Cerebrovascular reactivity MRI as a biomarker for cerebral small vessel disease–related cognitive decline: Multi‐site validation in the MarkVCID Consortium

Author:

Liu Peiying12,Lin Zixuan1,Hazel Kaisha1,Pottanat George1,Xu Cuimei1,Jiang Dengrong1,Pillai Jay J.13,Lucke Emma1,Bauer Christopher E.4,Gold Brian T.4,Greenberg Steven M.5,Helmer Karl G.6,Jann Kay7,Jicha Gregory8,Kramer Joel9,Maillard Pauline10,Mulavelil Rachel M.11,Rodriguez Pavel11,Satizabal Claudia L.11,Schwab Kristin5,Seshadri Sudha11,Singh Herpreet6,Velarde Dediós Ángel G.11,Wang Danny J. J.7,Kalyani Rita R.12,Moghekar Abhay13,Rosenberg Paul B.14,Yasar Sevil12,Albert Marilyn13,Lu Hanzhang11516ORCID

Affiliation:

1. Department of Radiology Johns Hopkins University School of Medicine Baltimore Maryland USA

2. Department of Diagnostic Radiology & Nuclear Medicine University of Maryland School of Medicine Baltimore Maryland USA

3. Department of Division of Neuroradiology Mayo Clinic College of Medicine and Science Rochester Minnesota USA

4. Department of Neuroscience University of Kentucky Lexington Kentucky USA

5. Department of Neurology Massachusetts General Hospital Stroke Research Center Harvard Medical School Boston Massachusetts USA

6. Department of Radiology Massachusetts General Hospital Charlestown Massachusetts USA

7. Laboratory of Functional MRI Technology Keck School of Medicine Stevens Neuroimaging and Informatics Institute University of Southern California Los Angeles California USA

8. Department of Neurology University of Kentucky Lexington Kentucky USA

9. Department of Neurology University of California, San Francisco San Francisco California USA

10. Department of Neurology University of California, Davis Sacramento California USA

11. Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases UT Health San Antonio San Antonio Texas USA

12. Department of Medicine Johns Hopkins University School of Medicine Baltimore Maryland USA

13. Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland USA

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

15. Department of Biomedical Engineering Johns Hopkins University School of Medicine Baltimore USA

16. F.M. Kirby Center for Functional Brain Imaging Kennedy Krieger Institute Baltimore Maryland USA

Abstract

AbstractINTRODUCTIONVascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. The present study examined the relationship between cerebrovascular reactivity (CVR) measured by magnetic resonance imaging (MRI) and cognitive function in a multi‐site study, using a predefined hypothesis.METHODSWe conducted the study in a total of three analysis sites and 263 subjects. Each site performed an identical CVR MRI procedure using 5% carbon dioxide inhalation. A global cognitive measure of Montreal Cognitive Assessment (MoCA) and an executive function measure of item response theory (IRT) score were used as outcomes.RESULTSCVR and MoCA were positively associated, and this relationship was reproduced at all analysis sites. CVR was found to be positively associated with executive function.DISCUSSIONThe predefined hypothesis on the association between CVR and a global cognitive score was validated in three independent analysis sites, providing support for CVR as a biomarker in VCID.Highlights This study measured a novel functional index of small arteries referred to as cerebrovascular reactivity (CVR). CVR was positively associated with global cognition in older adults. This finding was observed in three independent cohorts at three sites. Our statistical analysis plan was predefined before beginning data collection.

Funder

National Institutes of Health

Publisher

Wiley

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