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Peer-reviewedCC BY 4.0Molecular Psychiatry

The choroid plexus, cognitive decline, and incident dementia: insights from the UK Biobank

  • Tianyu Yu1,2
  • Xiaolei Han2,3
  • Xin Huang2,3
  • Hongli Chang2
  • Xinyu Liu1,2
  • Minle Tian2,3
  • Xiaomeng Li2,3
  • Yiming Guo2
  • Jiahao Ding2
  • Xuewei Li2,3
  • Ming Mao2,3
  • Yi Dong2,3
4 more authors
  • Yifeng Du2,3
  • Lin Lu2,4
  • Chengxuan Qiu2,3,5
  • Yongxiang Wang1,2,3,5
5 affiliations
  1. 1Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong P.R. China
  2. 2Institute of Brain Science and Brain-inspired Research, Shandong Provincial Key Laboratory of Brain Science, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong P.R. China
  3. 3Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Department of Neurology, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong P.R. China
  4. 4Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, Beijing, P.R. China
  5. 5Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University, Stockholm, Sweden
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Abstract

The choroid plexus (CP) plays a crucial role in cerebrospinal fluid secretion and the maintenance of brain homeostasis. Its structure and function have been implicated in the pathogenesis of dementia; however, the longitudinal associations of CP with dementia and structural brain biomarkers remain unclear. This prospective cohort study utilized data from the UK Biobank, including 45,306 participants (mean age, 64 years; 47.2% men) who underwent 3.0 T multiparametric brain MRI scans. CP volume and signal intensity were quantified by FreeSurfer software. Measures of grey or white matter macrostructures or microstructures were derived from structural or diffusion MRI. Dementia outcomes were identified using linkage of hospital admission records or death register. Tests for global and domain-specific cognitive functions were administrated at baseline and follow up. Data were analyzed using Cox proportional hazards, Mendelian randomization, linear mixed-effects models, and mediation models. Advancing age was correlated with increased CP volume (R = 0.49, P < 0.001) and decreased CP signal intensity (R = −0.44, P < 0.001). Meanwhile, greater CP volume was associated with an increased risk of all-cause dementia (hazard ratio, 1.61; 95% confidence interval, 1.32–1.97), while higher CP intensity was correlated with a reduced dementia risk (0.44; 0.36–0.55). Reduced volumes of the hippocampus, amygdala, and nucleus accumbens, increased white matter hyperintensity volume, mean diffusivity, and isotropic compartment volume fraction, and decreased intracellular volume fraction significantly mediated up to 42.9% of these associations. This study provides evidence supporting a causal relationship between CP morphological parameters and dementia risk that is partly mediated by specific brain phenotypes, and further suggests that the CP parameters may be valuable biomarkers for structural brain aging and dementia.

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Cite

BibTeXRIS
BibTeX
@article{yu2026choroid,
  title = {{The choroid plexus, cognitive decline, and incident dementia: insights from the UK Biobank}},
  author = {Tianyu Yu and Xiaolei Han and Xin Huang and Hongli Chang and Xinyu Liu and Minle Tian and Xiaomeng Li and Yiming Guo and Jiahao Ding and Xuewei Li and Ming Mao and Yi Dong and Yifeng Du and Lin Lu and Chengxuan Qiu and Yongxiang Wang},
  journal = {Molecular Psychiatry},
  year = {2026},
  month = jul,
  doi = {10.1038/s41380-026-03739-5},
  url = {https://doi.org/10.1038/s41380-026-03739-5},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The choroid plexus, cognitive decline, and incident dementia: insights from the UK Biobank
AU  - Tianyu Yu
AU  - Xiaolei Han
AU  - Xin Huang
AU  - Hongli Chang
AU  - Xinyu Liu
AU  - Minle Tian
AU  - Xiaomeng Li
AU  - Yiming Guo
AU  - Jiahao Ding
AU  - Xuewei Li
AU  - Ming Mao
AU  - Yi Dong
AU  - Yifeng Du
AU  - Lin Lu
AU  - Chengxuan Qiu
AU  - Yongxiang Wang
PY  - 2026
DA  - 2026/07/09
JO  - Molecular Psychiatry
DO  - 10.1038/s41380-026-03739-5
UR  - https://doi.org/10.1038/s41380-026-03739-5
AB  - The choroid plexus (CP) plays a crucial role in cerebrospinal fluid secretion and the maintenance of brain homeostasis. Its structure and function have been implicated in the pathogenesis of dementia; however, the longitudinal associations of CP with dementia and structural brain biomarkers remain unclear. This prospective cohort study utilized data from the UK Biobank, including 45,306 participants (mean age, 64 years; 47.2% men) who underwent 3.0 T multiparametric brain MRI scans. CP volume and signal intensity were quantified by FreeSurfer software. Measures of grey or white matter macrostructures or microstructures were derived from structural or diffusion MRI. Dementia outcomes were identified using linkage of hospital admission records or death register. Tests for global and domain-specific cognitive functions were administrated at baseline and follow up. Data were analyzed using Cox proportional hazards, Mendelian randomization, linear mixed-effects models, and mediation models. Advancing age was correlated with increased CP volume (R = 0.49, P < 0.001) and decreased CP signal intensity (R = −0.44, P < 0.001). Meanwhile, greater CP volume was associated with an increased risk of all-cause dementia (hazard ratio, 1.61; 95% confidence interval, 1.32–1.97), while higher CP intensity was correlated with a reduced dementia risk (0.44; 0.36–0.55). Reduced volumes of the hippocampus, amygdala, and nucleus accumbens, increased white matter hyperintensity volume, mean diffusivity, and isotropic compartment volume fraction, and decreased intracellular volume fraction significantly mediated up to 42.9% of these associations. This study provides evidence supporting a causal relationship between CP morphological parameters and dementia risk that is partly mediated by specific brain phenotypes, and further suggests that the CP parameters may be valuable biomarkers for structural brain aging and dementia.
SN  - 1359-4184
SN  - 1476-5578
ER  -