MRI Free Water Mediates the Association Between Diffusion Tensor Image Analysis Along the Perivascular Space and Executive Function in Four Independent Middle to Aged Cohorts

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2024 Dec 31

PMID 39740225

Authors

Xiaodan Liu

Pauline Maillard

Giuseppe Barisano

Arvind Caprihan

Steven Cen

Xingfeng Shao

Kay Jann

John M Ringman

Hanzhang Lu

Konstantinos Arfanakis

Charles S DeCarli

Brian T Gold

Sudha Seshadri

Claudia L Satizabal

Alexa S Beiser

Mohamad Habes

Joel H Kramer

Lara Stables

Herpreet Singh

Karl G Helmer

Steven M Greenberg

Danny J J Wang

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

MRI free water mediates the association between diffusion tensor image analysis along the perivascular space and executive function in four independent middle to aged cohorts.

Liu X, Maillard P, Barisano G, Caprihan A, Cen S, Shao X Alzheimers Dement. 2024; 21(2):e14453.

PMID: 39740225 PMC: 11851321. DOI: 10.1002/alz.14453.

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