Analysis Multidimensional Physical Fitness and Dementia Risk with UK Biobank

Overview

Dementia affects over 55 million people worldwide, yet whether distinct domains of physical fitness independently protect against neurodegeneration through shared or divergent biological mechanisms remains unknown. Using the UK Biobank, we integrated epidemiological, proteomic, and neuroimaging analyses to systematically characterize the multidimensional fitness-dementia relationship.

Higher handgrip strength, cardiorespiratory fitness, and pulmonary function were each independently associated with reduced dementia risk, with stronger associations in women and younger individuals. Plasma proteomic profiling revealed domain-specific molecular signatures, including neurofilament light chain for muscular and cardiorespiratory fitness and inflammatory mediators such as GDF15 for pulmonary function, with multiple proteins per domain independently predicting dementia and converging on neuroinflammatory and neurovascular pathways.

Brain MRI analyses identified hippocampal volume as a significant structural mediator, indicating structural preservation as one of multiple mechanistic pathways. These findings reveal that multidimensional physical fitness shapes dementia risk through distinct yet converging neuroinflammatory, neurovascular, and structural brain mechanisms, with implications for life-course prevention.

Detailed description and discussion can be found in paper:
To cite:

@article{sun2026multidimensional,
  title={Multidimensional physical fitness is associated with reduced dementia risk through proteomic and neuroimaging pathways: a prospective cohort study of the UK Biobank},
  author={Sun, Yiqing and Lin, Runyu and Qin, Jiayue and Pan, Feiyue and Li, Bingjie and Yao, Zhigang},
  journal={arXiv preprint arXiv:2604.03952},
  year={2026}
}