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A Uniform Approach to Modeling Risk Factor Relationships for Ischemic Lesion Prevalence and Extent: The Women’s Health Initiative Magnetic Resonance Imaging Study

Background: Both the prevalence and extent of brain magnetic resonance imaging (MRI) abnormalities are related to risk factors for dementia. Typically these associations have been explored separately, but an integrated modeling approach would allow the separate relationships to be consistently described and contrasted. Methods: Region-specific measures of ischemic lesion volumes were obtained from standardized brain MRI from 1,403 women enrolled in the Women’s Health Initiative hormone therapy trials. Mixed-effects mixed-distribution models were fitted to explore jointly the relationships that the region-specific prevalence of ischemic lesions and region-specific ischemic lesion volumes had with risk factors and scores from tests of cognitive function. Results: Women with greater probabilities (prevalence) of having ischemic lesions in brain regions also tended to have larger volumes (extent) of ischemic lesions within the affected regions (p < 0.001). Across the 5 regions included in analyses (frontal, limbic, occipital, parietal and temporal), prevalence and extent varied (p < 0.001). Each was increased among women who were older, had hypertension or who had previously been classified as cognitively impaired (p < 0.01). Additionally, extent was significantly increased among women with a history of smoking (p = 0.02). Cognitive function tests were more strongly related to the extent than prevalence of ischemic lesions and relationships varied among cognitive domains (p < 0.001). Conclusions: Mixed-effects mixed-distribution models provide a coherent basis for examining relationships involving the prevalence and extent of ischemic brain lesions. Across the cohort and regions we examined, relationships with risk factors and cognitive function appeared to be stronger for extent than for prevalence.