Poor glymphatic function is associated with mild cognitive impairment and its progression to Alzheimer's disease: A DTI-ALPS study.

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The Journal of Prevention of Alzheimer's Disease Pub Date : 2025-04-11 DOI:10.1016/j.tjpad.2025.100156

Cuiping Bao, Hongbin Luo, Jiao Wang, Xuehuan Liu, Yiming Li, Jun Yang, Chong Chen, Rongrong Yang, Weili Ba, Xinying Lian, Michelle Dunk, Jun Liu, Weili Xu

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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]: 2.0-4.9 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 approximately 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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不良的淋巴功能与轻度认知障碍及其发展为阿尔茨海默病有关：一项DTI-ALPS研究

背景：我们旨在探讨ALPS指数与认知正常MCI （CN）和MCI进展性AD发生率之间的关系，以及潜在的中介因素。方法：本研究纳入来自阿尔茨海默病神经影像学倡议的519名成年人，其中253名（48.75%）CN和266名（51.25%）MCI参与者。基线时采用弥散张量图像测量淋巴功能（沿血管周围间隙[ALPS]指数评估）。神经生物标志物（脑脊液、血浆和PET中的Aβ和tau）和认知功能作为介质。采用Cox、Laplace回归和中介分析对数据进行分析。结果：在随访期间（中位3.6年，四分位数间距[IQR]: 2.0-4.9年），CN队列中有30名（11.86%）参与者发展为MCI， MCI队列中有73名（27.4%）参与者发展为AD。MCI和AD较高ALPS指数的风险比（95%可信区间[ci]）分别为0.605（0.386 ~ 0.948）和0.501（0.356 ~ 0.706）。此外，高ALPS指数的参与者MCI和AD的发病时间分别延长了3.837年和3.466年。脉络丛中的Aβ(17.1%)，皮层中的tau[颞下（21.1%），中颞（av1451: 17.0%, FTP: 15.5%），颞上（7.7%），上颞（av1451: 17.5%, FTP: 16.6%）]和执行功能（14.1%）介导了ALPS与MCI-AD进展之间的关联。结论：高ALPS指数可降低MCI风险，并将MCI进展为AD的时间延迟约3.5年。脉络膜丛中的Aβ、皮层中的tau和执行功能可能部分介导MCI-AD进展与ALPS指数的关系。

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来源期刊

The Journal of Prevention of Alzheimer's Disease Medicine-Psychiatry and Mental Health

CiteScore

9.20

自引率

0.00%

发文量

期刊介绍： The JPAD Journal of Prevention of Alzheimer’Disease will publish reviews, original research articles and short reports to improve our knowledge in the field of Alzheimer prevention including: neurosciences, biomarkers, imaging, epidemiology, public health, physical cognitive exercise, nutrition, risk and protective factors, drug development, trials design, and heath economic outcomes.JPAD will publish also the meeting abstracts from Clinical Trial on Alzheimer Disease (CTAD) and will be distributed both in paper and online version worldwide.We hope that JPAD with your contribution will play a role in the development of Alzheimer prevention.