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

Peiying Liu; Zixuan Lin; Kaisha Hazel; George Pottanat; Cuimei Xu; Dengrong Jiang; Jay J. Pillai; Emma Lucke; Christopher E. Bauer; Brian T. Gold; Steven M. Greenberg; Karl G. Helmer; Kay Jann; Gregory Jicha; Joel Kramer; Pauline Maillard; Rachel M. Mulavelil; Pavel Rodriguez; Claudia L. Satizabal; Kristin Schwab; Sudha Seshadri; Herpreet Singh; Ángel G. Velarde Dediós; Danny J.J. Wang; Rita R. Kalyani; Abhay Moghekar; Paul B. Rosenberg; Sevil Yasar; Marilyn Albert; Hanzhang Lu

doi:10.1002/alz.13888

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

Peiying Liu
, Zixuan Lin
, Kaisha Hazel
, George Pottanat
, Cuimei Xu
, Dengrong Jiang
, Jay J. Pillai
, Emma Lucke
, Christopher E. Bauer
, Brian T. Gold
, Steven M. Greenberg
, Karl G. Helmer
, Kay Jann
, Gregory Jicha
, Joel Kramer
, Pauline Maillard
, Rachel M. Mulavelil
, Pavel Rodriguez
, Claudia L. Satizabal
, Kristin Schwab

Sudha Seshadri, Herpreet Singh, Ángel G. Velarde Dediós, Danny J.J. Wang, Rita R. Kalyani, Abhay Moghekar, Paul B. Rosenberg, Sevil Yasar, Marilyn Albert, Hanzhang Lu

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

18 Scopus citations

Abstract

INTRODUCTION: Vascular 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. METHODS: We 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. RESULTS: CVR and MoCA were positively associated, and this relationship was reproduced at all analysis sites. CVR was found to be positively associated with executive function. DISCUSSION: The 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.

Original language	English
Pages (from-to)	5281-5289
Number of pages	9
Journal	Alzheimer's and Dementia
Volume	20
Issue number	8
DOIs	https://doi.org/10.1002/alz.13888
State	Published - Aug 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Funding

This study was supported in part by NIH UH3 NS100588 (to H.L.), NIH UH3 NS100606 (to G.J.), NIH UH3 NS100605 (to S.S.), NIH UH3 NS100614 (to D.W.), NIH U24 NS100591 (to S.G.), NIH R01 NS115771 (to P.L.), and NIH P41 EB031771 (to H.L.).

Funders	Funder number
National Institutes of Health (NIH)	R01 NS115771, U24 NS100591, UH3 NS100606, UH3 NS100605, UH3 NS100614, P41 EB031771, UH3 NS100588
National Institutes of Health (NIH)

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Montreal Cognitive Assessment
blood oxygenation level dependent
carbon dioxide
cerebrovascular reactivity
cognitive function
magnetic resonance imaging
vascular cognitive impairment
vascular cognitive impairment and dementia

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

Access to Document

10.1002/alz.13888

Cite this

Liu, P., Lin, Z., Hazel, K., Pottanat, G., Xu, C., Jiang, D., Pillai, J. J., Lucke, E., Bauer, C. E., Gold, B. T., Greenberg, S. M., Helmer, K. G., Jann, K., Jicha, G., Kramer, J., Maillard, P., Mulavelil, R. M., Rodriguez, P., Satizabal, C. L., ... Lu, H. (2024). Cerebrovascular reactivity MRI as a biomarker for cerebral small vessel disease–related cognitive decline: Multi-site validation in the MarkVCID Consortium. Alzheimer's and Dementia, 20(8), 5281-5289. https://doi.org/10.1002/alz.13888

@article{81e18e29b6df4650bcc39f41048faded,

title = "Cerebrovascular reactivity MRI as a biomarker for cerebral small vessel disease–related cognitive decline: Multi-site validation in the MarkVCID Consortium",

abstract = "INTRODUCTION: Vascular 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. METHODS: We 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. RESULTS: CVR and MoCA were positively associated, and this relationship was reproduced at all analysis sites. CVR was found to be positively associated with executive function. DISCUSSION: The 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.",

keywords = "Montreal Cognitive Assessment, blood oxygenation level dependent, carbon dioxide, cerebrovascular reactivity, cognitive function, magnetic resonance imaging, vascular cognitive impairment, vascular cognitive impairment and dementia",

author = "Peiying Liu and Zixuan Lin and Kaisha Hazel and George Pottanat and Cuimei Xu and Dengrong Jiang and Pillai, \{Jay J.\} and Emma Lucke and Bauer, \{Christopher E.\} and Gold, \{Brian T.\} and Greenberg, \{Steven M.\} and Helmer, \{Karl G.\} and Kay Jann and Gregory Jicha and Joel Kramer and Pauline Maillard and Mulavelil, \{Rachel M.\} and Pavel Rodriguez and Satizabal, \{Claudia L.\} and Kristin Schwab and Sudha Seshadri and Herpreet Singh and \{Velarde Dedi{\'o}s\}, \{{\'A}ngel G.\} and Wang, \{Danny J.J.\} and Kalyani, \{Rita R.\} and Abhay Moghekar and Rosenberg, \{Paul B.\} and Sevil Yasar and Marilyn Albert and Hanzhang Lu",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2024",

month = aug,

doi = "10.1002/alz.13888",

language = "English",

volume = "20",

pages = "5281--5289",

number = "8",

}

Liu, P, Lin, Z, Hazel, K, Pottanat, G, Xu, C, Jiang, D, Pillai, JJ, Lucke, E, Bauer, CE, Gold, BT, Greenberg, SM, Helmer, KG, Jann, K, Jicha, G, Kramer, J, Maillard, P, Mulavelil, RM, Rodriguez, P, Satizabal, CL, Schwab, K, Seshadri, S, Singh, H, Velarde Dediós, ÁG, Wang, DJJ, Kalyani, RR, Moghekar, A, Rosenberg, PB, Yasar, S, Albert, M & Lu, H 2024, 'Cerebrovascular reactivity MRI as a biomarker for cerebral small vessel disease–related cognitive decline: Multi-site validation in the MarkVCID Consortium', Alzheimer's and Dementia, vol. 20, no. 8, pp. 5281-5289. https://doi.org/10.1002/alz.13888

TY - JOUR

T1 - Cerebrovascular reactivity MRI as a biomarker for cerebral small vessel disease–related cognitive decline

T2 - Multi-site validation in the MarkVCID Consortium

AU - Liu, Peiying

AU - Lin, Zixuan

AU - Hazel, Kaisha

AU - Pottanat, George

AU - Xu, Cuimei

AU - Jiang, Dengrong

AU - Pillai, Jay J.

AU - Lucke, Emma

AU - Bauer, Christopher E.

AU - Gold, Brian T.

AU - Greenberg, Steven M.

AU - Helmer, Karl G.

AU - Jann, Kay

AU - Jicha, Gregory

AU - Kramer, Joel

AU - Maillard, Pauline

AU - Mulavelil, Rachel M.

AU - Rodriguez, Pavel

AU - Satizabal, Claudia L.

AU - Schwab, Kristin

AU - Seshadri, Sudha

AU - Singh, Herpreet

AU - Velarde Dediós, Ángel G.

AU - Wang, Danny J.J.

AU - Kalyani, Rita R.

AU - Moghekar, Abhay

AU - Rosenberg, Paul B.

AU - Yasar, Sevil

AU - Albert, Marilyn

AU - Lu, Hanzhang

PY - 2024/8

Y1 - 2024/8

N2 - INTRODUCTION: Vascular 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. METHODS: We 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. RESULTS: CVR and MoCA were positively associated, and this relationship was reproduced at all analysis sites. CVR was found to be positively associated with executive function. DISCUSSION: The 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.

AB - INTRODUCTION: Vascular 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. METHODS: We 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. RESULTS: CVR and MoCA were positively associated, and this relationship was reproduced at all analysis sites. CVR was found to be positively associated with executive function. DISCUSSION: The 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.

KW - Montreal Cognitive Assessment

KW - blood oxygenation level dependent

KW - carbon dioxide

KW - cerebrovascular reactivity

KW - cognitive function

KW - magnetic resonance imaging

KW - vascular cognitive impairment

KW - vascular cognitive impairment and dementia

UR - https://www.scopus.com/pages/publications/85197576906

UR - https://www.scopus.com/pages/publications/85197576906#tab=citedBy

U2 - 10.1002/alz.13888

DO - 10.1002/alz.13888

M3 - Article

C2 - 38951718

AN - SCOPUS:85197576906

SN - 1552-5260

VL - 20

SP - 5281

EP - 5289

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 8

ER -

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

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this