Poor glymphatic function is associated with mild cognitive impairment and its progression to Alzheimer's Disease: A DTI-ALPS Study - 03/04/25

Doi : 10.1016/j.tjpad.2025.100156

Cuiping Bao ¹, Hongbin Luo ², Jao Wang ³, Xuehuan Liu ¹, Yiming Li ¹, Jun Yang ¹, Chong Chen ⁴, Rongrong Yang ⁵, Weili Ba ¹, Xinying Lian ⁶, Michelle Dunk ⁷, Jun Liu ^6,^8,^⁎ , Weili Xu ⁷
¹ Department of Radiology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, 300121, China
² Tianjin Jinnan District Center for Disease Control and Prevention, 28 Highway Road, Jinnan District, Tianjin 300350, China
³ Department of Epidemiology, College of Preventive Medicine, Third Medical University, Chongqing 400038, China
⁴ Department of Clinical Laboratory, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, 300121, China.
⁵ Public Health Science and Engineering College, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
⁶ Tianjin Fourth Central Hospital, The Affiliated Hospital of Tianjin Medical University, Zhongshan Rord 1st Tianjin, 300140, China
⁷ Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Skockholm, Sweden
⁸ Tianjin Fourth Central Hospital, Tianjin University, Zhongshan Rord 1st Tianjin, 300140, China

^⁎Corresponding to: Jun Liu, Tianjin Fourth Central Hospital, The Affiliated Hospital of Tianjin Medical University, Tianjin Fourth Central Hospital, Tianjin University, Zhongshan Rord 1st Tianjin, 300140, ChinaTianjin Fourth Central Hospital, The Affiliated Hospital of Tianjin Medical University, Tianjin Fourth Central HospitalTianjin UniversityZhongshan Rord 1stTianjin300140China

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Highlights

•	Low ALPS index was significantly associated with high risk of MCI, and the risk of MCI decreased linearly with a higher ALPS index
•	High ALPS index was dose-dependently associated with a decreased progression from MCI to AD
•	High ALPS index may delay the MCI onset about 3.8 years among CN participants and delay MCI progression to AD by 3.5 years in MCI group
•	Aβ in choroid plexus, tau in part of the cortex and executive function were partially mediate ALPS-AD association

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Abstract

BACKGROUND

We aimed to explore the association between ALPS index and both risks of MCI from cognitively normal (CN) and incident AD progressed from MCI, as well as potential mediating factors.

METHODS

This study included 519 adults including 253 (48.75 %) CN and 266 (51.25 %) MCI participants from Alzheimer's Disease Neuroimaging Initiative. Glymphatic function (assessed by along the perivascular space [ALPS] index) was measured by diffusion tensor image at baseline. Neurobiomarkers (Aβ and tau from CSF, plasma and PET) and cognitive functions were served as mediators. Data were analyzed using Cox and Laplace regression and mediation analysis.

RESULTS

During follow-up (median 3.6 years, interquartile range [IQR]: 2.0 to 4.9 years), 30 (11.86%) participants developed MCI in the CN cohort and 73 (27.4%) participants progressed to AD in the MCI cohort. The hazard ratios (95% confidence intervals [CIs]) of the higher ALPS index was 0.605 (0.386–0.948) for MCI and 0.501 (0.356–0.706) for AD. In addition, participants with high ALPS index had 3.837 and 3.466 years prolonged onset of MCI and AD, separately. Aβ in choroid plexus (17.1%), tau in cortex [Inferiortemporal (21.1%), Middletemporal (AV1451:17.0%, FTP:15.5%, Superiortemporal(7.7%,), Meta_temporal (AV1451:17.5%, FTP:16.6%)], and executive function (14.1%) mediated the association between ALPS and MCI-AD progression.

CONCLUSION

High ALPS index decreases MCI risk and delays MCI progression to AD by 3.5 years. Aβ in choroid plexus, tau in cortex, and executive function may partially mediate the MCI-AD progression in relation to ALPS index.

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Keywords : Glymphatic function, Along the perivascular spaces, Alzheimer's disease