Controlled Oral Word Association Test Research Articles

The impact of incident stroke on cognitive trajectories in later life

BackgroundCognitive impairment is common after stroke, and a large proportion of stroke patients will develop dementia. However, there have been few large prospective studies which have assessed cognition both prior to and after stroke. This study aims to determine the extent to which incident stroke impacts different domains of cognitive function in a longitudinal cohort of older community-dwelling individuals.Methods19,114 older individuals without cardiovascular disease or major cognitive impairment were recruited and followed over a maximum 11 years. Stroke included ischaemic and haemorrhagic stroke and was adjudicated by experts. Cognitive function was assessed regularly using Modified Mini-Mental State Examination (3MS), Hopkins Verbal Learning Test–Revised (HVLT-R), Symbol Digit Modalities Test (SDMT), and Controlled Oral Word Association Test (COWAT). Linear mixed models were used to investigate the change in cognition at the time of stroke and decline in cognitive trajectories following incident stroke.ResultsDuring a median follow-up period of 8.4 [IQR: 7.2, 9.6] years, 815 (4.3%) participants experienced a stroke. Over this time, there was a general decline observed in 3MS, HVLT-R delayed recall, and SDMT scores across participants. However, for individuals who experienced a stroke, there was a significantly greater decline across all cognitive domains immediately after the event immediately after the event (3MS: -1.03 [95%CI: -1.45, -0.60]; HVLT-R: -0.47 [-0.70, -0.24]; SDMT: -2.82 [-3.57, -2.08]; COWAT: -0.67 [-1.04, -0.29]) and a steeper long-term decline for three of these domains (3MS -0.62 [-0.88, -0.35]; COWAT: -0.30 [-0.46, -0.14]); HVLT-R: -0.12 [95%CI, -0.70, -0.24]). However individuals with stroke experienced no longer-term decline in SDMT compared to the rest of the participants.ConclusionsThese findings highlight the need for comprehensive neuropsychology assessments for ongoing monitoring of cognition following incident stroke; and potential early intervention.

Association between Multiple Trace Elements, Executive Function, and Cognitive Impairment with No Dementia in Older Adults.

Many studies suggest a significant association between individual essential trace elements (ETEs) and cognitive impairment in older adults, but evidence of the synchronized effect of multiple ETEs on cognitive function is lacking. We investigated the association between multiple ETEs, cognitive impairment with no dementia (CIND), and executive function in older Korean adults, using the Bayesian kernel machine regression (BKMR) model. Three hundred and thirty-six older adults were included as the study population and classified as the CIND and control groups. Blood manganese (Mn), copper (Cu), zinc (Zn), selenium (Se), and molybdenum (Mo) were measured as relevant ETEs. The frontal/executive tests included digit symbol coding (DSC), the Korean color word Stroop test (K-CWST), a controlled oral word association test (COWAT), and a trial-making test (TMT). Overall, the BKMR showed a negative association between multiple ETEs and the odds of CIND. Mn was designated as the most dominant element associated with the CIND (PIP = 0.6184), with a U-shaped relationship. Cu and Se levels were positively associated with the K-CWST percentiles (β = 31.78; 95% CI: 13.51, 50.06) and DSC percentiles (β = 25.10; 95% CI: 7.66, 42.53), respectively. Our results suggest that exposure to multiple ETEs may be linked to a protective mechanism against cognitive impairment in older adults.

Language impairments in seropositive and seronegative autoimmune encephalitis.

Autoimmune encephalitis (AE) is a rare neuroinflammatory disease affecting the central nervous system. To examine language functions in patients with different subsets of AE consisting of seropositive and seronegative groups. Fifty-two patients were recruited from neurology departments in Melbourne, Australia, who met clinical criteria for possible AE. Language tests include the Naming Test from the Sydney Language Battery (SydBat), the semantic fluency trial from the Controlled Oral Word Association Test (COWAT), and the Vocabulary and Similarities subtests of the Weschler Abbreviated Scale of Intelligence-Second Edition. The results were standardised with normative data. The mean age of our cohort was 52.5years old, with the average time from hospital admission to recruitment being 38.41months. At an aggregate level, none of the mean language test z-scores were below normative data. At the patient level, impairment rates were 18.37% for COWAT (animals), 28.57% for SydBat (naming), 4.65% for Similarities, and 4.55% for Vocabulary. Chi-squared goodness of fit tests indicated that observed performances were significantly below expected performances for the SydBat (naming) test (p < 0.0001) and COWAT (animals) (p = 0.004). While, on average, language functions were within normal limits in patients with AE, but a subgroup exhibited lower performance in semantic fluency and visual confrontation naming, with impairment rates below expected norms. To advance understanding of language in chronic AE patients, exploring the impact of seizure burden, antiseizure medication use, and the relationship of language functions with other cognitive functions is crucial.

Neurocognitive Outcomes over the First 3 Months after Chimeric Antigen Receptor T-Cell (CAR T) Therapy: Preliminary Findings from a Longitudinal Study

Introduction People treated with systemic therapies for cancer may exhibit changes in neurocognitive functioning over time, affecting domains such as memory, processing speed, and executive functioning. There is a need for prospective data regarding neurocognitive outcomes among patients treated with Chimeric Antigen Receptor T-Cell (CAR T) therapy. The purpose of this study was to investigate the trajectory of neurocognitive performance and self-reported cognitive functioning over the first 3 months of CAR T therapy. Methods As part of a larger cohort study of patients treated with CAR T, neurocognitive outcomes were assessed prior to starting CAR T and again at 1- and 3- months post-CAR T. Neurocognitive performance was measured using standardized neuropsychological tests including measures of verbal memory (Hopkins Verbal Learning Test-Revised (HVLT-R) - immediate recall, delayed recall, retention), processing speed (Trail-making Test - Part A (TMT-A)) and executive functioning (Trail-making Test Part B (TMT-B), Controlled Oral Word Association Test (COWAT)). Raw test scores were converted to z-scores (Mean 0, SD 1) based on norms adjusted for age, sex, and education, where applicable. Impairment on individual tests was defined by a z score ≤ -1.64. Participants were categorized as showing overall impairment if they had at least two tests with a z-score of ≤ -1.5 or a z-score ≤ -2.0 on one test. Self-reported cognitive functioning was measured using the Functional Assessment of Cancer Therapy - Cognition, Perceived Cognitive Impairment score (FACT-Cog3 PCI) and the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire C-30, Cognitive Functioning scale (EORTC QLQ-C30 CF). Demographic and clinical data were collected through self-report and patient records. Frequencies of impairment were determined at each time point, with clinically significant changes on individual test scores in the first month determined based on z-score changes of ≥1.0 or minimal clinically important differences for self-report questionnaires. Linear mixed models were generated to estimate the trajectory of neurocognitive performance and self-reported cognitive functioning over time from baseline to 3 months. Results Neurocognitive outcomes were available for 37 participants at baseline, with follow-up data available for 29 patients at 1 month and 17 patients at 3 months. Participants were 54% male, had a mean age 58.4 years (sd 11.3) and a mean 15.5 years (sd 3.2) education. All patients had a diagnosis of non-Hodgkin lymphoma (53% diffuse large B-cell lymphoma (DLBCL), 31% transformed DLBCL from follicular lymphoma). Immune effector cell-associated neurotoxicity syndrome (ICANS) affected 32% of patients (5% Grade 4, 3% Grade 3, 8% Grade 2, 16% Grade 1). Cytokine release syndrome (CRS) affected 97% of patients (3% Grade 3, 76% Grade 2, 19% Grade 1). Frequency of overall impairment at each time point was 10/37 (27%) at baseline, 12/29 (41.4%) at 1 month, and 3/17 (17.6%) at 3 months. At each time point, impairment was most common on tests of executive functioning and memory. Based on individual test score changes between baseline and 1 month, rates of decline on individual tests of neurocognitive performance ranged from 11.5% (TMT-A) to 34.6% (COWAT). Decline on self-reported cognitive functioning was observed for 14.3% (FACT-Cog PCI) and 28.6% (EORTC QLQ-C30 CF) of participants. Based on mixed models (Table 1), there was a statistically significant decline in estimated mean z-scores on a test of executive function (COWAT: -0.52, 95% CI -0.89-(-0.16), p=0.007) at 1-month compared to baseline. At three months, there was a statistically significant improvement in estimated mean z-scores on memory (HVLT-R immediate recall: 0.56, 95% CI 0.11-1.01, p=0.017) and executive functioning (TMT-B: 0.87, 95% CI 0.17-1.57, p=0.019; COWAT: 0.68, 95% CI 0.19-1.16, p=0.009) compared to baseline. Conclusions Impairment is present in a subgroup of patients prior to starting CAR T therapy. Patients may demonstrate declines on performance-based measures and report worsening cognitive symptoms in the first month after CAR T therapy, but also improved performance in some domains by three months. Enrollment and long-term follow-up of patients in this study is ongoing. Future analyses will explore differences in trajectories among subgroups, such as those who have experienced ICANS and CRS.

Rationale and design of a randomized clinical trial evaluating the efficacy of mechanical neuroprotection in reducing the risk of silent brain infarcts associated with percutaneous left atrial appendage closure: study protocol for a LAAC-SBI trial

BackgroundLeft atrial appendage closure (LAAC) procedures prevent cardioembolic stroke in patients with atrial fibrillation who have contraindications to oral anticoagulant medications. However, these procedures carry certain risks of peri-procedural complications. One such complication is silent brain infarcts (SBI), which can lead to cognitive impairment and mood disturbances. The implementation of mechanical neuroprotection systems during LAAC procedures may reduce the risk of SBI and associated cognitive and mood disorders.MethodsThe LAAC-SBI trial is a prospective, multicenter, randomized, and double-blind interventional study. The study aims to enroll a total of 240 patients, with 120 patients allocated to each group. The study group will evaluate the use of the Sentinel CPS during LAAC, while the control group will undergo LAAC procedures without the Sentinel CPS. The primary endpoint of the study is the number of new SBIs or stroke foci detected by diffusion-weighted magnetic resonance imaging (DW MRI). Secondary endpoints include deterioration of cognitive function, development of dementia syndrome, and occurrence of depressive disorders. These endpoints will be assessed using questionnaire tools such as the Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT), Controlled Oral Word Association Test (COWAT), and Hospital Anxiety and Depression Scale (HADS). The observational period for patients in the study is 2 years.DiscussionIf the study demonstrates a favorable outcome with reduced incidence of SBI and improved cognitive and mood outcomes in patients receiving cerebral protection devices during LAAC, it will have significant implications for clinical management standards. This would support the use of neuroprotection devices not only for LAAC but also in procedures such as atrial fibrillation ablation or transcatheter mitral valve interventions, where the risk of embolic events and subsequent brain injury may also be present.Trial registrationClinicalTrials.gov NCT05369195. Registration on 11.05.2022.

Influence of Nutritional Status and Physical Fitness on Cognitive Domains among Older Adults: A Cross-Sectional Study.

The health issues presented by the aging population can result in reduced muscle mass, poorer physical function, and cognitive impairment. The goal of this study was to determine how nutritional status and physical fitness relate to cognitive impairment in older adults. A cross-sectional descriptive and analytical study involving 100 participants was carried out to analyze the impact of nutritional status and physical fitness on cognitive impairment. Nutritional status was assessed with the Eating Assessment Tool (EAT-10) and The Mini Nutritional Assessment-Short Form (MNA-SF); physical fitness via the implementation of manual grip evaluation, the 4-m walking test (4-MWT), and the Timed Up and Go (TUG) test; and cognitive impairment evaluation was conducted using the Mini-Mental State Examination (MMSE), the Boston Naming Test (BNT) and the Controlled Oral Word Association Test (COWAT). Data analysis revealed that higher malnutrition status was associated with fewer correct responses in the COWAT (R2 = 0.421), while a correlation between higher MMSE and BNT scores, faster completion times for the 4-m walking and TUG tests, and an increase in handgrip strength load was also observed. The analysis of the data revealed that those individuals with superior nutritional status and greater levels of physical fitness outperformed others on the cognitive evaluation.

5 Large-Scale Network Connectivity and Cognitive Function after Exercise Training in Older Adults

Objective:Despite growing evidence regarding the association between exercise training (ET) and functional brain connectivity, little is known about the effects of ET on within- and between-network functional connectivity (FC) of core brain networks. We investigated the effects of ET on within- and between-network functional connectivity of the default mode network (DMN), frontoparietal network (FPN), and salience network (SAL) in older adults with intact cognition (CN) and older adults diagnosed with mild cognitive impairment (MCI). We further examined whether the ET-induced changes in FC were associated with changes in cognitive performance.Participants and Methods:33 older adults (78.0±7.0 years; 16 MCI and 17 CN) participated in the present study. Before and after a 12-week walking ET intervention, participants underwent cardiorespiratory fitness tests, the Controlled Oral Word Association Test (COWAT), the Rey Auditory Verbal Learning test (RAVLT), a narrative memory test (logical memory; LM), and a resting-state fMRI scan. We examined the within- and between-network connectivity of the DMN, FPN, and SAL before and after ET. We also used linear regression to examine associations between ET-related changes in the within- and between-network connectivity and cognitive function.Results:There were significant improvements in VO2peak, COWAT, RAVLT, and LM after ET across participants. Significant increases in within-network connectivity of the DMN and SAL were observed in response to ET across participants. FC between the DMN-FPN, DMN-SAL, and FPN-SAL were also increased after ET. Moreover, greater SAL within connectivity and FPN-SAL between connectivity were associated with enhanced LM immediate recall performance after ET. There were no significant interactions between Time (before vs after ET) and Group (CN vs MCI) for network connectivity or cognitive function.Conclusions:Our findings suggest that increased within- and between-network connectivity following 12-weeks of walking exercise may subserve improvements in memory performance in older individuals with intact cognition and in those diagnosed with MCI.

19 Accuracy of Self- and Informant-Reported Domain-Specific Cognitive Ratings

Objective:Diagnostic criteria for mild cognitive impairment (MCI) include a report of cognitive decline from the patient or a close informant. It is therefore important to understand the relationship between self- and informant-rated cognition and actual patient performance. Furthermore, it is unknown whether the nature of the relationship between the patient and their informant impacts accuracy of subjective reports. This study aimed to determine the association between informant report, self-report and objective cognitive performance based on relationship factors. We predicted that informant report would be more closely associated with objective performance than self-report after controlling for demographics and mood (Geriatric Depression Scale [mean= 1.4, SD=2]), especially among those who live with the participant and those who are spouses/partners.Participants and Methods:Participants (n = 338; age= 73.5 ±6.7) of varying diagnoses and their respective informants were drawn from the longitudinal cohort of the Michigan Alzheimer’s Disease Research Center (MADRC). The majority of informants were spouses/significant others (55.6%), followed by 23.7% being other family members and 20.7% were non- family members; 58.9% of informants live with the participant. Both respondents completed the Cognitive Change Index (CCI) to rate the patient’s cognitive status (higher scores indicating worsening cognition) across three domains: memory (12 questions), language (1 question), and attention/executive functioning (7 questions). These domains were matched to objective cognitive performance measured using the MADRC neuropsychological battery. Executive functioning and attention were assessed using Number Span Test Forward and Backward (NSF, NSB) and Trail Making Test Part B and Trail- Making Test Part A and B ratio (TMTB, TMTB: A); memory was measured using Craft Story 21 (Immediate and Delayed), Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall, Delayed Recall, and Benson Complex Figure (BCF) Delayed Recall; and Language was measured by the Controlled Oral Word Association Test (COWAT) and Animal fluency.Results:Linear regression adjusted for sex, race, and mood indicated that both patient and informant CCI ratings were significantly (p&lt;.05) associated with objective cognitive performance. For every one unit increase on executive CCI items, there was a significant decline in executive functioning (NSF patient and informant ß= -0.09, NSB: [ßP= -.14; ßp-0.13]) and TMTB [ßP= 3.85; ß= 3.10 [% change]). Memory performance also declined per unit increase on CCI memory items: (Craft Story 21 Immediate [ßP=-0.32; ß= -0.37] and Delayed [ßP=-.40; ßp -.47], HVLT-R Total Recall [ßP= -.31; ßI=-.37] and Delayed Recall [ßP= -.16; ß=-.20], and BCF Delayed Recall [ßP= -.18; ß= -.23]. Similarly, one unit increase on the single CCI language item was associated with a decline in COWAT (ßP= -2.27; ß= -4.61) and Animal fluency (ßP= -1.88; ß= -3.03). Effect modification by participant-informant relationship type or participant-informant cohabitation was not significant.Conclusions:Patient and informant ratings are associated with objective measures of cognition regardless of the relationship between informant and patient or if they live together. This study was limited by a well-educated sample (mean= 16.1 years of education, SD= 2.4 years) with relatively limited diversity among participant-informant relationships. Future studies should replicate analyses across a larger and more diverse sample.

6 Depressive Symptoms are Associated With Decline Over Time in Verbal Fluency Performance in Female but not Male Community-Dwelling Older Adults

Objective:Late-life depression is prevalent among older adults and the presence of depressive symptoms has been shown to be associated cross-sectionally with worse verbal fluency performance. There is limited and mixed evidence as to whether depressive symptoms impact change in verbal fluency performance over time, and whether gender impacts this relationship.Participants and Methods:Participants were community-dwelling older adults who were dementia-free at baseline (N = 522; M age = 75.96, SD + 6.46 years). Baseline depressive symptoms were measured using the Geriatric Depression Scale. Category fluency and letter fluency performance, using the Controlled Oral Word Association Test (COWAT), were examined annually. Linear mixed effects models stratified by gender examined whether associations between baseline depressive symptoms and changes in fluency performance over five years were different in female (n = 289) as compared to male (n = 233) participants. Sensitivity analyses excluding participants with prevalent or incident mild cognitive impairment (MCI) (n = 141), excluding participants with incident dementia (n = 28), and excluding participants with prevalent or incident MCI or incident dementia (n = 169) were run. All analyses were adjusted for age, years of education, estimated premorbid functioning, and health comorbidities.Results:Depression was minimal across participants (m = 4.72, SD + 3.96). A subset of participants (n = 44) reported “possible depression,” namely levels suggestive of subclinical depression, according to clinical cutoffs. The “possible depression” group included 31 females (10.73% of females) and 13 males (5.58% of males), and the “no depression” group included 258 females (89.27% of females) and 220 males (94.42% of males). Baseline levels of depressive symptoms suggestive of subclinical depression were associated with worse decline in category fluency performance during longitudinal follow-up in females (estimate = -0.16, p = .002) but not males (estimate = -0.03, p = .658). Results remained the same when excluding prevalent and incident MCI cases (estimate = -0.19, p = .005), excluding incident dementia cases (estimate = -0.12, p = .017), and excluding prevalent and incident MCI and incident dementia cases (estimate = -0.20, p = .004). Letter fluency performance did not decline over time and was not influenced by levels of depressive symptoms in females (estimate = -0.03, p = .502) or males (estimate = 0.05, p = .452).Conclusions:Baseline presence of depressive symptoms suggestive of subclinical depression was associated with worse decline in category fluency performance during longitudinal follow-up in female but not male participants. Letter fluency performance did not decline and was not impacted by levels of depressive symptoms. Results remained significant when accounting for covariates and potential confounders. The present study elucidated the combined influence of gender and depressive symptoms on change in fluency performance in older adults and can aid in identifying individuals who may be at a greater risk of cognitive decline.

34 The Influence of Bilingualism in Young Adults

Objective:The research examining the influence of bilingualism on cognition continues to grow. Past research shows that monolingual speakers outperformed bilingual speakers on language, memory, and attention and processing speed tasks. However, the opposite has been found favoring bilingual speakers, when comparing executive functioning abilities. Furthermore, researchers have reported that no differences in executive functioning abilities exist between young adult monolingual speakers compared to young adult bilingual speakers. Moreover, limited research exists examining cognition abilities between monolinguals, bilinguals that learn a language (e.g., English) first, and bilinguals that learn the same language (e.g., English) second. We examined young adult monolinguals cognition abilities (e.g., memory) compared to young adult bilinguals that learned English as a first or second language. It was expected that the monolingual group would outperform both bilingual groups on memory, language, and attention and processing tasks, but no differences would be found on executive functioning tasks.Participants and Methods:The sample consisted of 149 right-handed undergraduate students with a mean age of 19.58 (SD = 1.90). Participants were neurologically and psychologically healthy and divided into three language groups: English first language (EFL) monolingual speakers, EFL bilingual speakers, and English second language (ESL) bilingual speakers. All the participants completed a background questionnaire and comprehensive neuropsychological battery that included memory, language, executive functioning, and attention and processing speed tasks in English. A series of ANOVA’s were used to evaluate cognitive tasks (e.g., Boston Naming Test, Trail Making Test) between the language groups. Participants demonstrated adequate effort on one performance validity test.Results:Language groups were well demographically matched. We found the EFL monolingual group outperformed the ESL bilingual group on the Wide Range Achievement Test, fourth edition task and the Controlled Oral Word Association Test (COWAT) phonemic task, p’s &lt; .05, np’s2 = .04-.05. Additionally, results revealed both monolingual groups outperformed the ESL bilingual group on the Wechsler Adult Intelligence Scale, Third edition vocabulary task and the Boston Naming Test, p’s &lt; .05, np’s2 = .06-.15. No significant differences were found on any of the cognitive tasks between the EFL monolingual group and the EFL bilingual group.Conclusions:As expected, the ESL bilingual group performed worse on language tasks compared to both monolingual groups, specifically the EFL monolingual group. However, in the opposite direction, we found the EFL monolingual demonstrated better phonemic verbal fluency abilities on the COWAT compared to the ESL bilingual group. The current data suggest that bilingualism influences cognitive abilities (e.g., language, executive functioning) more ESL bilingual speakers compared to EFL monolingual speakers. A possible explanation may be due to the type of interaction that ESL bilingual speakers may prefer to have (i.e., mix language conversations) compared to EFL speaking groups. Future studies with a larger bilingual speaking sample should investigate if the Adaptive Control Hypothesis which suggest that different types of conversations may be placing different demands of language control influences cognitive abilities.

86 The Examination Between Credible and Non-Credible Groups on Embedded PVT Tests

Objective:Performance validity tests (PVTs) are included in neuropsychological testing to ensure examinees are performing to the best of their abilities. There are two types of PVTs: embedded and free standing. Embedded PVTs are tests that are derived from standard neuropsychological tests of various cognitive domains. Freestanding PVTs are tests that are designed with the intention of being a PVT. Research studies show that undergraduate samples do not always performed to the best of their abilities. The purpose of this study was to cross-validate previous research on the topic of performance validity in a college sample. It was predicted that the non-credible group would demonstrate higher failure rates on embedded PVTs compared to the credible group.Participants and Methods:The sample consisted of 198 neurologically and psychologically healthy undergraduate students with a mean age of 19.69 (SD = 2.11). Participants were broken into two groups: non-credible (i.e., participants that failed two or more PVTs) and credible (i.e., participants that did not failed two or more PVTs). The Rey-Osterrith copy test, Comalli Stroop part A (CSA), B (CSB), and C (CSC), Trail Making Test part A and B, Symbol Digit Modalities Test written (SDMT-W) and oral (SDMT-O) parts, Controlled Oral Word Association Test (COWAT) letter fluency, and Finger Tapping Test were used to evaluate failure rates in our sample. PVT cutoff scores were use from previously validated in the literature. Chi-square analysis was used to evaluate failure rates between the groups.Results:Chi-square analysis revealed significant failure rate differences between groups on several PVTs. Results revealed that 15% of the non-credible group failed the CSA compared to 1% of the credible group, X2=14.77, p=.000. Meanwhile, 26% of the non-credible group failed the CSB compared to 2% of the credible group, X2=24.72, p=.000. Furthermore, results showed that 11% of the non-credible group failed the CSC compared to 1% of the credible group, X2=13.05, p=.000.Next, 48% of the non-credible group failed the Trail Making Test part A compared to 8% of the credible group, X2=31.61, p=.000. We also found that 15% of the non-credible group failed the SDMT-W part compared to 1% of the credible group,X2=19.18, p=.000. Meanwhile, on the SDMT-O part 19% of the non-credible group failed compared to 1% of the credible group, X2=25.52, p =.000. On the COWAT letter fluency task 74% of the non-credible group failed compared to 19% of the credible group, X2=36.90, p=.000. Finally, results revealed on the Finger Tapping Test 19% of the non-credible group failed compared to 3% of the credible group, X2=10.01, p=.002.Conclusions:As expected, the non-credible participants demonstrated significantly higher PVT failure rates compared to credible participants. A possible explanation driving higher failure rates in our sample can be due to cultural variables (e.g., bilingualism). It was suggested by researchers that linguistic factors may be impacting higher PVT failure rates and developing a false-positive error. Future research using undergraduate samples need to identify which PVT’s are being impacted by linguist factors.

Executive functions in adolescents with gender dysphoria

Aim: Aim of this study is evaluating EF by performing neurocognitive tests, and to identify gender-related differences in EF between adolescents with and without GD. Methods: 8 Female-to-Male transgender adolescents (FtMs), and 14 Male-to-Female transsexual adolescents (MtFs) (Gender Dysphoria Group, GDG) and 29 boys, 21 girls (Control Group, CG), were tested in a cross-sectional study, using the Wisconsin Card Sorting Test (WCST), Controlled Oral Word Association Test (COWAT), and Stroop Color and Word Test (SCWT). The psychiatric diagnoses were established by using the KD-SADS. Results: Among GDG 72.7%, had at least one psychopathology. There weren’t any significant differences in, estimated IQ scores, or WCST subtest scores between the 2 groups. COWAT total word count and SCWT-5 total duration test scores were better in the CG. Conclusion: CG had better performance on verbal fluency and response inhibition whereas no differences found on set shifting abilities. In consideration of the existence of EF-related impairment in adolescents with GD, appropriate support and interventions are expected to improve their adaptation skills and comorbid psychopathologies. These results should be interprete cautiously and additional larger scale studies are needed to obtain more comprehensive data related to gender differences in EF of adolescents with GD.

Advancing beyond the Hippocampus to Preserve Cognition for Patients with Brain Metastases: Dosimetric Results from a Phase 2 Trial of Memory-Avoidance Whole Brain Radiotherapy

Recent advances to preserve neurocognitive function in patients treated for brain metastases include stereotactic radiosurgery (SRS), hippocampal avoidance whole brain radiation therapy (HA-WBRT), and memantine administration. However, 23% of patients receiving HA-WBRT and memantine on NRG-CC001 still experienced executive function deterioration at 4 months, with 12% experiencing total recall and delayed recognition deterioration at 6 months. The hippocampus, corpus callosum, fornix, and amygdala are key neurocognitive substructures with a low propensity for brain metastases. Herein, we report our preliminary experience using an advanced "memory-avoidance" WBRT (MA-WBRT) approach sparing these substructures for patients with multiple (>15) brain metastases. Ten consecutive patients treated with MA-WBRT on a phase 2 clinical trial (OSU-21074) were reviewed. In each patient, the hippocampi, amygdalae, corpus callosa, and fornix were contoured. Patients were not eligible for MA-WBRT if they had metastases in these substructures. A memory- avoidance region created using a 5mm volumetric expansion around these substructures. Hotspots were avoided in the hypothalamus and pituitary gland. Dose constraints for these avoidance structures were modeled after NRG CC-001 and include a D100% ≤ 9 Gy and a D0.03 cc ≤ 16 (acceptable to 20 Gy). Coverage of brain metastases was prioritized over memory avoidance dose constraints. Linac-based volumetric modulated arc therapy (VMAT) plans were generated for a prescription dose of 30 Gy in 10 fractions. On average, the memory avoidance structure volume was 37.1 ccs (Range: 25.2-44.6 ccs), occupying 2.5% of the entire whole brain target volume. All treatment plans met the D100% dose constraint, and 8/10 plans met the D0.03cc constraint, with priority given to tumor coverage for the remaining 2 cases. VMAT spared the memory avoidance structures with a median dose range of 10.8-14.2 Gy and a maximum dose (D0.03cc) range of 15.6-22.7 Gy. The mean dose to the memory avoidance structures was 12.7 Gy (Range: 11.5-13.8 Gy). Target coverage (D98% > 25 Gy) and homogeneity (D2% ≤ 37.5 Gy) were achieved for all plans. Modern VMAT techniques allow for sparing of the hippocampus, amygdala, corpus callosum, and fornix with good target coverage and homogeneity. Prospective quality of life and cognitive data including are being collected and include the Functional Assessment of Cancer Therapy - Brain (Fact-Br), Hopkins Verbal Learning Test (HLVT-R), Trail Making Test A/B (TMT-A/B) and Controlled Oral Word Association Test (COWAT). After enrollment is completed, these data will be evaluated to assess the efficacy of MA-WBRT to mitigate declines in quality of life and cognition after whole brain radiation.

Normative Data for Single-Letter Controlled Oral Word Association Test in Older White Australians and Americans, African-Americans, and Hispanic/Latinos.

The Controlled Oral Word Association Test (COWAT) is a commonly used measure of verbal fluency. While a normal decline in verbal fluency occurs in late adulthood, significant impairments may indicate brain injury or diseases such as Alzheimer's disease. Normative data is essential to identify when test performance falls below expected levels based on age, gender, and education level. This study aimed to establish normative performance data on single-letter COWAT for older community-dwelling adults. Over 19,000 healthy men and women, without a diagnosis of dementia or a Modified Mini-Mental State Examination score below 77/100, were recruited for the ASPREE trial. Neuropsychological assessments, including the COWAT with letter F, were administered at study entry. Median participant age was 75 years (range 65-98), with 56.5% being women. The majority of participants had 9-11 years of education in Australia and over 12 years in the U.S. The COWAT performance varied across ethno-racial groups and normative data were thus presented separately for 16,335 white Australians, 1,084 white Americans, 896 African-Americans, and 316 Hispanic/Latinos. Women generally outperformed men in the COWAT, except for Hispanic/Latinos. Higher education levels consistently correlated with better COWAT performance across all groups, while the negative association with age was weaker. This study provides comprehensive normative data for the COWAT stratified by ethno-racial groups in Australia and the U.S., considering age, gender, and education level. These norms can serve as reference standards for screening cognitive impairments in older adults in both clinical and research settings.

Investigation of Neurocognitive Deficits, Quality of Life, and Functional Performance in Ultra-High-Risk Individuals Compared to Familial High-Risk Individuals for Schizophrenia.

Objective: This study aimed to investigate neurocognitive functioning, quality of life, and global functional performance in Ultra-High Risk (UHR) individuals compared to Familial High-Risk (FHR) individuals for developing schizophrenia. Method : An observational cross-sectional study was conducted using a convenient sampling method at Roozbeh Hospital in Tehran, Iran, from June 2017 to January 2020. The study included 40 UHR individuals based on the Structured Interview for Psychosis Syndrome (SIPS) interview, as well as 34 FHR individuals due to genetic risk. Neurocognitive functioning, quality of life, and global functional performance were assessed by using the Cambridge Automated Neuropsychological Test Battery (CANTAB) and Controlled Oral Word Association Test (COWAT), Quality of Life Scale (QLS), and Global Assessment of Functioning (GAF). Results: UHR individuals for schizophrenia demonstrated significant lower scores in phonemic and semantic verbal fluency (t = 6.218, P < 0.001; t = 4.184, P < 0.001, respectively), more total errors for spatial working memory (t = -5.874, P < 0.001), and fewer problems solved in minimum moves in Stocking of Cambridge (SOC) (t = -2.706, P < 0.01) compared to FHR individuals. Intra-Extra Dimension (IED) did not differ significantly between the two groups. Moreover, the study indicated significant GAF decline (F = 79.257, P < 0.001) and lower total score on the QLS (t = -10.655, P < 0.001) in UHR compared to FHR individuals. Conclusion: It is possible to differentiate UHR individuals from FHR individuals through neurocognitive, quality of life, and global functioning assessment.

Impacts of baseline biomarkers on cognitive trajectories in subjective cognitive decline: the CoSCo prospective cohort study

BackgroundSubjective cognitive decline (SCD) is a risk factor for Alzheimer’s disease (AD); however, the rates of cognitive decline are variable according to underlying pathologies and biomarker status. We conducted an observational study and aimed to investigate baseline characteristics and biomarkers related with cognitive declines in SCD. Our study also assessed whether SCD participants showed different cognitive and biomarker trajectories according to baseline amyloid deposition.MethodsThis study is a part of a longitudinal cohort study conducted in multi-centers in South Korea between 2018 and 2021. Individuals (≥ 60 years old) with persistent cognitive complaint despite of normal cognitive functions were eligible for the study. All participants underwent neuropsychological tests, florbetaben PET scans, plasma amyloid markers, and brain MRI scans. Annual follow-up evaluations included neuropsychological tests and assessments for clinical progressions. Regional brain volumetry and amyloid burden represented by PET-based standardized uptake value ratio (SUVR) were measured. We compared cognitive and brain atrophic changes over 24 months between amyloid positive-SCD (Aβ + SCD) and amyloid negative-SCD (Aβ-SCD) groups. Baseline factors associated with cognitive outcomes were investigated.ResultsA total of 120 participants with SCD were enrolled and 107 completed follow-up evaluations. Aβ + SCD participants (n = 20, 18.5%) were older and more frequently APOE4 carriers compared with Aβ-SCD participants (n = 87). Baseline cognitive scores were not different between the two groups, except the Seoul Verbal Learning Test (SVLT) scores showing lower scores in the Aβ + SCD group. After 24 months, plasma amyloid markers were higher, and regional volumes (entorhinal, hippocampal, and pallidum) were smaller in the Aβ + SCD participants compared with Aβ-SCD participants adjusted by age, sex, and baseline volumes. SVLT delayed recall and controlled oral word association test (COWAT) scores indicated more declines in Aβ + SCD participants. Baseline left entorhinal volumes were related to verbal memory decline, while baseline frontal volumes and global SUVR values were related to frontal functional decline.ConclusionAβ + SCD participants showed more cognitive decline and medial temporal atrophic changes during 24 months. Baseline neurodegeneration and amyloid burden were related with future cognitive trajectories in SCD.Trial registrationThis study was registered at CRIS (KCT0003397).

Social support network factors associated with verbal fluency among vulnerable persons living with HIV

ABSTRACT Vulnerable persons living with HIV (PLWH) are at high risk of cognitive impairment and challenges accessing quality social support in later life. Impaired verbal fluency (VF), a cognitive domain linked to HIV, could impede social support associated with health and well-being for already vulnerable PLWH. We examined the structure of social support, using latent class analysis, and the associations among quantity, specific forms and quality of social support and VF among PLWH. Participants enrolled in the BEACON study (n = 383) completed the Controlled Oral Word Association test (COWAT) and a social support network inventory. Latent class analysis with count variables was used to determine the number of classes of PLWH based on their social network characteristics. The majority of PLWH were male (61.4%) and African American (85.9%). Two distinct latent classes, with a major distinction in the number of network members who were female, knew participants’ HIV status and HIV medication usage. Fewer support network members (β = -.13, p < 0.01), greater negative interactions (β = -.16, p < 0.01), and less positive interactions with network members (β = .15, p < 0.05) were significantly associated with lower COWAT scores. Comprehensive screening of high-risk PLWH and early intervention with those with cognitive impairment are important for addressing social support needs.

Hepatitis C Virus (HCV) Infection and Neurocognitive Impairment in Subjects with Mild Liver Disease.

Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis, hepatocellular carcinoma, and liver-related deaths. It is estimated that 40-74% of patients with hepatitis C will experience at least one extrahepatic manifestation within their lifetime. The finding of HCV-RNA sequences in post-mortem brain tissue raises the possibility that HCV infection may affect the central nervous system and be the source of subtle neuropsychological symptoms, even in non-cirrhotic. Our investigation aimed to evaluate whether asymptomatic, HCV-infected subjects showed cognitive dysfunctions. Twenty-eight untreated asymptomatic HCV subjects and 18 healthy controls were tested using three neuropsychological instruments in a random sequence: Symbol Digit Modalities Test (SDMT), Controlled Oral Word Association Test (COWAT), and Continuous Visual Attention Test (CVAT). We performed depression screening, liver fibrosis assessment, blood tests, genotyping, and HCV-RNA viral load. A MANCOVA and univariate ANCOVAS were performed to examine group differences (HCV vs. healthy controls) in four scores of the CVAT (omission errors, commission errors, reaction time-RT, and variability of RT-VRT), and the scores derived from the SDMT, and the COWAT. A discriminant analysis was performed to identify which test variables effectively discriminate HCV-infected subjects from healthy controls. There were no group differences in the scores of the COWAT, SDMT, and in two variables of the CVAT (omission and commission errors). In contrast, the performance of the HCV group was poorer than the controls in RT (p = 0.047) and VRT (p = 0.046). The discriminant analysis further indicated that the RT was the most reliable variable to discriminate the two groups with an accuracy of 71.7%. The higher RT exhibited by the HCV group may reflect deficits in the intrinsic-alertness attention subdomain. As the RT variable was found to be the best discriminator between HCV patients and controls, we suggest that intrinsic-alertness deficits in HCV patients may affect the stability of response times increasing VRT and leading to significant lapses in attention. In conclusion, HCV subjects with mild disease showed deficits in RT and intraindividual VRT as compared to healthy controls.

Sleep-disordered breathing and neurocognitive function in multiple sclerosis: Differential associations across cognitive domains

Background: Sleep disorders are common in people with multiple sclerosis (PwMS) and could contribute to cognitive dysfunction. However, effects of pathological sleep on cognitive domains are insufficiently characterized. Objective: To evaluate associations between cognitive performance and polysomnographic (PSG)-based sleep disturbances in PwMS. Methods: PwMS with known/suspected untreated obstructive sleep apnea (OSA, N = 131) underwent PSG and cognitive tests: Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test-II (CVLT-II), Brief Visuospatial Memory Test-Revised (BVMT-R Total and Delayed), Judgment of Line Orientation (JLO), Controlled Oral Word Association Test (COWAT), Trail Making Test, Go/No-Go, and Nine-Hole Peg Test (NHPT). Results: Apnea severity measures were associated with worse processing speed, attention, and working memory (SDMT); immediate and delayed visual memory (BVMT-R Total and Delayed); attention, psychomotor speed, and cognitive flexibility (Trails); and manual dexterity and visuomotor coordination (NHPT) (ps ⩽ 0.011). Sleep macrostructure measures showed stronger associations with verbal memory and response inhibition (CVLT-II Total Recognition Discriminability Index), and immediate visual memory (BVMT-R Total) (ps ⩽ 0.011). Conclusions: Pathological sleep, including hypoxia, sleep fragmentation, and disturbances in sleep/wake states, are differentially associated with worse cognitive performance in PwMS. These findings could inform future personalized approaches to cognitive impairment in PwMS with sleep disorders. Trial registration: ClinicalTrials.gov identifier: NCT02544373 (https://clinicaltrials.gov/ct2/show/NCT02544373).

Large-Scale Network Connectivity and Cognitive Function Changes After Exercise Training in Older Adults with Intact Cognition and Mild Cognitive Impairment.

Despite growing evidence regarding the association between exercise training (ET) and functional brain network connectivity, little is known about the effects of ET on large-scale within- and between-network functional connectivity (FC) of core brain networks. We investigated the effects of ET on within- and between-network functional connectivity of the default mode network (DMN), frontoparietal network (FPN), and salience network (SAL) in older adults with intact cognition (CN) and older adults diagnosed with mild cognitive impairment (MCI). The association between ET-induced changes in FC and cognitive performance was examined. 33 older adults (78.0±7.0 years; 16 MCI and 17 CN) participated in this study. Before and after a 12-week walking ET intervention, participants underwent a graded exercise test, Controlled Oral Word Association Test (COWAT), Rey Auditory Verbal Learning Test (RAVLT), a narrative memory test (logical memory; LM), and a resting-state fMRI scan. We examined the within (W) and between (B) network connectivity of the DMN, FPN, and SAL. We used linear regression to examine associations between ET-related changes in network connectivity and cognitive function. There were significant improvements in cardiorespiratory fitness, COWAT, RAVLT, and LM after ET across participants. Significant increases in DMNW and SALW, and DMN-FPNB, DMN-SALB, and FPN-SALB were observed after ET. Greater SALW and FPN-SALB were associated with enhanced LM immediate recall performance after ET in both groups. Increased within- and between-network connectivity following ET may subserve improvements in memory performance in older individuals with intact cognition and with MCI due to Alzheimer's disease.