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Neurofilament light chain (NfL), a plasma-based biomarker for neurodegeneration, is a promising marker for early Alzheimer disease (AD) detection in individuals at increased risk. We previously reported that Presenilin1 (PSEN1) E280A carriers have increased levels of plasma NfL relative to non-carrier family members twenty years before the onset of clinical symptoms. Abstract reasoning is one of the first cognitive abilities to deteriorate in AD. Here, we examined whether levels of plasma NfL were associated with non-verbal abstract reasoning performance in non-demented PSEN1-E280A carriers and non-carriers.
Participants and Methods:
A total of 798 members of the Colombian kindred with the PSEN1 E280A mutation (462 cognitively-unimpaired and 336 non-carriers; mean age= 34.02 (10.53), mean education= 8.23(4.60), 57% females and 43% males) were included in the study. Participants completed the Raven’s Progressive Matrices (RPM), Mini Mental State Examination (MMSE), and underwent blood sampling. Plasma NfL concentrations were measured with a single molecule array (Simoa) method. Mann-Whitney U test and education-adjusted Spearman partial correlation were used to examine group differences and associations between abstract reasoning performance and NfL levels.
Results:
Non-carriers were older (p<.001) and had higher levels of education than carriers (p=.025). Compared to non-carriers, carriers had higher levels of NfL (p=.014), lower performance on the MMSE (p<.001) and on the RPM (p=.001). In the whole sample, performance on the RPM was significantly associated with age (r= -.144, p<.001), and MMSE score (r=.198, p<.001). In carriers only, performance on the RPM was negatively associated with NfL levels (r=-.121, p=.009). This association was not significant in non-carriers.
Conclusions:
Our findings support the hypothesis that plasma NfL levels may be indicators of disease progression and early cognitive dysfunction in autosomal dominant AD. Future work with NfL, abstract reasoning and memory with larger samples across the preclinical/prodromal spectrum will allow a more comprehensive examination of these associations.
Executive function (EF) abilities tend to decline with age, and disproportionately so for people with neurodegenerative disorders such as Parkinson’s Disease (PD), where EF deficits are commonly seen in the early stages of the disease. Due to their nature, EF are essential for performing tasks of daily life, particularly for the more complex instrumental activities of daily living (IADL), and deficits can impair the ability to execute IADL in PD participants. The aim of this study was to examine how EF impairments relate to IADL deficits in both healthy elderly controls and PD participants.
Participants and Methods:
Seventy-four participants with idiopathic PD and 66 elderly controls were recruited. All participants were non-demented. A comprehensive neuropsychological assessment was administered including the following measures of EF: Hayling Sentence Completion, Brixton Spatial Anticipation, Trail Making Test A and B, Stroop Color-Word Test, Symbol Span (Wechsler Memory Scale-III), Digit Span (Wechsler Adult Intelligence Scale-III), F-A-S test, and Semantic Fluency (Animals and Actions). Z scores were calculated from respective test manuals. Independence was measured using the 8-item Lawton IADL Scale where items are coded from 0 (dependent) to 1 (independent) and the total score ranges from 0 to 8. Motor impairments were assessed using Part III of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale. Regression models were run with each cognitive measure as the dependent variable, with group (control vs. PD), age, sex, education, and motor severity as predictors, to examine the effect of group on each cognitive variable. Correlations were then run between the total IADL score, demographic variables, and cognitive variables for each participant group separately to identify the relationship between IADL and EF measures.
Results:
PD participants were predominantly males (n=51, 68.9%), with an average age of 70.64±6.03 and 15.22±2.78 education years. Controls were predominantly female (n=34, 51.5%) and had an average age of 71.19±7.75 and 15.85±2.82 education years. Regarding IADL function, all participants were relatively independent in their IADLs (PD: 7.72±0.69, range 4-8, Controls: 7.98±0.13, range 7-8). The most difficult IADL items for PD participants were shopping (8.2% dependent) and food preparation (12.2% dependent). When correcting for age, education, sex, and motor severity, only the Stroop Interference z-score was significant for participant group (b=0.44, t=2.14, p=0.034), where controls had slightly lower scores (-0.33±0.77) than PD participants (-0.31±0.91). Correlations in controls were significant between IADL total score and Hayling trials 1 (r=0.35, p=0.005) and 2 (r=0.33, p=0.008), and semantic fluency actions trial (r=0.34, p=0.006). In PD participants, IADL total score was only correlated with semantic fluency (animals trial, r=0.26, p=0.028).
Conclusions:
There were only weak associations between EF abilities and IADL in both healthy controls and PD participants, suggesting that impairments in EF do not necessarily translate into worse ability to execute IADL in PD. More correlations were found in the control group, which may be confounded by the inclusion (in both groups) of participants who already had cognitive impairment. This highlights a further need to examine whether EF impairments in people with PD influence IADL functioning above and beyond normal aging and whether specific deficits have more real-life consequences not attainable through IADL questionnaires.
Autistic youth have impaired executive functioning (EF) and these challenges increase throughout adolescence. Deficits in EF have been associated with poor adult outcomes, decreased availability for learning, and linked to academic outcomes. Specifically, flexible problem solving is greatly reduced in autistic youth. We aim to investigate how flexibility contributes to learning in autistic youth and their typically developing peers.
Participants and Methods:
Participants included 44 teens with (n=22) and without (n=22) ASD. All teens were 14-18 years old (ASD M = 15.77, SD = 1.05; TD M = 15.73, SD = .96) with FSIQ 3 70 (ASD M = 105.92, SD= 16.17; TD M = 107.93, SD = 10.14). Teens with ASD met DSM-5 criteria for autism supported by the SCQ and/or ADOS-2. All participants completed the California Verbal Learning Task (Child or Third Edition) over zoom. Parents reported on their child’s flexibility skills on the Flexibility Questionnaire (FQ) which encompasses 5 subscales: routines/rituals, transitions, special interests, social flexibility, and generativity. Independent samples t-tests examined group differences in performance on the CVLT, measured by the long delay recall and learning slope. Bivariate correlations examined the relationship between learning and flexibility in the autistic group. Linear regression was used to determine how flexibility contributes to learning above and beyond age, gender, and diagnosis.
Results:
Autistic youth had significantly lower scores on the CVLT long-delay recall (t = 2.311, p = .026) and the learning slope (t = 1.186, p = .038) than their typically developing peers. Special interests on the FQ were related to both performance on the first trial of the CVLT (r = -.482 p = .023) and the short delay cued recall (r = -.469 p = .028) in the autistic group. Fewer transition related problems were predictive of higher scores on the CVLT above and beyond age, gender, and diagnosis (R2 = .366, B = - .088, p = .030).
Conclusions:
Learning was significantly lower in autistic teens compared to their typically developing peers. Additionally, autistic youth had a less steep learning slope than their typically developing peers. Autistic youth may focus on the first group of words only and don’t flexibly update their list to add new words as the trials go on. Autistic youth with more restricted interests have difficulty with the first trial due to the shifting required when starting a new unfamiliar task. Additionally, youth with a greater focus on their own interests had more difficulty on cued recall indicating that these youth may have had trouble shifting when prompted to use semantic categories. Fewer challenges with transitions were a significant predictor of learning above and beyond age, gender, and diagnosis. Previous research has shown large discrepancies between parent-report and laboratory-based tasks in autistic youth. This project highlights two unique measures of different modalities that show similarities in their ratings emphasizing their potential as good representations of overall skills. Future research should utilize a larger sample size to continue to examine the role of flexible problem solving in working memory and learning in autistic youth.
A previous review of the syndrome of Agenesis of the Corpus Callosum (ACC) identified three primary deficits: reduced interhemispheric transfer of sensory motor information, slowed cognitive processing, and deficits in complex problem solving (Brown & Paul, 2019). Interaction of these three deficits contributes to a variety of secondary cognitive and psychosocial deficiencies across domains. Recent research has also identified a possible fourth core deficit in ACC: restricted capacity for elaborative thought and creativity (Renteria et al., 2022; Bogen & Bogen 1988). We examined the syndrome of ACC using an exploratory factor analysis of neuropsychological test data (not including data regarding interhemispheric transfer) and hypothesized it would organize into factors of (1) reduced cognitive processing speed, (2) difficulty with complex problem solving, and (3) difficulty with creative tasks.
Participants and Methods:
The present study analyzed archival data from individuals with ACC (N=60) acquired from common neuropsychological instruments: D-KEFS, WAIS-III, and WRAT-2. Among the participants, 13 had partial ACC, 1 was unspecified, and the remainder had complete ACC. The participants’ ages ranged from 7 to 55 years (M = 21.55, SD = 12.36), with an education level that ranged from 2 to 19 years (M = 11.59, SD = 3.77). All participants had complete data for at least one assessment and all available data was included. Missing values (49.85%) were excluded from analysis. Factor analysis (principal factor solution with promax rotation) was conducted with 33 commonly derived summary (standard) scores. Horn’s Parallel Analysis recommended a 4-factor solution, but we elected to generate a 3-factor model that would more closely follow previous literature.
Results:
Factor one involved processing speed and was comprised primarily of D-KEFS Color Word Interference Word Reading (1.02) and Color Naming (.78), D-KEFS Trail Making Test Visual Scanning (.86) and Number Sequencing (.74), and WAIS-III Processing Speed Index (.68). The second factor included several problem solving measures [e.g. D-KEFS Sorting Test Free Sorting (.90) and Sort Recognition (.90), and WAIS-III Perceptual Organization Index (.72)], as well as several additional measures including WAIS-III Working Memory Index (.84), WRAT-2 Arithmetic (.83), and WAIS-III Verbal Comprehension Index (.80). Finally, the third factor involved several measures requiring mental flexibility and cognitive control [e.g. D-KEFS Twenty Questions Test Achievement Score (.70), D-KEFS Design Fluency Switching Condition (.56), and D-KEFS Trail Making Test Number-Letter Switching Condition (.44)], as well as a measure of single word reading [WRAT-2 Reading (.66)].
Conclusions:
The findings support inclusion of slowed cognitive processing speed as a core feature of the neurocognitive syndrome in ACC described by Brown and Paul (2019). The second factor is partially consistent with a deficit in complex problem solving, but is not restricted to that cognitive domain. Likewise, the third factor is largely related to mental flexibility and control (one aspect of creativity), but is not restricted to that domain. Future attempts to model the neurocognitive syndrome of ACC may provide greater clarity by including a wider range of cognitive and psychosocial indices and excluding individuals with comorbid neuropathology.
Engagement in sporting activities has shown improvement in executive function among youth (Contreras-Osorio et al., 2021). Additionally, participation in specific sports such as soccer has been shown to enhance executive function in youth athletes compared to same-aged non-athletes (Yongtawee et al., 2021). The present study aimed to examine the effects of competitive participation in the United States’ four most popular sports on executive function among youth athletes. The most popular sports, as defined by viewership, revenue, and youth participation in the U.S. are American football, basketball, baseball, and soccer (Injai, 2022; Aspen Institute, 2020).
Participants and Methods:
Data from the following three executive functioning subtests were analyzed in a sample of youth athletes (n=76), aged 8-18 years (mean age=11.94): Delis-Kaplan Executive Function System Trail Making Letter-Number Sequencing (cognitive flexibility), Wechsler Intelligence Scale for Children Fourth Edition Working Memory Index, and Golden Stroop Color-Word Inhibition. Participants completed these measures as part of a larger neuropsychological baseline assessment. Multivariate General Linear Model (GLM) regression was used to examine the influence of total cumulative years playing in one or more of the four most popular sports on executive functioning. A multivariate GLM regression also investigated the unique contributions of total years playing soccer (n=40; mean age=12.40) and total years playing American football (n=32; mean age=12.03) on subtest performance. The unique contributions of basketball (n=14) and baseball (n=21) were not analyzed due to small sample size.
Results:
Total cumulative years playing > one of the four most popular sports significantly predicted cognitive flexibility (p=.007) and working memory (p=.002), but not inhibition (p=0.639). Total years playing soccer also significantly predicted cognitive flexibility (p=.029) and working memory (p=0.05), but not inhibition (p=.310). Total years playing American football did not significantly predict performance on tasks requiring cognitive flexibility (p=.186), working memory (p=0.150), or inhibition (p=0.277).
Conclusions:
In congruence with previous research, sports participation predicted enhanced cognitive flexibility and working memory on certain executive tasks. Among youth athletes, prolonged competitive participation in one or more of the four most popular sports in the U.S. predicted better performance on measures of cognitive flexibility and working memory. Furthermore, protracted participation in soccer predicted enhanced performance on measures of cognitive flexibility and working memory, whereas extended participation in American football did not. Future research should examine this effect in larger samples within all four sports. Examining the cumulative length of competitive participation in these popular sports on executive function could present a favorable developmental outcome of youth participation if competitive participation is sustained. Additionally, the present data on executive function performance between lasting soccer participation and lasting American football participation suggests that executive function development and performance may be influenced by the sport played. The direction of this possible influence is unclear. More research is needed to establish this observed difference, and to better understand its existence and directionality.
Mild cognitive impairment (MCI) is characterized by subjective and objective memory concerns, though additional cognitive concerns are commonly reported, including changes in executive functions (EF). Rabin et al. (2006) showed that a sample of research participants with MCI endorsed problems with their EFs, especially working memory. Similarly, those with subjective cognitive dysfunction (SCD) also reported greater difficulty with aspects of their EF than a healthy comparison sample of older adults (HC). In the present study, we investigated subjective EF in clinical samples of older adults with MCI or SCD, which represents a more naturalistic sample relative to a research sample. Furthermore, we evaluated whether subjective EF varied in these groups depending on whether patients were "young-old" versus "old-old" given prior research indicating objective cognitive differences between these age groups.
Participants and Methods:
Participants were 135 older adults (53 MCI, 52 SCD, and 30 HC) matched for age (p = .116) and education (p = .863). Dichotomous categorization of age used the sample median (72 years) as cutoff score with 72 participants in the young-old group (mean age = 65.8 ± 4.7 years) and 63 in the old-old group (mean age = 78.1 ± 3.7 years). Participants completed the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A), assessing executive functions in everyday life over the past month. The BRIEF-A yields an overall score (Global Executive Composite [GEC]) composed of two index scores (Behavioral Regulation Index [BRI] and Metacognition Index [MI]) and nine clinical scales (Inhibit, Shift, Emotional Control, Self-Monitor, Initiate, Working Memory, Plan/Organize, Task Monitor, and Organization of Materials). A diagnosis by age-group multivariate analysis of variance (MANOVA) with post-hoc comparisons for diagnosis using a Tukey HSD correction was conducted using SPSS Version 24.
Results:
MCI and SCD groups endorsed worse EF on all three index scores (ps < .005) and all nine clinical scales (ps < .05) relative to the HC group, and the MCI group reported worse initiation relative to the SCD group. Additionally, worse executive functions on all three index scores (ps < .05) and four clinical scales (ps < .05; emotional control, self-monitoring, planning/organization, and task monitoring) were reported by the young-old group relative to the old-old group. No diagnosis by age-group interactions were observed.
Conclusions:
Problems with aspects of EF were endorsed by older adults with MCI and SCD compared to HCs across all indices and clinical scales; however, only initiation was reported to be worse in MCI than those with SCD. Additionally, the young-old group endorsed having worse EF than the old-old group across BRIEF-A indices and several more specific aspects of EF, without a moderating effect of diagnosis. These findings highlight the importance of assessing subjective EF in older adults, as they may be early indicators of cognitive change, prior to objective evidence of cognitive decline. Furthermore, results also point to differences in how the young-old and old-old perceive their EF in everyday life.
Spontaneous speech involves tight coordination of a constellation of cognitive mechanisms (including planning, lexical selection, grammatical encoding, internal & external monitoring). Recent years brought a flurry of interest in detailed analysis of spontaneous speech in search of markers of prodromal Alzheimer’s disease. This work dates back to the nun studies by Snowdon et al (1996) and reveals promise for early detection through identification of subtle but significant changes in the nature of speech output years prior to diagnosis of dementia. A major challenge for neuropsychology is to develop methods to harness the potential sensitivity of language to subtle cognitive changes when testing individuals in clinical settings. In this talk I will present two lines of research that illustrate how reading aloud can be used to engage the cognitive mechanisms of spontaneous speech production in a manner that provides an easily accessible measure of Alzheimer’s disease/risk.
Participants and Methods:
In the first study, Spanish-English bilinguals with mild-to-moderate Alzheimer’s disease (n=20) and proficiency matched controls (n=29) read aloud mixed-language paragraphs with a small number of language-switched words, and we recorded the number of times they automatically translated switch words by accident (e.g., saying pero instead of but; effectively autocorrecting language switches to avoid producing switches overtly). In the second study, cognitively normal monolinguals at risk for AD based on CSF biomarkers (n=14) and controls (n=50) read aloud short paragraphs in which ten critical target words were replaced with autocorrect targets (e.g., The player who scored that final [paint] for the local team reported [him] experience). Participants were instructed to avoid autocorrecting (e.g., avoid saying point instead of paint or his instead of him), and we recorded the number of times they autocorrected by accident.
Results:
Bilinguals with AD translated switch words more often than controls, and ROC curves revealed good-to-excellent discrimination between patients and controls based solely on the number of errors produced during reading aloud (AUC or Area Under the Curve values ranged from .71-.92). In the second study, cognitively normal monolinguals with high CSF Tau/Aß42 (i.e., an AD-like biomarker profile) produced more autocorrect errors (e.g., saying point instead of paint)than those below the biomarker threshold, and autocorrection errors showed potential for discriminating individuals with higher AD risk from controls (AUC=.76; 95%CI .62-.90).
Conclusions:
Difficulty stopping automatic translation of language switch words and autocorrection during reading aloud reveals promise as a diagnostic tool. Reading aloud elicits rapid production of hundreds of words while maintaining tight experimental control over the content of speech and harnessing the power and complexity of language to enable detection of very subtle cognitive changes through simple analysis of critical targets. I will discuss the theoretical implications of this work for understanding how bilinguals choose a single language for production, the nature of cognitive impairments in early AD and areas of need for further research to maximize the potential utility of reading aloud for detection of cognitive impairment.
Depression is highly prevalent in persons with multiple sclerosis (pwMS). A reformulated version of the learned helplessness theory posits that individuals who attribute the cause of negative events to personal factors (internal), perceive that the cause persists for a long period of time (stable), and believe it is present in all situations (global) are at an increased risk for depression. As such, it is critical to examine possible modifiable factors that buffer against the deleterious effects of negative attributional style. Therefore, the current study investigated whether stress moderates the relationship between negative attributional style and depression symptoms in an MS sample.
Participants and Methods:
Thirty-six pwMS (30 Female, 6 Male) completed a comprehensive neuropsychological test battery and psychosocial questionnaires that assessed cognitive attributional style, daily stressors, and depression symptoms. The Attributional Style Questionnaire (ASQ) was used to create internal, stable, and global attribution dimension scores, as well as an overall attributional style score combining the three dimensions. Stress was quantified as the total score of perceived hassles from the Hassles and Uplifts Scale (HUS). Depression symptoms were measured using the Beck Depression Inventory-Fast Screen (BDI-FS). Hierarchical linear regressions were conducted with depression symptoms as the outcome variable. Each dimension of attributional style (internal, stable, global, or overall ASQ), stress, and their interactions were included as predictors. Simple effects tests were used to clarify the pattern of any significant interaction.
Results:
Regression analyses revealed that the interaction between overall attributional style and stress was significant (p = .025). Simple effects tests revealed that overall attributional style was associated with depression symptoms only in pwMS with high levels of stress (p = .015). For the individual dimensions of the ASQ, several interactions were also significant. The interaction between the internal dimension and stress was significant (p= .009), such that internal attributions were associated with depression symptoms only in pwMS with high levels of stress (p = .002). The interaction between the stable dimension and stress was also significant (p = .01); stable attributional style was associated with depression symptoms only in pwMS with high levels of stress (p = .009). The interaction between the global dimension and stress was not significant.
Conclusions:
Stress moderated the relationship between negative attributional style and depression symptoms in pwMS. Specifically, the internal and stable dimensions and overall attributional style were associated with increased depression symptoms only in pwMS who reported high levels of stress, but not in those with low levels of stress. Interventions aimed at reducing and managing stress may help protect against the effects of negative cognitive schemas on depression symptoms in MS. Additionally, previous research demonstrates that attributional style may be a malleable target of evidence-based psychotherapy (Seligman et al., 1988; Proudfoot et al., 2009). Our findings suggest that cognitive therapy specifically targeting the internal and stable dimensions of attributional style may be effective in modifying attributional style, perceptions of stress and, subsequently, improve depression outcomes in MS.
Cardiovascular disease (CVD) is a well-known risk factor for cognitive impairment and dementia, particularly among minoritized groups that have experienced a history of low childhood socioeconomic status (SES). Although previous literature has linked all levels of SES to varying degrees of stress exposure, children raised in higher SES households have more access to resources and services that encourage optimal growth and development than children who grow up in lower SES households. Given the disproportionate burden of dementia and cognitive deficits within minoritized groups, the present study examined whether childhood SES is associated with later life cognition among Black and White older adults and if this association persists after accounting for hypertension, a possible mediator of the relationship between childhood SES.
Participants and Methods:
1,184 participants were from the first wave of the STAR (n = 397 Black [Mage= 75.0 ±6.8 years]) and KHANDLE (386 Black [Mage= 76.2 ±7.2 years] and 401 White [Mage= 78.4 ±7.5 years]) cohorts. We used general linear models to examine the relationship between childhood SES and later-life executive function, semantic memory, and verbal memory scores, and midlife hypertension. Childhood SES was measured by self-reported perceived financial status (with participants given the following options: ‘pretty well off financially’, ‘about average’, ‘poor’, or ‘it varied’). These models were assessed in the full sample and also stratified by race.
Results:
In the full sample, childhood financial status was not associated with semantic memory, verbal episodic memory, or executive function. Financial status was associated with semantic memory in Black adults (β = -.124, t(771) = -2.52, p = .01) and this association persisted after accounting for hypertension (β = -.124, t(770) = -2.53, p = .01). There was no association between childhood financial status and later life semantic memory among White adults. There was no association between childhood financial status and later life verbal episodic memory or executive function in either Black or White adults in models with or without adjustment for hypertension.
Conclusions:
Our findings showed no relationship between childhood SES and cognition, except for semantic memory in Black participants; this relationship persisted after accounting for midlife CVD. Future analyses will assess both direct and indirect effects of more predictive measures of childhood SES on late-life cognition with midlife CVD as a mediator.
There are two forms of intra-individual variability (IIV) in the literature: inconsistency, or variability on one task across many time points, and dispersion, or variability across many tasks at one time point. These forms of IIV are often lumped together into one construct, but there is limited evidence supporting this practice, as few studies have examined the relationship between these measures. Additionally, it is not clear how stable these constructs are over time. Therefore, the goal of the present study was (1) to explore the relationship between (a) inconsistency and dispersion and (b) IIV and mean performance, and (2) to determine whether these relationships are stable over a one- to two-year follow-up interval.
Participants and Methods:
A total of 123 community-dwelling older adults (Mage=69.5, Meducation=15.6 years) from an archival database completed the Push-Turn-Taptap task to assess inconsistency and the Delis-Kaplan Executive Functioning System (D-KEFS) to assess dispersion. These measures were selected because both are highly executive, thereby allowing us to hold the cognitive domain constant across forms of IIV. Dispersion was calculated by taking the standard deviation of the executive conditions of four D-KEFS subtests (Verbal Fluency, Design Fluency, Trail Making, and Color Word Interference). Follow-up data were collected one to two and a half years after baseline. Bivariate and partial correlations controlling for time to follow-up were examined.
Results:
Inconsistency and dispersion were not correlated at baseline but were weakly correlated at follow-up (r=.281, p=.012). Additionally, both forms of IIV were moderately correlated with themselves across the follow-up interval (inconsistency: r=.450, p<.001; dispersion: r=.448, p<.001). The partial correlations were nearly identical to bivariate correlations.
Additionally, inconsistency was correlated with poorer mean executive functioning (EF) performance on both the PTT (baseline: r=.281, p<.001, follow-up: r=.435, p<.001) and D-KEFS (baseline: r= -.270, p=.003, follow-up: r=-.573, p<.001). In contrast, dispersion was correlated with mean EF performance only on the D-KEFS at baseline (r= -.292, p<.001) but with both measures at follow-up (PTT: r=.232, p=.039; D-KEFS: r= -.378, p<.001). When controlling for follow-up interval, inconsistency was no longer correlated with baseline mean PTT performance, but all other relationships remained the same (i.e., dispersion and inconsistency displayed the same pattern of correlations with mean EF).
Conclusions:
Although inconsistency and dispersion are both forms of IIV, they are weakly related. In other words, although they may have shared mechanisms, these two methods of measuring IIV likely represent different constructs. In the future, authors should take care to specify the form of IIV being investigated in their publications rather than referring to either form as IIV generally. Additionally, both forms of IIV are weakly to moderately correlated with mean EF performance, indicating that IIV is related to but separate from mean-level performance. Interestingly, IIV and mean performance were more strongly correlated at follow-up, which may be suggestive of incipient cognitive decline. Lastly, it seems that both inconsistency and dispersion are somewhat stable across a one- to two-year follow-up interval, suggesting that IIV may be a trait-level construct to some extent. However, IIV may also be influenced by state-level contextual factors, and more research examining the stability of and contributors to IIV is necessary.
Evidence has shown that the environment is an often overlooked social determinant of health (SDoH) of emotional, neural, and cognitive development. Aspects of the built environment relate to health factors and equity in living conditions, and may contribute to racial, ethnic, or economic health disparities. For example, urbanicity is linked with negative factors including less access to green space (i.e. gray space), increase in air pollution, temperatures, and socio-economic inequalities. While there is existing research on access to green space on some mental health and cognitive outcomes, there is limited research on the presence of gray space linked with cognitive functioning in youth. While some studies have shown that aspects of the neighborhood environment (e.g. access to healthy food, air pollution, heat exposure, and walkability) can impact neural and cognitive functioning, few to date have disentangled unique contributions of these factors in a large, national cohort. Therefore, the aim of the present study was to identify the best fitting model testing multiple SDoHs related to gray space on overall cognitive functioning in youth enrolled in the Adolescent Brain Cognitive Development (ABCD) Study.
Participants and Methods:
Using baseline data (n = 8,802) from ABCD 4.0 data, this study used environmental measures and linked external databases to characterize SDoH variables predicting youths’ cognitive functioning via the NIH Toolbox (e.g. total cognitive composite score). This study used geospatial mapping to estimate exposure to air pollutants and heat. Additionally, the National Walkability Index was linked to assess walkability of neighborhood. Exposure to gray space (e.g. impervious surfaces) and access to healthy food were assessed via the Child Opportunity Index 2.0. An exhaustive search for the best subsets of these variables (gray space, access to healthy food, walkability, air pollution, and heat exposure) predicting cognitive performance was run to examine the best fitting model based on adjusted R2, using the 'leaps’ package in R. Then, a multiple linear mixed effects regression model, using the lmer package in R, was fitted adjusting for various and relevant demographic factors.
Results:
The results of the regression indicated that walkability index (F(1, 1322.4) = 11.07, p < 0.001) and heat exposure (F(1, 81.1) = 5.54, p < 0.001) explained a significant amount of the variance (Adjusted R2 = 20%) predicting total cognitive performance while controlling for sex, age, household income, parent education, marital status, family relatedness, and site.
Conclusions:
Findings suggest that walkability of the neighborhood and heat exposure may play a role in cognitive development over and above other SDoHs and demographic factors. However, this study was limited to baseline assessment and a single measurement of total composite cognitive score, thus it is crucial for future research to investigate relationships over the life course across cognitive domains to further clarify these findings. The present study can help inform future public policy on improving lived and built environments, which may aid in supporting cognitive development in youth. These findings identify key factors, walkability and heat exposure, to consider when investigating the interaction between poverty, health, and environmental justice.
Individuals with sickle cell disease (SCD) are at increased risk for developing impairment across cognitive domains, although the most common deficits are thought to be related to processing speed and executive functions. One of the most common ways of evaluating cognitive functioning is through the administration of intellectual tests. While lower overall intellectual functioning in individuals with SCD compared to healthy controls has been found, the specific pattern of strengths and weaknesses across indices is not well known. Anecdotally, it has been observed at our clinic that individuals with SCD are more likely to show relative or significant weaknesses in visuospatial abilities, but this has not been formally investigated. Further, based on the extant research, individuals with SCD would likely demonstrate lower working memory and processing speed indices, but, as far as we are aware, this has not been investigated either. The purpose of the present study is to examine the intellectual profiles, including areas of relative and significant strengths and weaknesses, of children and adolescents with SCD.
Participants and Methods:
Participants are children and adolescents (age 6-16) with SCD who were referred for a neuropsychological evaluation at Montefiore Medical Center’s Neuropsychological Assessment Service from 2015 to 2022. These participants (N=54) were identified through a thorough review of patients seen through this service and were administered the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V; Wechsler, 2014). Mean scores were calculated for WISC-V indices. In addition, differences were calculated between WISC-V indices (e.g., VCI-VSI, etc.), and a discrepancy analysis was conducted comparing the base rates of these differences in the present sample to the WISC-V standardization sample.
Results:
In our sample, the mean total FSIQ of our sample was 85 (SD=14.5). The following mean scores were obtained across indices: VCI, SS=90 (SD=14.5); VSI, SS=86.5 (SD=14.9); FRI, SS=90 (15.5); WMI, SS=89 (SD=15.6); and PSI, SS=82 (SD=17.4). Many of the index score discrepancy base rates were similar to the standardization sample. However, our sample had greater discrepancies between several indices compared to the standardization sample. In particular, the following base rate discrepancies between index scores emerged as being different in our sample compared to the standardization sample: VCI>VSI and VCI>PSI. Notably, a 30+ point difference VCI>VSI was found in 6% of our sample (compared to 1.6% of the standardization sample) and a 30+ point difference between VCI>PSI was found in 12% of our sample (compared to 4.6% of the standardization sample). In addition, a 10+ point difference found between VCI>PSI was found in 50% of our sample (compared to 29% of standardization sample).
Conclusions:
In our sample, FSIQ and index scores fell approximately 0.5-1.33 SD below the standardization sample means, with the lowest index scores being PSI and VSI. Consistent with the literature, the PSI (but not WMI) emerged as an area most discrepant to other indices (particularly VCI). In line with our observations, the VSI emerged as an area of relative difficulty as compared to the VCI. These results suggest that, in addition to processing speed, visuospatial/constructional ability is an area that warrants consideration in the assessment of individuals with SCD.
When deciding between now and later, the tendency to devalue later outcomes is known as temporal discounting. The degree of devaluing is known as one’s discounting rate. Steeper temporal discounting rates indicate preferences for immediate gains and delayed losses, reflecting a desire for instant gratification and greater loss aversion, respectfully. Considering that decrements in decision-making abilities may precipitate cognitive dysfunction and decline, a better understanding of decision-making preferences among older adults represents an important endeavor. Thus, the current study aimed to investigate whether differences among temporal discounting rates for gains and losses exist when outcomes are monetary or interpersonal in nature.
Participants and Methods:
One hundred and forty community-dwelling older adults aged 50 to 90 (75% female, Mage=71.6) completed a hypothetical discounting task in which they chose between smaller immediate outcomes and larger delayed outcomes presented at various delay periods of one week, one month, six months, and one year. An iterative algorithm determined the indifference point for each delay period. Indifference points were fit to hyperbolic models using nonlinear regressions to determine discounting rates within each condition. Nonparametric Wilcoxon Signed-Rank tests compared discounting rates.
Results:
Older adults more steeply discounted monetary gains as compared to monetary losses (Z=-6.88, p<.001), as well as for social gains compared to social losses (Z=-4.81, p<.001). They also discounted social gains more steeply than monetary gains (Z=-5.44, p<.001), and social losses more steeply than monetary losses (Z=-4.44, p<.001).
Conclusions:
Preliminary findings suggest older adults displayed a greater desire for instant gratification of rewards, particularly social rewards, yet also displayed lower loss aversion, particularly for monetary losses. Stronger preferences for instant gratification of gains in certain contexts may inform ways in which healthier lifestyle choices or changes could be framed to appeal to older adults.
Schizophrenia is often disguised as a crisis of adolescence. We want to understand how schizophrenia manifests itself in speech. We expect the difference in the Word Fluency Association Task (WFAT) in Normality Index and Time Delay.
Participants and Methods:
The analyses data was collected by the WFAT (authored by V.Kritskaya). WFAT actualize speech connections based on past experience. Stimuli - various syllables of 2-letters (20 pcs.), 3-letters (30 pcs.), varying in frequency of use (compiled on the basis of the Corpuses of the Russian language). Instruction: “Now I will tell you a syllable, your task is to complete the proposed syllable to words as quickly as possible, your words must be real”. For study purposes we subdivided the sample into two subgroups: 12-14 years, 15-17 years. For statistical analysis we used U-criterion, Mann-Whitney. Analyzed parameters:
Normality index (NI) - the ratio of productive nouns to the amount of the standard associations
Time delay (TD) - response delay of the subject (sec., millisec.)
Study involved 57 participants: 27 adolescents with schizophrenia (Cl_G) aged from 12 to 18 years, assessed in the hospital setting (DS: F20.xx, F21.xx) and 30 normotypal peers (Co_G) assessed in the school setting. Exclusion criteria: patients in the acute psychotic phase, left-handers.
Results:
NI grouped with the following rates: subgroup 1- Co_G 70,4, Cl_G 58,5, subgroup 2 - Co_G 65,2, Cl_G 56,1 There was no statistically significant difference between Cl_g Co_g in NI (P=0,000 and p=0,002 respectively). TD grouped with the following rates: subgroup 1-Co_G 2,42, Cl_G 22,63, subgroup 2 - Co_G 4,48, Cl_G 3,14 There was statistically significant difference between Cl_g Co_g in TD (P=0,432 and p=0,25 respectively).
Conclusions:
Temporal indicators of cognitive activity differ in the clinical and control groups, which testifies to the significance of this indicator in the context of WFAT. There is no difference in terms of semantics. However, we expect to see it, because such difference has previously been shown in a group of adult patients with a severe type of schizophrenia. In the future, we would like to expand the group and select additional methods that evaluate the semantic component.
Partial agenesis of the corpus callosum (PACC) is a rare brain birth defect characterized by incomplete development of the corpus callosum, the primary white matter bundle that connects the right and left hemispheres. PACC can be associated with other congenital abnormalities, including malformation of the brain’s ventricular system, such as colpocephaly or ventriculomegaly, and it is typically considered a pediatric diagnosis. Clinically, this condition may present with a broad continuum of cognitive and socioemotional difficulties ranging from significant day-to-day impairment to relative independence. Newly diagnosed PACC with ventriculomegaly in adults is very rare (0.0200.025%) and little is known about neuropsychological functioning in adults with this condition. The aim of this case study is to add to the literature base for better PACC neuropsychological conceptualization.
Participants and Methods:
This case study involves neuropsychological evaluation of cognitive and behavioral health functioning of a 37-year-old active duty service member (ADSM) with recently identified PACC and ventriculomegaly (via incidental imaging finding). The ADSM reported a history of learning difficulty, though she was able to earn rank of sergeant first class in a low density military occupation specialty (i.e., Mortuary Affairs) over an 18.5 year active duty career.
Results:
Cognitive testing was notable for consistently low to exceptionally low attention and processing speed scores. Mild executive dysfunction was also noted in the areas of planning and inhibition. Emotionally, she endorsed mild somatic and depression symptoms. Interpersonally, she was shy and avoidant with longstanding characterological traits characterized by worry, insecurity, and general tendency to catastrophize.
Conclusions:
This case adds to the broad clinical presentation of PACC with ventriculomegaly, and highlights that even in the context of a significant congenital brain deformity and longstanding cognitive deficits, independent functioning can be achieved.
Gulf War Illness (GWI) is a debilitating multi-symptom condition that affects nearly a third of 1990-91 Gulf War (GW) veterans. Symptoms include chronic pain, debilitating fatigue, gastrointestinal issues, and cognitive decrements. Prior studies have documented reduced cognitive functioning in this affected population, particularly in the areas of memory, attention and response inhibition. To date, research has focused on cognitive functioning in male and female veterans together. Very limited research has reported on GW women's cognitive functioning separately mostly due to scarcity of data on women veterans. In this study, we had the unique opportunity to utilize a newly combined neuropsychological test dataset from women GW veterans in the Boston, Biorepository and Integrative Network (BBRAIN) for GWI. The aim was to compare neuropsychological outcomes with toxicant exposures in women veterans with and without GWI.
Participants and Methods:
Cognitive data from the BBRAIN biorepository was used for this study. The sample consisted of 62 women veterans who were deployed to the Persian Gulf War from 1990-91. Neuropsychological test scores included the Conners Continuous Performance Test Third Edition (CPT3), Delis-Kaplan Executive Function System (D-KEFS) Color-Word Interference, and the California Verbal Learning Test Second Edition (CVLT-II). War-related exposure to chemical weapons, anti-nerve gas pills and pesticides were measured by a self-reported survey. For analysis, war-related exposure was classified into three groups: controls with 0-6 days of exposure; cases with 0-6 days of exposure and cases with 7 or more days of exposure. Multiple linear regression modeling was used to measure differences in neuropsychological scores across the three groups by each war-related exposure.
Results:
After adjusting for age, education and other exposures, an increase in duration of exposure to pesticides was significantly associated with worse CPT3 commission errors, fewer words correct in the CVLT-II trials 1-5, and an increase in self-corrected errors on DKEFS Color-Word Interference Test Trials 1, 2 and 4 (p<0.05). More days reported hearing chemical alarms and seeing smoke from oil well fires was significantly associated with fewer words correct on all CVLT-II trials, and more self-corrected errors on Color-Word Interference Trials 2 and 4 (p<0.05). An increase in exposure duration to pyridostigmine bromide anti-nerve gas pills was associated with fewer words correct on the CVLT-II learning Trials 1-5 and short delay recall and an increase in self-corrected errors on Color-Word Interference Trials 2, 3, and 4 (p<0.05). When associations were adjusted for PTSD, all significant associations stayed constant (p<0.05).
Conclusions:
In this study, women veterans with GWI who had higher levels of exposure to pesticides, oil well fires and who took more antinerve gas pills during the war are showing increased learning difficulties and more deficits in attention and response inhibition. Future research should examine if similar patterns of neuropsychological symptoms are also present in male GW veterans with higher war-time related toxicant exposures.
Veterans from the 1991 Gulf War (GW) experienced several neurotoxicant exposures, including chemical weapons, pesticide sprays and creams, oil well fires and pyridostigmine bromide anti-nerve gas pills during the war. Research has shown these exposures to affect cognition and mood. Moreover, MR diffusion imaging has shown microstructural changes in the white matter that may be related to psychomotor slowing. Over a third of all GW veterans suffer from a chronic multi-symptom disorder called Gulf War Illness (GWI). The Kansas Criteria for GWI consists of six distinct criteria including symptoms of fatigue/sleep problems, pain symptoms, neurologic/cognitive/mood symptoms, gastrointestinal symptoms, respiratory symptoms, and skin symptoms. The Boston Gulf War Illness Consortium (GWIC) was a multi-site study designed to assess symptoms of GWI. After the conclusion of the GWIC study, the Boston Biorepository Recruitment and Integrative Network for Gulf War Illness (BBRAIN) was developed to harmonize retrospectively collected GW Veteran data while simultaneously collecting Time 2 data and samples from GW veterans who participated in the original study. This analysis includes the first 58 participants who have completed the GWIC study and the BBRAIN study.
Participants and Methods:
We conducted a longitudinal analysis of cognitive outcomes from the BBRAIN data repository. Verbal learning, memory, attention, and executive functioning were assessed using neuropsychological tests including the Continuous Performance Test (CPT3), Trail Making Test A, Delis-Kaplan Executive Function System (DKEFS), California Verbal Learning Test (CVLT-II). A total of 58 participants were re-evaluated from the original GWIC cohort with a total of 47 cases and 11 controls. Paired t-tests for the cognitive measures were completed separately for GWI cases and healthy GW veteran controls for each of the neuropsychological test measures. Average time between assessments was four years.
Results:
The overall sample was on average 56 years old, 84% male and 75% White. The average level of education was 15 years. GWI cases showed significantly more commission errors and slower reaction times on the CPT3 at Time 2 compared to Time 1 (p < 0.05). Cases also showed a slowing in time to completion on Trails A at the second time point (p<0.05). On the other hand, controls only showed significantly slower reaction times on the CPT3 at Time 2 (p<0.05).
Conclusions:
These results showed that veterans with GWI are showing more decline over time in cognitive functioning particularly on psychomotor slowing and impulsivity than control veterans. It is important to document illness trajectories for veterans with GWI in order to devise strategies for interventions and treatments. The importance of studying longitudinal cohorts is to document changes in the same individuals over time. The next steps are to assess if this accelerated aging develops into neurodegenerative conditions by using brain imaging and other biomarkers in addition to cognitive evaluations. This could identify individuals who should be the focus of targeted treatment strategies while there is still time to intervene.
Women tend to perform better than men on episodic verbal memory tests across the age span, which may contribute to gender-related disparities in diagnosis of Mild Cognitive Impairment and dementia. Patterns of learning performance may be better indicators of potential memory problems and address gender differences. The serial position effect, specifically a J-curve (reduced primacy relative to recency), is predictive of dementia, but few studies have examined gender differences in serial position. Learning ratio (LR) is a recently developed calculation for the extent to which an individual benefits from repeated exposure to a word list. LR has shown strong relationships to memory performance and memory impairment. Gender differences on LR have been inconsistently identified. Whether or not men and women show differential relationships of serial position or LR to other memory indicators, however, has not been examined. In the four papers within this symposium, we examine the relationship of serial position and LR to memory outcomes in four samples of older adults, with a focus on whether gender moderates these relationships. We also examine the relationship of memory process variables to cortisol. The first two papers used the RBANS. Alexander et al. found that, within a sample of 203 healthy older adults (133 women) with no diagnosis of MCI or dementia, men and women did not differ on LR and there was no differential prediction for LR by gender with delayed memory variables. Do and colleagues demonstrated that, within a sample of 338 older adults (228 women) with no diagnosis of MCI or dementia, men and women did not differ in primacy, but men did worse on recency. While 23% of the sample showed a J-curve pattern, this did not differ by gender, and the pattern was highly predictive of memory performance for both men and women. Thus, at least for the RBANS, these two studies suggest LR and primacy avoid gender confounds seen in traditional memory measures. The last two papers included assessment of cortisol. Lambertus et al. found that, in a sample of 60 older adults, 26 of whom were caregivers for persons with dementia, caregivers performed worse on recency, but not primacy. They also reported more stress but were not different in hair cortisol concentration. Within the full sample, perceived stress was related to recency, but not primacy; hair cortisol was not related to either perceived stress or primacy/recency. Finally, Pizzonia and colleagues report AVLT learning process findings from a sample of 100 healthy older adults (44 men). They found that women were better on both LR and primacy, but not recency. However, LR and primacy were not differentially related to memory outcomes in men and women, although there were differential relationships of recency to AVLT. Potential gender moderation of relationships between cortisol and LR/primacy performance were also observed. Overall, findings suggest that there may be gender differences in AVLT-related learning process tests, but that their relationship to memory outcome variables may be similar across genders. Implications of these findings for assessment will be discussed.
To examine associations between executive function (EF) domains (attentional control, information processing, cognitive flexibility, and goal setting) and math computation performance at 7 and 13 years in children born very preterm (VP; <30 weeks' gestation), and secondly, to investigate the associations of 7-year EF with change in math performance from 7 to 13 years.
Participants and Methods:
In the prospective, longitudinal Victorian Infant Brain Studies (VIBeS) cohort of children born VP, assessment of EF and math performance was undertaken at 7 (n = 187) and 13 years (n = 174). Univariable and multivariable regression models (including all domains of EF) were used to examine associations between EF domains at both timepoints with math performance, as well as associations between EF at 7 years with change in math from 7 to 13 years.
Results:
At 7 and 13 years, all EF domains were positively associated with concurrent math performance, with multivariable models finding information processing, cognitive flexibility and goal setting independently contributed to math performance at both ages. All EF domains were positively associated with improvement in math performance from 7 to 13 years, with multivariable models finding that goal setting contributed unique variance to improvement in math over this period.
Conclusions:
This study provides evidence for a strong, consistent association between EF and math performance in children born VP and emphasizes the importance of goal setting capacity for later improvement in math performance.
Recent research has found associations between the Five Factor Model (FFM) personality traits (Openness to Experience, Conscientiousness, Extraversion, Agreeableness, and Neuroticism) and risk of developing subjective cognitive decline (SCD), mild cognitive impairment (MCI), and/or dementia. It has therefore been proposed that personality should be incorporated into conceptual models of dementia risk, as personality assessments have utility as readily available, low-cost measures to predict who is at greater risk for developing pathological cognitive decline. The objective of the present study was to explore the relationship between FFM personality traits and predementia cognitive syndromes including SCD, amnestic MCI (aMCI), and non-amnestic MCI (naMCI). The first aim was to compare baseline personality traits between participants who transitioned from healthy cognition or SCD to aMCI vs. naMCI. The second aim was to determine the relationship between FFM personality traits and risk of transition between predementia cognitive states. The third aim was to explore relationships between levels of FFM personality traits and performance on a comprehensive cognitive battery.
Participants and Methods:
The participants for this study were 562 (Aim 3; Mean Age = 78.90) older adults from the Einstein Aging Study, 378 of which had at least one follow-up assessment (Aims 1 & 2; Mean Age = 78.60). Baseline levels of FFM personality traits were measured in the EAS using the 50-item International Personality Item Pool (IPIP) version of the NEO-Personality Inventory. Baseline levels of anxiety and depressive symptoms, medical history, performance on a cognitive battery and age sex, and years of education were also collected. A multistate Markov approach was used to model the risk of transition across the four predementia states (cognitively healthy, SCD, aMCI, and naMCI) with each FFM personality trait as covariates.
Results:
Regarding Aim 1, Mann-Whitney U tests revealed no differences in levels of FFM personality traits between participants who developed aMCI compared to those who developed naMCI. Regarding Aim 2, the multistate Markov model revealed that higher levels of conscientiousness were protective against developing SCD while higher levels of neuroticism resulted in an increased risk of developing SCD. Further, the model revealed that higher levels of extraversion were protective against developing naMCI. Finally, regarding Aim 3, exploratory correlations revealed many positive associations between levels of openness to experience and performance on neuropsychological tests. Few associations were found for the other FFM personality traits.
Conclusions:
Results from this study suggest that premorbid personality traits may play a predictive role in the risk for or protection against specific predementia syndromes. Thus, FFM personality traits may be useful in improving predictions of who is at greatest risk for developing specific predementia syndromes. These personality measures could be used (in addition to other established risk factors for cognitive decline) to enrich clinical trials by targeting individuals who are at greatest risk for developing specific forms of cognitive decline. Such measures may also be useful in diagnostic prediction models for predementia syndromes. These results should be replicated in future studies with larger sample sizes and younger participants.