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Effects of regional brain volumes on cognition in sickle cell anemia: A developmental perspective

BACKGROUND AND OBJECTIVES: Cognitive difficulties in people with sickle cell anemia (SCA) are related to lower processing speed index (PSI) and working memory index (WMI). However, risk factors are poorly understood so preventative strategies have not been explored. Brain volumes, specifically white...

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Autores principales: Hamdule, Shifa, Kölbel, Melanie, Stotesbury, Hanne, Murdoch, Russell, Clayden, Jonathan D., Sahota, Sati, Hood, Anna Marie, Clark, Christopher A., Kirkham, Fenella Jane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968851/
https://www.ncbi.nlm.nih.gov/pubmed/36860579
http://dx.doi.org/10.3389/fneur.2023.1101223
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author Hamdule, Shifa
Kölbel, Melanie
Stotesbury, Hanne
Murdoch, Russell
Clayden, Jonathan D.
Sahota, Sati
Hood, Anna Marie
Clark, Christopher A.
Kirkham, Fenella Jane
author_facet Hamdule, Shifa
Kölbel, Melanie
Stotesbury, Hanne
Murdoch, Russell
Clayden, Jonathan D.
Sahota, Sati
Hood, Anna Marie
Clark, Christopher A.
Kirkham, Fenella Jane
author_sort Hamdule, Shifa
collection PubMed
description BACKGROUND AND OBJECTIVES: Cognitive difficulties in people with sickle cell anemia (SCA) are related to lower processing speed index (PSI) and working memory index (WMI). However, risk factors are poorly understood so preventative strategies have not been explored. Brain volumes, specifically white matter volumes (WMV) which increases through early adulthood, have been associated with better cognition in healthy typically developing individuals. In patients with SCA, the reduced WMV and total subcortical volumes noted could explain cognitive deficits. We therefore examined developmental trajectories for regional brain volumes and cognitive endpoints in patients with SCA. METHODS: Data from two cohorts, the Sleep and Asthma Cohort and Prevention of Morbidity in SCA, were available. MRI data included T1-weighted axial images, pre-processed before regional volumes were extracted using Free-surfer. PSI and WMI from the Weschler scales of intelligence were used to test neurocognitive performance. Hemoglobin, oxygen saturation, hydroxyurea treatment and socioeconomic status from education deciles were available. RESULTS: One hundred and twenty nine patients (66 male) and 50 controls (21 male) aged 8–64 years were included. Brain volumes did not significantly differ between patients and controls. Compared with controls, PSI and WMI were significantly lower in patients with SCA, predicted by increasing age and male sex, with lower hemoglobin in the model for PSI but no effect of hydroxyurea treatment. In male patients with SCA only, WMV, age and socioeconomic status predicted PSI, while total subcortical volumes predicted WMI. Age positively and significantly predicted WMV in the whole group (patients + controls). There was a trend for age to negatively predict PSI in the whole group. For total subcortical volume and WMI, age predicted decrease only in the patient group. Developmental trajectory analysis revealed that PSI only was significantly delayed in patients at 8 years of age; the rate of development for the cognitive and brain volume data did not differ significantly from controls. DISCUSSION: Increasing age and male sex negatively impact cognition in SCA, with processing speed, also predicted by hemoglobin, delayed by mid childhood. Associations with brain volumes were seen in males with SCA. Brain endpoints, calibrated against large control datasets, should be considered for randomized treatment trials.
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spelling pubmed-99688512023-02-28 Effects of regional brain volumes on cognition in sickle cell anemia: A developmental perspective Hamdule, Shifa Kölbel, Melanie Stotesbury, Hanne Murdoch, Russell Clayden, Jonathan D. Sahota, Sati Hood, Anna Marie Clark, Christopher A. Kirkham, Fenella Jane Front Neurol Neurology BACKGROUND AND OBJECTIVES: Cognitive difficulties in people with sickle cell anemia (SCA) are related to lower processing speed index (PSI) and working memory index (WMI). However, risk factors are poorly understood so preventative strategies have not been explored. Brain volumes, specifically white matter volumes (WMV) which increases through early adulthood, have been associated with better cognition in healthy typically developing individuals. In patients with SCA, the reduced WMV and total subcortical volumes noted could explain cognitive deficits. We therefore examined developmental trajectories for regional brain volumes and cognitive endpoints in patients with SCA. METHODS: Data from two cohorts, the Sleep and Asthma Cohort and Prevention of Morbidity in SCA, were available. MRI data included T1-weighted axial images, pre-processed before regional volumes were extracted using Free-surfer. PSI and WMI from the Weschler scales of intelligence were used to test neurocognitive performance. Hemoglobin, oxygen saturation, hydroxyurea treatment and socioeconomic status from education deciles were available. RESULTS: One hundred and twenty nine patients (66 male) and 50 controls (21 male) aged 8–64 years were included. Brain volumes did not significantly differ between patients and controls. Compared with controls, PSI and WMI were significantly lower in patients with SCA, predicted by increasing age and male sex, with lower hemoglobin in the model for PSI but no effect of hydroxyurea treatment. In male patients with SCA only, WMV, age and socioeconomic status predicted PSI, while total subcortical volumes predicted WMI. Age positively and significantly predicted WMV in the whole group (patients + controls). There was a trend for age to negatively predict PSI in the whole group. For total subcortical volume and WMI, age predicted decrease only in the patient group. Developmental trajectory analysis revealed that PSI only was significantly delayed in patients at 8 years of age; the rate of development for the cognitive and brain volume data did not differ significantly from controls. DISCUSSION: Increasing age and male sex negatively impact cognition in SCA, with processing speed, also predicted by hemoglobin, delayed by mid childhood. Associations with brain volumes were seen in males with SCA. Brain endpoints, calibrated against large control datasets, should be considered for randomized treatment trials. Frontiers Media S.A. 2023-02-13 /pmc/articles/PMC9968851/ /pubmed/36860579 http://dx.doi.org/10.3389/fneur.2023.1101223 Text en Copyright © 2023 Hamdule, Kölbel, Stotesbury, Murdoch, Clayden, Sahota, Hood, Clark and Kirkham. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Hamdule, Shifa
Kölbel, Melanie
Stotesbury, Hanne
Murdoch, Russell
Clayden, Jonathan D.
Sahota, Sati
Hood, Anna Marie
Clark, Christopher A.
Kirkham, Fenella Jane
Effects of regional brain volumes on cognition in sickle cell anemia: A developmental perspective
title Effects of regional brain volumes on cognition in sickle cell anemia: A developmental perspective
title_full Effects of regional brain volumes on cognition in sickle cell anemia: A developmental perspective
title_fullStr Effects of regional brain volumes on cognition in sickle cell anemia: A developmental perspective
title_full_unstemmed Effects of regional brain volumes on cognition in sickle cell anemia: A developmental perspective
title_short Effects of regional brain volumes on cognition in sickle cell anemia: A developmental perspective
title_sort effects of regional brain volumes on cognition in sickle cell anemia: a developmental perspective
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968851/
https://www.ncbi.nlm.nih.gov/pubmed/36860579
http://dx.doi.org/10.3389/fneur.2023.1101223
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