| Title: | Longitudinal associations of cardiovascular-kidney-metabolic syndrome with midlife or late-life mental disorders and dementia, and the mediating role of metabolomic signature |
| Journal: | Communications Medicine |
| Published: | 28 Apr 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42050355/ |
| DOI: | https://doi.org/10.1038/s43856-026-01608-4 |
| URL: | https://www.nature.com/articles/s43856-026-01608-4_reference.pdf |
Publication 17818
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Abstract
BackgroundCardiovascular-Kidney-Metabolic (CKM) syndrome assesses the interconnections among metabolic, kidney, and cardiovascular diseases, rendering significant prognostic value for age-related chronic diseases and mortality. We aimed to investigate the effects of CKM syndrome on transitions between healthy status, mental disorders, and dementia and evaluate the potential mediating role of a CKM-related metabolomic signature in these associations.MethodsThis prospective longitudinal study used UK Biobank data from 375,203 midlife and older adults at baseline and 188,018 with metabolomic information. CKM was staged from 0 to 4. Mental disorders and dementia were identified via ICD-10. Multi-state models analyzed the impact of CKM on transitions from healthy status to mental disorders and dementia. Competing risk (death) models assessed the associations of CKM with specific mental disorders and dementia. Mediation role of CKM-related metabolomic signature was evaluated.ResultsWe show that per-stage CKM increase elevates hazards of transitioning from healthy to mental disorders (HR = 1.24[1.22-1.26]) and subsequently to dementia (HR = 1.38[1.21-1.58]), or directly to dementia (HR = 1.27[1.21-1.33]). Worsening CKM stages are associated with bipolar, depressive, and anxiety disorders; whilst only advanced stages (3/4) associated with all dementia types. The CKM metabolomic signature mediates 34.9% and 8.1% of associations of CKM with pre-dementia mental disorders and dementia, respectively.ConclusionsCKM syndrome is associated with pre-dementia mental disorders and dementia, emphasizing the need for regular monitoring and early intervention to manage CKM progression and reduce geriatric neuropsychiatric disturbances.</p>
9 Authors
- Xuhao Zhao
- Zhiying Lin
- Haoran Zhang
- Wanheng Zhang
- Zuyun Liu
- Christopher Chen
- Hongwei Ji
- Shaohua Hu
- Xin Xu
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