ArticleBlood advances2023
Structural connectivity mediates the relationship between blood oxygenation and cognitive function in sickle cell anemia.
Article in Blood advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- Better 10-Year Cerebrovascular Outcome After Transplant Than on Standard-Care in Sickle Cell Anemia: DREPAGREFFE Trial.American journal of hematology · 2026Trial
- Surface-based brain age index reflects hematological impacts on cognitive development in children with beta-thalassemia major.iScience · 2026Article
- Dose-dependent impairment of brain functional and microstructural connectivity during leukaemia chemotherapy.British journal of haematology · 2026Observational
- Cerebral blood flow trajectories in paediatric sickle cell anaemia by age, region, and treatment associations.British journal of haematology · 2026Article
- Investigating Disruptions in Information Flow due to Sickle Cell Disease Using Granger Causality.Human brain mapping · 2025Article
- Assessment of Inter-Reader Reliability of Fazekas Scoring on Magnetic Resonance Imaging of the Brain in Adult Patients with Sickle Cell Disease.Diagnostics (Basel, Switzerland) · 2025Article
- Brain Age Modeling and Cognitive Outcomes in Young Adults With and Without Sickle Cell Anemia.JAMA network open · 2025Article
- The Association Between Sickle Cell Anemia and Cognitive Dysfunction: A Systematic Review.Cureus · 2024Review
- Executive Function and Processing Speed in Children Living with Sickle Cell Anemia.Children (Basel, Switzerland) · 2023Article
- Effects of regional brain volumes on cognition in sickle cell anemia: A developmental perspective.Frontiers in neurology · 2023Article
- Mind the gap: trajectory of cognitive development in young individuals with sickle cell disease: a cross-sectional study.Frontiers in neurology · 2023Article
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Authors and funding
18 authors at 7 institutions in 1 country.
Funding
Abstract
In sickle cell disease, the relative importance of reduced hemoglobin (Hb) and peripheral oxygen saturation on brain structure remains uncertain. We applied graph-theoretical analysis to diffusion magnetic resonance imaging data to investigate the effect of structural brain connectivity on cognitive function, alongside the presence or absence, number, and volume of silent cerebral infarction. In patients, we investigated the relationships between network properties, blood oxygenation, and cognition (working memory and processing speed indices). Based on streamline counts and fractional anisotropy, we identified a subnetwork with weakened connectivity in 92 patients with sickle cell disease (91 homozygous for HbS [HbSS], 1 heterozygote with HbSβ0 thalassemia; 49 males; aged 8.0 to 38.8 y), compared with 54 control subjects (22 males; aged 6.7 to 30.6 y). Multiple regression analyses showed a significant effect of Hb on full-network edge density (P < .05) and of peripheral oxygen saturation on streamline-weighted subnetwork efficiency (P < .01). There were effects of fractional anisotropy-weighted full-network and subnetwork efficiency on working memory index (both P < .05), and of streamline-weighted subnetwork efficiency on processing speed index (P = .05). However, there were no effects of presence, number or volume of silent cerebral infarcts. Streamline-weighted efficiency was progressively lower with lower oxygen saturation, with a downstream effect on the processing speed index. 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 oxygen saturation and processing speed index in patients, mediated by structural connectivity efficiency in a subnetwork of the brain differing from control subjects. 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 patients with sickle cell disease.
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