MRI free water as a biomarker for cognitive performance: Validation in the MarkVCID consortium

Pauline Maillard; Laura J. Hillmer; Hanzhang Lu; Konstantinos Arfanakis; Brian T. Gold; Christopher E. Bauer; Joel H. Kramer; Adam M. Staffaroni; Lara Stables; Danny J.J. Wang; Sudha Seshadri; Claudia L. Satizabal; Alexa Beiser; Mohamad Habes; Myriam Fornage; Thomas H. Mosley; Gary A. Rosenberg; Baljeet Singh; Herpreet Singh; Kristin Schwab; Karl G. Helmer; Steven M. Greenberg; Charles DeCarli; Arvind Caprihan

doi:10.1002/dad2.12362

MRI free water as a biomarker for cognitive performance: Validation in the MarkVCID consortium

Pauline Maillard, Laura J. Hillmer, Hanzhang Lu, Konstantinos Arfanakis, Brian T. Gold, Christopher E. Bauer, Joel H. Kramer, Adam M. Staffaroni, Lara Stables, Danny J.J. Wang, Sudha Seshadri, Claudia L. Satizabal, Alexa Beiser, Mohamad Habes, Myriam Fornage, Thomas H. Mosley, Gary A. Rosenberg, Baljeet Singh, Herpreet Singh, Kristin SchwabKarl G. Helmer, Steven M. Greenberg, Charles DeCarli, Arvind Caprihan

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Introduction: To evaluate the clinical validity of free water (FW), a diffusion tensor imaging–based biomarker kit proposed by the MarkVCID consortium, by investigating the association between mean FW (mFW) and executive function. Methods: Baseline mFW was related to a baseline composite measure of executive function (EFC), adjusting for relevant covariates, in three MarkVCID sub-cohorts, and replicated in five, large, independent legacy cohorts. In addition, we tested whether baseline mFW predicted accelerated EFC score decline (mean follow-up time: 1.29 years). Results: Higher mFW was found to be associated with lower EFC scores in MarkVCID legacy and sub-cohorts (p-values < 0.05). In addition, higher baseline mFW was associated significantly with accelerated decline in EFC scores (p = 0.0026). Discussion: mFW is a sensitive biomarker of cognitive decline, providing a strong clinical rational for its use as a marker of white matter (WM) injury in multi-site observational studies and clinical trials of vascular cognitive impairment and dementia (VCID).

Original language	English
Article number	e12362
Journal	Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume	14
Issue number	1
DOIs	https://doi.org/10.1002/dad2.12362
State	Published - 2022

Bibliographical note

Publisher Copyright:
© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.

Funding

The authors thank: Bruce Fischl, Department of Radiology, Massachusetts General Hospital; Arnold M. Evia, Rush Alzheimer's Disease Center, Rush University Medical Center; Nazanin Makkinejad, Department of Biomedical Engineering, Illinois Institute of Technology; Xin Li and Yang Li, Department of Radiology, Johns Hopkins University School of Medicine; Samantha Ma, Departments of Neurology and Radiology, Keck School of Medicine, University of Southern California; Elyas Fadaee, Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health San Antonio; Andrew Warren, Mitchell Horn, and Vanessa Gonzalez, Department of Neurology, Massachusetts General Hospital; and Linda McGavern from National Institute of Health (NIH) andNational Institute of Neurological Disorders and Stroke (NINDS). The Atherosclerosis Risk in Communities (AStudy is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I). Neurocognitive data are collected by U01 2U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, 2U01HL096917 from the NIH (NHLBI, NINDS, National Institute of Aging (NIA), and National Institute on Deafness and Communication Disorders (NIDCD), and with previous brain MRI examinations funded by R01‐HL70825 from the NHLBI. The authors thank the staff and participants of the ARIC study for their important contributions. U24NS100591; UH3NS100599; UH3NS100588; UH3NS100608; UH3NS100605; UH3NS100606; UH3NS100598; UH3NS100614; P30 AG 010129; 5UH2NS100614‐02; K23AG061253; P30 GM 122734. The PRISMA 3T upgrade at The Mind Research Network was supported by the NIH award S10OD025313. Dr. Konstantinos Arfanakis: R01AG064233 (support to institution); R01AG052200 (support to institution); Dr. Danny Wang: R01EB028297 (support to institution); R01NS114382 (support to institution); Dr. Joel Kramer: NIH funding (support to institution); Dr. Adam Staffaroni: NIH (support to institution), Bluefield Project to Cure Frontotemporal Dementia (support to institution); Dr. Karl Helmer: NIH (support to institution), Boston Scientific (support to institution), Minoryx (support to institution); Dr. Steven Greenberg: NIH (support to Dr. Greenberg); Dr. Charles DeCarli: NIH funding (support to institution); Dr. Claudia Satizabal: Texas Alzheimer's Research and Care Consortiium/State of Texas 2020‐58‐81‐CR (support to Dr. Satizabal and to institution). The authors thank: Bruce Fischl, Department of Radiology, Massachusetts General Hospital; Arnold M. Evia, Rush Alzheimer's Disease Center, Rush University Medical Center; Nazanin Makkinejad, Department of Biomedical Engineering, Illinois Institute of Technology; Xin Li and Yang Li, Department of Radiology, Johns Hopkins University School of Medicine; Samantha Ma, Departments of Neurology and Radiology, Keck School of Medicine, University of Southern California; Elyas Fadaee, Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health San Antonio; Andrew Warren, Mitchell Horn, and Vanessa Gonzalez, Department of Neurology, Massachusetts General Hospital; and Linda McGavern from National Institute of Health (NIH) andNational Institute of Neurological Disorders and Stroke (NINDS). The Atherosclerosis Risk in Communities (AStudy is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I). Neurocognitive data are collected by U01 2U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, 2U01HL096917 from the NIH (NHLBI, NINDS, National Institute of Aging (NIA), and National Institute on Deafness and Communication Disorders (NIDCD), and with previous brain MRI examinations funded by R01-HL70825 from the NHLBI. The authors thank the staff and participants of the ARIC study for their important contributions. U24NS100591; UH3NS100599; UH3NS100588; UH3NS100608; UH3NS100605; UH3NS100606; UH3NS100598; UH3NS100614; P30 AG 010129; 5UH2NS100614-02; K23AG061253; P30 GM 122734. The PRISMA 3T upgrade at The Mind Research Network was supported by the NIH award S10OD025313. Dr. Konstantinos Arfanakis: R01AG064233 (support to institution); R01AG052200 (support to institution); Dr. Danny Wang: R01EB028297 (support to institution); R01NS114382 (support to institution); Dr. Joel Kramer: NIH funding (support to institution); Dr. Adam Staffaroni: NIH (support to institution), Bluefield Project to Cure Frontotemporal Dementia (support to institution); Dr. Karl Helmer: NIH (support to institution), Boston Scientific (support to institution), Minoryx (support to institution); Dr. Steven Greenberg: NIH (support to Dr. Greenberg); Dr. Charles DeCarli: NIH funding (support to institution); Dr. Claudia Satizabal: Texas Alzheimer's Research and Care Consortiium/State of Texas 2020-58-81-CR (support to Dr. Satizabal and to institution).

Funders	Funder number
Department of Biomedical Engineering
Department of Medicine (Neurology)
Elyas Fadaee
Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health San Antonio
Nazanin Makkinejad
Rush University Medical Center
Texas Alzheimer's Research and Care Consortiium/State of Texas 2020-58-81-CR
Texas Alzheimer's Research and Care Consortiium/State of Texas 2020-58-81-CR
National Institutes of Health (NIH)
National Institute on Aging
National Heart, Lung, and Blood Institute Family Blood Pressure Program	2U01HL096899, U01 2U01HL096812, 2U01HL096814, 2U01HL096902, HHSN268201700003I, 2U01HL096917
National Heart, Lung, and Blood Institute Family Blood Pressure Program
National Institute on Deafness and Other Communication Disorders	UH3NS100608, P30 AG 010129, UH3NS100606, R01EB028297, K23AG061253, R01AG052200, 5UH2NS100614-02, P30 GM 122734, R01NS114382, S10OD025313, UH3NS100598, UH3NS100588, UH3NS100599, R01‐HL70825, R01AG064233, UH3NS100605, U24NS100591
National Institute on Deafness and Other Communication Disorders
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council
Massachusetts General Hospital
University of Southern California
Boston Scientific Corporation
Johns Hopkins University School of Medicine
Illinois Institute of Technology
Department of Radiology, Weill Cornell Medical College

Keywords

VCID
biomarker
diffusion tensor imaging
free water
small vessel disease
vascular contributions to cognitive impairment and dementia
white matter injury

ASJC Scopus subject areas

Clinical Neurology
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/dad2.12362

Cite this

Maillard, P., Hillmer, L. J., Lu, H., Arfanakis, K., Gold, B. T., Bauer, C. E., Kramer, J. H., Staffaroni, A. M., Stables, L., Wang, D. J. J., Seshadri, S., Satizabal, C. L., Beiser, A., Habes, M., Fornage, M., Mosley, T. H., Rosenberg, G. A., Singh, B., Singh, H., ... Caprihan, A. (2022). MRI free water as a biomarker for cognitive performance: Validation in the MarkVCID consortium. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, 14(1), Article e12362. https://doi.org/10.1002/dad2.12362

@article{02c9199047c044c88fe184f95404eab7,

title = "MRI free water as a biomarker for cognitive performance: Validation in the MarkVCID consortium",

abstract = "Introduction: To evaluate the clinical validity of free water (FW), a diffusion tensor imaging–based biomarker kit proposed by the MarkVCID consortium, by investigating the association between mean FW (mFW) and executive function. Methods: Baseline mFW was related to a baseline composite measure of executive function (EFC), adjusting for relevant covariates, in three MarkVCID sub-cohorts, and replicated in five, large, independent legacy cohorts. In addition, we tested whether baseline mFW predicted accelerated EFC score decline (mean follow-up time: 1.29 years). Results: Higher mFW was found to be associated with lower EFC scores in MarkVCID legacy and sub-cohorts (p-values < 0.05). In addition, higher baseline mFW was associated significantly with accelerated decline in EFC scores (p = 0.0026). Discussion: mFW is a sensitive biomarker of cognitive decline, providing a strong clinical rational for its use as a marker of white matter (WM) injury in multi-site observational studies and clinical trials of vascular cognitive impairment and dementia (VCID).",

keywords = "VCID, biomarker, diffusion tensor imaging, free water, small vessel disease, vascular contributions to cognitive impairment and dementia, white matter injury",

author = "Pauline Maillard and Hillmer, \{Laura J.\} and Hanzhang Lu and Konstantinos Arfanakis and Gold, \{Brian T.\} and Bauer, \{Christopher E.\} and Kramer, \{Joel H.\} and Staffaroni, \{Adam M.\} and Lara Stables and Wang, \{Danny J.J.\} and Sudha Seshadri and Satizabal, \{Claudia L.\} and Alexa Beiser and Mohamad Habes and Myriam Fornage and Mosley, \{Thomas H.\} and Rosenberg, \{Gary A.\} and Baljeet Singh and Herpreet Singh and Kristin Schwab and Helmer, \{Karl G.\} and Greenberg, \{Steven M.\} and Charles DeCarli and Arvind Caprihan",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Alzheimer's \& Dementia: Diagnosis, Assessment \& Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.",

year = "2022",

doi = "10.1002/dad2.12362",

language = "English",

volume = "14",

number = "1",

}

Maillard, P, Hillmer, LJ, Lu, H, Arfanakis, K, Gold, BT, Bauer, CE, Kramer, JH, Staffaroni, AM, Stables, L, Wang, DJJ, Seshadri, S, Satizabal, CL, Beiser, A, Habes, M, Fornage, M, Mosley, TH, Rosenberg, GA, Singh, B, Singh, H, Schwab, K, Helmer, KG, Greenberg, SM, DeCarli, C & Caprihan, A 2022, 'MRI free water as a biomarker for cognitive performance: Validation in the MarkVCID consortium', Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, vol. 14, no. 1, e12362. https://doi.org/10.1002/dad2.12362

TY - JOUR

T1 - MRI free water as a biomarker for cognitive performance

T2 - Validation in the MarkVCID consortium

AU - Maillard, Pauline

AU - Hillmer, Laura J.

AU - Lu, Hanzhang

AU - Arfanakis, Konstantinos

AU - Gold, Brian T.

AU - Bauer, Christopher E.

AU - Kramer, Joel H.

AU - Staffaroni, Adam M.

AU - Stables, Lara

AU - Wang, Danny J.J.

AU - Seshadri, Sudha

AU - Satizabal, Claudia L.

AU - Beiser, Alexa

AU - Habes, Mohamad

AU - Fornage, Myriam

AU - Mosley, Thomas H.

AU - Rosenberg, Gary A.

AU - Singh, Baljeet

AU - Singh, Herpreet

AU - Schwab, Kristin

AU - Helmer, Karl G.

AU - Greenberg, Steven M.

AU - DeCarli, Charles

AU - Caprihan, Arvind

PY - 2022

Y1 - 2022

N2 - Introduction: To evaluate the clinical validity of free water (FW), a diffusion tensor imaging–based biomarker kit proposed by the MarkVCID consortium, by investigating the association between mean FW (mFW) and executive function. Methods: Baseline mFW was related to a baseline composite measure of executive function (EFC), adjusting for relevant covariates, in three MarkVCID sub-cohorts, and replicated in five, large, independent legacy cohorts. In addition, we tested whether baseline mFW predicted accelerated EFC score decline (mean follow-up time: 1.29 years). Results: Higher mFW was found to be associated with lower EFC scores in MarkVCID legacy and sub-cohorts (p-values < 0.05). In addition, higher baseline mFW was associated significantly with accelerated decline in EFC scores (p = 0.0026). Discussion: mFW is a sensitive biomarker of cognitive decline, providing a strong clinical rational for its use as a marker of white matter (WM) injury in multi-site observational studies and clinical trials of vascular cognitive impairment and dementia (VCID).

AB - Introduction: To evaluate the clinical validity of free water (FW), a diffusion tensor imaging–based biomarker kit proposed by the MarkVCID consortium, by investigating the association between mean FW (mFW) and executive function. Methods: Baseline mFW was related to a baseline composite measure of executive function (EFC), adjusting for relevant covariates, in three MarkVCID sub-cohorts, and replicated in five, large, independent legacy cohorts. In addition, we tested whether baseline mFW predicted accelerated EFC score decline (mean follow-up time: 1.29 years). Results: Higher mFW was found to be associated with lower EFC scores in MarkVCID legacy and sub-cohorts (p-values < 0.05). In addition, higher baseline mFW was associated significantly with accelerated decline in EFC scores (p = 0.0026). Discussion: mFW is a sensitive biomarker of cognitive decline, providing a strong clinical rational for its use as a marker of white matter (WM) injury in multi-site observational studies and clinical trials of vascular cognitive impairment and dementia (VCID).

KW - VCID

KW - biomarker

KW - diffusion tensor imaging

KW - free water

KW - small vessel disease

KW - vascular contributions to cognitive impairment and dementia

KW - white matter injury

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U2 - 10.1002/dad2.12362

DO - 10.1002/dad2.12362

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VL - 14

JO - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring

JF - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring

IS - 1

M1 - e12362

ER -

MRI free water as a biomarker for cognitive performance: Validation in the MarkVCID consortium

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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