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Participants were classified using the American Heart Association CKM staging system (Stages 0\u20134). Brain MRI was performed across three waves to assess global\/regional volumes, white matter hyperintensity volume (WMHV) and diffusion tensor imaging (DTI) metrics. Adjusted linear regression and linear mixed\u2010effects models were used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 3038 participants (mean age 61.9\u2009years, 53.6% female), cross\u2010sectional analyses revealed that advanced CKM stages (3\u20134) were significantly associated with reduced total brain, grey matter and cerebral white matter volumes, and increased WMHV. Longitudinally, higher baseline CKM stages (particularly Stages 2\u20133) were associated with accelerated declines in these brain volumes and faster WMHV progression over a median 4.7\u2010year follow\u2010up. DTI analyses further demonstrated a stage\u2010dependent pattern of progressive white matter microstructural deterioration. This evolution progressed from focal alterations in early stages to widespread integrity loss in Stage 4, characterised by significant reductions in fractional anisotropy and elevated mean, axial and radial diffusivities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings indicate that CKM syndrome severity is associated with abnormalities in brain macrostructure and microstructure. This is evidenced by both progressive white matter microstructural deterioration, which is detectable early, and concomitant, albeit more modest, declines in brain macrostructure. These results underscore the importance of early identification and monitoring of CKM syndrome to help mitigate or delay subsequent decline in brain health.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70605","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:57:42Z","timestamp":1772967462000},"page":"4148-4161","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Cardiovascular\u2010Kidney\u2010Syndrome and Brain Macrostructure and Microstructure Injury: A Prospective Cohort Study"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9237-6771","authenticated-orcid":false,"given":"Guanyu","family":"Niu","sequence":"first","affiliation":[{"name":"Department of Neurology Beijing Tiantan Hospital, Capital Medical University  Beijing China"},{"name":"China National Clinical Research Center for Neurological Diseases  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