Related Experiment Video
Updated: Jun 4, 2025
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
MRI free water mediates the association between diffusion tensor image analysis along the perivascular space and
Xiaodan Liu1,2, Pauline Maillard3, Giuseppe Barisano4
1Laboratory of FMRI Technology (LOFT), Mark & Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, California, USA.
Introduction:
Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was proposed for assessing glymphatic clearance function. This study evaluated DTI-ALPS as a biomarker for cerebral small vessel disease (cSVD) related vascular cognitive impairment and dementia (VCID).
Methods:
Four independent cohorts were examined. A composite score of executive function (UDS3-EF) was used to evaluate EF status. The association between the ALPS index and UDS3-EF scores and the mediator effect of free water in white matter (WM-FW) on such association was analyzed.
Results:
The ALPS index was significantly associated with UDS3-EF scores in all cohorts. Additionally, WM-FW mediates the relationship between the ALPS index and UDS3-EF scores.
Discussion:
Lower ALPS index may be a surrogate marker of glymphatic dysfunction, which is associated with impaired EF, and this association is mediated by the interstitial fluid (ISF) drainage ISF in WM, providing a clinical rationale for using ALPS index as a biomarker for cSVD-related VCID.
Highlights:
This is the first study to investigate the mediation role of interstitial FW fraction (WM-FW) on the relationship between glymphatic clearance (ALPS index) and EF (UDS3-EF scores) in four independent middle to aged cohorts at risk for cSVD. This study identified that ALPS index was independently associated with UDS3-EF scores after adjusting for demographics, VRFs, and WM hyperintensity burden and that WM-FW mediated this association in all middle to aged cohorts. Our findings suggest that in middle to aged individuals, glymphatic dysfunction (reflected by ALPS index) is strongly associated with EF and that this association is mediated by the ISF drainage in WM. This study provides a strong clinical rationale for the use of the ALPS index as a marker of cognitive function in multi-site observational studies and clinical trials to monitor and prevent VCID.
Insights
The Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) index, a measure of glymphatic function, is linked to executive function deficits in cerebral small vessel disease. White matter free water mediates this association, suggesting ALPS as a biomarker for vascular cognitive impairment.
Area of Science:
- Neuroimaging and Neurology
- Cerebrovascular Diseases
- Cognitive Neuroscience
Background:
- Glymphatic system dysfunction is implicated in cognitive decline.
- Cerebral small vessel disease (cSVD) is a major cause of vascular cognitive impairment and dementia (VCID).
- Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) index is a potential biomarker for glymphatic clearance.
Purpose of the Study:
- To evaluate the DTI-ALPS index as a biomarker for cSVD-related VCID.
- To investigate the association between the ALPS index and executive function (EF).
- To examine the mediating role of white matter free water (WM-FW) in this association.
Main Methods:
- Analysis of four independent cohorts using the DTI-ALPS index.
- Assessment of executive function using a composite score (UDS3-EF).
- Statistical analysis to determine the association between ALPS index and UDS3-EF, and the mediation effect of WM-FW.
Main Results:
- A significant association was found between the ALPS index and UDS3-EF scores across all cohorts.
- White matter free water (WM-FW) was identified as a mediator in the relationship between the ALPS index and executive function.
- The ALPS index remained independently associated with UDS3-EF after adjusting for relevant covariates.
Conclusions:
- A lower ALPS index may indicate glymphatic dysfunction associated with impaired executive function.
- Interstitial fluid drainage in white matter, reflected by WM-FW, mediates the link between glymphatic function and executive function.
- The ALPS index shows clinical utility as a biomarker for monitoring and preventing cSVD-related VCID in observational studies and clinical trials.
