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

Article type: Research Article

Authors: Bahrani, Ahmed A.^{a; b; *} | Abner, Erin L.^{b; c} | DeCarli, Charles S.^d | Barber, Justin M.^b | Sutton, Abigail C.^b | Maillard, Pauline^d | Sandoval, Francisco^d | Arfanakis, Konstantinos^{e; f} | Yang, Yung-Chuan^e | Evia, Arnold M.^e | Schneider, Julie A.^{e; g} | Habes, Mohamad^{h; i} | Franklin, Crystal G.^h | Seshadri, Sudhaⁱ | Satizabal, Claudia L.ⁱ | Caprihan, Arvind^j | Thompson, Jeffrey F.^j | Rosenberg, Gary A.^k | Wang, Danny J.J. ^l | Jann, Kay^l | Zhao, Chenyang^l | Lu, Hanzhang^m | Rosenberg, Paul B.ⁿ | Albert, Marilyn S.^o | Ali, Doaa G.^b | Singh, Herpreet^p | Schwab, Kristin^p | Greenberg, Steven M.^p | Helmer, Karl G.^q | Powel, David K.^{r; s} | Gold, Brian T.^{b; r; s} | Goldstein, Larry B.^a | Wilcock, Donna M. ^{b; t} | Jicha, Gregory A.^{a; b}

Affiliations: [a] Department of Neurology, University of Kentucky, College of Medicine, Lexington, KY, USA | [b] Sanders-Brown Center on Aging, University of Kentucky, College of Medicine, Lexington, KY, USA | [c] Department of Epidemiology & Environmental Health, University of Kentucky, College of Public Health, Lexington, KY, USA | [d] Department of Neurology, University of California, Davis, CA, USA | [e] Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA | [f] Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA | [g] Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA | [h] Research Imaging Institute, University of Texas Health San Antonio, San Antonio, TX, USA | [i] Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases, University of Texas Health San Antonio, San Antonio, TX, USA | [j] The Mind Research Network, Albuquerque, NM, USA | [k] Center for Memory and Aging, University of New Mexico, Health Sciences Center, Albuquerque, NM, USA | [l] Departments of Neurology and Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA | [m] Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, MD, USA | [n] Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA | [o] Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA | [p] Department of Neurology, Massachusetts General Hospital, Boston, MA, USA | [q] Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA | [r] Department of Neuroscience, University of Kentucky, College of Medicine, Lexington, KY, USA | [s] Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA | [t] Department of Physiology, University of Kentucky, College of Medicine, Lexington, KY, USA

Correspondence: [*] Correspondence to: Ahmed A. Bahrani, PhD, Department of Neurology, College of Medicine, University of Kentucky, 740 Rose St., USA. Tel.: +1 859 323 5550; E-mail: ahmed.bahrani@uky.edu.

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.

Keywords: Aging, Alzheimer’s disease, cerebrovascular disease, dementia, longitudinal, MarkVCID, small vessel ischemic disease, white matter hyperintensity

DOI: 10.3233/JAD-230629

Journal: Journal of Alzheimer's Disease, vol. 96, no. 2, pp. 683-693, 2023