The University of Southampton
University of Southampton Institutional Repository

Structural connectivity mediates the relationship between blood oxygenation and cognitive function in sickle cell anemia

Structural connectivity mediates the relationship between blood oxygenation and cognitive function in sickle cell anemia
Structural connectivity mediates the relationship between blood oxygenation and cognitive function in sickle cell anemia
In sickle cell disease (SCD), the relative importance of reduced hemoglobin and peripheral oxygen saturation (SpO2) on brain structure remains uncertain. We applied graph-theoretical analysis to diffusion MRI data to investigate the effect of structural brain connectivity on cognitive function, alongside presence/absence, number and volume of silent cerebral infarction (SCI). In patients, we investigated the relationships between network properties, blood oxygenation and cognition (working memory, WMI, and processing speed, PSI, indices). Based on streamline counts and fractional anisotropy (FA), we identified a subnetwork with weakened connectivity in 92 SCA patients (49 males; 8.0-38.8 years), compared to 54 non-SCA controls (22 males; 6.7-30.6 years). Multiple regression analyses showed a significant effect of hemoglobin on full-network edge density (p<0.05), and of peripheral SpO2 on streamline-weighted subnetwork efficiency (p<0.01). There were effects of FA-weighted full-network and subnetwork efficiency on WMI (both p<0.05), and of streamline-weighted subnetwork efficiency on PSI (p=0.05) but no effects on SCI. Streamline-weighted efficiency was progressively lower with lower SpO2, with a downstream effect on PSI. In path analysis, indirect relationships between blood oxygenation and cognition, mediated by network properties, were better supported than direct alternatives, with an indirect relationship between low SpO2 and PSI in patients, mediated by structural connectivity efficiency in a subnetwork of the brain differing from controls. Our findings are consistent with the notion that cognitive impairment is primarily mediated by hypoxic-ischemic effects on normal-appearing white matter, and highlight the utility of network-based methods in providing biomarkers of cognitive dysfunction in SCA patients.
2473-9529
Clayden, Jonathan D
1f384d07-9591-4dd4-80e0-50244283d314
Stotesbury, Hanne
1104423d-f215-4585-bb50-29b7fdd6c518
Kawadler, Jamie M
425d1643-3623-453a-9db0-6505d8065e70
Slee, April
993ac4ad-4ee4-437a-9f42-e27f8a7046d0
Koelbel, Melanie
5d30eddf-daaf-49a5-9bda-1ec865467394
Saunders, Dawn E
0ceef8e6-dfd8-4c92-acf5-87543f449367
Hood, Anna M
aec0f143-3f19-4a0e-b13c-92ecfd3363a5
Wilkey, Olu
adb1eb81-8a3f-4966-820e-2d4d2d78a476
Layton, Mark
f1c49157-82fd-46a6-b308-f993c28f4b91
Inusa, Baba Pd
475127b2-d546-43d9-b4ef-eafbe53d1b12
Pelidis, Maria
8dcd6334-d986-4097-b4a2-e46656001b39
Chakravorty, Subarna
9f43bc47-7778-4320-a552-5aec14ddcb60
Rees, David C
05d66e55-4502-4f9b-88c9-f91dbecca84f
Howard, Jo
6c7512d5-7a3d-4a5c-b874-19c83eab11d2
Awogbade, Moji
f1a5cb60-e9d6-4f58-b50d-8f1a68024fba
Liossi, Christina
fd401ad6-581a-4a31-a60b-f8671ffd3558
Kirkham, Fenella J
1dfbc0d5-aebe-4439-9fb2-dac6503bcd58
Clark, Chris A
2aa6957f-c5e9-4cdc-ac2d-7565e8c6eae8
Clayden, Jonathan D
1f384d07-9591-4dd4-80e0-50244283d314
Stotesbury, Hanne
1104423d-f215-4585-bb50-29b7fdd6c518
Kawadler, Jamie M
425d1643-3623-453a-9db0-6505d8065e70
Slee, April
993ac4ad-4ee4-437a-9f42-e27f8a7046d0
Koelbel, Melanie
5d30eddf-daaf-49a5-9bda-1ec865467394
Saunders, Dawn E
0ceef8e6-dfd8-4c92-acf5-87543f449367
Hood, Anna M
aec0f143-3f19-4a0e-b13c-92ecfd3363a5
Wilkey, Olu
adb1eb81-8a3f-4966-820e-2d4d2d78a476
Layton, Mark
f1c49157-82fd-46a6-b308-f993c28f4b91
Inusa, Baba Pd
475127b2-d546-43d9-b4ef-eafbe53d1b12
Pelidis, Maria
8dcd6334-d986-4097-b4a2-e46656001b39
Chakravorty, Subarna
9f43bc47-7778-4320-a552-5aec14ddcb60
Rees, David C
05d66e55-4502-4f9b-88c9-f91dbecca84f
Howard, Jo
6c7512d5-7a3d-4a5c-b874-19c83eab11d2
Awogbade, Moji
f1a5cb60-e9d6-4f58-b50d-8f1a68024fba
Liossi, Christina
fd401ad6-581a-4a31-a60b-f8671ffd3558
Kirkham, Fenella J
1dfbc0d5-aebe-4439-9fb2-dac6503bcd58
Clark, Chris A
2aa6957f-c5e9-4cdc-ac2d-7565e8c6eae8

Clayden, Jonathan D, Stotesbury, Hanne, Kawadler, Jamie M, Slee, April, Koelbel, Melanie, Saunders, Dawn E, Hood, Anna M, Wilkey, Olu, Layton, Mark, Inusa, Baba Pd, Pelidis, Maria, Chakravorty, Subarna, Rees, David C, Howard, Jo, Awogbade, Moji, Liossi, Christina, Kirkham, Fenella J and Clark, Chris A (2022) Structural connectivity mediates the relationship between blood oxygenation and cognitive function in sickle cell anemia. Blood Advances. (doi:10.1182/bloodadvances.2021006751).

Record type: Article

Abstract

In sickle cell disease (SCD), the relative importance of reduced hemoglobin and peripheral oxygen saturation (SpO2) on brain structure remains uncertain. We applied graph-theoretical analysis to diffusion MRI data to investigate the effect of structural brain connectivity on cognitive function, alongside presence/absence, number and volume of silent cerebral infarction (SCI). In patients, we investigated the relationships between network properties, blood oxygenation and cognition (working memory, WMI, and processing speed, PSI, indices). Based on streamline counts and fractional anisotropy (FA), we identified a subnetwork with weakened connectivity in 92 SCA patients (49 males; 8.0-38.8 years), compared to 54 non-SCA controls (22 males; 6.7-30.6 years). Multiple regression analyses showed a significant effect of hemoglobin on full-network edge density (p<0.05), and of peripheral SpO2 on streamline-weighted subnetwork efficiency (p<0.01). There were effects of FA-weighted full-network and subnetwork efficiency on WMI (both p<0.05), and of streamline-weighted subnetwork efficiency on PSI (p=0.05) but no effects on SCI. Streamline-weighted efficiency was progressively lower with lower SpO2, with a downstream effect on PSI. In path analysis, indirect relationships between blood oxygenation and cognition, mediated by network properties, were better supported than direct alternatives, with an indirect relationship between low SpO2 and PSI in patients, mediated by structural connectivity efficiency in a subnetwork of the brain differing from controls. Our findings are consistent with the notion that cognitive impairment is primarily mediated by hypoxic-ischemic effects on normal-appearing white matter, and highlight the utility of network-based methods in providing biomarkers of cognitive dysfunction in SCA patients.

Text
bloodadvances.2021006751 - Version of Record
Restricted to Repository staff only
Request a copy

More information

Accepted/In Press date: 2 July 2022
e-pub ahead of print date: 10 August 2022
Additional Information: Copyright © 2022 American Society of Hematology.

Identifiers

Local EPrints ID: 470250
URI: http://eprints.soton.ac.uk/id/eprint/470250
ISSN: 2473-9529
PURE UUID: 5a602ff4-c04b-43ef-b8d0-cb3d874375eb
ORCID for Christina Liossi: ORCID iD orcid.org/0000-0003-0627-6377
ORCID for Fenella J Kirkham: ORCID iD orcid.org/0000-0002-2443-7958

Catalogue record

Date deposited: 05 Oct 2022 16:34
Last modified: 06 Oct 2022 01:40

Export record

Altmetrics

Contributors

Author: Jonathan D Clayden
Author: Hanne Stotesbury
Author: Jamie M Kawadler
Author: April Slee
Author: Melanie Koelbel
Author: Dawn E Saunders
Author: Anna M Hood
Author: Olu Wilkey
Author: Mark Layton
Author: Baba Pd Inusa
Author: Maria Pelidis
Author: Subarna Chakravorty
Author: David C Rees
Author: Jo Howard
Author: Moji Awogbade
Author: Chris A Clark

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×