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Neuropsychological Dysfunction and Neuroimaging Abnormalities in Neurologically Intact Adults With Sickle Cell Anemia
Open accessAbstract
CONTEXT: Sickle cell anemia (SCA) is a chronic illness causing progressive deterioration in quality of life. Brain dysfunction may be the most important and least studied problem affecting individuals with this disease. OBJECTIVE: To measure neurocognitive dysfunction in neurologically asymptomatic adults with SCA vs healthy control individuals. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study comparing neuropsychological function and neuroimaging findings in neurologically asymptomatic adults with SCA and controls from 12 SCA centers, conducted between December 2004 and May 2008. Participants were patients with SCA (hemoglobin [Hb] SS and hemoglobin level < or = 10 mg/dL) aged 19 to 55 years and of African descent (n = 149) or community controls (Hb AA and normal hemoglobin level) (n = 47). Participants were stratified on age, sex, and education. MAIN OUTCOME MEASURES: The primary outcome measure was nonverbal function assessed by the Wechsler Adult Intelligence Scale, third edition (WAIS-III) Performance IQ Index. Secondary exploratory outcomes included performance on neurocognitive tests of executive function, memory, attention, and language and magnetic resonance imaging measurement of total intracranial and hippocampal volume, cortical gray and white matter, and lacunae. RESULTS: The mean WAIS-III Performance IQ score of patients with SCA was significantly lower than that of controls (adjusted mean, 86.69 for patients with SCA vs 95.19 for controls [mean difference, -5.50; 95% confidence interval {CI}, -9.55 to -1.44]; P = .008), with 33% performing more than 1 SD (<85) below the population mean. Among secondary measures, differences were observed in adjusted mean values for global cognitive function (full-scale IQ) (90.47 for patients with SCA vs 95.66 for controls [mean difference, -5.19; 95% CI, -9.24 to -1.13]; P = .01), working memory (90.75 vs 95.25 [mean difference, -4.50; 95% CI, -8.55 to -0.45]; P = .03), processing speed (86.50 vs 97.95 [mean difference, -11.46; 95% CI, -15.51 to -7.40]; P < .001), and measures of executive function. Anemia was associated with poorer neurocognitive function in older patients. No differences in total gray matter or hippocampal volume were observed. Lacunae were more frequent in patients with SCA but not independently related to neurocognitive function. CONCLUSION: Compared with healthy controls, adults with SCA had poorer cognitive performance, which was associated with anemia and age.
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“The largest study to date of cognitive function in adults with SCD has shown that 33% of a cohort of patients with homozygous SCD and without severe complications performed 1 standard deviation worse than the population mean in cognitive tests and had a much higher prevalence of lacunar infarcts (13% versus 2%).”
From Pathophysiology of Sickle Cell Disease (2019) · cites this paper as [178]
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“However, there was no association between lacunae and cognitive function (178).”
From Pathophysiology of Sickle Cell Disease (2019) · cites this paper as [178]
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“The major findings are that (1) adults with SCA showed poorer performance on neurocognitive tests when compared with community controls; (2) anemia is associated with the age-related decline in cognitive performance; and (3) MRI findings do not explain the performance differences in the subset of patients with neuroim…”
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Kato, G. J., Piel, F. B., Reid, C. D., Gaston, M. H., Ohene-Frempong, K., Krishnamurti, L., Smith, W. R., Panepinto, J. A., Weatherall, D. J., Costa, F. F., et al. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.10 · Cited by 1,501
Self-citationPathophysiology of Sickle Cell Disease
Sundd, P., Gladwin, M. T., & Novelli, E. M. (2019) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012418-012838 · Cited by 813
Gale, S. A., Acar, D., & Daffner, K. R. (2018) · The American Journal of Medicine · doi:10.1016/j.amjmed.2018.01.022 · Cited by 788
DeBaun, M. R., Jordan, L. C., King, A. A., Schatz, J. C., Vichinsky, E. P., Fox, C. K., McKinstry, R. C., Telfer, P. T., Kraut, M. A., Daraz, L., et al. (2020) · Blood Advances · doi:10.1182/bloodadvances.2019001142 · Cited by 447
Self-citationDeBaun, M. R., Armstrong, F. D., McKinstry, R. C., Ware, R. E., Vichinsky, E. P., & Kirkham, F. J. (2012) · Blood · doi:10.1182/blood-2011-02-272682 · Cited by 346
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Metadata
- Authors
- Vichinsky, E. P.
- Affiliations
- UCSF Benioff Children's Hospital (US)
- Corresponding author
- Vichinsky, Elliott P.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2010-05-12
- Volume
- 303
- Issue
- 18
- Pages
- 1823
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC2892214
- OpenAlex
- W2132032699
- Cited by
- 296
- References
- 43
- Citations by year
- 2026: 12 · 2025: 9 · 2024: 19 · 2023: 18 · 2022: 20 · 2021: 22 · 2020: 28 · 2019: 19 · 2018: 15 · 2017: 19 · 2016: 20 · 2015: 16 · 2014: 19 · 2013: 20 · 2012: 14
- FWCI
- 8.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (U54HL070583, U54HL070587)
- Topics
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- sickle cell disease, neurocognitive impairment, nonverbal intelligence, performance IQ, working memory, processing speed, executive function, hippocampal volume, intracranial volume, white matter, lacunae, neuroimaging abnormalities, African Americans, hemoglobin SS, hemoglobin levels, language functions
- MeSH terms
- Adult, Age Factors, Anemia, Anemia, Sickle Cell, Brain, Hypoxia, Brain, Cognition Disorders, Cross-Sectional Studies, Female, Humans, Intelligence Tests, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Case-Control Studies
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