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.

Cognition has been identified as an area of priority in examining health impacts of COVID-19 infection, and evidence suggests the virus invades the brain, with potential for long-term cognitive impact. Studies utilizing screening measures have reported cognitive sequelae (e.g., attention disorder, executive dysfunction) of the post-COVID-19 condition (i.e., long-haulers). More extensive examination of cognitive difficulties via comprehensive neuropsychological assessment is critical to informing treatment for those experiencing cognitive or functional difficulties post-infection. We aimed to comprehensively evaluate cognitive resiliencies and vulnerabilities of acutely recovered COVID-19 patients, across key domains (i.e., attention, processing speed, language, visuospatial abilities, memory, executive functioning), compared to healthy controls.

Adults (N=103; aged 19-85; 69.2% female) who had COVID-19 at least three months prior (n=50) and those with no history of infection (n=53) completed demographic and health questionnaires via Qualtrics, along with measures of depressive (CES-D) and anxiety (GAD-7) symptoms, the Lawton-Brody Instrumental Activities of Daily Living (IADL) Scale, and a measure of subjective cognitive difficulties (SCD-Q). Participants (n=84) completed a teleneuropsychology assessment including a short interview and battery of neuropsychological tests assessing attention (BTA, Digit Span Forward), processing speed (DKEFS Colour Naming & Word Reading, SDMT), language (FAS, Animals, NAB Naming), visuospatial abilities (JLO, RCFT Copy), verbal and visual memory (HVLT-R, NAB Shape Learning, RCFT), and executive function (DKEFS Color-Word Interference & Switching, Digit Span Backward & Sequencing, BRIEF), and including multiple measures of cognitive effort/assessment validity (RFIT, RDS), and a self-report measure of symptom validity (SIMS). T-tests were used to examine demographic and health variables between COVID-19 and control groups. MANCOVA were used to examine group differences across each cognitive domain assessed, and across cognitive effort and symptom validity tasks, while controlling for English language status.

Group comparisons indicated that the COVID-19 group was slightly older (mean age = 40 vs. 34 yrs.; f=-2.101, p=0.04). Those who had COVID-19 reported more difficulties completing IADLs (f=2.204; p=0.03), more depressive symptoms (f=-2.299; p=0.02), and more subjective cognitive difficulties (f=-3.886; p<0.01). Examination of cognitive performance indicated a main effect of prior infection on executive function, controlling for language status (Wilks’ /\=0.817, F(6,73)=2.733, p=0.02). Specifically, having COVID-19 was associated with worse DKEFS Colour-Word Switching performance (p=0.01) and slightly higher selfreported difficulties on the BRIEF MI (p=0.04). No other significant group differences were seen across cognitive domains. There was also a main effect of COVID-19 infection on effort and symptom validity task performance (Wilks’ /\=0.705, F(10,70)=2.923, p<0.01). Specifically, prior infection was associated with higher SIMS Neurologic Impairment (p<0.01) and Amnestic Disorders (p<0.01) subscale scores, and paradoxically, slightly higher RFIT combined scores (p=0.02).

Interestingly, results indicate a significant role for subjective cognitive complaints and potential exaggeration of cognitive symptoms post-COVID-19 infection, in the absence of differences in objective performance in most cognitive domains. While subtle differences are seen on some executive function measures, mean group differences are small, and in the context of higher SIMS subscale scores, may not be readily interpretable. Studies employing similarly comprehensive neuropsychological assessments including validity measures in larger samples are needed to further disambiguate potential objective cognitive performance decrements from subjectively experienced difficulties.

To examine patterns of cognitive function among a clinical sample of patients seeking treatment for Post-Acute Sequelae of COVID-19 (PASC).

One hundred nineteen patients each completed a baseline neuropsychological evaluation, including clinical diagnostic interview, cognitive assessments, and a comprehensive battery of self-report questionnaires. Patients had a mean age of 50 years (range:18 to 74, SD=10.1) and a mean of 15.5 years (SD=2.54) of formal education. Patients were primarily female (74%) and of White/Caucasian race (75%). Hierarchical agglomerative clustering was used to partition the data into groups based on cognitive performance. Euclidean distance was used as the similarity measure for the continuous variables and within-cluster variance was minimized using Ward’s method. The optimal number of clusters was determined empirically by fitting models with 1 to 15 clusters, with the best number of clusters selected using the silhouette index. All analyses were conducted using the NbClust package, an R package for determining the relevant number of clusters in a data set.

Clustering yielded two distinct clusters of cognitive performance. Group 1 (n=57) performed worse than Group 2 (n=62) on most cognitive variables (including a brief cognitive screener and tests of attention/working memory, executive function, processing speed, learning and delayed recall). Of note, there were no significant differences between groups on an infection severity scale, hospitalizations/ICU admissions, initial or current COVID-19 symptoms, or prior comorbidities. Groups did not differ in age or gender, but Group 1 had a lower education level than Group 2 (M=14.7, SD=2.45 vs. M=16.2, SD=2.42; p=.001). Group 1 also had significantly more minorities than Group 2 (40% vs. 8%; p<.001). No other demographic differences (income, living arrangement, or marital status) were observed. In comparison to Group 2 patients, Group 1 patients self-reported significantly higher levels of anxiety and depression and functional impairment (Functional Activities Questionnaire: M=11.3, SD=8.33 vs. M=7.65, SD=7.97), perceived stress (Perceived Stress Scale: M=24.7, SD=7.90 vs. M=20.3, SD=7.89), insomnia (Insomnia Severity Index: M=16.0, SD=6.50 vs. M=13.1, SD=6.76), and subjective cognitive functioning (Cognitive Failures Questionnaire: M=58.8, SD=16.9 vs. M=50.3, SD=18.6; p’s<.05).

Findings indicate two predominant subtypes of patients seeking treatment for PASC, with one group presenting as more cognitively impaired and reporting greater levels of anxiety, depression, insomnia, perceived stress, functional limitations, and subjective cognitive impairment. Future directions include follow-up assessments with these patients to determine cognitive trajectories over time and tailoring treatment adjuncts to address mood symptoms, insomnia, functional ability, and lifestyle variables. Understanding mechanisms of differences in cognitive and affective symptoms is needed in future work. Limitations to the study were that patients were referred for evaluation based on the complaint of “brain fog” and the sample was a homogenous, highly educated, younger group of individuals who experienced generally mild COVID-19 course.

Cognitive sequelae are reported in 20-25% of patients following SARS-CoV-2 infection. It remains unclear whether post-infection sequelae cluster into a uniform cognitive syndrome. In this cohort study, we characterized post-COVID neuropsychological outcome clusters, identified factors associated with cluster membership, and examined 6-month recovery trajectories by cluster.

The Mayo Clinic Institutional Review Board approved study protocols. Informed consent was obtained from all participants. Participants (> 18 years old) were recruited from a hospital-wide registry of Mayo Clinic Florida patients who tested positive for SARS-CoV-2 infection from July 2020 to Feb 2022. We abstracted participant health history and COVID-19 disease severity (NIAID score) from the electronic health record and retrieved Area Deprivation Index (ADI) scores as a measure of neighborhood socioeconomic disadvantage. We assessed objective cognitive performance with the CNS Vital-Signs (CNSVS) and subjective neuropsychological symptoms with the Neuropsych Questionnaire-45 (NPQ-45). Results were used as input features in a K-means clustering analysis to derive neurophenotypes. Chi-square and analysis of variance (AnOvA) tests were used to identify clinical and sociodemographic factors associated with cluster membership. Participants repeated the CNS Vital Signs, NPQ-45, as well as the Medical Outcomes Survey (MOS SF-36) and a posttraumatic stress disorder (PTSD) checklist (PCL-C 17) 6 months following initial testing. Repeated-measures ANOVA was used to assess change in neurocognitive performance over time by cluster. Significance was set at P < 0.05.

Our cohort consisted of 205 participants (171 ambulatory, 34 hospitalized) who completed post-acute outcome assessment a mean of 5.7 (± 3.8) weeks following testing positive for SARS-CoV-2. K-means clustering with elbow method fitting identified three subgroups (see figure). The first cluster (N = 31) is characterized by executive dysfunction, greater socioeconomic disadvantage, and higher rates of obesity. The second cluster (N = 32) is characterized by memory and speed impairment, higher COVID severity, prevalent anosmia (70%), and greater severity of memory complaints, depression, anxiety, and fatigue. The third and largest cluster (N = 142) is absent cognitive impairment. Approximately 39% of participants completed the 6-month outcome assessment (N=79). Regardless of cluster membership, verbal memory, psychomotor speed, and reaction time scores improved over time. Regardless of timepoint, cluster 1 (dysexecutive) showed lower scores on cognitive flexibility and complex attention and cluster 2 (memory-speed impaired) showed lower scores on verbal memory, psychomotor speed, and reaction time. Modeling of cluster by timepoint interactions showed a steeper slope of improvement in complex attention and cognitive flexibility in cluster 1 (dysexecutive). Cluster 3 (normal) showed significant improvement in fatigue while cluster 2 (memory-speed impaired) continued to report moderate-severe fatigue, worse medical outcomes, and higher PTSD symptom severity scores at six months.

Most participants were cognitively normal or experienced cognitive recovery following SARS-CoV-2 infection. The 25-30% of participants who showed cognitive impairment cluster into two different neurophenotypes. The dysexecutive phenotype was associated with socioeconomic factors and medical comorbidities that are non-specific to COVID-19, while the amnestic phenotype was associated with COVID-19 severity and anosmia. These results suggest that cognitive sequelae following SARS-CoV-2 infection are not uniform. Deficits may be influenced by distinct patient- and disease-specific factors, necessitating differentiated treatment approaches.

To effectively diagnose and treat cognitive post-COVID-19 symptoms, it is important to understand objective cognitive difficulties across the range of acute COVID-19 severity. The aim of this meta-analysis is to describe objective neuropsychological test performance in individuals with non-severe (mild/moderate) COVID-19 cases in the post-acute stage of infection (>28 days after initial infection).

This meta-analysis was pre-registered with Prospero (CRD42021293124) and utilized the PRISMA reporting guidelines, with screening conducted by at least two independent reviewers for all aspects of the screening and data extraction process. Inclusion criteria were established before the article search and were as follows: (1) Studies using adult participants with a probable or formal and documented diagnosis of COVID-19 in the post-acute stage of infection; (2) Studies comparing cognitive functioning using objective neuropsychological tests in one or more COVID-19 groups and a comparison group, or one group designs using tests with normative data; (3) Asymptomatic, mild, or moderate cases of COVID-19. Twenty-seven articles (n=18,202) with three types of study designs and three articles with additional longitudinal data met our full criteria.

Individuals with non-severe initial COVID-19 infection demonstrated worse cognitive performance compared to healthy comparison participants (d=-0.412 [95% CI, -0.718, -0.176)], p=0.001). We used metaregression to examine the relationship between both average age of the sample and time since initial COVID-19 infection (as covariates in two independent models) and effect size in studies with comparison groups. There was no significant effect for age (b=-0.027 [95% CI (0.091, 0.038)], p=0.42). There was a significant effect for time since diagnosis, with a small improvement in cognitive performance for every day following initial acute COVID-19 infection (b=0.011 [95% CI (0.0039, 0.0174)], p=0.002). However, those with mild (non-hospitalized) initial COVID-19 infections performed better than did those who were hospitalized for initial COVID-19 infections (d=0.253 [95% CI (0.372, 0.134)], p<0.001). For studies that used normative data comparisons, there was a small, non-significant effect compared to normative data (d=-0.165 [95% CI (-0.333, 0.003)], p=0.055).

Individuals who have recovered from non-severe cases of COVID-19 may be at risk for cognitive decline or impairment and may benefit from cognitive health interventions.

Previous research has explored the performance of working memory in children with ADHD and individual co-occurring disorders, finding that internalizing disorders such as depression and anxiety, both independently negatively impact working memory performance (Saarinen, Fontell, Vuontela, Carlson, & Aronen, 2015; Kofler, Rapport, Bolden, Sarver, Raiker, & Alderson, 2011; Skogan, Zeiner, Egeland, Rohrer-Baumgartner, Urnes, Reichborn-Kjennerud & Aase, 2013). However, there is limited research on the impact of co-occurring depression and anxiety on working memory, which are common in children with ADHD. When depression is present, parts of the prefrontal cortex regions are hypoactive and therefore lead to impairment in executive functioning abilities (Snyder, 2013). In regard to anxiety, previous literature (Moran, 2016) has found that anxious arousal competes with processes located in the prefrontal cortex leaving limited neural resources for executive functioning skills (Moran, 2016). The current study will evaluate the influences of depression and anxiety on working memory in children with ADHD.

Participants were from an archived data set, which included 849 individual children ages 7-15 years old and their biological parents, recruited between 2009 and 2015. The 849 children included 76 sibling pairs. Families were part of an ongoing longitudinal study. The children completed a computerized version of a spatial working memory task identical to the spatial span task from CANTAB (De Luca et al., 2003). In regard to verbal working memory, children completed Digit Span from the WISC-IV, including both forward and backward conditions. Depression was measured by the Children’s Depression Inventory, 2nd edition (Kovac, 2004) and anxiety was measured by the Multidimensional Anxiety Scale for Children, 2nd edition (MASC-2) (March, 2012). ADHD was measured by having the parents and teachers complete two questionnaires: the ADHD rating scale (ADHD-RS; DuPaul et al. 1998), the Connor’s Rating Scale, 3rd edition (CRS-R, Connors 2003), and an in person semi-structured diagnostic interview (Kiddie Schedule for Affective Disorders and Schizophrenia -KSADS, Kaufman et al. 1997). A best estimate DSM-IV ADHD (American Psychiatric Association [APA], 1994) diagnosis was established by a multidisciplinary diagnostic team (ADHD diagnosis agreement kappa = .88). On cases where consensus was not achieved, they were excluded from the participant pool, and this became the clinical referred control group for the study.

The results indicated that children with ADHD and a co-occurring diagnosis of depression experience more difficulties with working memory abilities than those who do not have a co-occurring diagnosis of depression. Additionally, depression has a greater impact on verbal working memory in children with ADHD than anxiety does alone. This study also found that there were no significant gender differences between children with ADHD who identify as males and females on verbal or visual working memory tasks.

The findings of this study indicate the importance of addressing depressive symptoms in children with ADHD. With a holistic understanding of working memory deficits in children with ADHD as well as potential gender differences, caretakers and providers can integrate more effective intervention plans to help mitigate significant working memory deficits.

We previously reported the impact of hormonal changes during menopause on ADHD and associated symptoms. Here we provide findings from an expanded sample limited to those 46 and older.

Information was obtained from a reader survey sponsored by ADDitude Magazine. Responses were received from 3117 women of whom 2653 were 46 or older. Analyses were limited to this older group, since mean age of perimenopause is around 47 in the general population. The final sample ranged in age from 46 to 94 (mean=53) and 85% had been diagnosed with diagnosed with ADHD. Respondents were asked to indicate their age at diagnosis and the impact of 11 different symptoms or associated problems of ADHD at each of 5-time intervals: 0-9 years, 1019 years, 20-39 years, 40-59 years and 60+years. Co-morbidities were also considered.

Changes in ADHD Symptoms: Sixty-one percent reported that ADHD had the greatest impact on their daily lives between 40 and 59 years of age. The largest group of respondents (43%) were first diagnosed between ages 41 and 50. The reported prevalence of inattention, disorganization, poor time-management, emotional dysregulation, procrastination, impulsivity and poor memory/brain fog increased over the life span. More than half indicated that a sense of overwhelm, brain fog & memory issues, procrastination, poor time-management, inattention/distractibility and disorganization had a 'life altering impact’ during the critical menopausal/perimenopausal window. By contrast, complaints about significant hyperactivity, impulsivity, social struggles and perfectionism remained fairly constant over the lifespan, and were not among the most common complaints (i.e., only endorsed by 25% to 35% of the sample). Interestingly, while 61% reported that ADHD had its greatest impact on daily life between 40-59, only 3% reported the same thing for age 60 and above. Thus, in this expanded sample the first diagnosis of ADHD was most common in adulthood and peaked in the perimenopausal years. ADHD was also again most disruptive during the perimenopausal/menopausal window of time. This shift was most pronounced for symptoms of poor memory/brain fog and 'feeling overwhelmed.' Symptoms either diminished or they adjusted as they moved out of the transition years.

Comorbid Symptoms: Anxiety and depression were most common (73% and 63%, respectively) consistent with the literature. Also elevated, but much less frequent here, were learning, eating and sensory processing disorders (i.e., 10%-13% each). Thus, depression and anxiety may be the most frequent correlates of an ADHD diagnosis, irrespective of age of onset.

Hormonal change during the climacteric often is associated with worsening of cognitive complaints. Such increased complaints can lead to a first diagnosis of ADHD during this period, as well as a worsening of symptoms in those previously diagnosed. Moreover, this hormonal shift may underlie this diagnosis in a subset of the individuals currently characterized as having adult-onset ADHD. Lessoning of complaints in those ages 60 and above raises questions regarding the underlying mechanisms for this change (e.g., physiologic adaptation, compensation or decreased life demands).

Accurately interpreting cognitive change is an essential aspect of clinical care for older adults. Several approaches to identifying 'true’ cognitive change in a single cognitive measure are available (e.g., reliable change methods, regression-based norms); however, neuropsychologists in clinical settings often rely on simple score differences rather than advanced statistics, especially since multiple scores compose a typical battery. This study sought to establish quick-reference normative criteria to help neuropsychologists identify how frequently significant change occurs across multiple measures in cognitively normal older adults.

Data were obtained from the National Alzheimer’s Coordinating Center (NACC). Participants were 845 older adults who were classified as cognitively normal at baseline and at 24-month follow-up. In NACC, these clinical classifications are made separately from the assessment of cognitive performance, including cognitive change. The sample was 34.9% female, 83.5% White, 13.1% Black 2.3% Asian, and 1.1% other race with a mean age of 70.7 years (SD=10.2). Of the sample, 95.5% identified as non-Hispanic. Mean education was 16.1 years (SD=2.8). The cognitive battery entailed: Craft Story Immediate and Delayed Recall, Benson Copy and Delayed Recall, Number Span (Forward & Backward), Category Fluency (Animals & Vegetables), Trails A&B, Multilingual Naming Test, and Verbal Fluency (F&L). Change scores between baseline performance and follow-up were calculated for each measure. The natural distribution of change scores was examined for each measure and cut points representing the 5th and 10th percentile were applied to each distribution to classify participants who exhibited substantial declines in performance on each measure. We then examined the multivariate frequency of statistically rare change scores for each individual.

As expected in a normal sample, overall cognitive performance was generally stable between baseline and 24-month follow-up. Across cognitive measures, 81.9% of participants had at least one change score fall below the 10th percentile in the distribution of change scores, and 55.7% had at least one score below the 5th percentile, 49.3% of participants had two or more change scores that fell below the 10th percentile and 21.1% with two or more below the 5th percentile. There were 26.7% participants that had three or more change scores below the 10th percentile, and 6.4% of participants had three change scores below the 5th percentile.

Among cognitively normal older adults assessed twice at a 24-month interval with a battery of 13 measures, it was not uncommon for an individual to have at least one score fall below the 10th percentile (82% of the sample) or even the 5th percentile (56%) in the natural distribution of change scores. There were 27% participants that had three or more declines in test performance below the 10th percentile; in comparison, only 6% of the sample had three or more change scores at the 5th percentile. This suggests that individuals who exhibit more multivariate changes in performance than these standards are likely experiencing an abnormal rate of cognitive decline. Our findings provide a preliminary quick-reference approach to identifying clinically significant cognitive change. Future studies will explore additional batteries and examine multivariate frequencies of change in clinical populations.