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Peer-reviewedCC BYFrontiers in Aging Neuroscience

Circulating osteocalcin and incident dementia in the UK Biobank: a prospective cohort and exploratory multi-omics analysis

  • Xinxiang Su1
  • Xinxiang Su2
  • Yan Mao3
  • Chao Yang1
  • Hongmei Liao1
  • Hong Zhao1
  • Yingjun Zhang1
  • Wei Wei1
  • Shengxiang Bi1
  • Bo Liu1
  • Bo Liu4
  • Xiaoqian Fu1
11 more authors
  • Liang Ren1
  • Liang Ren5
  • Hongping Yu3
  • Hongping Yu6
  • Hongping Yu7
  • Hongping Yu8
  • Yihua Yang1
  • Yihua Yang3
  • Ming Liao1
  • Ming Liao4
  • Ming Liao9
9 affiliations
  1. 1Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
  2. 2Guilin Medical University, Guilin, China
  3. 3Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, China
  4. 4Guangxi Clinical Research Center for Reproductive Medicine, Nanning, China
  5. 5Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
  6. 6Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China
  7. 7Key Cultivated Laboratory of Cancer Molecular Medicine of Guangxi Health Commission, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
  8. 8Guangxi Zhuang Autonomous Region Molecular Medical Engineering Research Center for Cancer, Nanning, Guangxi, China
  9. 9Department of Epidemiology and Health Statistics, School of Public Health of Guangxi Medical University, Nanning, China
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Abstract

BackgroundWe examined baseline relative circulating osteocalcin (OCN) in relation to incident dementia in UK Biobank.MethodsThe longitudinal cohort comprised 43,942 participants; models used available complete records. Cox models used baseline OCN standardized per SD and follow-up censored at diagnosis, death, or November 27, 2024. Cognitive, MRI, and baseline molecular analyses were exploratory.ResultsIn the fully adjusted model, OCN was not clearly associated with all-cause dementia (HR 1.052; 95% CI, 0.988–1.120; p = 0.117; N = 40,253; 1,095 events). The vascular dementia estimate was nominally positive (HR 1.159; 95% CI, 1.010–1.328; p = 0.035), but did not survive Holm correction across three secondary outcomes (adjusted p = 0.105) and weakened after excluding baseline stroke. Adding OCN changed the mean fivefold cross-validated C index from 0.84628 to 0.84642 (ΔC = 0.00014). No baseline cognitive association survived Holm correction across four tests. Nominal hippocampal and WMH associations in the larger MRI sample were not evident in matched extensively adjusted samples. Repeated-visit cognitive models did not yield adequately sized multiple classes for interpretable class-membership regressions. Baseline measured-only molecular analyses identified OCN-related correlations, but age- and sex-adjusted BCAA correlations did not survive panel-wise Bonferroni correction.ConclusionBaseline relative OCN did not show a clear fully adjusted all-cause dementia association or useful incremental discrimination. Subtype, cognitive, imaging, and molecular findings remain exploratory. These data do not establish a compensatory mechanism or clinical predictive utility.

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Cite

BibTeXRIS
BibTeX
@article{su2026circulating,
  title = {{Circulating osteocalcin and incident dementia in the UK Biobank: a prospective cohort and exploratory multi-omics analysis}},
  author = {Xinxiang Su and Xinxiang Su and Yan Mao and Chao Yang and Hongmei Liao and Hong Zhao and Yingjun Zhang and Wei Wei and Shengxiang Bi and Bo Liu and Bo Liu and Xiaoqian Fu and Liang Ren and Liang Ren and Hongping Yu and Hongping Yu and Hongping Yu and Hongping Yu and Yihua Yang and Yihua Yang and Ming Liao and Ming Liao and Ming Liao},
  journal = {Frontiers in Aging Neuroscience},
  year = {2026},
  month = oct,
  doi = {10.3389/fnagi.2026.1974960},
  url = {https://doi.org/10.3389/fnagi.2026.1974960},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Circulating osteocalcin and incident dementia in the UK Biobank: a prospective cohort and exploratory multi-omics analysis
AU  - Xinxiang Su
AU  - Xinxiang Su
AU  - Yan Mao
AU  - Chao Yang
AU  - Hongmei Liao
AU  - Hong Zhao
AU  - Yingjun Zhang
AU  - Wei Wei
AU  - Shengxiang Bi
AU  - Bo Liu
AU  - Bo Liu
AU  - Xiaoqian Fu
AU  - Liang Ren
AU  - Liang Ren
AU  - Hongping Yu
AU  - Hongping Yu
AU  - Hongping Yu
AU  - Hongping Yu
AU  - Yihua Yang
AU  - Yihua Yang
AU  - Ming Liao
AU  - Ming Liao
AU  - Ming Liao
PY  - 2026
DA  - 2026/10/26
JO  - Frontiers in Aging Neuroscience
DO  - 10.3389/fnagi.2026.1974960
UR  - https://doi.org/10.3389/fnagi.2026.1974960
AB  - BackgroundWe examined baseline relative circulating osteocalcin (OCN) in relation to incident dementia in UK Biobank.MethodsThe longitudinal cohort comprised 43,942 participants; models used available complete records. Cox models used baseline OCN standardized per SD and follow-up censored at diagnosis, death, or November 27, 2024. Cognitive, MRI, and baseline molecular analyses were exploratory.ResultsIn the fully adjusted model, OCN was not clearly associated with all-cause dementia (HR 1.052; 95% CI, 0.988–1.120; p = 0.117; N = 40,253; 1,095 events). The vascular dementia estimate was nominally positive (HR 1.159; 95% CI, 1.010–1.328; p = 0.035), but did not survive Holm correction across three secondary outcomes (adjusted p = 0.105) and weakened after excluding baseline stroke. Adding OCN changed the mean fivefold cross-validated C index from 0.84628 to 0.84642 (ΔC = 0.00014). No baseline cognitive association survived Holm correction across four tests. Nominal hippocampal and WMH associations in the larger MRI sample were not evident in matched extensively adjusted samples. Repeated-visit cognitive models did not yield adequately sized multiple classes for interpretable class-membership regressions. Baseline measured-only molecular analyses identified OCN-related correlations, but age- and sex-adjusted BCAA correlations did not survive panel-wise Bonferroni correction.ConclusionBaseline relative OCN did not show a clear fully adjusted all-cause dementia association or useful incremental discrimination. Subtype, cognitive, imaging, and molecular findings remain exploratory. These data do not establish a compensatory mechanism or clinical predictive utility.
SN  - 1663-4365
ER  -