Cohort studies demonstrate that people who later develop schizophrenia, on average, present with mild cognitive deficits in childhood and endure a decline in adolescence and adulthood. Yet, tremendous heterogeneity exists during the course of psychotic disorders, including the prodromal period. Individuals identified to be in this period (known as CHR-P) are at heightened risk for developing psychosis (~35%) and begin to exhibit cognitive deficits. Cognitive impairments in CHR-P (as a singular group) appear to be relatively stable or ameliorate over time. A sizeable proportion has been described to decline on measures related to processing speed or verbal learning. The purpose of this analysis is to use data-driven approaches to identify latent subgroups among CHR-P based on cognitive trajectories. This will yield a clearer understanding of the timing and presentation of both general and domain-specific deficits.

Participants included 684 young people at CHR-P (ages 12–35) from the second cohort of the North American Prodromal Longitudinal Study. Performance on the MATRICS Consensus Cognitive Battery (MCCB) and the Wechsler Abbreviated Scale of Intelligence (WASI-I) was assessed at baseline, 12-, and 24-months. Tested MCCB domains include verbal learning, speed of processing, working memory, and reasoning & problem-solving. Sex- and age-based norms were utilized. The Oral Reading subtest on the Wide Range Achievement Test (WRAT4) indexed pre-morbid IQ at baseline. Latent class mixture models were used to identify distinct trajectories of cognitive performance across two years. One- to 5-class solutions were compared to decide the best solution. This determination depended on goodness-of-fit metrics, interpretability of latent trajectories, and proportion of subgroup membership (>5%).

A one-class solution was found for WASI-I Full-Scale IQ, as people at CHR-P predominantly demonstrated an average IQ that increased gradually over time. For individual domains, one-class solutions also best fit the trajectories for speed of processing, verbal learning, and working memory domains. Two distinct subgroups were identified on one of the executive functioning domains, reasoning and problem-solving (NAB Mazes). The sample divided into unimpaired performance with mild improvement over time (Class I, 74%) and persistent performance two standard deviations below average (Class II, 26%). Between these classes, no significant differences were found for biological sex, age, years of education, or likelihood of conversion to psychosis (OR = 1.68, 95% CI 0.86 to 3.14). Individuals assigned to Class II did demonstrate a lower WASI-I IQ at baseline (96.3 vs. 106.3) and a lower premorbid IQ (100.8 vs. 106.2).

Youth at CHR-P demonstrate relatively homogeneous trajectories across time in terms of general cognition and most individual domains. In contrast, two distinct subgroups were observed with higher cognitive skills involving planning and foresight, and they notably exist independent of conversion outcome. Overall, these findings replicate and extend results from a recently published latent class analysis that examined 12-month trajectories among CHR-P using a different cognitive battery (Allott et al., 2022). Findings inform which individuals at CHR-P may be most likely to benefit from cognitive remediation and can inform about the substrates of deficits by establishing meaningful subtypes.

Adequate effort by examinees during neurocognitive testing is a prerequisite to valid interpretation of test results. Utilizing performance validity tests (PVTs) is strongly recommended within pediatric mild Traumatic Brain Injury (mTBI) populations. PVTs have historically been created based on majority-white and monolingual groups; investigating their validity in additional patient populations remains essential. The Automatized Sequencing Task (AST) was developed as a brief validity measure within mTBI youth (Kirkwood, et.al., 2014). This study aimed to examine the clinical utility of the AST among youth identifying as Hispanic/Latino and/or bilingual within a mTBI clinical sample.

Participants ages 8-17 (N=103, M age=14.08, SD=2.2, 51.5% male, 42.7% Hispanic/Latino, 23.6% bilingual) were drawn from an outpatient mTBI/concussion program within the past 2.6 years. Median time of evaluation since injury was 3.7 weeks. Eligibility criteria included: 1) evaluated for a mTBI (GCS . 13) and 2) 8 through 17 years of age. Language status included English only and English-Spanish bilingual youth. Of the bilingual youth, 95% were considered English dominant. Youth were timed while reciting four well-learned (i.e., automatized) sequences as rapidly as possible: 1) the alphabet, 2) counting from 1-20, 3) the days of the week, and 4) the months of the year. Pass rates for the AST were examined using chi-square tests to compare performance based on ethnic/cultural identity (Hispanic vs Non-Hispanic), language status, age (children 8-12; teens 13-17), and gender.

In the clinical sample, 11.7% (n=12) could not complete AST months; 75% of non-completers were Hispanic/Latino. Participants who identified as Hispanic/Latino compared to Non-Hispanic/Latino participants were significantly more likely to fail the 4-item AST, χ2(1) =4.3, p<.05. The odds of failing the 4-item AST was 2.3 times higher if patients identified as Hispanic/Latino. Further, patients identifying as bilingual were even more likely to fail the 4-item AST, χ2(1) =4.5, p<.05. The odds of failing the 4-item AST was 3.0 times higher if patients were bilingual. There were no ethnicity or bilingual group differences in AST failure when examining performance on the 3-item AST. Neither age nor gender were a significant predictor of failure on the 3-item or 4-item AST.

Results suggest that the month item on the AST does not function consistently across Hispanic/Latino and bilingual youth. It cannot be presumed to be ‘automatic’ as a significant number of Hispanic/Latino and/or bilingual patients were unable to complete the month item, but with otherwise intact performance on the first three items. Administering only the first three items on the AST appears to be a more culturally sensitive alternative given the increased odds of 4-item failure in Hispanic/Latino and bilingual youth. Additional research is needed to explore the predictive validity of the AST as a PVT in varying ethnic, culturally, linguistically, and socioeconomically diverse mTBI pediatric populations.

Process-based measures of verbal learning, such as the recently described learning ratio (LR; Hammers et al., 2022) may add valuable data to neuropsychological assessment. Women tend to have higher episodic verbal memory ability compared to men at all ages, including older adulthood (Golchert et al., 2019; Maitland et al., 2004). However, it is unclear whether gender is related to the process of learning, as quantified through measures of learning slope and ratio. To date only one study has examined this, with Hammers et al. (2021) finding no gender differences on LR in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS); therefore, further study is necessary. We examined whether men and women differed in LR, learning over time (LOT), and raw learning slope (RLS) in a healthy older adult sample, as well as whether these learning process variables predicted delayed memory equally for men and women.

203 cognitively healthy community-dwelling adults aged 50 and above (mean age 67.7; 133 women) were taken from a larger archival database; all were administered the RBANS in the context of other studies. LR, LOT, and RLS were calculated from the List Learning task. We examined whether men and women differed in these learning process measures. We then examined whether process measures differentially predicted performance on list recall and delayed memory index (DMI) of the RBANS for men and women.

Men and women did not differ in age or years of education. After accounting for age and education, there were no gender differences on LR (p=.455) or RLS (p=.502) but LOT was lower in women (p=.013).

LR was equally predictive of list recall across genders (p<.001 for LR; p=.21 for gender). Correlations between LR and list recall were r=.65 (p<.001) for men and r=.56 (p<.001) for women. Both LR (p<.001) and gender (p=.008) predicted DMI but the interaction was nonsignificant. Correlations between LR and DMI were r=.52 for men (p<.001) and r=.46 for women (p<.001).

RLS predicted list recall equally across genders (p<.001 for RLS; p=.07 for gender; p=.18 for interaction). Correlations between RLS and list recall were r=.43 for men (p<.001) and r=.23 for women (p=.008). RLS (p<.001) and gender (p=.002; p=.19 for interaction) predicted DMI scores. Correlations between RLS and DMI were r=.31 for men (p=.008) and r=.21 for women (p=.015).

LOT predicted list recall equally across genders (p<.001; p=.97 for gender; p=.80 for interaction). Correlations between LOT and list recall were r=-.50 for men (p<.001) and r=-.60 for women (p<.001). LOT also predicted DMI equally across genders (p<.001; p=.084 for gender; p=.159 for interaction). Correlations between LOT and DMI were r=-.46 for men (p<.001) and r=-.49 for women (p<.001).

Of the three process variables, LR was the only one that did not show gender differences and was related to delayed memory outcomes with medium to large effect across both genders. Results suggest that LR can be used consistently across genders. As this sample consisted of healthy, independently-living older adults, future study should examine LR by gender in MCI and dementia samples.

There are gender-related disparities in age of diagnosis of Mild Cognitive Impairment (MCI) or dementia, with women often receiving delayed diagnoses compared to men. These delays may be related to the general female advantage in episodic verbal memory across aging. Thus, it is important to identify methods of examining memory performance that can help to reduce disparities in diagnosis. The serial position effect, a pattern where individuals tend to remember more words at the beginning (primacy) and end (recency) of a list, is predictive of dementia and may provide an avenue for this endeavor. Whereas healthy adults tend to exhibit a prototypical U-shaped serial position profile, those with MCI or dementia tend to show reduced primacy relative to recency (i.e., a J-shaped profile). To date, few studies have examined gender differences in the serial position effect. There is some evidence to suggest that older, cognitively healthy women perform better than men on middle and recency, but more research is needed to clarify the relationship between gender and the serial position effect, which was the focus of this study.

We utilized data across three archival datasets, which included a total of 338 participants (67.5% female; Mage=66.9, SDage=9.4) divided into three age groups (50-64, 65-75, 76+). Scores on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) immediate and delayed memory indices (IMI and DMI, respectively) were used to assess verbal episodic memory abilities. Performances across learning trials of the List Learning task were utilized to examine the serial position effect. ANCOVA analyses were conducted and utilized regional scoring of list learning performance, which examined the percentage of correctly recalled words in each portion of the list (primacy, middle, and recency). We also calculated the relative strength of primacy to list learning to examine the relationship between J-curve performance and gender. Years of education was included as a covariate in all analyses.

Consistent with prior literature, men performed worse performance on both IMI F(1, 331)=17.20, p<.001, and DMI, F(1, 331)=6.87, p=.009, across aging. Repeated measured GLM showed that the serial position effect was seen across the full sample, F(1.93, 639.874)=5.66, p=.004, and interacted with gender, F(1.933, 639.874)=5.70, p=.004, and education, F(1.933, 639.874)=6.13, p = .003. Although men and women did not differ in primacy, p = .67, women performed better in middle, p < .001, and recency, p = .03, performance. Higher education was associated with better primacy, but not middle or recency, performance. Additionally, 23.1% of the sample exhibited a J-curve pattern, and there was a main effect of J-curve pattern for both IMI, F(1, 334)=12.33, p<.001, and DMI, F(1, 334)=15.62, p<.001, with those showing a J=curve having worse memory performance.

Our finding of no gender difference in primacy suggests that focusing on primacy performance in verbal list learning may help to address gender-related disparities in MCI or dementia diagnosis. Additionally, given evidence of education being associated with primacy, but not middle or recency, performance, future research should investigate the development of education-based normative data for primacy performance.

The serial position effect is the tendency to recall items at the beginning (primacy) and end (recency) of a word list best and middle items the worst, demonstrated by a 'U-shaped’ profile. Individuals with memory impairment often demonstrate a 'J-shaped’ profile, with a diminished primacy effect. An attenuated primacy effect could be one of the earliest indicators of cognitive decline in older adults. Chronic elevations in cortisol are related to hippocampal atrophy and decreased learning and recall. Given the rehearsal and encoding required to recall words at the beginning of a list, we hypothesized that reduced primacy would be related to higher cortisol levels, measured via hair cortisol concentration, in older adults, particularly caregivers of people with dementia (PWD), who are under increased stress.

Data were taken from a deidentified dataset of 60 community-dwelling older adults (> 50) with no evidence of dementia who participated in a larger study on memory and caregiving stress; 26 identified themselves as caregivers of PWD. The sample was 83% women and 98% White, with a mean age of 67.58 (SD=8.85) and 80% holding at least a college degree. Stress was measured with the Perceived Stress Scale. The List Learning and List Recall subtests from the Repeatable Battery for the Assessment of Neuropsychological Status were used to assess the serial position effect. Primacy and recency were determined by the first three and last three words on the list, respectively, and were measured for trials 1-4. Relative strength of primacy versus recency at delayed recall was also calculated such that positive scores indicate better primacy than recency and negative scores indicate worse primacy than recency (J-shaped profile). Hair samples were collected, and the first one cm of hair was used to assay hair cortisol concentration, reflecting the past month of cortisol.

Caregivers were younger than non-caregivers (p<.001), but groups did not differ in gender (p=.412). Age was controlled for in all subsequent analyses. Caregivers reported more stress (p<.001), but groups were not different in hair cortisol (p=.093). On memory tasks, caregivers showed lower list learning raw scores (p=.002) and lower list recall raw score (p=.046); groups were not different in primacy learning (p=.114), but caregivers showed worse recency over learning trials (p<.001). Caregivers were not more likely to show the J-shaped serial position profile at recall (p=.285). Collapsed across groups, perceived stress was not related to cortisol (p=.124) but was related to recency (p=.001) and list learning raw (p=.004), but not list recall raw (p=.485) or primacy (p=.109). Cortisol was not related to primacy (p=.277) or recency (p=.538).

Contrary to predictions, caregivers were not worse on primacy but were worse on recency. Caregivers also reported more stress; collapsed across groups, stress was associated with recency performance. This may suggest that stress is related more to poor attention and short-term memory (recency) than encoding and recall related memory problems (primacy).

Learning process variables such as the serial position effect and learning ratio (LR) are predictive of cognitive decline and dementia. Gender differences on memory measures are well documented, but there is inconsistent evidence for gender effects on learning process variables. In the present study, we examined the relationship of serial position and LR to memory performance and to cortisol levels, considering gender as a potential moderator.

Data were taken from a deidentified dataset of a study on stress and aging in which 123 healthy community-dwelling adults over age 50 completed various assessments. Our analyses included 100 participants (56% female, 93% white, Mage 60.65, Meducation 15.22 years) who completed all measures of interest. LR, primacy effect, and recency effect were calculated from the learning trials of the Auditory Verbal Learning Test (AVLT). Additional memory measures included recall measures from the AVLT and from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). AUC cortisol was calculated from salivary cortisol samples taken across 6 time points in the study.

Women performed better than men on LR, primacy, and traditional memory measures (ps=<.001 to .018) but not on recency (p=.40). LR was moderately correlated with primacy (r=.481, p<.001) and weakly correlated with recency (r=.271, p=.008), after controlling for age, gender, and education. After controlling for age, gender, and education, better LR was related to better memory performance across all measures (rs=.276-.693, ps= <.001-.007) and better recency was related to better performance on all memory measures (rs=.212-.396, ps=<.001-.038). Better primacy was related to better AVLT immediate and delayed recall and RBANS Immediate Memory Index (rs=.326-.532, p<.001) but not RBANS delayed (r=.115, p=.263).

Hierarchical linear regressions were conducted to examine gender as a moderator of relationships between learning process variables and memory performance, after accounting for age, gender, and education. There were no gender by LR (ps=.349-.830) or gender by primacy interactions (ps=.124-.671). There was an interaction between gender and recency on AVLT memory measures (ps=.006-.022), but not on RBANS measures (ps=.076-.745). For men, higher recency was related to higher AVLT immediate and delayed recall (rs=.501-.541, ps<.001), but not for women (rs=.-.029-.020, ps=.839-.888), after controlling for age and education. The relationship of AUC salivary cortisol to learning process measures was also moderated by gender (LR/gender interaction p=.055; primacy/gender interaction p=.047; but not recency/gender p=.79). Interestingly, for women, higher cortisol was related to higher LR (r=.16) and higher primacy (r=.36), while for men, it was related to lower LR (r=-.22) and not to primacy (r=-.05). Cortisol was not related to recency (rs=-.04 to -.07).

Women performed better on LR and primacy, as well as on other traditional memory variables, but gender did not appear to differentially impact the relationship of LR or primacy to memory outcomes. Findings suggest some differential relationships of recency to memory outcomes by gender. Results also suggested potential gender differences in the relationship of cortisol to learning process variables, but further study is necessary, especially with samples of individuals with memory impairment.

In recent decades, a large body of evidence has linked prenatal exposure to environmental neurotoxins to adverse intellectual, neurodevelopmental, and psychiatric outcomes in offspring. This evidence has clearly highlighted the widespread impact of neurotoxin exposure on the developing brain; however, it is unclear how and why these exposures alter brain development in a way that appears to increase risk for multiple, seemingly disparate outcomes.

Shifting our focus from describing links between neurotoxin exposure and symptoms of offspring mental/cognitive problems considered categorically, to investigating how neurotoxins adversely affect domains of functioning known to cut across risk for multiple problems in offspring may be critical to answering these questions. This presentation will discuss how combining research in developmental neurotoxicology with novel systems that take dimensional approaches to understanding emotions, cognition, and behaviour (i.e., the NIHM Research Domain Criteria (RDoC)) may provide a fruitful future research direction for the field. The RDoC framework aims to understand neuropsychological outcomes (i.e., mental health, mental illness, IQ) across major domains of human emotion, cognition, behaviour, and social functioning, rather than within distinct diagnostic categories.

Using lead exposure as an example, this presentation will outline a framework for how researchers can use this dimensional approach to develop more specific hypotheses that can reveal how and why neurotoxin exposure increases risk for multiple adverse outcomes and elucidate the mechanisms that may underly these links.

Additionally, given that adverse development within domains of functioning can be detected prior to the onset of full-blown diagnoses, this research could enable us to develop more precise, targeted prevention and risk reduction campaigns. Adopting a dimensional framework will provide a more complete picture of the overall impact of prenatal exposure to neurotoxins - critical for informing public health policy.

Early life exposures to lead, mercury, polychlorinated biphenyls (PCBs), polybromide diphenyl ethers (PBDEs), organophosphate pesticides (OPPs), and phthalates have been associated with diminished IQ scores in children. Some studies suggest that these neurotoxicants impact boys and girls differently. We conducted a systematic review and meta-analysis to identify and quantify sex differences in IQ deficits from pre- and post-natal exposures to these developmental neurotoxicants.

We used PubMed and PsychINFO to screen abstracts of articles published between January 1, 1950 and December 31, 2021 for empirical studies of six neurotoxicants [lead, mercury, PCBs, PBDEs, OPPs, and/or phthalates] that (1) used an individualized biomarker; (2) measured exposure during the prenatal period or within the first six years of life; and (3) provided different effect estimates on children's intellectual abilities by sex. We assessed each study for risk of bias using Navigation Guide (Woodruff & Sutton, 2014). For studies with combinable data, we performed separate random effects meta-analyses for boys and girls with subgroup analyses by neurotoxicant. To homogenize the magnitude of effect observed in each study, we recalculated results to be expressed as the absolute change in intellectual abilities for a relative change of 1.5 times (i.e., 50% increase) in the exposure variable.

Of 3205 studies screened, 53 met inclusion criteria: 34 evaluated prenatal exposure, 11 postnatal exposure, and 8 both pre- and post-natal exposure. We generally rated these studies as "low" to "probably low" risk of bias. Among the studies examining prenatal exposure, 27 reported no significant differences between the sexes, 7 found negative associations in boys, 4 found negative associations in girls, 5 found negative nonsignificant associations in boys and positive nonsignificant associations in girls, and 3 found no clear pattern, where differences by sex depended on the specific phthalate compound or outcome measurement. Among the studies examining postnatal exposure, 14 reported no significant differences between the sexes, 1 found a negative association in boys, 2 found negative associations in girls, and 2 found positive associations for either boys or girls. In our meta-analysis of 16 studies (4 lead, 4 mercury, 2 PBDEs, 2 OPPs, 4 phthalates), we found that prenatal exposure to developmental neurotoxicants was associated with decreased full-scale intelligence in boys (B = -0.26; 95% CI: -0.45, -0.08), but not girls (B = 0.09; 95% CI: -0.14, 0.31). In subgroup analyses by neurotoxicant, prenatal exposure to lead (B = -1.07; 95% CI: -1.63, -0.52), and ZPBDEs (B = -0.57; 95% CI: -1.14, -0.01) were associated with decreased full-scale intelligence in boys, whereas the girls' effect sizes were consistently near zero.

During fetal development, boys appear to be more vulnerable than girls to IQ deficits from neurotoxic exposures, and especially from lead and PBDEs. More research is needed to examine the nuanced sex-specific effects found for postnatal exposures to toxic chemicals.

Fluoride exposure has been associated with thyroid dysfunction, but fluoride's impact on thyroid function in pregnancy is unclear, especially during early gestation when the fetus is dependent on maternal thyroid hormone. We examined the potential thyroid-disrupting effects of maternal fluoride exposure in pregnancy and tested whether thyroid disruption in pregnancy mediates the association between maternal fluoride exposure and child intelligence quotient (IQ) among Canadian mother-child dyads living in areas with optimal fluoridation.

We measured fluoride concentrations in drinking water and in spot urine samples collected in each trimester from pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals study. We also measured thyroid hormone (thyroid stimulating hormone [TSH], free thyroxine [FT4], and total thyroxine [TT4]) levels during the first trimester of pregnancy and categorized women as euthyroid (n=1301), subclinical hypothyroid (n=100), or primary hypothyroid (n=28). Those categorized as primary hypothyroid were combined with an additional 79 women who reported clinical diagnoses at time of study enrolment (total n=107). In a sample of 1508 women, we used logistic regression to estimate the association between fluoride exposure and risk of either subclinical or primary hypothyroidism, separately, and linear regression to estimate associations between fluoride exposure and women's thyroid hormone levels (TSH, FT4, TT4). We tested effect modification by child sex and thyroid peroxidase (TPO) antibody status. In a subsample of 439 mother-child pairs, we measured child Full-Scale IQ (FSIQ) at 3-4 years of age using the Wechsler Preschool and Primary Scale of Intelligence. We used linear regression to test associations between maternal hypothyroidism or thyroid hormone levels, and children's FSIQ scores. Finally, mediation analysis in the counterfactual framework was used to estimate the proportion of the effect of maternal fluoride exposure on child FSIQ mediated by maternal hypothyroidism, through evaluation of the natural direct (not through hypothyroidism) and indirect (through hypothyroidism) effects.

Using categorical measures of thyroid status, a 0.5 mg/L increase in water fluoride concentration was associated with a 1.64 (95% confidence interval [CI], 1.04 to 2.58) increased odds of primary hypothyroidism. This association was stronger among women with normal TPO antibody levels (< 5.61 IU/mL) (odds ratio, 2.80; 95% CI, 1.24 to 6.36). In contrast, we did not find a significant association between maternal urinary fluoride and hypothyroidism. For continuous measures of thyroid hormone levels, a 1 mg/L increase in maternal urinary fluoride was associated with a 35% (p=0.01) increase in TSH among women pregnant with a female fetus. In our subsample analyses, children born to women with primary hypothyroidism had lower FSIQ than children of euthyroid women, especially among boys (B, 8.78; 95% CI, -16.78 to -0.79). In contrast, maternal TSH, FT4, and TT4 levels were not significantly associated with child FSIQ scores. Maternal primary hypothyroidism did not significantly mediate the relationship between maternal water fluoride concentration and child FSIQ (p natural indirect effect= .35).

Fluoride in drinking water may increase the risk of hypothyroidism in pregnancy. Thyroid dysfunction in pregnancy may be one mechanism underlying developmental neurotoxicity of fluoride.

Approximately 73% of the United States (US) population on public water systems receives fluoridated water for tooth decay prevention. In Los Angeles (LA) County, 89% of cities are at least partially fluoridated. Drinking water is the primary source of fluoride exposure in the US. Studies conducted in Mexico and Canada suggest that prenatal fluoride exposure, at levels relevant to the US, may contribute to poorer neurodevelopment in offspring. However, data on biomarkers and patterns of fluoride exposure among US pregnant women are scarce. This study examined urinary fluoride levels according to sociodemographic factors and metal co-exposures among pregnant women in the US.

Participants were from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort based in Los Angeles, California. There were 293 and 490 women with urine fluoride measured during the first and third trimesters of pregnancy, respectively. An intra-class correlation coefficient examined consistency of specific gravity-adjusted maternal urinary fluoride (MUFsg) between trimesters. Kruskal-Wallis and Mann-Whitney U tests examined associations of MUFsg with sociodemographic variables. Spearman correlations examined associations of MUFsg with blood and urine metals within and between trimesters. A False Discovery Rate (FDR) correction accounted for multiple comparisons. The criterion for statistical significance was an alpha of 0.05.

Participants were approximately 29 years old on average, and 80% were Hispanic or Latina. Median (IQR) MUFsg during trimesters one and three was 0.65 (0.5) mg/L and 0.8 (0.59) mg/L, respectively. MUFsg levels were moderately consistent between trimesters (N=292, ICC = 0.46, 95%CI: 0.32,0.57). Maternal age was positively associated with MUFsg during first (p = 0.16, p = 0.006) and third (p = 0.18, p < 0.001) trimesters. MUFsg differed by race/ethnicity during first and third trimesters (N = 293, H (3) = 7.99, p = 0.046; N = 486, H (3) = 25.31, p < 0.001, respectively). Specifically, MUFsg was higher for White, Non-Hispanic participants (first trimester Median (IQR) =1.03 (1.31) mg/L; third trimester Median (IQR) = 1.32 (1.24) mg/L) than for Hispanic participants in both trimesters (first trimester Median (IQR) =0.64 (0.48) mg/L; third trimester Median (IQR) = 0.76 (0.55) mg/L). Additionally, during trimester three, MUFsg was higher for White, Non-Hispanic participants than for Black Non-Hispanic participants (Median (IQR) = 0.82 (0.49) mg/L). MUFsg also differed by education during trimester one (N = 293, H (4) = 10.61, p = 0.031), and was higher for participants with some graduate training than for those with high school or some college/technical school education (ps = 0.03 and 0.04, respectively). After FDR correction, MUFsg was associated with blood lead (N =91, p = 0.29, p = 0.024) and urinary cadmium (N =279, p = 0.19, p = 0.042), copper (N=279, p = 0.16, p = 0.042), and tungsten (N=279, p = 0.16, p = 0.049) during trimester three.

Consistent with studies conducted in Canada and Mexico, MUFsg increased across pregnancy. Lower MUFsg among Hispanic and Non-Hispanic Black participants may reflect lower tap water consumption. Metal co-exposures are important to consider when examining potential neurodevelopmental impacts of fluoride.

Exposure to toxic chemicals during early brain development increases the risk of neurodevelopmental problems in children. Parents' and prospective parents' understanding of the impact of toxic chemicals on brain development and the efficacy of translation tools for children's environmental health literacy are poorly understood. We developed and validated a questionnaire, PRevention of Toxic chemicals in the Environment for Children Tool (PRoTECT) to assess knowledge of toxic chemicals and neurodevelopment, intentions to reduce exposures to toxic chemicals, and preferences for actions by government and industry to prevent neurodevelopmental disorders. Using PRoTECT, we surveyed people of child-bearing age across five countries (Canada, United States (US), United Kingdom (UK), India, and Australia) to identify general patterns of responses on this questionnaire by demographic characteristics, including country, age, gender, parental status, pregnancy status, and education. We also employed a randomized control design to examine the efficacy of a knowledge translation video to instill knowledge and prompt behavioral changes to reduce exposures to toxic chemicals immediately following its presentation and after a six-week follow-up period.

We recruited 15,594 participants, ages 18 to 45, via CloudResearch's Prime Panels between October-December 2021. After completing the PRoTECT survey, participants were randomly assigned to watch the video Little Things Matter: Impact of Toxic Chemicals on Brain Development (i.e., the experimental group) or to serve as the control group. Next, both groups answered a series of questions to assess their knowledge of toxic chemicals, their intentions to reduce exposures to toxic chemicals, and barriers to changing their behaviours. After six-weeks, we recontacted a subset (N=4,842) of participants to repeat PRoTECT and answer the same series of behavioural questions assessing whether they modified any of their behaviours to reduce exposure and why or why not.

Most participants (i.e., 75-85%) agreed that toxic chemicals can impact brain development and endorsed preferences (∼85%) for allocating more resources to prevent neurodevelopmental disorders, especially people with higher education, parents and pregnant women, and people who lived in India. Despite this, a large proportion of participants (∼50%) trusted industry and believed that government effectively regulated toxic chemicals. After the six-week follow-up, experimental participants showed greater changes in scores on PRoTECT (i.e., between 5-15% change), indicating greater knowledge about harms posed by toxic chemicals, more intentions to reduce exposure, and stronger preferences for prevention as compared to the control group. Differences were larger among people from the US, those who were more highly educated, and people in their thirties. However, the differences between groups in making behavioural changes to reduce exposures were attenuated at the six-week follow up as compared to baseline. Significant barriers to reduce exposure to toxic chemicals were reported by both groups and included cost, inconvenience, and not knowing how to determine whether a product is non-toxic or where to purchase non-toxic products.

We observed greater knowledge and concerns about toxic chemicals among more affluent respondents, pregnant women and parents, and people living in India across both groups. While the video enhanced participants' knowledge about toxic chemicals and intentions to reduce exposure, they indicated that barriers hindered them from making behavioral changes.

In the United States, Black individuals have suffered from 300 years of racism, bias, segregation and have been systematically and intentionally denied opportunities to accrue wealth. These disadvantages have resulted in disparities in health outcomes. Over the last decade there has been a growing interest in examining social determinants of health as upstream factors that lead to downstream health disparities. It is of vital importance to quantify the contribution of SDH factors to racial disparities in order to inform policy and social justice initiatives. This demonstration project uses years of education and white matter hyperintensities (WMH) to illustrate two methods of quantifying the role of a SDH in producing health disparities.

The current study is a secondary data analysis of baseline data from a subset of the National Alzheimer's Coordinating Center database with neuroimaging data collected from 2002-2019. Participants were 997 cognitively diverse, Black and White (10.4% Black) individuals, aged 60-94 (mean=73.86, 56.5% female), mean education of 15.18 years (range= 0-23, SD=3.55). First, mediation, was conducted in the SEM framework using the R package lavaan. Black/White race was the independent variable, education was the mediator, WMH volume was the dependent variable, and age/sex were the covariates. Bootstrapped standard errors were calculated using 1000 iterations. The indirect effect was then divided by the total effect to determine the proportion of the total effect attributable to education. Second, a population attributable fraction (PAF) or the expected reduction in WMH if we eliminated low education and structural racism for which Black serves as a proxy was calculated. Two logistic regressions with dichotomous (median split) WMH as the dependent variable, first with low (less than high school) versus high education, and second with Black/White race added as predictors. Age/sex were covariates. PAF of education, and then of Black/White race controlling for education were obtained. Subsequently, a combined PAF was calculated.

In the lavaan model, the total effect of Black/White race on WMH was not significant (B=.040, se=.113, p=.246); however, Black/White race significantly predicted education (B= -.108, se=.390, p=.001) and education significantly predicted WMH burden (B=-.084, se=.008, p=.002). This resulted in a significant indirect effect (effect=.009, se=.014, p=.032). 22.6 % of the relationship between Black/White race and WMH was mediated by education. In the logistic models, the PAF of education was 5.3% and the additional PAF of Black/White race was 2.7%. The combined PAF of Black race and low education was 7.8%.

From our mediation we can conclude that 22.6% of the relationship between Black/White race and WMH volume is explained by education. Our PAF analysis suggests that we could reduce 7.8% of the cases with high WMH burden if we eliminated low education and the structural racism for which Black serves as a proxy. This is an under estimation of the role that education and structural racism play in WMH burden due to our positively selected sample and crude measure of education. However, these methods can help researchers quantify the contribution of SDH to disparities in older adulthood and provide targets for policy change.

In the U.S, Black and Latinx individuals disproportionately experience daily acts of discrimination. To counteract the psychological distress, many individuals develop coping mechanisms, like vigilant coping, where behaviors are modified to attempt to prevent discriminatory experiences. Researchers have investigated how coping mechanisms moderate the relationship between discrimination and psychological stress, but not their role in the relationship between discrimination and cognitive function. Prior research has shown a link between discrimination and poor episodic memory. The current study examined vigilant coping as a potential moderator in the relationship between discrimination and memory among Black and Latinx people.

We partnered with 1317 non-Latinx Black (n= 291) and Latinx (n= 1026) individuals who participated in the Offspring Study of Racial and Ethnic Disparities in Alzheimer's Disease. Participants were assessed in English or Spanish, according to their preference. Experiences of discrimination were measured on two scales: Major (civil rights violations) and Everyday (daily hassles), and were coded according to yearly chronicity. Vigilance was measured among people with at least one reported experience of discrimination on either scale, using a 5-item survey which was dichotomized as low and high vigilant coping. The Selective Reminding Test, a 12-item word list task with 6 learning trials and a delayed recall trial, yielded scores for total immediate recall and delayed memory. Linear regression models were used to assess if vigilance moderated the relationship between discrimination and memory, with years of education and age as covariates.

Participants ranged in age from 27 to 91, with a mean age of 56.5 (SD=11.0) years, a mean education of 12.7 (SD=3.7) years, and were 67% women. High vigilant coping was associated with more experiences of major (b = 1.7, 95% CI = 0.9,2.5) and everyday (b = 90.3, 95% CI=66.2,114.3) discrimination. Memory was not associated with reported everyday discrimination, but lower delayed recall was observed among people who reported more experiences of major discrimination (b= -0.04, 95% CI = -0.07,-0.01). This relationship was moderated by vigilance, such that among people with low vigilant coping, major experiences of discrimination predicted lower memory (b= -0.06, 95% CI = -0.12,-0.01), but the association between discrimination and memory was weakened among people with high use of vigilant coping (b= -0.02, 95% CI = -0.05,0.01).

This study builds on Black researchers' work that laid the foundations for examination of stress and coping in marginalized populations. Future studies on discrimination and cognitive health should consider coping mechanisms as key aspects of pathways linking structural racism and inequalities to cognitive health among Black and Latinx individuals.

Area Deprivation Index (ADI) is a measurement of neighborhood disadvantage. Evidence suggests that living in a disadvantaged neighborhood has a negative impact on health outcomes independent of socioeconomic status, including increased risk for Alzheimer's disease (AD). However, less is known about the biological mechanisms that drive these associations. We examined how ADI influences structural imaging variables and cognitive performance in community-dwelling older adults. We hypothesized that greater neighborhood disadvantage would predict atrophy and worse cognitive trajectory over time.

Participants included the legacy cohort from the Vanderbilt Memory and Aging Project (n=295, 73±7 years of age, 16±3 years of education, 42% female, 85% non-Hispanic White) who lived in the state of Tennessee. T1-weighted and T2-weighted fluid-attenuated inversion recovery brain MRIs and a comprehensive neuropsychological assessment were acquired at baseline, 18-month, 3-year, 5-year and 7-year follow-up time (mean follow-up time=5.2 years). Annual change scores were calculated for all neuropsychological and structural MRI outcome variables. Baseline state ADI was calculated using the University of Wisconsin School of Medicine and Public Health Neighborhood Atlas (Kind & Buckingham, 2018) and was based on deciles where 1 represents the least deprived area and 10 represents the most. Mixed effects regression models related baseline ADI to longitudinal brain structure (volume, thickness, white matter hyperintensities) and neuropsychological trajectory (one test per model). Analyses adjusted for age, sex, race/ethnicity, education, Framingham Stroke Risk Profile score, (apolipoprotein) APOE-e4 status, cognitive status, and intracranial volume (for MRI outcomes). Models were repeated testing interactions with APOE-e4 status, sex, and cognitive status. A false discovery rate (FDR) correction for multiple comparisons was performed.

On average, the sample was from relatively less disadvantaged neighborhoods in Tennessee (ADI state decile=2.4±1.8). Greater neighborhood disadvantage at study entry predicted more thinning of an AD-signature composite over time (ß=-0.002, p=0.005, pFDR=0.06); however, all other models testing MRI and neuropsychological outcomes were null (p-values>0.05, pFDR-values>0.51). Baseline ADI interacted with sex on longitudinal cortical thinning captured on the AD-signature composite (ß=0.004, p=0.006, pFDR=0.08) as well as several longitudinal cognitive outcomes including an executive function composite score (ß=0.033, p<0.001, pFDR=0.01), naming (ß=0.10, p=0.01, pFDR=0.12), visuospatial functioning (ß=0.083, p=0.02, pFDR=0.09), and an episodic memory composite score (ß=0.021, p=0.02, pFDR=0.07). In stratified models by sex, greater ADI predicted greater cortical thinning over time and worse longitudinal neuropsychological performance among men only. All stratified models in women were null except for executive function composite score, which did not survive correction for multiple comparisons (ß=-0.013, p=0.03, pFDR=0.61). Interactions by APOE-e4 and cognitive status were null (p-values>0.06, pFDR-values>0.61).

Among community-dwelling older adults, greater neighborhood disadvantage predicted greater cortical thinning over the mean 5-year follow-up in anatomical regions susceptible to AD-related neurodegeneration. Neighborhood disadvantage also interacted with sex on cortical thickness and several cognitive domains, with stronger effects found among men versus women. By contrast, there were no interactions between neighborhood disadvantage and genetic risk for AD or cognitive status. This study provides valuable evidence for sociobiological mechanisms that may underlie health disparities in aging adults whereby neighborhood deprivation is linked with neurodegeneration over time.

In the wake of the national controversy over demographically corrected normative comparisons used in neuropsychological assessment, the field finds itself in need of adopting better practices and providing stronger instruction in norm selection and application when assessing underrepresented populations. Neuropsychologists must employ critical thinking within their clinical decision-making that takes into account patient demographics, analysis of the measures themselves, normative samples, and statistical adjustments employed in normative studies. Not doing so may result in erroneous diagnostic conclusions, exposing underserved patient populations to poor or harmful clinical care and even misdiagnosis. The following case series presents several demographic considerations illustrating how selection and application of different (at times, ill-fitting) normative reference groups can affect treatment outcomes in the Latinx community. We examined the performance of various published norms when applied to monolingual and bilingual Spanish speakers.

This study samples three demographically diverse (i.e., education, age, and sex) clinical cases and applies regression-based and stratified norms to raw scores to demonstrate the possible differential outcomes when using different reference groups. One example is Ms. Congeniality, a 69-year-old, Spanish and English bilingual woman with 12 years of education who presented for a third revaluation at our clinic due to progressive memory loss. Her prior Spanish language profiles demonstrated impaired confrontation naming and steadily decreasing letter fluency over the past 10 years.

Her performance on semantic fluency (i.e., animal naming) showed relative stability based on her raw scores (10 in 2012, 11 in 2016, and 12 in 2022). Using the Neuropsi A&M norms, which stratify performance across nine age ranges between ages 6-85 and three education ranges between 0-10+ years, her performance over the past 10 years ranged between the less than 1st percentile to the 9th percentile (1%, 1%, and 9%, respectively). However, using the NP-NUMBRS norms, which use regression-based continuous age (19-60) and education (0-20) predictors of test performance, her scores corresponded to steadily improved performance (8%, 28%, and 86%). Thus, this qualitative comparison demonstrates a likely overcorrection for individuals of advanced age when using norms based on samples that are a poor fit because they lack representation of older adults, as in NP-NUMBRS, and a possible undercorrection when using norms with overly broad education stratifications (e.g., 10-22 years, as in Neuropsi).

Application of ill-fitting normative standards can have far-reaching implications for interpretation of neuropsychological test results. Moreover, this case series exemplifies the need for higher-order instruction in norm selection, specifically for underserved communities who run the risk of being misdiagnosed. Through case examples, this study underscores the importance of understanding the unique effects of different demographic corrections in the context of limited available normative reference groups. This abstract is the first illustration in a series of papers aimed at facilitating the decision-making process within the framework of socially responsible neuropsychological practice.

brain white matter integrity as a result of vascular burden is associated with a form of late-life depression, known as vascular depression (VaDep). Black older adults may be particularly vulnerable to developing VaDep due to a higher prevalence of vascular conditions compared to White older adults. The current study examined whether clinical and imaging markers of vascular burden predicted depressive symptoms in an older Black sample. Based on the literature in primarily White samples, we expected greater clinical vascular burden and white matter hyperintensity (WMH) volume to predict greater depressive symptoms both cross-sectionally and over 4-year follow-up. We additionally hypothesized that participants with operationally-defined VaDep would have worse cognitive performance and slower gait speed compared to those without VaDep. Exploratory analyses examined race (Black vs. White) as an additional predictor.

This study used publicly available data from 113 Black older adults who were followed for four years in the Healthy Brain Project (a substudy of the Health, Aging, and Body Composition Study). Clinical vascular burden was defined as the number of vascular conditions (e.g., hypertension, diabetes, stroke); total WMH volume and WMH volume in the uncinate fasciculus, superior longitudinal fasciculus, and cingulum were considered imaging markers of vascular burden. Clinical and imaging-defined vascular burden were used to predict baseline depressive symptoms and average depressive symptoms over follow-up as measured by the Center for Epidemiologic Studies Depression Scale (CES-D). We then formed groups based on cutoffs for vascular burden (two or more conditions) and depressive symptoms (upper tertile of CES-D scores) to compare cognitive (Digit Symbol Substitution Test and 15-Item Executive Interview) and gait speed performance at baseline and changes over four years in VaDep, non-vascular depression, vascular only, and healthy groups. Exploratory analyses included 179 White older adults from the Healthy Brain Project dataset to examine race differences.

Total WMH volume and WMH volume in the uncinate fasciculus predicted higher depressive symptoms both cross-sectionally and longitudinally. However, no similar pattern emerged when using clinically-defined vascular burden as the predictor. The VaDep group had the slowest processing speed but the trajectory of decline over time did not differ between groups. The non-vascular depression group’s executive performance improved over time while performance by the other groups remained stable. Both VaDep and non-vascular depression groups’ gait speed declined over time. There was a stronger association between depression and uncinate fasciculus WMH in Black compared to White individuals, and the Black VaDep group had the slowest baseline processing speed of all groups.

This research supports the validity of the VaDep framework in Black older adults by showing the impact of WMH, particularly in the uncinate fasciculus, on depressive symptoms and identifying cognitive risks associated with VaDep in this population. Moreover, results suggest WMH may confer a greater risk for depression in Black compared to White older adults, and that VaDep disproportionately impacts processing speed in Black older adults. This work addresses an important gap in the VaDep literature by examining a group that has historically been underserved.

Obstructive sleep apnea (OSA) may be a modifiable risk factor for late-life cognitive impairment. We previously demonstrated that non-Hispanic Black older adults are less likely to be diagnosed with OSA despite having equal or greater health risk for OSA compared to non-Hispanic White older adults, and this disparity in diagnosis was strongest among individuals with lower education. Here, we aimed to determine 1) whether there are racial differences in continuous positive airway pressure (CPAP) treatment, 2) how CPAP treatment may influence OSA-cognition associations, and 3) whether CPAP differentially influences OSA-cognition associations across racial groups.

Cross-sectional data were obtained from 424 socioeconomically diverse community-dwelling adults ages 55-83 (63.4±3.2 years, 41.7% male, 53.5% Black) from the Michigan Cognitive Aging Project. Physician-diagnosed OSA and current CPAP use were self-reported. Global cognition was operationalized as a composite of five factor scores derived from a comprehensive neuropsychological battery. Racial group differences were investigated with chi-square and Fisher’s exact tests with statistical significance set at the .05 level. Associations between OSA and cognition (adjusted for age, gender, race, and years of education) were investigated with linear regressions. Subsequent models isolated effects of uncontrolled OSA by excluding individuals using CPAP. Racial differences in OSA-cognition associations were investigated with race-stratified models.

Fewer Black participants (9.2%) reported diagnosed OSA compared to White participants (12.3%; x2 (1, N=424) =5.314, p=.021, cp=.112). In the whole sample, 47.3% of participants with diagnosed OSA reported CPAP use, and this proportion did not differ across race (x2 [1, N=86] =.048, p=.826). In the whole sample, OSA diagnosis was only associated with cognition when CPAP users were excluded (excluding CPAP users: ß=-.085, SE=.037, p=.024; including CPAP users: ß=-.067, SE=.036, p=.062). In race-stratified models, diagnosed OSA was only associated with cognition among Black participants, and this association was stronger when CPAP users were excluded (excluding CPAP users: ß=-.142, SE=.060, p=.018; including CPAP users: ß=-.126, SE=.058, p=.030). Diagnosed OSA was not associated with cognition among White participants, irrespective of whether CPAP users were included (excluding CPAP users: ß=-.084,SE=.068, p=.215; including CPAP users: ß=-.056, SE=.064, p=.378).

Our findings support CPAP treatment as a potential intervention to mitigate late-life cognitive impairment among those with OSA. Despite being less likely to receive a diagnosis of OSA, Black older adults were equally likely to engage in CPAP treatment as White older adults when diagnosed. The detrimental impact of OSA on cognition may be more salient among Black older adults, which may reflect racial disparities in cardiovascular risk and/or resources that promote cognitive reserve. However, CPAP appears to be an effective treatment to reduce OSA-related cognitive impairment for Black older adults, highlighting the critical importance of diagnosis and treatment in this group. Intervention efforts that abate racial inequalities in access to quality healthcare in order to facilitate acquisition of a formal OSA diagnosis and CPAP treatment may help to reduce preventable cognitive health disparities among older adults.

The Youth Risk Behavior Survey (YRBS), conducted by the United States Centers for Disease Control and Prevention (CDC) in 2019, revealed that a large percentage of boys (30%) and girls (45%) reported serious difficulty concentrating, remembering, or making decisions as a result of a physical, mental, or emotional problem. In 2021, the CDC conducted the Adolescent Behaviors and Experiences Survey (ABES). The ABES included similar methodology and content as the YRBS. This study analyzed ABES data to examine correlates of perceived cognitive impairment among high school students in the United States during the COVID-19 pandemic.

The ABES was a one-time, online survey that was conducted to assess and evaluate the challenges that high-school aged youth experienced during the COVID-19 pandemic. Students’ perceived cognitive impairment was assessed using the same question used in the 2019 YRBS: 'Because of a physical, mental, or emotional problem, do you have serious difficulty concentrating, remembering, or making decisions?' Response options were binary: 'Yes’ or 'No.' The students’ responses were evaluated in relation to nine adversity, mental health, and lifestyle variables.

Participants were 6,992 students, age 14 to 18, with 3,294 boys (47%) and 3,698 girls (53%). A large proportion endorsed experiencing serious difficulties concentrating, remembering, and making decisions (45%). Girls (56%) were significantly more likely to endorse perceived cognitive impairment compared to boys (33%) [X2(1)=392.55, p<.001; OR=2.66, 95% CI=2.41-2.93]. Youth who reported that their mental health was poor most of the time or always were very likely to report perceived cognitive impairment (boys: 67%; girls: 81%). Binary logistic regressions were used to examine the associations between perceived cognitive impairment, adversity, and lifestyle variables while controlling for mental health. These analyses were conducted separately for boys [X2(9)=596.70, p<.001; Nagelkerke R2=.24] and girls [x2(9)=883.35, p<.001; Nagelkerke R2=.30]. After controlling for current mental health, significant independent predicters of cognitive problems in boys and girls included: a lifetime history of discrimination based on race or ethnicity, lifetime history of being sexually assaulted or abused, lifetime history of using illicit drugs, being bullied in the past year, current marijuana use, and getting insufficient sleep (5 of fewer hours per night). Participation in sports and exercising regularly were both independently associated with lower rates of cognitive impairment.

Perceived cognitive impairment was endorsed by a strikingly high percentage of high school students in 2021 during the COVID-19 pandemic. More than half of high school aged girls and one third of boys reported having serious difficulty concentrating, remembering, and making decisions. These rates are considerably higher than in 2019. Current mental health, unfair treatment because of race or ethnicity, being sexually assaulted, being bullied, drug use, and insufficient sleep were associated with perceived cognitive impairment. Indicators of a physically active lifestyle (participation in sports and exercising regularly) were associated with lower rates of cognitive problems.