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The primary outcome was longitudinal changes in measures of AD pathology, namely development of pathological amyloid deposition, medial temporal lobe atrophy, and cognitive decline in a prospective cohort study including 394 adults without AD dementia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>High\u2010risk groups defined by phenotype\u2010informed AD PRSs had significantly steeper volume decline in medial temporal cortices, and the high\u2010risk group defined by the cardiovascular\u2010informed AD PRS had significantly increased hazard ratio of pathological amyloid deposition, compared to low\u2010risk groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>AD PRSs informed by inflammatory disorders or cardiovascular risk factors and diseases are associated with development of AD pathology markers and may improve identification of subjects at risk for progression of 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