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 (US) |
|---|---|
| Article number | e12362 |
| Journal | Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring |
| Volume | 14 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2022 |
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
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In: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, Vol. 14, No. 1, e12362, 2022.
Research output: Contribution to journal › Article › peer-review
}
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
N1 - Funding Information: 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). Funding Information: 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). Publisher Copyright: © 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.
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
UR - http://www.scopus.com/inward/record.url?scp=85145047473&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85145047473&partnerID=8YFLogxK
U2 - 10.1002/dad2.12362
DO - 10.1002/dad2.12362
M3 - Article
C2 - 36523847
AN - SCOPUS:85145047473
SN - 2352-8729
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 -