Fagundes, Christopher P2024-08-302024-082024-07-29August 202Chung, E-Lim Lydia Wu. From stress to dementia risk: An examination of psychological, immunological, and neurobiological mechanisms underlying increased risk for Alzheimer's disease and related dementias in widow(er)s. (2024). PhD diss., Rice University. https://hdl.handle.net/1911/117803https://hdl.handle.net/1911/117803EMBARGO NOTE: This item is embargoed until 2025-08-01Being widowed is associated with poorer cognitive function and higher incidence rates of Alzheimer’s disease and related dementias (ADRD). The mechanisms underlying the link between spousal bereavement and ADRD risk remain relatively unexplored. Individual differences in health may be examined within a biopsychosocial framework, which posits that biological, psychological, and interpersonal factors independently and interactively affect health. For example, within the context of stress and ADRD, experiencing a significant psychological stressor, such as spousal bereavement, may be particularly detrimental for individuals who also display additional psychosocial and biological risk factors of ADRD. To understand how bereavement may enhance ADRD risk and which widow(er)s may be at heightened risk, I used psychological, immunological, and neuroimaging approaches to examine individual differences in neurocognitive health 1) between bereaved spouses and nonbereaved controls and 2) among bereaved spouses. Across 3 datasets, recently bereaved spouses and nonbereaved adults completed neuropsychological assessments, self-report questionnaires on psychosocial well-being, and provided venous blood samples for inflammatory assays. A subset of bereaved and nonbereaved adults also completed a structural magnetic resonance imaging scan for quantification of cortical thickness and provided blood samples for plasma amyloid beta assays. Widow(er)s and nonbereaved adults showed significant differences in working memory performance and brain morphology. Among widow(er)s, depressive symptoms and cortical thickness in ADRD-related brain regions were associated with several cognitive domains. The relationship between psychosocial well-being (e.g., depressive symptoms, loneliness) and cognitive inhibition depended on widow(er)s’ levels of systemic inflammation and cortical thinning in ADRD-related brain regions. Tentative relationships between inflammation, plasma amyloid, and cortical thickness were also observed. Findings suggest that differences in cognitive function and brain morphology among widow(er)s and between widow(er)s and nonbereaved adults are evident as early as the first few months of bereavement. Notably, the present study replicated patterns previously observed in the cognitive neuroscience and depression literature and identified novel, psychobiological mechanisms of neurocognitive aging. Beyond its contribution to the bereavement literature, this research broadens our understanding of the mechanisms linking stressful life events to increased disease risk.application/pdfengCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.biopsychosocialdepressionAlzheimer's diseaseinflammationcortical thicknesslonelinesswidowhoodspousal bereavementgriefamyloidworking memoryexecutive functionoverall cognitive functionstressful life eventsThesis2024-08-30