Cognitive Assessment in Brazilian Adults with Sickle Cell Disease (SCD): The Burdens of Sociocultural Background and Correlations with Neuroimaging Findings

Introduction: Sickle Cell Disease patients are at increased risk of developing silent cerebral infarcts. These can lead to cognitive impairment, reflected, for instance, in low academic and occupational performance, and the recognition of patients affected by cognitive decline is important to create focused therapeutic plans. Our aim was to screen the cognitive function of adult SCD patients through the Montreal Cognitive Assessment (MoCA) questionnaire and correlate these findings with possible predictive factors for test performance, including clinical and demographic data and anatomical findings of brain imaging.

Methods: This study included 124 adult patients with SCD followed at a specialized Hematology Center in southeastern Brazil. The MoCA questionnaire was applied with the aim of detecting cognitive decline (a punctuation of 25 or less in a 30-point score) by analyzing 7 domains of cognitive function: visual-spatial; executive; attention; concentration and executive memory; language and orientation. The demographic, clinical and laboratorial data acquired from patients' medical records were evaluated for associations with MoCA results. Magnetic Resonance Imaging (MRI) with voxel-based morphometric analysis (VBM) was also used to analyze alterations in the macrostructure of the brain in 28 of these patients.

Results: 124 patients (68 males, 56 females) were included: 79 homozygous SS, 28 HbSC, 10 Sβ⁰ e 07 Sβ⁺; and the median age was 44 (19-70) years. The median MoCA score was 23 points (8-30) and 87 (70%) patients scored less than 26, suggesting some level of cognitive impairment. The study did not reveal significant associations between MoCA results and any of the clinical or laboratorial data: hemoglobin levels; cell counts; hemolysis/inflammation markers; genotype; hydroxyurea use; body mass index; transfusion load throughout life and clinical complications (retinopathy, strokes, bone necrosis, leg ulcers, chronic kidney disease, priapism and acute chest syndrome). However, important correlations were shown with: age (Pearson correlation: r= -0.316; p<0.001); age at first job (r=0.221;p=0.018); personal income (r=0.23;p=0.012), per capita family income (r=0.303;p=0.001); educational status (schooling in years) of the patient (r=0.61;p=0) and of their parents (mother: r=0.536,p = 0; father: r=0.441,p=0). Morphometric images of the gray matter of 28 patients in this cohort were compared to 50 healthy controls and showed areas of significant atrophy in patients' cerebellum, left frontal and occipital lobes and bilateral temporal lobe. 9 of these patients repeated the MRI after 1 year (all HbSS, ranging from 36 to 55 y.o.), and progressive atrophy was observed in the right temporal and left frontal lobes and basal ganglia, despite the short interval time.

Discussion: These results demonstrate the high prevalence and impact of cognitive decline in adult SCD patients, despite the lack of documentation of acute ischemic events. The results of the cognitive tests were mirrored in the neuroimaging of some of these patients, with documentation of atrophy in important areas related to information processing and executive function. In addition, the importance of the influence of sociodemographic conditions on the cognitive performance of Brazilian patients can be observed, as perceived by the association between the worse results in the MoCA and the low education of parents and patients, low income and need to work at an early age. We speculate that the impact of the unfavorable socioeconomic environment to which these patients are exposed is expressive to the point that the observation of the associations with other possible determinants of cognitive deficits, such as the occurrence of previous stroke and parameters of inflammation and hemolysis, is prevented.

Costa:Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Global Survey HCP Steering Committee for Global Blood Therapeutics (GBT): Consultancy. Benites:Vifor: Honoraria; Fresenius Kabi: Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; EMS: Consultancy.