School racial composition, effect modification by caring teacher/staff presence, and mid/late-life depressive symptoms: findings from the Study of Healthy Aging among African Americans.

For Black students in the United States, attending schools with a higher proportion of White students is associated with worse mental and physical health outcomes in adolescence/early adulthood. No prior studies evaluate K-12 school racial composition and later-life mental health. In a cohort of Black adults ages 50+ in Northern California who retrospectively self-reported school racial composition for grades 1, 6, 9, and 12, we assessed the association between attending a school with mostly Black students vs. not and mid/late-life depressive symptoms (8-item PROMIS depression score, standardized to US adult population) using age-, sex/gender-, southern US birth-, and parental education-adjusted generalized estimating equations, and assessed effect modification by caring teacher/staff presence. Later-life depressive symptoms were lower among those who attended schools with mostly Black students in grades 1 and 6 (b=-0.12, 95% CI: -0.23, 0.00 and b=-0.11, 95% CI: -0.22, 0.00, respectively). In grade 6, this difference was larger for students without an adult at school who cared about them (b=-0.29, 95% CI: -0.51, -0.07 vs. b=-0.04, 95% CI: -0.17, 0.09). Among Black Americans, attending early school with mostly Black students may have later life mental health benefits; this protective association appears more important for students without caring teachers/staff.

The Association Between Physical Activity and Cognition in a Racially/Ethnically Diverse Cohort of Older Adults: Results From the Kaiser Healthy Aging and Diverse Life Experiences Study.

OBJECTIVE: Most prior research on physical activity (PA) and cognition is based on predominantly white cohorts and focused on associations of PA with mean (average) cognition versus the distribution of cognition. Quantile regression offers a novel way to quantify how PA affects cognition across the entire distribution. METHODS: The Kaiser Healthy Aging and Diverse Life Experiences study includes 30% white, 19% black, 25% Asian, and 26% Latinx adults age 65+ living in Northern California (n = 1600). The frequency of light or heavy PA was summarized as 2 continuous variables. Outcomes were z-scored executive function, semantic memory, and verbal episodic memory. We tested associations of PA with mean cognition using linear regression and used quantile regression to estimate the association of PA with the 10th-90th percentiles of cognitive scores. RESULTS: Higher levels of PA were associated with higher mean semantic memory (b = 0.10; 95% CI: 0.06, 0.14) and executive function (b = 0.05; 95% CI: 0.01, 0.09). Associations of PA across all 3 cognitive domains were stronger at low quantiles of cognition. CONCLUSION: PA is associated with cognition in this racially/ethnically diverse sample and may have larger benefits for individuals with low cognitive scores, who are most vulnerable to dementia.

Race, community disadvantage, and cognitive decline: Findings from KHANDLE and STAR.

INTRODUCTION: Community disadvantage is associated with late-life cognition. Few studies examine its contribution to racial disparities in cognition/cognitive change. METHODS: Inverse probability weighted models estimated expected mean differences in cognition/cognitive change attributed to residing in less advantaged communities, defined as cohort top quintile of Area Deprivation Indices (ADI): childhood 66-100; adulthood ADI 5-99). Interactions by race tested. RESULTS: More Black participants resided in less advantaged communities. Semantic memory would be lower if all participants had resided in less advantaged childhood (b = -0.16, 95% confidence interval [CI] = -0.30, -0.03) or adulthood (b = -0.14, 95% CI = -0.22, -0.04) communities. Race interactions indicated that, among Black participants, less advantaged childhood communities were associated with higher verbal episodic memory (interaction p-value = 0.007) and less advantaged adulthood communities were associated with lower semantic memory (interaction p-value = 0.002). DISCUSSION: Examining racial differences in levels of community advantage and late-life cognitive decline is a critical step toward unpacking community effects on cognitive disparities.

Timing and level of educational attainment and late-life cognition in the KHANDLE study.

INTRODUCTION: The timing of educational attainment may modify its effects on late-life cognition, yet most studies evaluate education only at a single time point. METHODS: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study cohort participants (N = 554) reported educational attainment (dichotomized at any college education) at two time points, and we classified them as having low, high, or later-life high educational attainment. Linear mixed-effects models estimated associations between educational attainment change groups and domain-specific cognitive outcomes (z-standardized). RESULTS: Compared to low educational attainment, high (ß= 0.59 SD units; 95% confidence interval [CI]: 0.39, 0.79) and later-life high educational attainment (ß = 0.22; 95% CI: 0.00, 0.44) were associated with higher executive function. Only high educational attainment was associated with higher verbal episodic memory (ß = 0.27; 95% CI: 0.06, 0.48). DISCUSSION: Level and timing of educational attainment are both associated with domain-specific cognition. A single assessment for educational attainment may inadequately characterize protective associations with late-life cognition. HIGHLIGHTS: Few studies have examined both level and timing of educational attainment on cognition. Marginalized populations are more likely to attain higher education in adulthood. Higher educational attainment in late life is also associated with higher cognition.

A systematic review of pediatric neuropsychological outcomes with proton versus photon radiation therapy: A call for equity in access to treatment.

OBJECTIVE: There is increasing interest in the utilization of proton beam radiation therapy (PRT) to treat pediatric brain tumors based upon presumed advantages over traditional photon radiation therapy (XRT). PRT provides more conformal radiation to the tumor with reduced dose to healthy brain parenchyma. Less radiation exposure to brain tissue beyond the tumor is thought to reduce neuropsychological sequelae. This systematic review aimed to provide an overview of published studies comparing neuropsychological outcomes between PRT and XRT. METHOD: PubMed, PsychINFO, Embase, Web of Science, Scopus, and Cochrane were systematically searched for peer-reviewed published studies that compared neuropsychological outcomes between PRT and XRT in pediatric brain tumor patients. RESULTS: Eight studies were included. Six of the studies utilized retrospective neuropsychological data; the majority were longitudinal studies (n = 5). XRT was found to result in lower neuropsychological functioning across time. PRT was associated with generally stable neuropsychological functioning across time, with the exception of working memory and processing speed, which showed variable outcomes across studies. However, studies inconsistently included or considered medical and sociodemographic differences between treatment groups, which may have impacted neuropsychological outcomes. CONCLUSIONS: Despite methodological limitations, including limited baseline neuropsychological evaluations, temporal variability between radiation treatment and first evaluation or initial and follow-up evaluations, and heterogenous samples, there is emerging evidence of sociodemographic inequities in access to PRT. With more institutions dedicating funding towards PRT, there may be the opportunity to objectively evaluate the neuropsychological benefits of patients matched on medical and sociodemographic variables.

Tumor region associated with specific processing speed outcomes.

OBJECTIVE: Processing speed (PS) is a vulnerable cognitive skill in pediatric cancer survivors as a consequence of treatments and, less consistently, tumor region. Studies conventionally examine graphomotor PS; emerging research suggests other aspects of PS may be impacted. This study examined types of PS in pediatric brain tumor survivors to determine which aspects are impaired. Given discordance across studies, we additionally investigated the relationship between brain region and PS. METHODS: The sample consisted of 167 pediatric brain tumor patients (100 supratentorial). PS (oral naming, semantic fluency, phonemic fluency, motor speed, graphomotor speed, visual scanning) was gathered via clinical neuropsychological assessment. To examine PS by region, infratentorial and supratentorial groups were matched on age at diagnosis and neuropsychological assessment, and time since diagnosis. RESULTS: The whole sample performed below normative means on measures of oral naming (p < .001), phonemic fluency (p < .001), motor speed (p = .03), visual scanning (p < .001), and graphomotor speed (p < .001). Only oral naming differed by region (p = .03), with infratentorial tumors associated with slower performance. After controlling for known medical and demographic risk factors, brain region remained a significant predictor of performance (p = .04). Among the whole sample, greater than expected proportions of patients with impairment (i.e., >1 standard deviation below the normative mean) were seen across all PS measures. Infratentorial tumors had higher rates of impairments across all PS measures except phonemic fluency. CONCLUSIONS: Results indicate pediatric brain tumor survivors demonstrate weaknesses in multiple aspects of PS, suggesting impairments are not secondary to peripheral motor slowing alone. Additionally, tumor region may predict some but not all neuropsychological outcomes in this population.

Characterization of Neuropsychological Outcomes in a Cohort of Pediatric Patients with Moyamoya Arteriopathy.

INTRODUCTION: Moyamoya arteriopathy is a severe, progressive cerebral arteriopathy that places affected children at high risk for stroke. Moyamoya has been associated with a range of neuropsychological deficits in adults, but data on many cognitive domains remain limited in the pediatric population and little is known about the neuropsychological profile of children with syndromic moyamoya. METHODS: This is a single-center, retrospective cohort study of children with moyamoya arteriopathy followed at our center who underwent neuropsychological testing between 2003 and 2021. Test scores were extracted from neuropsychological reports. Medical records were reviewed with attention to individual neuropsychological test results, medical comorbidities, presence of infarct(s) on neuroimaging, and history of clinical ischemic stroke. RESULTS: Of the 83 children with moyamoya followed at our center between 2003 and 2021, 13 had completed neuropsychological testing across multiple cognitive domains. Compared to age-based normative data, children in this sample had lower scores in overall intelligence (p = 0.003), global executive functioning (p = 0.005), and overall adaptive functioning (p = 0.015). There was no significant difference in overall intelligence between children with (n = 6) versus without (n = 7) a history of clinical stroke (p = 0.368), though children with any radiographic infarct scored lower in this domain (p = 0.032). CONCLUSION: In our cohort, children with moyamoya demonstrated impaired intelligence and executive functioning, even in the absence of clinical stroke. Neuropsychological evaluation should be considered standard of care for all children with moyamoya, even those without a history of clinical stroke.

Working Memory and Processing Speed Predict Math Skills in Pediatric Brain Tumor Survivors.

OBJECTIVE: Childhood brain tumor (BT) survivors are at risk for working memory (WM) and processing speed (PS) deficits, which impact other cognitive domains. This study aimed to characterize WM, PS, and untimed mathematics calculation performance in pediatric BT survivors at least 2 years post-diagnosis, identify medical factors associated with deficits in mathematics, and examine whether WM and/or PS predict mathematics performance in this clinical sample. METHODS: Retrospective data were gathered from 72 BT survivors between 7 and 21 years of age ( M =13.64 y, SD =4.01 y) for a clinical neuropsychologic evaluation. All participants completed Wechsler measures of WM and PS and a measure of untimed mathematics calculation. RESULTS: WM, PS, and the mathematics calculation were significantly lower than the normative mean. Math scores were not correlated with any of the examined medical factors. PS was negatively correlated with the Neurological Predictor Scale and positively correlated with age at diagnosis. Both WM and PS were associated with math outcomes and accounted for 30.4% and 19.2% of the variance, respectively. CONCLUSIONS: The findings indicate that WM and PS contribute to mathematics performance in pediatric BT survivors. Examining mathematics performance should be a part of clinical neuropsychological evaluations. Interventions to improve mathematics performance in this population should also focus on WM and compensatory strategies for slowed PS.

Improving Outcomes for Bronchiolitis Patients After Implementing a High-Flow Nasal Cannula Holiday and Standardizing Discharge Criteria in a PICU.

OBJECTIVES: To decrease length of high-flow nasal cannula (HFNC), PICU, and hospital length of stay (LOS). DESIGN: Quality improvement project. SETTING: A quaternary academic PICU. PATIENTS: Patients with bronchiolitis less than 24 months old. INTERVENTIONS: After initial implementation of a respiratory therapist (RT)-driven HFNC protocol (Plan-Do-Study-Act [PDSA] 1) in October 2017, additional interventions included adjusting HFNC wean rate (PDSA 2) in July 2020, a HFNC holiday (PDSA 3), and standardized discharge criteria (PDSA 4) in October 2021. MEASUREMENTS AND MAIN RESULTS: Duration of HFNC was used as the primary outcome measure. PICU LOS and hospital LOS were used as secondary outcome measures. Noninvasive ventilation use, invasive mechanical ventilation use, and 7-day PICU and hospital readmission rates were used as balancing measures. A total of 1,310 patients were included in this study. Patients in PDSA 2, PDSA 3 and 4 groups were older compared with pre-intervention and PDSA 1 (median of 9 and 10 mo compared with 8 mo; p = 0.01). HFNC duration decreased from 2.5 to 1.8 days after PDSA 1, then to 1.3 days after PDSA 2. PICU LOS decreased from 2.6 to 2.1 days after PDSA 1, 1.8 days after PDSA 2, and 1.5 days after PDSA 3 and 4. Hospital LOS decreased from 5.7 to 4.5 days after PDSA 1, 3.1 days after PDSA 2, and 2.7 days after PDSA 3 and 4. The use of noninvasive ventilation and invasive mechanical ventilation decreased throughout the study from 23.2% in the pre-intervention group, to 6.9% at the end of the project. The 7-day PICU and hospital readmission rates did not increase after implementation. The percentage of patients discharged from the PICU increased from 6.2% to 21.5%. CONCLUSIONS: Modifications to an existing RT-driven HFNC protocol and standardization of discharge criteria led to an improvement in outcomes for patients admitted to the PICU with bronchiolitis without an increase in adverse events.

Association of primary lifetime occupational cognitive complexity and cognitive decline in a diverse cohort: Results from the KHANDLE study.

INTRODUCTION: Higher occupational complexity has been linked to favorable cognitive outcomes, but rarely examined in racially and ethnically diverse populations. METHODS: In a diverse cohort (n = 1536), linear mixed-effects models estimated associations between main lifetime occupational complexity and domain-specific cognitive decline (z-standardized). Occupational complexity with data, people, and things were classified using the Dictionary of Occupational Titles. RESULTS: For occupational complexity with data, highest tertile (vs. lowest) was associated with higher baseline executive function (ß = 0.11; 95% confidence interval [CI] 0.00-0.22) and slower annual rate of decline (ß = 0.03; 95% CI 0.01-0.06), and higher baseline semantic memory (ß = 0.14; 95% CI 0.04-0.25). Highest tertile of occupational complexity with people was associated with higher baseline executive function (ß = 0.29; 95% CI 0.18-0.40), verbal episodic memory (ß = 0.12; 95% CI 0.00-0.24), and semantic memory (ß = 0.23; 95% CI 0.12-0.34). DISCUSSION: In a diverse cohort, higher occupational complexity is associated with better cognition. Findings should be verified in larger cohorts. HIGHLIGHT: Few studies have examined associations of occupational complexity with cognition in diverse populations. Racial and ethnic minorities are disproportionately exposed to lower occupational complexity. Occupational complexity with data and people are associated with better cognition.

Evaluating interpersonal discrimination and depressive symptoms as partial mediators of the effects of education on cognition: Evidence from the Study of Healthy Aging in African Americans (STAR).

INTRODUCTION: Education is correlated with positive health outcomes, but associations are sometimes weaker among African Americans. The extent to which exposure to discrimination and depressive symptoms attenuates the education-cognition link has not been investigated. METHODS: Study of Healthy Aging in African Americans (STAR) participants (n = 764; average age 69 years) completed the Spanish and English Neuropsychological Assessment Scales. We assessed everyday and major lifetime discrimination and depressive symptoms as mediators of education effects on cognition using G-estimation with measurement error corrections. RESULTS: Education was correlated with greater major lifetime and everyday discrimination but lower depressive symptoms. Accounting for discrimination and depressive symptoms slightly reduced the estimated effect of education on cognition. The estimated total effect of graduate education (vs 

Neighborhood segregation and cognitive change: Multi-Ethnic Study of Atherosclerosis.

INTRODUCTION: We investigated associations between neighborhood racial/ethnic segregation and cognitive change. METHODS: We used data (n = 1712) from the Multi-Ethnic Study of Atherosclerosis. Racial/ethnic segregation was assessed using Getis-Ord (Gi*) z-scores based on American Community Survey Census tract data (higher Gi* = greater spatial clustering of participant's race/ethnicity). Global cognition and processing speed were assessed twice, 6 years apart. Adjusted multilevel linear regression tested associations between Gi* z-scores and cognition. Effect modification by race/ethnicity, income, education, neighborhood socioeconomic status, and neighborhood social support was tested. RESULTS: Participants were on average 67 years old; 43% were White, 11% Chinese, 29% African American/Black, 17% Hispanic; 40% had high neighborhood segregation (Gi* > 1.96). African American/Black participants with greater neighborhood segregation had greater processing speed decline in stratified analyses, but no interactions were significant. DISCUSSION: Segregation was associated with greater processing speed declines among African American/Black participants. Additional follow-ups and comprehensive cognitive batteries may further elucidate these findings. HIGHLIGHTS: A study of neighborhood racial/ethnic segregation and change in cognition. Study was based on a racially and geographically diverse, population-based cohort of older adults. Racial/ethnic segregation (clustering) was measured by the Getis-ord (Gi*) statistic. We saw faster processing speed decline among Black individuals in segregated neighborhoods.

Pragmatic approaches to handling practice effects in longitudinal cognitive aging research.

INTRODUCTION: The challenge of accounting for practice effects (PEs) when modeling cognitive change was amplified by the COVID-19 pandemic, which introduced period and mode effects that may bias the estimation of cognitive trajectory. METHODS: In three Kaiser Permanente Northern California prospective cohorts, we compared predicted cognitive trajectories and the association of grip strength with cognitive decline using three approaches: (1) no acknowledgment of PE, (2) inclusion of a wave indicator, and (3) constraining PE based on a preliminary model (APM) fit using a subset of the data. RESULTS: APM-based correction for PEs based on balanced, pre-pandemic data, and with current age as the timescale produced the smallest discrepancy between within-person and between-person estimated age effects. Estimated associations between grip strength and cognitive decline were not sensitive to the approach used. DISCUSSION: Constraining PEs based on a preliminary model is a flexible, pragmatic approach allowing for meaningful interpretation of cognitive change. HIGHLIGHTS: The magnitude of practice effects (PEs) varied widely by study. When PEs were present, the three PE approaches resulted in divergent estimated age-related cognitive trajectories. Estimated age-related cognitive trajectories were sometimes implausible in models that did not account for PEs. The associations between grip strength and cognitive decline did not differ by the PE approach used. Constraining PEs based on estimates from a preliminary model allows for a meaningful interpretation of cognitive change.

The structural and social determinants of Alzheimer's disease related dementias.

INTRODUCTION: The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. METHODS: In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. RESULTS: Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. DISCUSSION: Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. HIGHLIGHTS: Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro-level determinants have been understudied in the AD/ADRD literature.

Global rural health disparities in Alzheimer's disease and related dementias: State of the science.

INTRODUCTION: Individuals living in rural communities are at heightened risk for Alzheimer's disease and related dementias (ADRD), which parallels other persistent place-based health disparities. Identifying multiple potentially modifiable risk factors specific to rural areas that contribute to ADRD is an essential first step in understanding the complex interplay between various barriers and facilitators. METHODS: An interdisciplinary, international group of ADRD researchers convened to address the overarching question of: "What can be done to begin minimizing the rural health disparities that contribute uniquely to ADRD?" In this state of the science appraisal, we explore what is known about the biological, behavioral, sociocultural, and environmental influences on ADRD disparities in rural settings. RESULTS: A range of individual, interpersonal, and community factors were identified, including strengths of rural residents in facilitating healthy aging lifestyle interventions. DISCUSSION: A location dynamics model and ADRD-focused future directions are offered for guiding rural practitioners, researchers, and policymakers in mitigating rural disparities. HIGHLIGHTS: Rural residents face heightened Alzheimer's disease and related dementia (ADRD) risks and burdens due to health disparities. Defining the unique rural barriers and facilitators to cognitive health yields insight. The strengths and resilience of rural residents can mitigate ADRD-related challenges. A novel "location dynamics" model guides assessment of rural-specific ADRD issues.

Changes in executive function in pediatric brain tumor survivors.

OBJECTIVE: Pediatric oncology survivors are at risk for executive function (EF) and working memory (WM) deficits, which can be measured via performance-based measures or rating scales. Previous studies have shown these measurement methods to be weakly correlated. This study aimed to describe parent-rated EF and performance-based WM (PBWM) in pediatric brain tumor (BT) survivors, examine change in EF and PBWM across time, and investigate the relationship between parent-rated WM and PBWM. METHOD: The sample included 56 patients diagnosed with a BT in childhood (Mage  = 6.94 years; SD = 4.05) seen twice for clinical neuropsychological evaluation. PBWM was examined via the auditory WM scale from a Wechsler intelligence measure or Differential Ability Scales-II. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF)/BRIEF-P/BRIEF-2 as a measure of global EF (Global Executive Composite [GEC]), metacognitive skills (Metacognitive Index/Cognitive Regulation Index [MI/CRI]), behavioral regulation (Behavior Regulation Index [BRI]), and emotional regulation (Emotion Regulation Index [ERI]). RESULTS: GEC, MI/CRI, and ERI at Time 1 were significantly above the mean (p < .01); BRI and PBWM did not differ from the normative mean. All measures were significantly higher than the normative mean at Time 2 (p < .05). PBWM was both clinically and statistically elevated (p < .001). There was a significant change across time in PBWM (p < .05), but not GEC, MI/CRI, ERI, or BRI. PBWM was weakly correlated with the BRIEF WM subscale at Time 1 and Time 2 (all p > .05). CONCLUSIONS: Multiple measures of EF should be considered when providing diagnoses and recommendations for pediatric BT survivors. Furthermore, given declines across time, findings document need for continued monitoring and reassessment of survivors as they get further out from treatment.

Association of Social Integration with Cognitive Status in a Multi-Ethnic Cohort: Results From the Kaiser Healthy Aging and Diverse Life Experiences Study.

We evaluated overall and race-specific relationships between social integration and cognition in older adults. Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) cohort participants included 1343 Asian, Black, Latino, or non-Latino White Kaiser Permanente Northern California members. We estimated the effect of social integration on verbal episodic memory, semantic memory, and executive function derived from the Spanish and English Neuropsychological Assessment (SENAS) Scales. Social integration scores included marital status; volunteer activity; and contact with children, relatives, friends, and confidants. We estimated covariate-adjusted linear mixed-effects models for baseline and 17-month follow-up cognition. Social integration was associated with higher baseline cognitive scores (average  ß = 0.066 (95% confidence interval: 0.040, 0.092)) overall and in each racial/ethnic group. The association did not vary by race/ethnicity. Social integration was not associated with the estimated rate of cognitive change. In this cohort, more social integration was similarly associated with better late-life cognition across racial/ethnic groups.

Sluggish cognitive tempo profiles in survivors of childhood cancer as compared to children with attention-deficit/hyperactivity disorder.

PURPOSE: Neurocognitive late effects including problems with attention have been reported in pediatric oncology survivors. While some researchers have characterized these late effects as similar to symptoms of attention-deficit/hyperactivity disorder, inattentive presentation (ADHD-I), there remains some controversy as to whether these concerns in oncology patients are best conceptualized according to an ADHD-I or sluggish cognitive tempo (SCT) framework. The aim of this study was to describe SCT symptoms in children with ADHD-I or oncology diagnoses; identify groups of SCT symptoms among children with brain tumors (BT), acute lymphoblastic leukemia (ALL), or ADHD-I; and identify whether specific SCT profiles are associated with these diagnoses. METHODS: The sample was comprised of 364 youth (146 BT, 149 ADHD-I, 69 ALL) referred for a neuropsychological evaluation at an academic medical center. Caregivers completed the SCT scale as part of the clinical evaluation. RESULTS: Groups differed on mean scores for the SCT scales (Total, Sleepy/sluggish, Low initiation, and Daydreamy) by diagnosis (all p < 0.05), with the ADHD-I group having higher SCT symptoms on all scales. Latent profile analysis showed significant differences between latent SCT classes according to ADHD-I versus cancer diagnosis. The ADHD-I group was significantly more likely to be in the high SCT class compared to the oncology groups. CONCLUSION: Findings add to the understanding of SCT symptoms in pediatric oncology survivors. There is utility in applying the SCT framework to the oncology population; however, pediatric survivors are likely to be rated differently than youth with ADHD-I. Implications and future directions are discussed.

Loss of tumor protein 53 protects against alcohol-induced facial malformations in mice and zebrafish.

BACKGROUND: Alcohol exposure during the gastrulation stage of development causes the craniofacial and brain malformations that define fetal alcohol syndrome. These malformations, such as a deficient philtrum, are exemplified by a loss of midline tissue and correspond, at least in part, to regionally selective cell death in the embryo. The tumor suppressor protein Tp53 is an important mechanism for cell death, but the role of Tp53 in the consequences of alcohol exposure during the gastrulation stage has yet to be examined. The current studies used mice and zebrafish to test whether genetic loss of Tp53 is a conserved mechanism to protect against the effects of early developmental stage alcohol exposure. METHODS: Female mice, heterozygous for a mutation in the Tp53 gene, were mated with Tp53 heterozygous males, and the resulting embryos were exposed during gastrulation on gestational day 7 (GD 7) to alcohol (two maternal injections of 2.9 g/kg, i.p., 4 h apart) or a vehicle control. Zebrafish mutants or heterozygotes for the tp53zdf1  M214K mutation and their wild-type controls were exposed to alcohol (1.5% or 2%) beginning 6 h postfertilization (hpf), the onset of gastrulation. RESULTS: Examination of GD 17 mice revealed that eye defects were the most common phenotype among alcohol-exposed fetuses, occurring in nearly 75% of the alcohol-exposed wild-type fetuses. Tp53 gene deletion reduced the incidence of eye defects in both the heterozygous and mutant fetuses (to about 35% and 20% of fetuses, respectively) and completely protected against alcohol-induced facial malformations. Zebrafish (4 days postfertilization) also demonstrated alcohol-induced reductions of eye size and trabeculae length that were less common and less severe in tp53 mutants, indicating a protective effect of tp53 deletion. CONCLUSIONS: These results identify an evolutionarily conserved role of Tp53 as a pathogenic mechanism for alcohol-induced teratogenesis.

Racial/Ethnic Disparities in Young Adulthood and Midlife Cardiovascular Risk Factors and Late-life Cognitive Domains: The Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study.

BACKGROUND: Midlife cardiovascular risk factors (CVRF) increase dementia risk. Less is known about whether CVRF identified before midlife impact late-life cognition in diverse populations. METHODS: Linear regression models examined hypertension, hyperlipidemia, and overweight/obesity at ages 30 to 59 with late-life executive function, semantic memory, verbal episodic memory, and global cognition in a cohort of Asians, blacks, Latinos, and whites (n=1127; mean age=75.8, range=65 to 98). Models adjusted for age at CVRF, age at cognitive assessment, sex, race/ethnicity, participant education, and parental education. RESULTS: Overall, 34% had 1 CVRF at ages 30 to 59; 19% had 2+. Blacks (26%) and Latinos (23%) were more likely to have 2+ CVRF than Asians (14%) or whites (13%). Having 2+ CVRF was associated with lower global cognition [ß=-0.33; 95% confidence interval (CI)=-0.45, -0.21], executive function (ß=-0.26; 95% CI=-0.39, -0.13), verbal episodic memory (ß=-0.34; 95% CI=-0.48, -0.20), and semantic memory (ß=-0.20; 95% CI=-0.33, -0.07). Interaction by age (P=0.06) indicated overweight/obesity was negatively associated with executive function at ages 30 to 39 but not at ages 40 to 59. Race/ethnic-specific effects showed disparities in CVRF prevalence impact population disparities in late-life cognition. CONCLUSION: Being overweight/obese in early adulthood and having 2+ CVRF in early adulthood/midlife are modifiable targets to redress racial/ethnic disparities in cognitive impairment and dementia.