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.

Public Health Relevance

(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.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Scientist Development Award - Research & Training (K01)
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Chavez, Mark
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University of Pittsburgh
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Smagula, Stephen F; DuPont, Caitlin M; Miller, Megan A et al. (2018) Rest-activity rhythms characteristics and seasonal changes in seasonal affective disorder. Chronobiol Int 35:1553-1559
Wallace, Meredith L; Smagula, Stephen F (2018) Promise and Challenges of Using Combined Moderator Methods to Personalize Mental Health Treatment. Am J Geriatr Psychiatry 26:678-679
Smagula, Stephen F; Krafty, Robert T; Thayer, Julian F et al. (2018) Rest-activity rhythm profiles associated with manic-hypomanic and depressive symptoms. J Psychiatr Res 102:238-244
Wallace, Meredith L; Stone, Katie; Smagula, Stephen F et al. (2018) Which Sleep Health Characteristics Predict All-Cause Mortality in Older Men? An Application of Flexible Multivariable Approaches. Sleep 41:
Gebara, Marie Anne; Kasckow, John; Smagula, Stephen F et al. (2018) The role of late life depressive symptoms on the trajectories of insomnia symptoms during antidepressant treatment. J Psychiatr Res 96:162-166
Hughes, Timothy M; Lockhart, Samuel N; Smagula, Stephen F (2018) Blood Pressure's Role in Alzheimer Disease Pathology. Am J Geriatr Psychiatry 26:23-24
Smagula, Stephen F; Karim, Helmet T; Rangarajan, Anusha et al. (2018) Association of Hippocampal Substructure Resting-State Functional Connectivity with Memory Performance in Older Adults. Am J Geriatr Psychiatry 26:690-699
Smagula, Stephen F; Krafty, Robert T; Taylor, Briana J et al. (2017) Rest-activity rhythm and sleep characteristics associated with depression symptom severity in strained dementia caregivers. J Sleep Res 26:718-725
Simning, Adam; Smagula, Stephen F (2017) Engaging Early-Career Geriatric Mental Health Investigators as Associate Editorial Board Members. Am J Geriatr Psychiatry 25:438-439