1130 results
Examining the unique relationships between problematic use of the internet and impulsive and compulsive tendencies: network approach
- Chang Liu, Kristian Rotaru, Lei Ren, Samuel R. Chamberlain, Erynn Christensen, Mary-Ellen Brierley, Karyn Richardson, Rico S. C. Lee, Rebecca Segrave, Jon E. Grant, Edouard Kayayan, Sam Hughes, Leonardo F. Fontenelle, Amelia Lowe, Chao Suo, René Freichel, Reinout W. Wiers, Murat Yücel, Lucy Albertella
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- Journal:
- BJPsych Open / Volume 10 / Issue 3 / May 2024
- Published online by Cambridge University Press:
- 09 May 2024, e104
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Background
Both impulsivity and compulsivity have been identified as risk factors for problematic use of the internet (PUI). Yet little is known about the relationship between impulsivity, compulsivity and individual PUI symptoms, limiting a more precise understanding of mechanisms underlying PUI.
AimsThe current study is the first to use network analysis to (a) examine the unique association among impulsivity, compulsivity and PUI symptoms, and (b) identify the most influential drivers in relation to the PUI symptom community.
MethodWe estimated a Gaussian graphical model consisting of five facets of impulsivity, compulsivity and individual PUI symptoms among 370 Australian adults (51.1% female, mean age = 29.8, s.d. = 11.1). Network structure and bridge expected influence were examined to elucidate differential associations among impulsivity, compulsivity and PUI symptoms, as well as identify influential nodes bridging impulsivity, compulsivity and PUI symptoms.
ResultsResults revealed that four facets of impulsivity (i.e. negative urgency, positive urgency, lack of premeditation and lack of perseverance) and compulsivity were related to different PUI symptoms. Further, compulsivity and negative urgency were the most influential nodes in relation to the PUI symptom community due to their highest bridge expected influence.
ConclusionsThe current findings delineate distinct relationships across impulsivity, compulsivity and PUI, which offer insights into potential mechanistic pathways and targets for future interventions in this space. To realise this potential, future studies are needed to replicate the identified network structure in different populations and determine the directionality of the relationships among impulsivity, compulsivity and PUI symptoms.
546 Using Contingency Management to Understand the Cardiovascular, Immune and Psychosocial Benefits of Reduced Cocaine Use: A Protocol for a Randomized Controlled Trial
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- Sean Regnier, Jennifer R. Havens, Thomas P. Shellenberg, David H. Cox, Thomas S. Baker, Joshua A. Lile, Craig R. Rush, Reuben Adatorwovor, Lon R. Hays, Danielle M. Anderson, Mary B. Fisher, Suzanne C. Segerstrom, Joy M. Schmitz, William W. Stoops
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue s1 / April 2024
- Published online by Cambridge University Press:
- 03 April 2024, p. 163
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OBJECTIVES/GOALS: Contingency management (CM) procedures yield measurable reductions in cocaine use. This poster describes a trial aimed at using CM as a vehicle to show the biopsychosocial health benefits of reduced use, rather than total abstinence, the currently accepted metric for treatment efficacy. METHODS/STUDY POPULATION: In this 12-week, randomized controlled trial, CM was used to reduce cocaine use and evaluate associated improvements in cardiovascular, immune, and psychosocial well-being. Adults aged 18 and older who sought treatment for cocaine use (N=127) were randomized into three groups in a 1:1:1 ratio: High Value ($55) or Low Value ($13) CM incentives for cocaine-negative urine samples or a non-contingent control group. They completed outpatient sessions three days per week across the 12-week intervention period, totaling 36 clinic visits and four post-treatment follow-up visits. During each visit, participants provided observed urine samples and completed several assays of biopsychosocial health. RESULTS/ANTICIPATED RESULTS: Preliminary findings from generalized linear mixed effect modeling demonstrate the feasibility of the CM platform. Abstinence rates from cocaine use were significantly greater in the High Value group (47% negative; OR = 2.80; p = 0.01) relative to the Low Value (23% negative) and Control groups (24% negative;). In the planned primary analysis, the level of cocaine use reduction based on cocaine-negative urine samples will serve as the primary predictor of cardiovascular (e.g., endothelin-1 levels), immune (e.g., IL-10 levels) and psychosocial (e.g., Addiction Severity Index) outcomes using results from the fitted models. DISCUSSION/SIGNIFICANCE: This research will advance the field by prospectively and comprehensively demonstrating the beneficial effects of reduced cocaine use. These outcomes can, in turn, support the adoption of reduced cocaine use as a viable alternative endpoint in cocaine treatment trials.
280 Enhancing Nephrology Care Access: Development and Implementation of a Telenephrology Dashboard Through Human-Centered Design
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- Melissa L. Swee, Bradley S. Dixon, M. Lee Sanders, Kantima Phisitkul, Angie Thumann, Mary Vaughan Sarrazin, Qianyi Shi, Benjamin R. Griffin, Meenakshi Sambharia, Masaaki Yamada, Heather Reisinger, Diana I. Jalal
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue s1 / April 2024
- Published online by Cambridge University Press:
- 03 April 2024, p. 85
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OBJECTIVES/GOALS: Our objective is to develop a Telenephrology dashboard for the 150,000 Veterans that obtain care through the Iowa City Veterans Affairs Health Care System. Our goal is to create a comprehensive and user-friendly tool for monitoring kidney health and facilitating remote nephrology consultations. METHODS/STUDY POPULATION: We structured our intervention according to the five stages of human-centered design: (1) Empathize, (2) Define, (3) Ideate, (4) Prototype and (5) Test. During the empathy stage, the principal investigator spent 10 hours immersed in the clinical setting observing how nephrologists approach a remote nephrology consultation. These observations were augmented by unstructured interviews with clinicians and patients to better understand the process and dynamics. Following this, a rapid ideation workshop was convened to generate creative solutions that balance technical requirements with the needs of clinicians and patients. These led to rapid prototyping and testing to identify what elements of the prototypes worked and which needed improvement. RESULTS/ANTICIPATED RESULTS: Through the empathy and define stages, three needs were identified: (1) clarity in visualizing data, (2) accuracy of information, and (3) balancing standardization with individualization. During the rapid ideation workshop, the concept of a four-frame dashboard was settled upon. This led to the creation of five prototypes, which were tested. These were reconciled and modified to make a final product. This final product, the Telenephrology Dashboard, contains 5 elements that support nephrologists and supporting staff: (1) a graph of kidney function over time, (2) tables synthesizing lab data, (3) options to drill down events to specific times, (4) customization of views, and (5) integration of kidney disease progression models. DISCUSSION/SIGNIFICANCE: A Telenephrology dashboard was created to facilitate remote nephrology consultations through a Human-Centered Design process. Our next steps include determining if this dashboard may improve end-user satisfaction, referring clinician satisfaction, access to specialist care, and patient outcomes.
Oxygen Isotope Measurements of Albite-Quartz-Zeolite Mineral Assemblages, Hokonui Hills, Southland, New Zealand
- Mary L. Stallard, J. R. Boles
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- Clays and Clay Minerals / Volume 37 / Issue 5 / October 1989
- Published online by Cambridge University Press:
- 02 April 2024, pp. 409-418
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The oxygen isotopes of albite, quartz, and zeolites from the Hokonui Hills, New Zealand, constrain crystallization temperatures and the type of pore fluids present during diagenesis. A section of altered vitric tuffs in this region contains an extremely sharp reaction boundary between a heulandite-chlorite assemblage containing fresh detrital plagioclase and a laumontite-albite-quartz assemblage. A laumontite vein follows the local joint pattern and forms the reaction boundary, suggesting that laumontitization occurred as a result of fracturing and increased fluid flow during uplift. The albite (δ18O = +15.0)-quartz (δ18O = +19.9 to +20.5) geothermometer constrains the temperature of alteration between 145° and 170°C with a pore water δ18O of +1.8 to +3.5. The tuff was buried to an estimated maximum temperature of about 225°C, indicating that alteration occurred after maximum burial.
Framework oxygen was extracted from zeolites by reaction with ClF3 after the zeolites were thermally dehydrated in a vacuum. Laumontite was dehydrated at 300°C, and stilbite at 150°C. The precision of the method is typically about ±0.45‰. Fractionation curves for dehydrated zeolites are based on a general expression from the literature for feldspars, which depends only on the Si/Al ratio of the mineral. Measured δ18O values for laumontite in the groundmass of the altered tuff were +14.4‰. The laumontite-quartz pair constrains the temperature to between 139° and 162°C, in excellent agreement with the albite-quartz pair, and supporting the petrographic observation of co-crystallizing albite-laumontite.
Oxygen isotope values for fracture-filling laumontite in the vitric tuff, as well as those for groundmass and vein laumontite from other parts of the stratigraphic section, cluster around +14.5, suggesting that laumontite probably crystallized under similar conditions throughout much of the section. Oxygen isotope values for stilbite veins from various parts of the section indicate that this mineral crystallized at lower temperatures than the laumontite, for a given fluid isotopic composition, in agreement with the observed cross-cutting of laumontite by stilbite.
Effects of esketamine nasal spray on depressive symptom severity in adults with treatment-resistant depression and associations between the Montgomery–Åsberg Depression Rating Scale and the 9-item Patient Health Questionnaire
- Jennifer Kern Sliwa, Ronaldo R. Naranjo, Jr, Ibrahim Turkoz, Mary Pat Petrillo, Patricia Cabrera, Madhukar Trivedi
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- CNS Spectrums / Volume 29 / Issue 3 / June 2024
- Published online by Cambridge University Press:
- 01 April 2024, pp. 176-186
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Objective
To examine the effect of esketamine nasal spray (ESK) plus newly initiated oral antidepressant (OAD) versus OAD plus placebo nasal spray (PBO) on the association between Montgomery–Åsberg Depression Rating Scale (MADRS) and 9-item Patient Health Questionnaire (PHQ-9) scores in adults with treatment-resistant depression (TRD).
MethodsData from TRANSFORM-1 and TRANSFORM-2 (two similarly designed, randomized, active-controlled TRD studies) and SUSTAIN-1 (relapse prevention study) were analyzed. Group differences for mean changes in PHQ-9 total score from baseline were compared using analysis of covariance. Associations between MADRS and PHQ-9 total scores from TRANSFORM-1/TRANSFORM-2 were assessed using simple parametric, nonparametric, and multiple regression models.
ResultsIn TRANSFORM-1/TRANSFORM-2 (ESK + OAD, n = 343; OAD + PBO, n = 222), baseline PHQ-9 mean scores were 20.4 for ESK + OAD and 20.6 for OAD + PBO (severe depression). At day 28, significant group differences were observed in least squares mean change (SE) in PHQ-9 scores from baseline (−12.8 [0.46] vs −10.3 [0.53], P < .001) and in clinically substantial change in PHQ-9 scores (≥6 points; 77.1% vs 64%, P < .001) in ESK + OAD and OAD + PBO groups, respectively. A nonlinear relationship between MADRS and PHQ-9 was observed; total scores demonstrated increased correlation over time. In SUSTAIN-1, 57.3% of patients receiving ESK + OAD (n = 89) versus 44.2% receiving OAD + PBO (n = 86) retained remission status (PHQ-9 score ≤4) at maintenance treatment end point (P = .044).
ConclusionsIn adults with TRD, ESK + OAD significantly improved severity of depressive symptoms, and more patients achieved clinically meaningful changes in depressive symptoms based on PHQ-9, versus OAD + PBO. PHQ-9 outcomes were consistent with those of clinician-rated MADRS.
Trial registrationClinicalTrials.gov: NCT02417064, NCT02418585, NCT02493868.
Determinants of confrontation naming deficits on the Boston Naming Test associated with transactive response DNA-binding protein 43 pathology
- Carling G. Robinson, Austin W. Goodrich, Stephen D. Weigand, Nha Trang Thu Pham, Arenn F. Carlos, Marina Buciuc, Melissa E. Murray, Aivi T. Nguyen, R. Ross Reichard, David S. Knopman, Ronald C. Petersen, Dennis W. Dickson, Rene L. Utianski, Jennifer L. Whitwell, Keith A. Josephs, Mary M. Machulda
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- Journal of the International Neuropsychological Society , First View
- Published online by Cambridge University Press:
- 25 March 2024, pp. 1-9
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Objective:
To determine whether poorer performance on the Boston Naming Test (BNT) in individuals with transactive response DNA-binding protein 43 pathology (TDP-43+) is due to greater loss of word knowledge compared to retrieval-based deficits.
Methods:Retrospective clinical-pathologic study of 282 participants with Alzheimer’s disease neuropathologic changes (ADNC) and known TDP-43 status. We evaluated item-level performance on the 60-item BNT for first and last available assessment. We fit cross-sectional negative binomial count models that assessed total number of incorrect items, number correct of responses with phonemic cue (reflecting retrieval difficulties), and number of “I don’t know” (IDK) responses (suggestive of loss of word knowledge) at both assessments. Models included TDP-43 status and adjusted for sex, age, education, years from test to death, and ADNC severity. Models that evaluated the last assessment adjusted for number of prior BNT exposures.
Results:43% were TDP-43+. The TDP-43+ group had worse performance on BNT total score at first (p = .01) and last assessments (p = .01). At first assessment, TDP-43+ individuals had an estimated 29% (CI: 7%–56%) higher mean number of incorrect items after adjusting for covariates, and a 51% (CI: 15%–98%) higher number of IDK responses compared to TDP-43−. At last assessment, compared to TDP-43−, the TDP-43+ group on average missed 31% (CI: 6%–62%; p = .01) more items and had 33% more IDK responses (CI: 1% fewer to 78% more; p = .06).
Conclusions:An important component of poorer performance on the BNT in participants who are TDP-43+ is having loss of word knowledge versus retrieval difficulties.
ACTIVE REMODELLING OF TISSUES TO DESCRIBE BIPHASIC RHEOLOGICAL RESPONSES
- DOMENIC P. J. GERMANO, STEPHANIE KHUU, ADRIANNE L. JENNER, JAMES M. OSBORNE, MARY R. MYERSCOUGH, MARK B. FLEGG
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- Journal:
- The ANZIAM Journal / Volume 65 / Issue 3 / July 2023
- Published online by Cambridge University Press:
- 26 February 2024, pp. 195-214
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Tissues form from collections of cells that interact together mechanically via cell-to-cell adhesion, mediated by transmembrane cell adhesion molecules. Under a sufficiently large amount of induced stress, these tissues can undergo elastic deformation in the direction of tension, where they then elongate without any topological changes, and experience plastic deformation within the tissue. In this work, we present a novel mathematical model describing the deformation of cells, where tissues are elongated in a controlled manner. In doing so, the cells are able to undergo remodelling through elastic and then plastic deformation, in accordance with experimental observation. Our model describes bistable sizes of a cell that actively deform under stress to elongate the cell. In the absence of remodelling, the model reduces to the standard linear interaction model. In the presence of instant remodelling, we provide a bifurcation analysis to describe the existence of the bistable cell sizes. In the case of general remodelling, we show numerically that cells within a tissue may populate both the initial and elongated cell sizes, following a sufficiently large degree of stress.
Cost-effectiveness of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) testing and isolation strategies in nursing homes
- Sarah M. Bartsch, Colleen Weatherwax, Marie F. Martinez, Kevin L. Chin, Michael R. Wasserman, Raveena D. Singh, Jessie L. Heneghan, Gabrielle M. Gussin, Sheryl A. Scannell, Cameron White, Bruce Leff, Susan S. Huang, Bruce Y. Lee
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 45 / Issue 6 / June 2024
- Published online by Cambridge University Press:
- 15 February 2024, pp. 754-761
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- June 2024
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Objective:
Nursing home residents may be particularly vulnerable to coronavirus disease 2019 (COVID-19). Therefore, a question is when and how often nursing homes should test staff for COVID-19 and how this may change as severe acute respiratory coronavirus virus 2 (SARS-CoV-2) evolves.
Design:We developed an agent-based model representing a typical nursing home, COVID-19 spread, and its health and economic outcomes to determine the clinical and economic value of various screening and isolation strategies and how it may change under various circumstances.
Results:Under winter 2023–2024 SARS-CoV-2 omicron variant conditions, symptom-based antigen testing averted 4.5 COVID-19 cases compared to no testing, saving $191 in direct medical costs. Testing implementation costs far outweighed these savings, resulting in net costs of $990 from the Centers for Medicare & Medicaid Services perspective, $1,545 from the third-party payer perspective, and $57,155 from the societal perspective. Testing did not return sufficient positive health effects to make it cost-effective [$50,000 per quality-adjusted life-year (QALY) threshold], but it exceeded this threshold in ≥59% of simulation trials. Testing remained cost-ineffective when routinely testing staff and varying face mask compliance, vaccine efficacy, and booster coverage. However, all antigen testing strategies became cost-effective (≤$31,906 per QALY) or cost saving (saving ≤$18,372) when the severe outcome risk was ≥3 times higher than that of current omicron variants.
Conclusions:SARS-CoV-2 testing costs outweighed benefits under winter 2023–2024 conditions; however, testing became cost-effective with increasingly severe clinical outcomes. Cost-effectiveness can change as the epidemic evolves because it depends on clinical severity and other intervention use. Thus, nursing home administrators and policy makers should monitor and evaluate viral virulence and other interventions over time.
The Effects of Oxyanion Adsorption on Reactive Oxygen Species Generation by Titanium Dioxide
- Mary R. Arenberg, Yuji Arai
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- Clays and Clay Minerals / Volume 67 / Issue 5 / October 2019
- Published online by Cambridge University Press:
- 01 January 2024, pp. 410-418
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The growing use of nano titanium dioxide (TiO2) in consumer and agricultural products has accelerated its introduction into terrestrial environments, where its impact has not been documented extensively. TiO2 toxicity arises primarily from its ability to photochemically generate reactive oxygen species (ROS), including hydrogen peroxide (H2O2). While common ligands in soil porewaters can either hinder or enhance the degradation of organic contaminants by TiO2, their effects on ROS production by TiO2 have not been understood clearly. The objective of this study was to assess the effect of phosphate (P) and nitrate on UV-irradiated anatase, nano-TiO2. Accordingly, H2O2-generation kinetics experiments were conducted in UV-irradiated TiO2 under environmentally relevant concentrations of the ligands (0, 50, 100, and 250 μM) and pH values (4.00 ± 0.02 and 8.00 ± 0.02) from 0–100 min. Under all conditions, H2O2 grew logarithmically and reached between 5.38 and 22.98 μM after 100 min. At pH 4.00 ± 0.02, H2O2 production was suppressed by P but not by nitrate. Conversely, at pH 8.00 ± 0.02, nitrate did not affect H2O2 concentration while P increased it. Non-specific, minimal adsorption of nitrate prevented interference with the photoreactivity of TiO2. Due to the pH-dependent behavior of suspended TiO2 and H2O2 degradation rates, specific adsorption of P on TiO2 impeded its ability to produce H2O2 photochemically at pH 4.00 ± 0.02 but amplified it at pH 8.00 ± 0.02.
Updating and evaluating a research best practices training course for social and behavioral research professionals
- Elias Samuels, Mary R. Janevic, Alexandra E. Harper, Angela K. Lyden, Gina M. Jay, Ellen Champagne, Susan L. Murphy
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- Journal of Clinical and Translational Science / Volume 8 / Issue 1 / 2024
- Published online by Cambridge University Press:
- 27 December 2023, e12
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Introduction:
The clinical and translational research workforce involved in social and behavioral research (SBR) needs to keep pace with clinical research guidance and regulations. Updated information and a new module on community and stakeholder engagement were added to an existing SBR training course. This article presents evaluation findings of the updated course for the Social and Behavioral Workforce.
Methods and Materials:Participants working across one university were recruited. Course completers were sent an online survey to evaluate the training. Some participants were invited to join in a focus group to discuss the application of the training to their work. We performed descriptive statistics and conducted a qualitative analysis on focus group data.
Results:There were 99 participants from diverse backgrounds who completed the survey. Most reported the training was relevant to their work or that of the study teams they worked with. Almost half (46%) indicated they would work differently after participating. Respondents with community or stakeholder engaged research experience vs. those without were more likely to report that the new module was relevant to study teams they worked with (t = 5.61, p = 0.001), and that they would work differently following the training (t = 2.63, p = 0.01). Open-ended survey responses (n = 99) and focus group (n = 12) data showed how participants felt their work would be affected by the training.
Conclusion:The updated course was rated highly, particularly by those whose work was related to the new course content. This course provides an up-to-date resource for the training and development for the Social and Behavioral Workforce.
36 Naming in Monolingual and Bilingual Children with Epilepsy
- Melanie R. Silverman, Mary Lou Smith, William S. MacAllister, Nahal Heydari, Robyn M. Busch, Robert Fee, Marla J. Hamberger
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 35-36
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Objective:
Word finding or “naming” difficulty is a symptom of multiple neurological disorders; therefore, naming assessment is an integral component of neuropsychological evaluation. Prior work has found weaker second-language naming in healthy proficient bilingual youth than monolingual youth, and similar findings have been shown in adults with epilepsy. Considering the potential influences of both early onset epilepsy and bilingualism on brain development, we compared naming in English second language (ESL) and monolingual youth with epilepsy. To assess the impact of bilingualism independent of the known effects of seizure laterality (i.e., poor naming in those with left, dominant-hemisphere seizures), we excluded patients with left language dominance and unilateral seizures. We hypothesized that like other groups, naming would be weaker in ESL than in monolingual youth with epilepsy.
Participants and Methods:Participants included 84 children with seizures that could not be lateralized clinically (n=36), bilateral seizures (n=20), centrotemporal spikes (n=3), and those with unilateral seizures and atypical language dominance (n=25), ages 6-15 years old: 66 monolingual, English (mean age: 10.87 ± 2.70 years) and 18 ESL (mean age: 10.78 ± 2.88 years). Those with FSIQ < 70 and vocabulary SS < 6 were excluded to ensure English proficiency. Independent samples t-tests, multivariate ANOVA, and chi-square tests compared groups on demographic factors and test performance. All measures (FSIQ, WISC/WASI Vocabulary, letter and category fluency, Children’s Auditory (AN) and Visual Naming (VN) Tests) were administered in English.
Results:Monolingual and ESL groups did not differ in: age, sex, SES, seizure type (i.e., non-lateralized, bilateral, centrotemporal spikes, or atypical language dominance), epilepsy onset age, or number of AEDs. Comparisons also showed no differences in FSIQ, vocabulary, letter fluency, or category fluency (all ps > 0.05). By contrast, auditory and visual naming performances were weaker among ESL patients than monolingual patients: AN accuracy, F(1,81) = 10.89, p = 0.001; AN tip-of-the-tongues (TOTs), F(1,81) = 6.35, p = 0.014; AN Summary Scores (SS), F(1,81) = 6.17, p = 0.015; VN accuracy, F(1,81) = 4.66, p = 0.034; VN SS, F(1,81) = 4.87, p = 0.030, with the exception of VN TOTs, which approached significance, F(1,81) = 3.55, p = 0.063.
Conclusions:Consistent with findings in bilingual healthy youth and ESL adults with epilepsy, naming in ESL youth with epilepsy was weaker than in monolingual children. The groups did not differ on other aspects of language. Thus, unlike other expressive verbal functions, naming is adversely affected in the second language of bilingual people with epilepsy across the age span. These results suggest that poor naming in ESL patients cannot be used to infer a naming deficit, and/or left (dominant) temporal lobe dysfunction.
82 Behavioral, Emotional, and Adaptive Functioning in a Pediatric anti-NMDARE Population
- Madeline R King, Marie C McGrath, Ashley Higgins, Nina Hattiangadi Thomas
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 74-75
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Objective:
Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is a complex, yet treatable autoimmune disorder characterized by a fairly abrupt onset of a constellation of symptoms attributable to diffuse brain dysfunction (Tarantino et al., 2021). Despite the potential for a severe disease course, most patients have a favorable outcome with substantial recovery (Dalmau et al., 2011; Titulaer et al., 2013). Nevertheless, there is limited literature discussing the long-term outcomes in patients with anti-NMDARE, particularly in pediatric patients. The primary objective of this study is to examine and describe behavioral, emotional, adaptive, and executive functioning outcomes in pediatric and young adult patients with this disease. This study also sought to provide information on the perceived health-related quality of life (HRQoL) of patients and their parents and investigate the impact of anti-NMDARE on parents and family functioning.
Participants and Methods:All individuals known to have been diagnosed and treated for anti-NMDARE at The Children’s Hospital of Philadelphia (CHOP) between January 1, 2005, and October 1, 2020, were contacted with both patients and their parents/guardians invited to participate. Eighteen pediatric patients between the ages of 6 and 26 and/or their parents/caregivers participated in the study. Of the 18 patients represented in the sample, 50% were white/Caucasian, and 67% were female. The mean duration of time since symptom onset was 7.1 years. Primary outcomes were measured through standardized questionnaires of emotional, behavioral, and adaptive functioning (BASC-3) and executive functioning (BRIEF2 or BRIEF-A). Secondary outcomes related to family functioning and HRQoL were measured through (PedsQL™ and PedsQL™ Family Impact Module.)
Results:All aggregate T-scores for the BASC and BRIEF placed children with anti-NMDARE within an age-appropriate range regarding behavioral, emotional, adaptive, and executive functioning outcomes. Children with anti-NMDARE were not found to have lower HRQoL compared to their healthy same-age peers. Moreover, parents of children with anti-NMDARE did not endorse a prolonged impact of this illness on family functioning and adjustment.
Conclusions:This study aimed to better understand the neurobehavioral profile and the long-term outcomes of children diagnosed with anti-NMDARE, with the ultimate goal of advancing understanding of this encephalitis. Consistent with findings from several reviewed studies on long-term follow-up, the present study suggests that most children with a history of anti-NMDARE show good functional recovery over time. However, data on the neurobehavioral sequelae, quality of life, and adaptive behavior in patients diagnosed with anti-NMDARE are still sparse, especially at pediatric age. In order to understand and learn to manage the needs of patients with anti-NMDARE, particularly regarding the impact this disease can have on daily life and school performance, additional neuropsychological research involving larger samples, longitudinal studies, and increased methodological consistency is required.
2 Choline as a neurodevelopmental intervention for children with fetal alcohol spectrum disorder: Long-term associations with white matter microstructure and executive function
- Blake A. Gimbel, Mary E. Anthony, Abigail M. Ernst, Donovan J. Roediger, Erik de Water, Judith K. Eckerle, Christopher J. Boys, Joshua P. Radke, Bryon A. Mueller, Anita J. Fuglestad, Steven H. Zeisel, Michael K. Georgieff, Jeffrey R. Wozniak
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 613-614
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Objective:
Fetal alcohol spectrum disorder (FASD) is a life-long condition, and few interventions have been developed to improve the neurodevelopmental course in this population. Early interventions targeting core neurocognitive deficits have the potential to confer long-term neurodevelopmental benefits. Time-targeted choline supplementation is one such intervention that has been shown to provide neurodevelopmental benefits that emerge with age during childhood. We present a long-term follow-up study evaluating the neurodevelopmental effects of early choline supplementation in children with FASD approximately 7 years on average after an initial efficacy trial. In this study, we examine treatment group differences in executive function (EF) outcomes and diffusion MRI of the corpus callosum using the Neurite Orientation Dispersion and Density Index (NODDI) biophysical model.
Participants and Methods:The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2.5- to 5-year-olds with FASD. Participants in this long-term follow-up study included 18 children (9 placebo; 9 choline) seen 7 years on average following initial trial completion. The mean age at follow-up was 11 years old. Diagnoses were 28% fetal alcohol syndrome (FAS), 28% partial FAS, and 44% alcohol-related neurodevelopmental disorder. The follow-up evaluation included measures of executive functioning (WISC-V Picture Span and Digit Span; DKEFS subtests) and diffusion MRI (NODDI).
Results:Children who received choline early in development outperformed those in the placebo group across a majority of EF tasks at long-term follow-up (effect sizes ranged from -0.09 to 1.27). Children in the choline group demonstrated significantly better performance on several tasks of lower-order executive function skills (i.e., DKEFS Color Naming [Cohen's d = 1.27], DKEFS Word Reading [Cohen's d = 1.13]) and showed potentially better white matter microstructure organization (as indicated by lower orientation dispersion; Cohen's d = -1.26) in the splenium of the corpus callosum compared to the placebo group. In addition, when collapsing across treatment groups, higher white matter microstructural organization was associated with better performance on several EF tasks (WISC-V Digit Span; DKEFS Number Sequencing and DKEFS Word Reading).
Conclusions:These findings highlight long-term benefits of choline as a neurodevelopmental intervention for FASD and suggest that changes in white matter organization may represent an important target of choline in this population. Unique to this study is the use of contemporary biophysical modeling of diffusion MRI data in youth with FASD. Findings suggest this neuroimaging approach may be particularly useful for identifying subtle white matter differences in FASD as well as neurobiological responses to early intervention associated with important cognitive functions.
40 Positive and Negative Emotional Outcomes Following Alzheimer’s Disease Biomarker Disclosure in Cognitively Symptomatic Older Adults
- Mary R. Lesniak, Marie Milliken, Sara Feldman, Scott J. Roberts, Benjamin M. Hampstead, Annalise M. Rahman-Filipiak
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 248-249
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Objective:
There are many potential benefits of early identification of those with Alzheimer’s disease (AD), including more opportunity for early intervention to slow AD progression (e.g., treatment, lifestyle changes, etc.) and to plan for the future. Positron emission tomography (PET) scans for abnormal amyloid and tau are commonly conducted in research settings. Despite strong interest in learning AD biomarker results, participants rarely receive their research data, in part due to concern about the possibility of undue distress based on results. We aimed to explore both positive and negative emotional reactions following PET biomarker disclosure as a function of result received.
Participants and Methods:Forty-three older adults (age = 72.0±6.21 years, education = 16.5±2.62 years, 49% Female, 88% White Non-Hispanic) completed PET amyloid and tau testing and disclosure. Sixty-three percent were diagnosed with mild cognitive impairment (MCI) while the remainder of participants were diagnosed with Dementia Alzheimer’s type (DAT). Participants completed pre-disclosure biomarker education and a decisional capacity assessment followed by baseline measures. Participants then completed a disclosure session where they received personal PET amyloid and tau results on an elevated vs. not elevated scale for each ligand. Results were discussed in relation to presence/absence of Alzheimer’s disease, how the result relates to their cognitive difficulties, and risk of developing Dementia-Alzheimer’s Type. At baseline (pre-disclosure), immediately post-disclosure, and 1-week post-disclosure, participants completed the Beck Anxiety Inventory (BAI), The Geriatric Depression Scale - 15 Item (GDS-15), Impact of Neuroimaging in AD (INI-AD) Scale, and the Positive and Negative Affective Scale - Short Form (PANAS-SF). All questionnaires were modified to apply to Alzheimer’s disease and related experiences.
Results:Of the 43 participants who participated in disclosure, 74% received biomarker positive results (either A+T- or A+T+); all others were biomarker negative. We conducted a series of mixed analysis of variance (ANOVA) tests to determine the effect of disclosure and biomarker status for each of the outcomes of interest. Neither the effect of time nor the time by biomarker status interaction was significant for any of the outcomes (all p>.05). The main effect of biomarker status was significant for BAI (F(1)=5.12, p=.031, n,p2=.146) and INI-AD Distress (F(1)=12.70, p=.001, np2=.241) and Positive (F(1)=34.57, p<.001, np2=.464) subscale scores with A+T-/A+T+ participants reporting higher negative affect than those who were A-/T-; however, even among biomarker positive individuals, scores did not exceed clinical thresholds. GDS-15, PANAS-Negative and Positive Subscale scores did not differ significantly by biomarker status (all p>.05) and no significant adverse events occurred following disclosure. Additionally, no participants cited regret about receiving their results.
Conclusions:While disclosure of biomarker positivity may result in mild increases in acute anxiety or distress, or fewer positive emotions, it does not result in clinically significant emotional reactions and was not associated with regret. Overall, findings are consistent with literature indicating safety of biomarker disclosure procedures for symptomatic individuals. Future research should follow participants over longer periods to evaluate the impacts of biomarker disclosure.
3 Stricker Learning Span criterion validity: remote self-administration of a computer adaptive word list memory test shows similar ability to differentiate PET-defined biomarker groups as in-person Rey Auditory Verbal Learning Test performance in cognitively unimpaired individuals on the Alzheimer’s continuum
- Nikki H. Stricker, John L. Stricker, Aimee J. Karstens, Jay S. Patel, Teresa J. Christianson, Winnie Z. Fan, Sabrina M. Albertson, Ryan D. Frank, Mary M. Machulda, Walter K. Kremers, Julie A. Fields, Jonathan Graff-Radford, Clifford R. Jack, Jr, David S. Knopman, Michelle M. Mielke, Ronald C. Petersen
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 407-408
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Objective:
The Stricker Learning Span (SLS) is a computer-adaptive word list memory test specifically designed for remote assessment and self-administration on a web-based multi-device platform (Mayo Test Drive). Given recent evidence suggesting the prominence of learning impairment in preclinical Alzheimer’s disease (AD), the SLS places greater emphasis on learning than delayed memory compared to traditional word list memory tests (see Stricker et al., Neuropsychology in press for review and test details). The primary study aim was to establish criterion validity of the SLS by comparing the ability of the remotely-administered SLS and inperson administered Rey Auditory Verbal Learning Test (AVLT) to differentiate biomarkerdefined groups in cognitively unimpaired (CU) individuals on the Alzheimer’s continuum.
Participants and Methods:Mayo Clinic Study of Aging CU participants (N=319; mean age=71, SD=11; mean education=16, SD=2; 47% female) completed a brief remote cognitive assessment (∼0.5 months from in-person visit). Brain amyloid and brain tau PET scans were available within 3 years. Overlapping groups were formed for 1) those on the Alzheimer’s disease (AD) continuum (A+, n=110) or not (A-, n=209), and for 2) those with biological AD (A+T+, n=43) vs no evidence of AD pathology (A-T-, n=181). Primary neuropsychological outcome variables were sum of trials for both the SLS and AVLT. Secondary outcome variables examined comparability of learning (1-5 total) and delay performances. Linear model ANOVAs were used to investigate biomarker subgroup differences and Hedge’s G effect sizes were derived, with and without adjusting for demographic variables (age, education, sex).
Results:Both SLS and AVLT performances were worse in the biomarker positive relative to biomarker negative groups (unadjusted p’s<.05). Because biomarker positive groups were significantly older than biomarker negative groups, group differences were attenuated after adjusting for demographic variables, but SLS remained significant for A+ vs A- and for A+T+ vs A-T- comparisons (adjusted p’s<.05) and AVLT approached significance (p’s .05-.10). The effect sizes for the SLS were slightly better (qualitatively, no statistical comparison) for separating biomarker-defined CU groups in comparison to AVLT. For A+ vs A- and A+T+ vs A-T- comparisons, unadjusted effect sizes for SLS were -0.53 and -0.81 and for AVLT were -0.47 and -0.61, respectively; adjusted effect sizes for SLS were -0.25 and -0.42 and for AVLT were -0.19 and -0.26, respectively. In secondary analyses, learning and delay variables were similar in terms of ability to separate biomarker groups. For example, unadjusted effect sizes for SLS learning (-.80) was similar to SLS delay (.76), and AVLT learning (-.58) was similar to AVLT 30-minute delay (-.55) for the A+T+ vs AT- comparison.
Conclusions:Remotely administered SLS performed similarly to the in-person-administered AVLT in its ability to separate biomarker-defined groups in CU individuals, providing evidence of criterion validity. The SLS showed significantly worse performance in A+ and A+T+ groups (relative to A- and A-T-groups) in this CU sample after demographic adjustment, suggesting potential sensitivity to detecting transitional cognitive decline in preclinical AD. Measures emphasizing learning should be given equal consideration as measures of delayed memory in AD-focused studies, particularly in the preclinical phase.
34 Specific Agitation Behaviors in Dementia Differentially Contribute to Caregiver Burden
- Karlee S Patrick, John Gunstad, John T Martin, Kimberly R Chapman, Jennifer Drost, Mary Beth Spitznagel
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 242-243
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Objective:
Agitation is a common neuropsychiatric symptom within the dementia spectrum, experienced by 70 percent of individuals with cognitive decline. Prior literature demonstrates a strong association between care recipient agitation and burden in caregivers of individuals with dementia, as these symptoms are often difficult to manage and predict. Understanding how agitation symptoms in the person with dementia may influence caregiver burden is imperative given these strong associations; however, both agitation and burden are complex, multidimensional constructs. Agitation in dementia involves a range of behaviors including increased motor activity, emotional distress, and aggressive behaviors. Caregiver burden is also multi-faceted and often incorporates dimensions of social/relationship, emotional, and physical health strain. The current study sought to determine whether specific presentations of agitation differentially relate to distinct patterns of caregiver burden.
Participants and Methods:Medical record data from an outpatient memory clinic were extracted for 609 persons with dementia and their caregivers. Caregivers completed the Zarit Burden Interview (ZBI) to assess caregiver burden and the Cohen-Mansfield Agitation Inventory (CMAI) to assess care recipient agitation behaviors. At their initial outpatient appointment, care recipients were also administered a measure of global cognitive functioning (either the Montreal Cognitive Assessment or the Mini-Mental State Examination). Demographic information was extracted from medical records. Exploratory factor analysis was used to determine ZBI and CMAI factor structures. Hierarchical multiple regression analyses then examined whether factors of the CMAI differentially predicted ZBI factors, controlling for dementia severity and demographic variables.
Results:Exploratory factor analysis yielded three domains of agitation on the CMAI ("Physically Aggressive," "Physically NonAggressive," "Verbally Agitated") and four domains of burden on the ZBI ("Impact on Life," "Guilt/Uncertainty," "Embarrassed/Frustrated," and "Overwhelm"). Regression analyses demonstrated all domains of agitation positively predicted overall burden. Regarding specific aspects of burden, Physically Aggressive behaviors predicted only Embarrassment/Frustration (B=.41, SE=.10, ß=.16, p<.001). Non-Aggressive behaviors predicted Impact on Life (B=.14, SE=.05, ß=.13, p<.01) and Guilt/Uncertainty (B=.05, SE=.02, ß=.10, p<.05). Verbally Agitated behaviors predicted all burden dimensions: Impact on Life (B=.35, SE=.06, ß=.32, p<.001), Guilt/Uncertainty (B=.12, SE=.03, ß=.22, p<.001), Embarrassment/Frustration (B=.17, SE=.02, ß=.38, p<.001), and Overwhelm (B=.16, SE=.02, ß=.40, p<.001).
Conclusions:Findings enhance understanding of the relationships between specific agitation symptoms and distinctive aspects of caregiver burden, suggesting that targeted interventions for aspects of caregiver burden based on agitation symptoms may be useful in alleviating burden. Interventions focused on caregivers' feelings of guilt, personal health decline, lack of time for themselves, and fear and uncertainty about the future may be effective when care recipients present with physically nonaggressive behaviors (e.g., pacing, restlessness, inappropriate dress or disrobing). When a care recipient presents with physically aggressive behaviors, helping the caregiver cope with embarrassment or anger may be of benefit. When a care recipient presents with verbally agitated behaviors, interventions targeting burden globally may be most useful. Future work should seek to replicate the current findings and explore such interventions.
1 Associations of Locus of Control and Memory Self-Awareness in Older Adults with and without MCI
- Mary E Garcia, Jeanine M Parisi, Sarah Cook, Ian McDonough, Alexandra J Weigand, Alexandra L Clark, Michael Marsiske, Kelsey R Thomas
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 676-677
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Objective:
While loss of insight into one’s cognitive impairment (anosognosia) is a feature in Alzheimer’s disease dementia, less is known about memory self-awareness in cognitively unimpaired (CU) older adults or mild cognitive impairment (MCI) or factors that may impact self-awareness. Locus of control, specifically external locus of control, has been linked to worse cognitive/health outcomes, though little work has examined locus of control as it relates to self-awareness of memory functioning or across cognitive impairment status. Therefore, we examined associations between locus of control and memory self-awareness and whether MCI status impacted these associations.
Participants and Methods:Participants from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study (mean age=73.51; 76% women; 26% Black/African American) were classified as CU (n=2177) or MCI (amnestic n=313; non-amnestic n=170) using Neuropsychological Criteria. A memory composite score measured objective memory performance and the Memory Functioning Questionnaire measured subjective memory. Memory self-awareness was defined as objective memory minus subjective memory, with positive values indicating overreporting of memory difficulties relative to actual performance (hypernosognosia) and negative values indicating underreporting (hyponosognosia). Internal (i.e., personal skills/attributes dictate life events) and external (i.e., environment/others dictate life events) locus of control scores came from the Personality in Intellectual Aging Contexts Inventory. General linear models, adjusting for age, education, sex/gender, depressive symptoms, general health, and vocabulary examined the effects of internal and external locus of control on memory self-awareness and whether MCI status moderated these associations.
Results:Amnestic and non-amnestic MCI participants reported lower internal and higher external locus of control than CU participants. There was a main effect of MCI status on memory self-awareness such that amnestic MCI participants showed the greatest degree of hyponosognosia/underreporting, followed by non-amnestic MCI, and CU participants slightly overreported their memory difficulties. While, on average, participants were fairly accurate at reporting their degree of memory difficulty, internal locus of control was negatively associated with self-awareness such that higher internal locus of control was associated with greater underreporting (ß=-.127, 95% CI [-.164, -.089], p<.001). MCI status did not moderate this association. External locus of control was positively associated with self-awareness such that higher external locus of control was associated with greater hypernosonosia/overreporting (ß=.259, 95% CI [.218, .300], p<.001). Relative to CU, amnestic, but not non-amnestic, MCI showed a stronger association between external locus of control and memory self-awareness. Specifically, higher external locus of control was associated with less underreporting of cognitive difficulties in amnestic MCI (ß=.107, 95% CI [.006, .208], p=.038).
Conclusions:In CU participants, higher external locus of control was associated with greater hypernosognosia/overreporting. In amnestic MCI, the lower external locus of control associations with greater underreporting of objective cognitive difficulties suggests that perhaps reduced insight in some people with MCI may result in not realizing the need for external supports, and therefore not asking for help from others. Alternatively, in amnestic participants with greater external locus of control, perhaps the environmental cues/feedback translate to greater accuracy in their memory self-perceptions. Longitudinal analyses are needed to determine how memory self-awareness is related to future cognitive declines.
1 Sluggish Cognitive Tempo in Children and Adolescents with Fetal Alcohol Spectrum Disorders: Associations with Executive Function and Subcortical Volumes
- Abigail M Ernst, Blake A Gimbel, Mary E Anthony, Donovan J Roediger, Erik de Water, Bryon A Mueller, Sarah N Mattson, Kelvin O Lim, Jeffrey R Wozniak
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 612-613
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Objective:
Fetal alcohol spectrum disorder (FASD) is a common neurodevelopmental condition associated with deficits in cognitive functioning (executive functioning [EF], attention, working memory, etc.), behavioral impairments, and abnormalities in brain structure including cortical and subcortical volumes. Rates of comorbid attention-deficit/hyperactivity disorder (ADHD) are high in children with FASD and contribute to significant functional impairments. Sluggish cognitive tempo (SCT) includes a cluster of symptoms (e.g. underactive/slow-moving, confusion, fogginess, daydreaming) found to be related to but distinct from ADHD, and previous research suggests that it may be common in FASD. We explored SCT by examining the relationship between SCT and both brain volumes (corpus callosum, caudate, and hippocampus) and objective EF measures in children with FASD vs. typically developing controls.
Participants and Methods:This is a secondary analysis of a larger longitudinal CIFASD study that consisted of 35 children with prenatal alcohol exposure (PAE) and 30 controls between the ages of 9 to 18 at follow-up. Children completed a set of cognitive assessments (WISC-IV, DKEFS, & NIH Toolbox) and an MRI scan, while parents completed the Child Behavior Checklist (CBCL), which includes a SCT scale. We examined group differences between PAE and controls in relation to SCT symptoms, EF scores, and subcortical volumes. Then, we performed within-and between-group comparisons with and without controlling for total intracranial volume, age, attention problems, and ADHD problems between SCT and subcortical brain volumes. Finally, we performed correlations between SCT and EF measures for both groups.
Results:Compared to controls, participants with PAE showed significantly more SCT symptoms on the CBCL (t [57] = 3.66, p = 0.0006), more parent-rated attention problems and ADHD symptoms, lower scores across several EF measures (DKEFS Trail-Making and Verbal Fluency; WISC-IV Digit Span, Symbol Search, and Coding; effect sizes ranging from 0.44 to 1.16), and smaller regional volumes in the caudate, hippocampus, and posterior areas of the corpus callosum. In the PAE group, a smaller hippocampus was associated with more SCT symptoms (controlling for parent-rated attention problems and ADHD problems, age, and intracranial volume). However, in the control group, a larger mid posterior and posterior corpus callosum were significantly associated with more SCT symptoms (controlling for parent-rated attention problems, intracranial volume, and age; r [24] = 0.499, p = 0.009; r [24] = 0.517, p = 0.007). In terms of executive functioning, children in the PAE group with more SCT symptoms performed worse on letter sequencing of the Trail-Making subtest (controlling attention problems & ADHD symptoms). In comparison, those in the control group with more SCT symptoms performed better on letter sequencing and combined number letter sequencing of the Trail-Making subtest (controlling attention problems).
Conclusions:Findings suggest that children with FASD experience elevated SCT symptoms compared to typically developing controls, which may be associated with worse performance on EF tasks and smaller subcortical volumes (hippocampus) when taking attention difficulties and ADHD symptoms into account. Additional research into the underlying causes and correlates of SCT in FASD could result in improved tailoring of interventions for this population.
65 Mayo Test Drive raw composite criterion validity: a brief remote self-administered digital cognitive composite shows similar ability to differentiate PET-defined biomarker groups as a global composite from a person-administered neuropsychological battery in cognitively unimpaired individuals on the Alzheimer’s continuum
- Nikki H. Stricker, Aimee J. Karstens, Teresa J. Christianson, John L. Stricker, Winnie Z. Fan, Sabrina M. Albertson, Ryan D. Frank, Mary M. Machulda, Walter K. Kremers, Jason Hassenstab, Julie A. Fields, Jonathan Graff-Radford, Clifford R. Jack, Jr., David S. Knopman, Michelle M. Mielke, Ronald C. Petersen
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 371-372
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Objective:
Mayo Test Drive (MTD): Test Development through Rapid Iteration, Validation and Expansion, is a web-based multi-device (smartphone, tablet, personal computer) platform optimized for remote self-administered cognitive assessment that includes a computer-adaptive word list memory test (Stricker Learning Span; SLS; Stricker et al., 2022; Stricker et al., in press) and a measure of processing speed (Symbols Test: Wilks et al., 2021). Study aims were to determine criterion validity of MTD by comparing the ability of the MTD raw composite and in-person administered cognitive measures to differentiate biomarkerdefined groups in cognitively unimpaired (CU) individuals on the Alzheimer’s continuum.
Participants and Methods:Mayo Clinic Study of Aging CU participants (N=319; mean age=71, SD=11, range=37-94; mean education=16, SD=2, range=6-20; 47% female) completed a brief remote cognitive assessment (∼0.5 months from in-person visit). Brain amyloid and brain tau PET scans were available within 3 years. Overlapping groups were formed for 1) those on the Alzheimer’s disease (AD) continuum (A+, n=110) or not (A-, n=209), and for 2) those with biological AD (A+T+, n=43) or with no evidence of AD pathology (A-T-, n=181). Primary outcome variables were MTD raw composite (SLS sum of trials + an accuracy-weighted Symbols response time measure), Global-z (average of 9 in-person neuropsychological measures) and an in-person screening measure (Kokmen Short Test of Mental Status, STMS; which is like the MMSE). Linear model ANOVAs were used to investigate biomarker subgroup differences and Hedge’s G effect sizes were derived, with and without adjusting for demographic variables (age, education, sex).
Results:Remotely administered MTD raw composite showed comparable to slightly larger effect sizes compared to Global-z. Unadjusted effect sizes for MTD raw composite for differentiating A+ vs. A- and A+T+ vs. A-T- groups, respectively, were -0.57 and -0.84 and effect sizes for Global-z were -0.54 and -0.73 (all p’s<.05). Because biomarker positive groups were significantly older than biomarker negative groups, group differences were attenuated after adjusting for demographic variables, but MTD raw composite remained significant for A+T+ vs A-T- (adjusted effect size -0.35, p=.007); Global-z did not reach significance for A+T+ vs A-T- (adjusted effect size -0.19, p=.08). Neither composite reached significance for adjusted analyses for the A+ vs A- comparison (MTD raw composite adjusted effect size= -.22, p=.06; Global-z adjusted effect size= -.08, p=.47). Results were the same for an alternative MTD composite using traditional z-score averaging methods, but the raw score method is preferred for comparability to other screening measures. The STMS screening measure did not differentiate biomarker groups in any analyses (unadjusted and adjusted p’s>.05; d’s -0.23 to 0.05).
Conclusions:Remotely administered MTD raw composite shows at least similar ability to separate biomarker-defined groups in CU individuals as a Global-z for person-administered measures within a neuropsychological battery, providing evidence of criterion validity. Both the MTD raw composite and Global-z showed greater ability to separate biomarker positive from negative CU groups compared to a typical screening measure (STMS) that was unable to differentiate these groups. MTD may be useful as a screening measure to aid early detection of Alzheimer’s pathological changes.
36 Lexical Frequency and Semantic Fluency Performances in Cognitively Normal APOEε4 Carriers
- Lauren Latham, Bonnie Sachs, James R Bateman, Mary Jo Cleveland, Samantha Rogers, Benjamin Williams, Mia Yang, Suzanne Craft
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 244-245
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Objective:
There is a pressing need for sensitive, non-invasive indicators of cognitive impairment in those at risk for Alzheimer’s disease (AD). One group at an increased risk for AD is APOEε4 carriers. One study found that cognitively normal APOEε4 carriers are less likely to produce low frequency (i.e., less common) words on semantic fluency tasks relative to non-carriers, but this finding has not yet been replicated. This study aims to replicate these findings within the Wake Forest ADRC clinical core population, and examine whether these findings extend to additional semantic fluency tasks.
Participants and Methods:This sample includes 221 APOEε4 non-carriers (165 females, 56 males; 190 White, 28 Black/African American, 3 Asian; Mage = 69.55) and 79 APOEε4 carriers (59 females, 20 males; 58 White, 20 Black/African American, 1 Asian; Mage = 65.52) who had been adjudicated as cognitively normal at baseline. Semantic fluency data for both the animal task and vegetable task was scored for total number of items as well as mean lexical frequency (attained via the SUBTLEXus database). Demographic variables and additional cognitive variables (MMSE, MoCA, AMNART scores) were also included from the participants’ baseline visit.
Results:APOEε4 carriers and non-carriers did not differ on years of education, AMNART scores, or gender (ps > 0.05). APOEε4 carriers were slightly younger and included more Black/African American participants (ps < 0.05). Stepwise linear regression was used to determine the variance in total fluency score and mean lexical frequency accounted for by APOEε4 status after including relevant demographic variables (age, sex, race, years of education, and AMNART score). As expected, demographic variables accounted for significant variance in total fluency score (p < 0.0001). Age accounted for significant variance in total fluency score for both the animal task (ß = -0.32, p <0.0001) and the vegetable task (ß = -0.29, p < 0.0001), but interestingly, not the lexical frequency of words produced. After accounting for demographic variables, APOEε4 status did not account for additional variance in lexical frequency for either fluency task (ps > 0.05). Interestingly, APOEε4 status was a significant predictor of total words for the vegetable semantic fluency task only (ß = 0.13, p = 0.01), resulting in a model that accounted for more variance (R2 = 0.25, F(6, 292) = 16.11, p < 0.0001) in total words than demographic variables alone (R2 = 0.23, F(5, 293) = 17.75, p < 0.0001).
Conclusions:Unsurprisingly, we found that age, AMNART, and education were significant predictors of total word fluency. One unexpected finding was that age did not predict the lexical frequency - that is - regardless of age, participants tended to retrieve words of the same lexical frequency, which stands in contrast to the notion that retrieval efficiency of infrequent words declines with age. With regard to APOEε4, we did not replicate existing work demonstrating differences in lexical frequency and semantic fluency tasks for ε4 carriers and non-carriers; possibly due to differences in the demographic characteristics of the sample.