Abstract
Cardiovascular health metrics are now widely recognized as modifiable risk factors for cognitive decline and dementia. Metabolic perturbations might play roles in the linkage of cardiovascular diseases and dementia. Circulating metabolites profiling by metabolomics may improve understanding of the potential mechanism by which cardiovascular risk factors contribute to cognitive decline. In a prospective community-based cohort in China (n = 725), 312 serum metabolic phenotypes were quantified, and cardiovascular health score was calculated including smoking, exercise, sleep, diet, body mass index, blood pressure, and blood glucose. Cognitive function assessments were conducted in baseline and follow-up visits to identify longitudinal cognitive decline. A better cardiovascular health was significantly associated with lower risk of concentration decline and orientation decline (hazard ratio (HR): 0.84–0.90; p < 0.05). Apolipoprotein-A1, high-density lipoprotein (HDL) cholesterol, cholesterol ester, and phospholipid concentrations were significantly associated with a lower risk of longitudinal memory and orientation decline (p < 0.05 and adjusted-p < 0.20). Mediation analysis suggested that the negative association between health status and the risk of orientation decline was partly mediated by cholesterol ester and total lipids in HDL-2 and -3 (proportion of mediation: 7.68–8.21%, both p < 0.05). Cardiovascular risk factors were associated with greater risks of cognitive decline, which were found to be mediated by circulating lipoproteins, particularly the medium-size HDL components. These findings underscore the potential of utilizing lipoproteins as targets for early stage dementia screening and intervention.
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Data Availability
The data sets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Abbreviations
- Apo:
-
Apolipoprotein
- CE:
-
Cholesterol ester
- CH:
-
Cholesterol
- FDR:
-
False discovery rate
- HDL:
-
High-density lipoprotein
- HDL-C:
-
High-density lipoprotein-cholesterol
- HR:
-
Hazard ratio
- LDL-C:
-
Low-density lipoprotein-cholesterol
- LP:
-
Total lipids including phospholipids, free cholesterol, triglycerides and cholesterol
- MMSE:
-
Mini-Mental State Examination
- MoCA:
-
Montreal Cognitive Assessment
- PL:
-
Phospholipids
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Acknowledgements
We are very grateful to all the participants in this study for their enthusiastic collaboration, the personnel from Fudan University Taizhou Institute of Health Sciences for their contributions on data collection, and staff of Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Fudan University, for their assistance in metabolomic analysis.
Funding
We acknowledge financial supports from the National Key Research and Development program of China (2022YFC3400700, 2022YFA0806400, 2021YFC2500100, 2020YFE0201600), the Science and Technology Innovation 2030 Major Projects (2022ZD0211600), the Shanghai Rising-Star Program (22QA1404000), Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), the Natural Science Foundation of Shanghai, China (22ZR1405300), the National Natural Science Foundation of China (31821002), the Key Research and Development Plans of Jiangsu Province, China (BE2021696), and the Greater Bay Area Institute of Precision Medicine (Guangzhou).
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JL, XC and YJ conceived of the study design. JL and QH performed the statistical analyses and drafted the work. YW, MC and YA performed the data visualization. KX, CS, ZL and LJ scrutinized the statistics. LJ, HT, XC and YJ supervised the study. HT, XC and YJ substantively revised the manuscript. All authors provided critical revisions of the draft and approved the submitted draft. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. YJ is the guarantor.
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Li Jin, Huiru Tang, Xingdong Chen are the Editorial Board members of Phenomics, and they were not involved in reviewing this paper.
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The TIS was approved by the Ethics Committee of the School of Life Sciences, Fudan University, and Fudan University Taizhou Institute of Health Sciences (institutional review board approval numbers: 496 and B017, respectively).
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All participants gave their written informed consent before data and biospecimen collection.
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Li, J., Huang, Q., Wang, Y. et al. Circulating Lipoproteins Mediate the Association Between Cardiovascular Risk Factors and Cognitive Decline: A Community-Based Cohort Study. Phenomics 4, 51–55 (2024). https://doi.org/10.1007/s43657-023-00120-2
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DOI: https://doi.org/10.1007/s43657-023-00120-2