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Tau PET imaging as a mediator between glymphatic dysfunction and cognitive decline: a cross-sectional and
Juyeon Ko1, Gayeong Son2, Ha Eun Seo3
1Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
European Journal of Nuclear Medicine and Molecular Imaging
|January 23, 2026
Summary
Impaired glymphatic function, measured by diffusion tensor imaging along the perivascular space (DTI-ALPS), is linked to cognitive decline. Tau pathology partially mediates this association, suggesting a pathway from glymphatic dysfunction to cognitive impairment.
Area of Science:
- Neuroimaging
- Neurology
- Gerontology
Background:
- Glymphatic system dysfunction is implicated in cognitive decline.
- The mediating role of tau pathology in this relationship is not fully understood.
Purpose of the Study:
- Investigate if tau burden mediates the link between DTI-ALPS and cognitive/atrophy.
- Determine if DTI-ALPS predicts longitudinal cognitive decline.
Main Methods:
- 144 participants (MCI, dementia, normal cognition) underwent MRI, PET scans, and neuropsychological tests.
- Mediation analyses explored tau's role between DTI-ALPS and cognition/MRI.
- Linear mixed-effects models analyzed longitudinal changes in 101 individuals.
Main Results:
- Lower DTI-ALPS index was observed in cognitively impaired individuals.
- Reduced DTI-ALPS correlated with higher tau burden and poorer cognition.
- Tau burden explained 21-27% of the DTI-ALPS and cognition association.
- Lower baseline DTI-ALPS predicted faster cognitive decline.
Conclusions:
- DTI-ALPS index may serve as an indirect marker of glymphatic dysfunction.
- Tau accumulation partially links impaired glymphatic clearance to cognitive decline.
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