{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:06:55Z","timestamp":1789416415420,"version":"build-2803163510"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>People with dementia are often prescribed cardiometabolic medications; however, the impact of this medication exposome on cognitive trajectories remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed data from National Alzheimer\u2019s Coordinating Center (n\u2009=\u200928\u00a0044), Australian Imaging, Biomarkers and Lifestyle study (n\u2009=\u20091708) and Health and Aging Brain Study: Health Disparities (n\u2009=\u20091425) to examine associations between seven classes of cardiometabolic medications and cognitive outcomes [CDR sum of boxes (CDR-SB)], using linear mixed-effects models with time-varying exposure. Subgroup analyses were conducted by sex, apolipoprotein E (APOE) \u03b54, baseline age group and four progression groups [i.e. non-progression, cognitively unimpaired-to-mild cognitive impairment (CU-to-MCI), CU\/MCI-to-Alzheimer\u2019s dementia (ADem) progression and ADem-stable group]. A meta-analysis was also performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Angiotensin-converting enzyme inhibitors and metformin were associated with a slower cognitive decline. Diuretics showed comparable associations, although these effects were restricted to specific subgroups. Statins exhibited divergent, stage-specific associations, with inverse associations observed in the CU\/MCI-to-ADem subgroup and positive associations in the ADem-stable subgroup. Angiotensin II receptor blockers were associated with a greater longitudinal increase in CDR-SB among participants in the non-progression subgroup. Calcium channel blockers showed limited subgroup-specific cognitive benefit but were also associated with an accelerated increase in CDR-SB over time. \u03b2-blockers demonstrated no consistent association with cognitive trajectories, with evidence of a lower CDR-SB slope observed only in a cohort-specific analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Future research should incorporate pharmacy-verified medication exposure, explicit dosing information and dynamically modelled trajectories, while routinely assessing baseline and follow-up cognitive outcomes in pharmacotherapy trials involving older adults.<\/jats:p>\n                  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