Abstract

Introduction: Associations between magnetic resonance imaging (MRI) markers of vascular pathology and dementia risk in older adults have been established, but it remains less clear how lifestyle factors may modify this association. We hypothesized that a weaker association between MRI markers of vascular pathology and incident dementia will be present among older adults with strong as compared to poor psychosocial health in mid-life. Methods: Social support and social isolation were assessed among ARIC participants, aged 46 - 68, via self-reported questionnaires (1990 - 1992). Following categorization of both factors, participants were classified as having strong or poor mid-life psychosocial health. From 2011 - 2013, 1977 participants, aged 67 - 90, underwent 3T brain MRI quantifying white matter hyperintensity (WMH) volume, subcortical cerebral microbleeds (sCMB), infarcts, and white matter integrity through diffusion tensor imaging. Incident dementia cases were identified from time of imaging through December 31, 2019 (median follow-up: 6.4 years) with ongoing surveillance. Relative contributions of psychosocial health and MRI markers to incident dementia were evaluated with demographic and vascular risk factor-adjusted Cox-proportional hazard regression models. Results: Among 1612 dementia-free participants with measures of psychosocial health, MRI markers were associated with dementia risk in the hypothesized direction. Mid-life psychosocial health significantly modified the associations between sCMB and WMH, each, with incident dementia risk (Table 1; greater risk of dementia shown in individuals with poor psychosocial health). Conclusions: The elevated risk of dementia associated with sCMB and WMH is reduced in participants with strong psychosocial health in mid-life. Future studies evaluating social factors through the life course and the mechanisms by which they modify the relationship between pathology and dementia are needed.

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