Multi-Site Cross-Site Inter-Rater and Test-Retest Reliability and Construct Validity of the MarkVCID White Matter Hyperintensity Growth and Regression Protocol

Author:

Bahrani Ahmed A.12,Abner Erin L.23,DeCarli Charles S.4,Barber Justin M.2,Sutton Abigail C.2,Maillard Pauline4,Sandoval Francisco4,Arfanakis Konstantinos56,Yang Yung-Chuan5,Evia Arnold M.5,Schneider Julie A.57,Habes Mohamad89,Franklin Crystal G.8,Seshadri Sudha9,Satizabal Claudia L.9,Caprihan Arvind10,Thompson Jeffrey F.10,Rosenberg Gary A.11,Wang Danny J.J.12,Jann Kay12,Zhao Chenyang12,Lu Hanzhang13,Rosenberg Paul B.14,Albert Marilyn S.15,Ali Doaa G.2,Singh Herpreet16,Schwab Kristin16,Greenberg Steven M.16,Helmer Karl G.17,Powel David K.1819,Gold Brian T.21819,Goldstein Larry B.1,Wilcock Donna M.220,Jicha Gregory A.12

Affiliation:

1. Department of Neurology, University of Kentucky, College of Medicine, Lexington, KY, USA

2. Sanders-Brown Center on Aging, University of Kentucky, College of Medicine, Lexington, KY, USA

3. Department of Epidemiology & Environmental Health, University of Kentucky, College of Public Health, Lexington, KY, USA

4. Department of Neurology, University of California, Davis, CA, USA

5. Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA

6. Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA

7. Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA

8. Research Imaging Institute, University of Texas Health San Antonio, San Antonio, TX, USA

9. Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases, University of Texas Health San Antonio, San Antonio, TX, USA

10. The Mind Research Network, Albuquerque, NM, USA

11. Center for Memory and Aging, University of New Mexico, Health Sciences Center, Albuquerque, NM, USA

12. Departments of Neurology and Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

13. Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, MD, USA

14. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA

15. Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA

16. Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

17. Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

18. Department of Neuroscience, University of Kentucky, College of Medicine, Lexington, KY, USA

19. Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA

20. Department of Physiology, University of Kentucky, College of Medicine, Lexington, KY, USA

Abstract

Background: White matter hyperintensities (WMH) that occur in the setting of vascular cognitive impairment and dementia (VCID) may be dynamic increasing or decreasing volumes or stable over time. Quantifying such changes may prove useful as a biomarker for clinical trials designed to address vascular cognitive-impairment and dementia and Alzheimer’s Disease. Objective: Conducting multi-site cross-site inter-rater and test-retest reliability of the MarkVCID white matter hyperintensity growth and regression protocol. Methods: The NINDS-supported MarkVCID Consortium evaluated a neuroimaging biomarker developed to track WMH change. Test-retest and cross-site inter-rater reliability of the protocol were assessed. Cognitive test scores were analyzed in relation to WMH changes to explore its construct validity. Results: ICC values for test-retest reliability of WMH growth and regression were 0.969 and 0.937 respectively, while for cross-site inter-rater ICC values for WMH growth and regression were 0.995 and 0.990 respectively. Word list long-delay free-recall was negatively associated with WMH growth (p < 0.028) but was not associated with WMH regression. Conclusions: The present data demonstrate robust ICC validity of a WMH growth/regression protocol over a one-year period as measured by cross-site inter-rater and test-retest reliability. These data suggest that this approach may serve an important role in clinical trials of disease-modifying agents for VCID that may preferentially affect WMH growth, stability, or regression.

Publisher

IOS Press

Subject

Psychiatry and Mental health,Geriatrics and Gerontology,Clinical Psychology,General Medicine,General Neuroscience

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