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Peer-reviewedCC BY-NC-NDTranslational psychiatry

Association of brain glymphatic system with risk of incident mortality and morbidity.

  • Ya-Ru Zhang1
  • Zhi-Bo Wang2
  • Shu-Yi Huang1
  • Jing Du3
  • Yan Fu4
  • Pei-Yang Gao4
  • Lan Tan4
  • Jian-Feng Feng5,6
  • Wei Cheng5,6
  • Jin-Tai Yu7
7 affiliations
  1. 1Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
  2. 2Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Center for Neurological Disorders, Beijing, China.
  3. 3Centre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry and Mental Health, School of Clinical Medicine, UNSW, Sydney, 1466, Australia.
  4. 4Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
  5. 5Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
  6. 6Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, China.
  7. 7Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China. [email protected].
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Abstract

Brain glymphatic system function as measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS) index has been associated with brain disorders, but its association with mortality and other diseases remains underexplored. This prospective study included 34,268 participants from the UK Biobank with MRI data collected since August 2014. The DTI-ALPS indices‌ of the left and right hemispheres and the average index were calculated‌. The incident mortality and morbidity were defined as the death and disease (cancer, cardiovascular, respiratory, digestive, and neurodegenerative disease) reported between the MRI collection date and December 2021. Cox proportional hazard regression analyses were used to assess the association of DTI-ALPS indices with all-cause and cause-specific mortality and morbidity. We found that a higher DTI-ALPS index, indicated better glymphatic function, was associated with reduced risks of all-cause mortality (HR, 95% CI: 0.85, 0.78-0.93; P < 0.001), cardiovascular disease (CVD)-specific mortality (HR, 95% CI: 0.77, 0.63-0.93; P = 0.01), and neurodegenerative disease-specific mortality (HR, 95% CI: 0.56, 0.37-0.84; P = 0.01). Furthermore, an elevated DTI-ALPS index was associated with reduced risks of CVD (HR, 95% CI: 0.92, 0.89-0.96; P < 0.001) and neurodegenerative disease (HR, 95% CI: 0.68, 0.58-0.80; P < 0.001). The findings deepen the understanding of the role of brain glymphatic system in health.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026association,
  title = {{Association of brain glymphatic system with risk of incident mortality and morbidity.}},
  author = {Ya-Ru Zhang and Zhi-Bo Wang and Shu-Yi Huang and Jing Du and Yan Fu and Pei-Yang Gao and Lan Tan and Jian-Feng Feng and Wei Cheng and Jin-Tai Yu},
  journal = {Translational psychiatry},
  year = {2026},
  month = aug,
  doi = {10.1038/s41398-026-04381-z},
  url = {https://europepmc.org/article/MED/43009471},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Association of brain glymphatic system with risk of incident mortality and morbidity.
AU  - Ya-Ru Zhang
AU  - Zhi-Bo Wang
AU  - Shu-Yi Huang
AU  - Jing Du
AU  - Yan Fu
AU  - Pei-Yang Gao
AU  - Lan Tan
AU  - Jian-Feng Feng
AU  - Wei Cheng
AU  - Jin-Tai Yu
PY  - 2026
DA  - 2026/08/14
JO  - Translational psychiatry
DO  - 10.1038/s41398-026-04381-z
UR  - https://europepmc.org/article/MED/43009471
AB  - Brain glymphatic system function as measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS) index has been associated with brain disorders, but its association with mortality and other diseases remains underexplored. This prospective study included 34,268 participants from the UK Biobank with MRI data collected since August 2014. The DTI-ALPS indices‌ of the left and right hemispheres and the average index were calculated‌. The incident mortality and morbidity were defined as the death and disease (cancer, cardiovascular, respiratory, digestive, and neurodegenerative disease) reported between the MRI collection date and December 2021. Cox proportional hazard regression analyses were used to assess the association of DTI-ALPS indices with all-cause and cause-specific mortality and morbidity. We found that a higher DTI-ALPS index, indicated better glymphatic function, was associated with reduced risks of all-cause mortality (HR, 95% CI: 0.85, 0.78-0.93; P < 0.001), cardiovascular disease (CVD)-specific mortality (HR, 95% CI: 0.77, 0.63-0.93; P = 0.01), and neurodegenerative disease-specific mortality (HR, 95% CI: 0.56, 0.37-0.84; P = 0.01). Furthermore, an elevated DTI-ALPS index was associated with reduced risks of CVD (HR, 95% CI: 0.92, 0.89-0.96; P < 0.001) and neurodegenerative disease (HR, 95% CI: 0.68, 0.58-0.80; P < 0.001). The findings deepen the understanding of the role of brain glymphatic system in health.
SN  - 2158-3188
ER  -