Catechol-O-methyltransferase gene (COMT) is associated with neurocognitive functioning in patients with sickle cell disease.

PURPOSE: Neurocognitive impairment is a common and debilitating complication of sickle cell disease (SCD) resulting from a combination of biological and environmental factors. The catechol-O-methyltransferase (COMT) gene modulates levels of dopamine availability in the prefrontal cortex. COMT has repeatedly been implicated in the perception of pain stimuli and frequency of pain crises in patients with SCD and is known to be associated with neurocognitive functioning in the general population. The current study aimed to examine the associations of genetic variants in COMT and neurocognitive functioning in patients with SCD. PATIENTS AND METHODS: The Sickle Cell Clinical Research and Intervention Program (SCCRIP) longitudinal cohort was used as a discovery cohort (n = 166). The genotypes for 5 SNPs (rs6269, rs4633, rs4818, rs4680, and rs165599) in COMT were extracted from whole genome sequencing data and analyzed using a dominant model. A polygenic score for COMT (PGSCOMT) integrating these 5 SNPs was analyzed as a continuous variable. The Cooperative Study of Sickle Cell Disease (CSSCD, n = 156) and the Silent Cerebral Infarction Transfusion (SIT, n = 114) Trial were used as 2 independent replication cohorts. Due to previously reported sex differences, all analyses were conducted separately in males and females. The Benjamini and Hochberg approach was used to calculate false discovery rate adjusted p-value (q-value). RESULTS: In SCCRIP, 1 out of 5 SNPs (rs165599) was associated with IQ at q<0.05 in males but not females, and 2 other SNPs (rs4633 and rs4680) were marginally associated with sustained attention at p<0.05 in males only but did not maintain at q<0.05. PGSCOMT was negatively associated with IQ and sustained attention at p<0.05 in males only. Using 3 cohorts' data, 4 out of 5 SNPs (rs6269, rs4633, rs4680, rs165599) were associated with IQ (minimum q-value = 0.0036) at q<0.05 among male participants but not female participants. The PGSCOMT was negatively associated with IQ performance among males but not females across all cohorts. CONCLUSION: Select COMT SNPs are associated with neurocognitive abilities in males with SCD. By identifying genetic predictors of neurocognitive performance in SCD, it may be possible to risk-stratify patients from a young age to guide implementation of early interventions.

Attitudes toward COVID-19 vaccine among pediatric patients with sickle cell disease and their caregivers.

OBJECTIVE: To evaluate attitudes toward vaccination and vaccine uptake regarding coronavirus disease 2019 (COVID-19) among pediatric patients with sickle cell disease (SCD) and their caregivers. PROCEDURE: Adolescent patients and caregivers of children with SCD were surveyed during routine clinic visits; we then conducted a logistic regression analysis to understand differences in vaccine status, while qualitative responses were coded thematically. RESULTS: Among respondents, the overall vaccination rate among adolescents and caregivers was 49% and 52%, respectively. Among the unvaccinated, 60% and 68% of adolescents and caregivers, respectively, preferred to remain unvaccinated, most commonly due to lack of perceived personal benefit from vaccination or mistrust in the vaccine. Multivariate logistic regression analysis showed that child's age (odds ratio [OR] = 1.1, 95% confidence interval [CI]: 1.0-1.2, p < .01) and caregiver education (measured by the Economic Hardship Index [EHI] score, OR = 0.76, 95% CI: 0.74-0.78, p < .05) were independent predictors of getting vaccinated. CONCLUSION: Despite the increased risk of severe illness due to COVID-19 in patients with SCD, vaccine hesitancy remains high in this population of families whose children have SCD. Fortunately, the reasons cited for deferring vaccination among those who are unvaccinated were largely due to barriers that may be overcome with quality communication around the utility of the vaccine and information about vaccine safety.

Intraindividual Cognitive Variability and Magnetic Resonance Imaging in Aging American Indians: Data from the Strong Heart Study.

BACKGROUND: American Indians have high prevalence of risk factors for Alzheimer's disease and related dementias (ADRD) compared to the general population, yet dementia onset and frequency in this population are understudied. Intraindividual cognitive variability (IICV), a measure of variability in neuropsychological test performance within a person at a single timepoint, may be a novel, noninvasive biomarker of neurodegeneration and early dementia. OBJECTIVE: To characterize the cross-sectional associations between IICV and hippocampal, total brain volume, and white matter disease measured by magnetic resonance imaging (MRI) among older American Indians. METHODS: IICV measures for memory, executive function, and processing speed, and multidomain cognition were calculated for 746 American Indians (aged 64-95) who underwent MRI. Regression models were used to examine the associations of IICV score with hippocampal volume, total brain volume, and graded white matter disease, adjusting for age, sex, education, body mass index, intracranial volume, diabetes, stroke, hypertension, hypercholesterolemia, alcohol use, and smoking. RESULTS: Higher memory IICV measure was associated with lower hippocampal volume (Beta = -0.076; 95% CI -0.499, -0.023; p = 0.031). After adjustment for Bonferroni or IICV mean scores in the same tests, the associations were no longer significant. No IICV measures were associated with white matter disease or total brain volume. CONCLUSION: These findings suggest that the IICV measures used in this research cannot be robustly associated with cross-sectional neuroimaging features; nonetheless, the results encourage future studies investigating the associations between IICV and other brain regions, as well as its utility in the prediction of neurodegeneration and dementia in American Indians.

Educational and Clinical Associations With Longitudinal Cognitive Function and Brain Imaging in American Indians: The Strong Heart Study.

BACKGROUND: Little is known about incidence of vascular and Alzheimer's dementias in American Indians. METHODS We conducted a large, heterogeneous, population-based, longitudinal cohort study of brain aging in community-dwelling American Indians aged 64-95 years from 11 tribes across 3 states, with neurological examinations, 1.5T magnetic resonance imaging (MRI), and extensive cognitive testing. Visit 1 in 2010-2013 (n=817) and Visit 2 in 2017-2019 (n=403) included all willing, surviving participants. Standardized cognitive tests at both visits included Modified Mini Mental Status Examination (3MSE), Wechsler Adult Intelligence Scale digit symbol coding (WAIS), Controlled Oral Word Association fas (COWA), California Verbal Learning Test short form (CVLT). Test materials added at follow-up included Wide Range Achievement (reading) Test (WRAT) and National Alzheimer's Coordinating Center Uniform Data Set cognitive battery (v3 form C2) , including Montreal Cognitive Assessment (MoCA). MRI neuroradiologists coded infarcts, hemorrhages, white matter hyperintensities, sulcal atrophy, and ventricle enlargement. RESULTS Mean time between exams was 6.7 years (SD 1.1, range 3.8-9.1). Years of formal education had modest correlation with WRAT reading score (r=0.45). Prevalence and incidence of infarcts were (respectively) 32% and 12.8/1000 person-years (PY); hemmorhages 6% and 4.4/1000 PY; worsening sulci 74% and 19.0/1000 PY; wosening ventricle 79% and 30.1/1000 PY; worsening leukoaraiosis 44% and 26.1/1000 PY. Linear losses per year in cognitive scores were 0.6% 3MSE, 1.2% WAIS, 0.6% COWA, 2.2% CVLT. Mean MoCA scores were 18.9 (SD 4.3). DISCUSSION These are the first data on longitudinal cognitive and imaging changes in American Indians, as well as first reports of AD related features. Mean scores in MoCA were similar or lower than standard cutoffs used to diagnose dementia in other racial/ethnic groups, suggesting that standardized cognitive tests may not perform well in this population. Test validation, adaptation, and score adjustment are warranted. Years of education was a poor proxy for premorbid function, suggesting novel methods for cognitive score contextualization is also needed in this population. Evaluation of selective survival suggests attrition from death and frailty should be accounted for in causal analyses. Overall, these data represent a unique opportunity to examine neurology topics of critical importance to an understudied population.

A configurational investigation of smartphone use disorder among adolescents in three educational levels.

INTRODUCTION: Smartphone use disorder in youth was associated with severe physical, psychological, and financial problems. Based on the ecological system theory of child development, this study examined a wide range of psychosocial characteristics in elementary-, middle-, and high-school adolescents with high scores on smartphone use disorder. METHODOLOGY: Existing research, which mainly adopted regression-based analytical techniques, found that gender, self-control, sensation seeking, loneliness, anxiety, perceived parent-adolescent relationship, and perceived parental monitoring are associated with smartphone use disorder. To complement traditional variable-centered approaches, the current study adopted a person-centered approach, fuzzy-set Qualitative Comparative Analysis (fsQCA) procedures, to examine adolescents with smartphone use disorder. RESULTS: The fsQCA procedure revealed four, nine, and thirteen distinct configurations that contributed to smartphone use disorder in adolescents for elementary school students, middle school students, and high school students respectively. A comparison across the three educational levels revealed four differences and two similarities. The results suggest that different groups of adolescents might be at risk for smartphone use disorder across the three educational levels. CONCLUSIONS: The fsQCA procedures generated solutions with satisfactory coverage and consistency. This demonstrates the promising value of fsQCA for researching smartphone use disorder and other behavior problems in adolescents. The results suggest that educators and mental health practitioners should consider educational level when helping adolescents with smartphone use disorder.