Reduced arterial compliance along the cerebrovascular tree predicts cognitive slowing in multiple sclerosis: Evidence for a neurovascular uncoupling hypothesis

Dinesh K. Sivakolundu, Kathryn L. West, Gayathri B. Maruthy, Mark Zuppichini, Monroe P. Turner, Dema Abdelkarim, Yuguang Zhao, Dylan Nguyen, Jeffrey S. Spence, Hanzhang Lu, Darin Okuda, Bart Rypma

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Cognitive slowing occurs in ~70% of multiple sclerosis (MS) patients. The pathophysiology of this slowing is unknown. Neurovascular coupling, acute localized blood flow increases following neural activity, is essential for efficient cognition. Loss of vascular compliance along the cerebrovascular tree would result in suboptimal vasodilation, neurovascular uncoupling, and cognitive slowing. Objective: To assess vascular compliance along the cerebrovascular tree and its relationship to MS-related cognition. Methods: We tested vascular compliance along the cerebrovascular tree by dividing cerebral cortex into nested layers. MS patients and healthy controls were scanned using a dual-echo functional magnetic resonance imaging (fMRI) sequence while they periodically inhaled room air and hypercapnic gas mixture. Cerebrovascular reactivity was calculated from both cerebral blood flow (arterial) and blood-oxygen-level-dependent signal (venous) increases per unit increase in end-tidal CO2. Results: Arterial cerebrovascular reactivity changes along the cerebrovascular tree were reduced in cognitively slow MS compared to cognitively normal MS and healthy controls. These changes were fit to exponential functions, the decay constant (arterial compliance index; ACI) of which was associated with individual subjects’ reaction time and predicted reaction time after controlling for disease processes. Conclusion: Such associations suggest prospects for utility of ACI in predicting future cognitive disturbances, monitoring cognitive deficiencies and therapeutic responses, and implicates neurovascular uncoupling as a mechanism of cognitive slowing in MS.

Original languageEnglish (US)
JournalMultiple Sclerosis Journal
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Compliance
Multiple Sclerosis
Blood Vessels
Cognition
Cerebrovascular Circulation
Vasodilation
Cerebral Cortex
Gases
Air
Magnetic Resonance Imaging
Oxygen

Keywords

  • Arterial compliance
  • cognition
  • fMRI
  • multiple sclerosis
  • vascular reactivity

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Reduced arterial compliance along the cerebrovascular tree predicts cognitive slowing in multiple sclerosis : Evidence for a neurovascular uncoupling hypothesis. / Sivakolundu, Dinesh K.; West, Kathryn L.; Maruthy, Gayathri B.; Zuppichini, Mark; Turner, Monroe P.; Abdelkarim, Dema; Zhao, Yuguang; Nguyen, Dylan; Spence, Jeffrey S.; Lu, Hanzhang; Okuda, Darin; Rypma, Bart.

In: Multiple Sclerosis Journal, 01.01.2019.

Research output: Contribution to journalArticle

Sivakolundu, Dinesh K. ; West, Kathryn L. ; Maruthy, Gayathri B. ; Zuppichini, Mark ; Turner, Monroe P. ; Abdelkarim, Dema ; Zhao, Yuguang ; Nguyen, Dylan ; Spence, Jeffrey S. ; Lu, Hanzhang ; Okuda, Darin ; Rypma, Bart. / Reduced arterial compliance along the cerebrovascular tree predicts cognitive slowing in multiple sclerosis : Evidence for a neurovascular uncoupling hypothesis. In: Multiple Sclerosis Journal. 2019.
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abstract = "Background: Cognitive slowing occurs in ~70{\%} of multiple sclerosis (MS) patients. The pathophysiology of this slowing is unknown. Neurovascular coupling, acute localized blood flow increases following neural activity, is essential for efficient cognition. Loss of vascular compliance along the cerebrovascular tree would result in suboptimal vasodilation, neurovascular uncoupling, and cognitive slowing. Objective: To assess vascular compliance along the cerebrovascular tree and its relationship to MS-related cognition. Methods: We tested vascular compliance along the cerebrovascular tree by dividing cerebral cortex into nested layers. MS patients and healthy controls were scanned using a dual-echo functional magnetic resonance imaging (fMRI) sequence while they periodically inhaled room air and hypercapnic gas mixture. Cerebrovascular reactivity was calculated from both cerebral blood flow (arterial) and blood-oxygen-level-dependent signal (venous) increases per unit increase in end-tidal CO2. Results: Arterial cerebrovascular reactivity changes along the cerebrovascular tree were reduced in cognitively slow MS compared to cognitively normal MS and healthy controls. These changes were fit to exponential functions, the decay constant (arterial compliance index; ACI) of which was associated with individual subjects’ reaction time and predicted reaction time after controlling for disease processes. Conclusion: Such associations suggest prospects for utility of ACI in predicting future cognitive disturbances, monitoring cognitive deficiencies and therapeutic responses, and implicates neurovascular uncoupling as a mechanism of cognitive slowing in MS.",
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AU - West, Kathryn L.

AU - Maruthy, Gayathri B.

AU - Zuppichini, Mark

AU - Turner, Monroe P.

AU - Abdelkarim, Dema

AU - Zhao, Yuguang

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