Table 1.

Study characteristics including the country where the study was conducted, mean age of participants, genotype, study quality number, adaptations, and primary findings of each study

StudyCountrySCD, n/control, nMean age (range), yGenotypeStudy qualityMeasuresLanguage and test adaptationPrimary findings
Ampomah et al50  Ghana 63/60 (age- and education-matched controls) 29.4 (18-50) HbSS, HbSC WRAT-4 RQCST, Trails A + B, MCST, DSST, grooved pegboard, recognition memory test, ROCF, cognitive features questionnaire None reported Individuals with SCD scored lower than the non-SCD comparison group in all cognitive domains
Individuals with SCD showed declines in visuospatial ability, executive functioning, and processing speed at 7-year follow-up 
Castro and Viana43  Brazil 64/64 (age- and sex-matched controls) SCD: 10.8 (7-13), no SCD: 10.9 (7-13) HbSS, HbSB0 3 WISC-III None reported Individuals with SCD had lower scores across all domains assessed (significantly lower processing speed, distraction resistance, and perceptual organization) than individuals without SCD 
Dias et al51  Brazil 60/74 (community controls) (6-11) Not reported 3 Raskin's optotype letter "E"; Ishihara test; Raven's colored progressive matrices test, special scale; testing trails, parts A and B; 5-digit test; WISC-IV scale digits subtest; Tower of London Standardized for Brazilian population Individuals with SCD aged 6-7 years displayed worsened attention interference on 5-digit test
Individuals with SCD aged 8-9 years displayed slower execution time in the counting stage
Individuals with SCD aged 10-11 years performed worse on working memory than non-SCD individuals 
Elalfy et al52  Egypt 32/11 (community controls) SCD: 15.25 (3.69), control: 17.73 (4.84) Not reported 3 WAIS-IV, Benton visual retention test None reported Nearly 2/3 individuals with SCD had an IQ of <90 
Erdem et al53  Turkey 100/82 (age-, sex-, and education-matched controls) Only median reported, SCD: 30 HbSS 4 MoCA Turkish adaptation of the MoCA54  Individuals with SCD had significantly lower MoCA scores than individuals without SCD
Individuals with SCD had poorer performance in visuospatial skills, executive function, attention, language, abstraction, delayed recall, and orientation
History of chronic/frequent headache episodes associated with significantly lower MoCA scores 
Ezenwosu et al55  Nigeria 90/90 (age- and sex-matched classmate controls) 8.88 (5-11) HbSS/HbSB0 6 DAPT Nigerian adaptation56  Individuals with SCD had significantly lower performance in English language
Nonsignificant difference between individuals with and without SCD on DAPT 
Fernandes et al57  Brazil 65/65 (sex- and age-matched) 9.5 (8-12) HbSS, HbSC 4 Academic performance test, WISC-III None reported Individuals with SCD had lower IQ scores than individuals without SCD 
Green et al58  Uganda 265/— 5.5 (1-12) HbSS/HbSB0 6 KABC-II, Mullen scales of early learning Translated into/validated in Luganda59-63  3% of children with SCD aged 1-4 years had abnormal scores (−2 or less z scores below age-specific norms)
16.7% of children with SCD aged 5-12 years had abnormal subscale scores with neurocognition related to previous stroke 
Jacob et al64  Tanzania 73/71 (healthy sibling controls) SCD: 11.9 (6-16), control: 11.1 (6-16) HbSS/HbSB0 4 WISC-IV (only PSI, PRI, WMI), Raven's standard progressive matrices Tests administered in Swahili Individuals with SCD performed worse than siblings on PSI, PRI, and WMI
Rates of score improvement were slower for individuals with SCD on coding/cancellation 
Knight et al65  West Indies 60/60 (sex- and age-matched controls) (15-18) HbSS 3 WISC-R, WAIS-R test item/direction wording modified for local conditions, vocabulary/picture arrangement subtests eliminated Individuals with SCD had lower IQ scores than individuals without SCD across domains
IQ was not correlated with age and did not differ by sex 
Matondo et al66  Tanzania 233/80 (healthy sibling controls) (9-15) HbSS/HbSB0 ROCF, KOH’s block design Validated in an in-house study at Muhimbili University of Health and Allied Sciences Individuals with SCD displayed greater impairment on an IQ measure than siblings
Negative association between age and neurocognitive performance 
Montanaro et al67  Nigeria 68/15 (age-matched sibling controls) SCD: 8.95 HbSS, HbSB+, HbSC WISC-III, WPPSI Assessments were adapted to Italian standardization and all tests were administered in Italian Bilingual immigrant individuals with SCD had a more noticeable and earlier onset of language difficulties compared with monolingual peers with SCD 
Nunes et al42  Brazil 15/— SCD: 10 (6-15) HbSS/HbSB0 NEPSY-II, WISC-III Brazilian adaptation of WISC-III 66.6% of participants performed within normal range, 26.6% scored below average range, and 6.6% scored above average on a measure of IQ
Below average performance on at least 1 NEPSY-II subtest for 60% of individuals
Individuals with a stroke history had lower performance on overall intellectual ability and across cognitive domains 
Olatunya et al68  Southwest Nigeria 101/101 (sociodemographic-matched classmate controls) SCD: 9.13, No SCD: 9.20 (4-12) HbSS/HbSB0 DAPT Validated for Nigerian children55  No difference between groups in school performance, but school absenteeism was associated with poorer performance across groups
School absenteeism independently predicted poor school performance in all participants 
Oluwole et al69  Nigeria 56/44 (healthy siblings and community controls) SCD: 9.2, No SCD: 9.41 HbSS WISC-IV English is teaching language of the population thus adaptations did not take place. Individuals with SCD had poorer neurocognitive performance (IQ and processing speed) than controls
Cognitive functioning was correlated with sociodemographic factors 
Prussien et al70  Nigeria 83/— SCD: 9.10 HbSS, HbSB0 Raven’s standard progressive matrices, Tower of London, WISC-IV Instructions were translated to Hausa for testing Children’s average score on Raven’s matrices below normative mean (corresponding IQ = 85)
Nigerian children did not differ from US children with SCD on working memory (WISC)
Significant association between higher transcranial Doppler velocity and lower executive planning efficiency 
Rajendran et al71  India 22/22 (age-, sex-, and community matched controls) Both SCD and no SCD: 9.9 (6-15) HbSS, HbSB0 MISIC, CPMS, PGI memory scale The MISIC is the Indian adaptation of the WISC. Translations to local language of the other measures took place.72  Individuals with SCD presented with lower IQ scores and tended to have more psychological problems compared with individuals without SCD 
Rodgers et al73  Haiti 22/— SCD: 24.50 (10-58) Not reported Conners continuous auditory test of attention None reported Individuals with SCD had no associations between disordered sleep, attention/emotion regulation, and attention in an impoverished community 
Salama et al74  Egypt 55/55 (age- and sex-matched healthy controls) SCD:10.7, no SCD: 12.5 HbSS, HbSB+ Stanford Binet intelligence scale None reported Over half of individuals with SCD had abnormal IQ scores, whereas individuals without SCD had higher IQ scores 
Martínez Triana et al75  Cuba 119/42 (healthy controls) SCD: (6-18) HbSS, HbSC HbBS0, HbSB+ WISC, WAIS Spanish adaptation Individuals with SCD showed a decrease in IQ compared with individuals without SCD
More severe (HbSS and HbSB0) genotypes were associated with a decrease in neurocognition 
Youssry et al76  Egypt 40/— SCD: (6-20) HbSS, HbSB0 Stanford Binet intelligence test Adaptation to the Arab Stanford Binet intelligence test Half of individuals with SCD had a below-average IQ
No association between SES and IQ 
StudyCountrySCD, n/control, nMean age (range), yGenotypeStudy qualityMeasuresLanguage and test adaptationPrimary findings
Ampomah et al50  Ghana 63/60 (age- and education-matched controls) 29.4 (18-50) HbSS, HbSC WRAT-4 RQCST, Trails A + B, MCST, DSST, grooved pegboard, recognition memory test, ROCF, cognitive features questionnaire None reported Individuals with SCD scored lower than the non-SCD comparison group in all cognitive domains
Individuals with SCD showed declines in visuospatial ability, executive functioning, and processing speed at 7-year follow-up 
Castro and Viana43  Brazil 64/64 (age- and sex-matched controls) SCD: 10.8 (7-13), no SCD: 10.9 (7-13) HbSS, HbSB0 3 WISC-III None reported Individuals with SCD had lower scores across all domains assessed (significantly lower processing speed, distraction resistance, and perceptual organization) than individuals without SCD 
Dias et al51  Brazil 60/74 (community controls) (6-11) Not reported 3 Raskin's optotype letter "E"; Ishihara test; Raven's colored progressive matrices test, special scale; testing trails, parts A and B; 5-digit test; WISC-IV scale digits subtest; Tower of London Standardized for Brazilian population Individuals with SCD aged 6-7 years displayed worsened attention interference on 5-digit test
Individuals with SCD aged 8-9 years displayed slower execution time in the counting stage
Individuals with SCD aged 10-11 years performed worse on working memory than non-SCD individuals 
Elalfy et al52  Egypt 32/11 (community controls) SCD: 15.25 (3.69), control: 17.73 (4.84) Not reported 3 WAIS-IV, Benton visual retention test None reported Nearly 2/3 individuals with SCD had an IQ of <90 
Erdem et al53  Turkey 100/82 (age-, sex-, and education-matched controls) Only median reported, SCD: 30 HbSS 4 MoCA Turkish adaptation of the MoCA54  Individuals with SCD had significantly lower MoCA scores than individuals without SCD
Individuals with SCD had poorer performance in visuospatial skills, executive function, attention, language, abstraction, delayed recall, and orientation
History of chronic/frequent headache episodes associated with significantly lower MoCA scores 
Ezenwosu et al55  Nigeria 90/90 (age- and sex-matched classmate controls) 8.88 (5-11) HbSS/HbSB0 6 DAPT Nigerian adaptation56  Individuals with SCD had significantly lower performance in English language
Nonsignificant difference between individuals with and without SCD on DAPT 
Fernandes et al57  Brazil 65/65 (sex- and age-matched) 9.5 (8-12) HbSS, HbSC 4 Academic performance test, WISC-III None reported Individuals with SCD had lower IQ scores than individuals without SCD 
Green et al58  Uganda 265/— 5.5 (1-12) HbSS/HbSB0 6 KABC-II, Mullen scales of early learning Translated into/validated in Luganda59-63  3% of children with SCD aged 1-4 years had abnormal scores (−2 or less z scores below age-specific norms)
16.7% of children with SCD aged 5-12 years had abnormal subscale scores with neurocognition related to previous stroke 
Jacob et al64  Tanzania 73/71 (healthy sibling controls) SCD: 11.9 (6-16), control: 11.1 (6-16) HbSS/HbSB0 4 WISC-IV (only PSI, PRI, WMI), Raven's standard progressive matrices Tests administered in Swahili Individuals with SCD performed worse than siblings on PSI, PRI, and WMI
Rates of score improvement were slower for individuals with SCD on coding/cancellation 
Knight et al65  West Indies 60/60 (sex- and age-matched controls) (15-18) HbSS 3 WISC-R, WAIS-R test item/direction wording modified for local conditions, vocabulary/picture arrangement subtests eliminated Individuals with SCD had lower IQ scores than individuals without SCD across domains
IQ was not correlated with age and did not differ by sex 
Matondo et al66  Tanzania 233/80 (healthy sibling controls) (9-15) HbSS/HbSB0 ROCF, KOH’s block design Validated in an in-house study at Muhimbili University of Health and Allied Sciences Individuals with SCD displayed greater impairment on an IQ measure than siblings
Negative association between age and neurocognitive performance 
Montanaro et al67  Nigeria 68/15 (age-matched sibling controls) SCD: 8.95 HbSS, HbSB+, HbSC WISC-III, WPPSI Assessments were adapted to Italian standardization and all tests were administered in Italian Bilingual immigrant individuals with SCD had a more noticeable and earlier onset of language difficulties compared with monolingual peers with SCD 
Nunes et al42  Brazil 15/— SCD: 10 (6-15) HbSS/HbSB0 NEPSY-II, WISC-III Brazilian adaptation of WISC-III 66.6% of participants performed within normal range, 26.6% scored below average range, and 6.6% scored above average on a measure of IQ
Below average performance on at least 1 NEPSY-II subtest for 60% of individuals
Individuals with a stroke history had lower performance on overall intellectual ability and across cognitive domains 
Olatunya et al68  Southwest Nigeria 101/101 (sociodemographic-matched classmate controls) SCD: 9.13, No SCD: 9.20 (4-12) HbSS/HbSB0 DAPT Validated for Nigerian children55  No difference between groups in school performance, but school absenteeism was associated with poorer performance across groups
School absenteeism independently predicted poor school performance in all participants 
Oluwole et al69  Nigeria 56/44 (healthy siblings and community controls) SCD: 9.2, No SCD: 9.41 HbSS WISC-IV English is teaching language of the population thus adaptations did not take place. Individuals with SCD had poorer neurocognitive performance (IQ and processing speed) than controls
Cognitive functioning was correlated with sociodemographic factors 
Prussien et al70  Nigeria 83/— SCD: 9.10 HbSS, HbSB0 Raven’s standard progressive matrices, Tower of London, WISC-IV Instructions were translated to Hausa for testing Children’s average score on Raven’s matrices below normative mean (corresponding IQ = 85)
Nigerian children did not differ from US children with SCD on working memory (WISC)
Significant association between higher transcranial Doppler velocity and lower executive planning efficiency 
Rajendran et al71  India 22/22 (age-, sex-, and community matched controls) Both SCD and no SCD: 9.9 (6-15) HbSS, HbSB0 MISIC, CPMS, PGI memory scale The MISIC is the Indian adaptation of the WISC. Translations to local language of the other measures took place.72  Individuals with SCD presented with lower IQ scores and tended to have more psychological problems compared with individuals without SCD 
Rodgers et al73  Haiti 22/— SCD: 24.50 (10-58) Not reported Conners continuous auditory test of attention None reported Individuals with SCD had no associations between disordered sleep, attention/emotion regulation, and attention in an impoverished community 
Salama et al74  Egypt 55/55 (age- and sex-matched healthy controls) SCD:10.7, no SCD: 12.5 HbSS, HbSB+ Stanford Binet intelligence scale None reported Over half of individuals with SCD had abnormal IQ scores, whereas individuals without SCD had higher IQ scores 
Martínez Triana et al75  Cuba 119/42 (healthy controls) SCD: (6-18) HbSS, HbSC HbBS0, HbSB+ WISC, WAIS Spanish adaptation Individuals with SCD showed a decrease in IQ compared with individuals without SCD
More severe (HbSS and HbSB0) genotypes were associated with a decrease in neurocognition 
Youssry et al76  Egypt 40/— SCD: (6-20) HbSS, HbSB0 Stanford Binet intelligence test Adaptation to the Arab Stanford Binet intelligence test Half of individuals with SCD had a below-average IQ
No association between SES and IQ 

CPMS, childhood psychopathology measurement schedule; DSST, digit symbol substitution test; Hb, hemoglobin; KABC-II, Kaufman assessment battery for children, second edition; MCST, modified card-sorting test; NEPSY-II, a developmental neuropsychological assessment; PRI, perceptual reasoning index; PSI, processing speed index; ROCF, Rey-Osterrieth complex figure test; RQCST, revised quick cognitive screening test; SES, socioeconomic status; WAIS-IV, WAIS fourth edition; WAIS-R, WAIS revised; WISC-III, WISC third edition; WISC-IV, WISC fourth edition; WISC-R, WISC revised; WMI, working memory index; WRAT-4, wide range achievement test fourth edition.

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