link together caregiving-related risk factors and dCGs' cognitive function. Generating this evidence will enable us to refine our current model, which links caregiving exposures with dGCs' cognitive outcomes via inter-related effects on circulating biomarkers and brain structure. We will use this evidence and refined model to target future research and preventive interventions aimed at protecting cognition in aging dCGs. Research in this vulnerable group of stressed dCGs also provides a cost-effective and accelerated means to generally understand how common exposures (e.g., psychosocial stress and sleep-wake disruption) impact common pathways to dementia (i.e., cerebrovascular disease and neurodegeneration). This application is responsive to NOT-AG-18-039 because it extends the scope of our ongoing work to develop a focus on Alzheimer's Disease and Alzheimer's-related Dementia.
(Unchanged from Parent Award): Late-life depression (LLD) impairs quality of life and has serious health consequences that disproportionally affect certain sub-groups of older adults, including informal providers of dementia care. In this K01 application we will test and refine a model of LLD pathogenesis in dementia caregivers that posits sleepwake activity disruption contributes to accelerated brain structural aging, which in turn, affects the key structural networks (executive and central visceral control) that underlie LLD risk. This will generate evidence regarding the specific alterations to brain structure connectivity, and behavioral drivers of these changes, which increase LLD vulnerability and thereby represent targets for deficit-based LLD prevention strategies.
