Association of Cardiovascular-Kidney-Syndrome and Brain Macrostructure and Microstructure Injury: A Prospective Cohort Study.

AIMS: This study aimed to examine the cross-sectional and longitudinal associations between cardiovascular-kidney-metabolic (CKM) syndrome stages and brain macrostructure and microstructure.

MATERIALS AND

METHODS

We conducted a prospective, community-based cohort study using data from 3067 adults aged 50-75 years. Participants were classified using the American Heart Association CKM staging system (Stages 0-4). 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-effects models were used.

RESULTS

Among 3038 participants (mean age 61.9 years, 53.6% female), cross-sectional analyses revealed that advanced CKM stages (3-4) were significantly associated with reduced total brain, grey matter and cerebral white matter volumes, and increased WMHV. Longitudinally, higher baseline CKM stages (particularly Stages 2-3) were associated with accelerated declines in these brain volumes and faster WMHV progression over a median 4.7-year follow-up. DTI analyses further demonstrated a stage-dependent 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.

CONCLUSIONS

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.