| Title: | Association of cardiovascular-kidney-metabolic health with structural brain imaging and the risk of specific-cause dementia: a cohort study |
| Journal: | American Journal of Geriatric Psychiatry |
| Published: | 1 Mar 2026 |
| DOI: | https://doi.org/10.1016/j.jagp.2026.03.205 |
Publication 17557
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Abstract
Objectives Cardiovascular-kidney-metabolic (CKM) syndrome may represent the coexistence of multiple risk factors for dementia; however, its large sample-based effects on the risk of specific-cause dementia and the alterations revealed by brain imaging remain unclear. Measurements We included 239,617 dementia-free participants from the UK Biobank in this study. Multivariate Cox regression analyses and stratifications were used to assess longitudinal associations. Linear regression analyses were employed to evaluate CKM-brain structure links. Sensitivity and Mendelian randomization (MR) analyses were performed to confirm the robustness of the results. Results Over a 13.6-year median follow-up duration, 3,503 participants developed dementia that included 1,526 Alzheimer's disease (AD) and 770 vascular dementia (VaD) cases. Advanced CKM syndrome stages showed a dose-dependent risk of dementia: stage 3 (Hazard Ratio [HR] = 1.74 vs. stage 0, χ² = 19.92, df = 1, p < 0.001) and stage 4 (HR = 1.92, χ² = 38.52, df = 1, p < 0.001). This pattern held for VaD but not AD, although CKM syndrome stage progression elevated the risk of AD by 130%. MR analysis confirmed significant associations. As a component of the CKM syndrome, metabolic disorders (abdominal obesity and metabolic syndrome) significantly elevated the risk of VaD but not that of AD. Notably, midlife adults, women, non-APOEε4 carriers, and those displaying low physical activity and education exhibited heightened susceptibility to dementia. Further, there was a spatial correlation pattern between CKM syndrome and brain atrophy (imaging biomarker of dementia): early sensorimotor-limbic shrinkage expanded to prefrontal-parietal and posterior cingulate regions, culminating in hippocampal degeneration. Conclusions and implications CKM syndrome stages may serve as a comprehensive predictor of dementia. Individualized monitoring of CKM factors across the lifespan of a person may mitigate progressive neurodegeneration and the risk of dementia</p>
6 Authors
- Heng Zhang
- Xinhui Liu
- Diyang Lyu
- Tingting Hou
- Fuzhong Xue
- Yifeng Du
1 Application
| Application ID | Title |
|---|---|
| 98273 | The causal relationship of environmental, lifestyle, and genetic factors with chronic diseases, mental health, and cancer. |
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