Letter-Number Sequencing Research Articles

Humanizing neuropsychological assessment: The role of empathy

Context Recent research and the majority of neuropsychological testing manuals emphasize the importance of establishing a proper relationship between the evaluator and the evaluatee. However, there is relatively little empirical research on this point. Objectives The objective of this study was to operationalize empathy in the evaluator/evaluatee relationship during neuropsychological assessment. The subsequent aim was to determine the impact of this empathy on the evaluator/evaluatee relationship and cognitive performance. Methods The participants, designated as “evaluatees”, were randomly assigned to complete a brief neuropsychological test in either an empathic (N = 47) or neutral condition (N = 47). The neuropsychological tests included the Stroop task from the GREFEX battery, the Letter-Number Sequencing from the WAIS-IV, and the d2 test of attention. Following the tests, participants completed scales indicating perceived relationship with the evaluator, lived experience of the test, and sociodemographic information. Results The manipulation check indicated that it was possible to manipulate empathy. Evaluators demonstrating empathy led to a better evaluator/evaluatee relationship. However, the results regarding cognitive performance were less consistent. Conclusions In conclusion, there is a need for improvement in clinical neuropsychological practice with regard to relational competencies during testing. This study proposes benchmarks to make the evaluator’s empathy perceptible. This technique has not been shown to have a consistent effect on cognitive performance.

Similarities and Differences in the WAIS-IV Performances in Korean and U.S. Populations.

This exploratory study examines the cognitive profiles of South Koreans using the WAIS-IV. It compares scores from the original U.S. version (USW) with those from the Korean version (KW) to identify potential cultural influences on performance. Raw scores corresponding to a scaled score of 10 for each subtest of the KW were used to compare the performances of South Koreans and Americans across subtests and composite indices. The impact of education was assessed through correlations with educational attainment ratios from both countries. When combined across all age groups, the scores of the South Korean sample were significantly lower than those of U.S. sample on the Similarities, Comprehension, and Picture Completion subtests, and Verbal Comprehension Index. However, younger South Koreans scored significantly higher on Block Design, Matrix Reasoning, Visual Puzzles, Figure Weights, Digit Span, Arithmetic, Letter-Number Sequencing, Symbol Search, and Coding and all composite scores except Verbal Comprehension. Older South Koreans scored significantly lower on Similarities, Vocabulary, Comprehension, Matrix Reasoning, Visual Puzzles, Picture Completion, and the composite scores of Verbal Comprehension and Perceptual Reasoning, compared to their U.S. counterparts. All subtest and composite scores were highly correlated with education. The South Korean and U.S. samples demonstrated distinct cognitive profiles on the WAIS-IV when comparing relative performances on subtests and composite measures. Cultural factors including socioeconomic changes, education quality, nuances in language characteristics, and implicit differences in cognitive processing were discussed as possible contributors to the unique cognitive profile of the South Korean sample.

Treatment as a moderator and executive function as a mediator of the effect of a mindfulness ecological momentary intervention for generalized anxiety disorder.

Theory and research indicated that executive functioning (EF) correlated with, preceded, and stemmed from worry in generalized anxiety disorder (GAD). The present secondary analysis (Zainal & Newman, 2023b) thus determined whether EF domains mediated the effect of a 14-day (5 prompts/day) mindfulness ecological momentary intervention (MEMI) against a self-monitoring control (SM) for GAD. Participants (N = 110) diagnosed with GAD completed self-reported (Attentional Control Scale, GAD Questionnaire, Perseverative Cognitions Questionnaire) and performance-based tests (Letter-Number Sequencing, Stroop, Trail Making Test-B, Verbal Fluency) at baseline, post-treatment, and one-month follow-up (1MFU). Causal mediation analyses determined if pre-post changes in EF domains preceded and mediated the effect of MEMI against SM on pre-1MFU changes in GAD severity and trait repetitive negative thinking (RNT). MEMI was more efficacious than SM in improving pre-post inhibition (β = -2.075, 95% [-3.388, -0.762], p = .002), working memory (β = 0.512, 95% [0.012, 1.011], p = .045), and set-shifting (β = -2.916, 95% [-5.142, -0.691], p = .010) but not verbal fluency and attentional control. Within groups, MEMI but not SM produced improvements in all examined pre-post EF outcomes except attentional control. Only pre-post improvements in inhibition mediated the effect of MEMI against SM on pre-1MFU reductions in GAD severity (β = -0.605, 95% [-1.357, -0.044], p = .030; proportion mediated = 7.1%) and trait RNT (β = -0.024, 95% [-0.054, -0.001], p = .040; proportion mediated = 7.4%). These patterns remained after conducting sensitivity analyses with non-linear mediator-outcome relations. Optimizing MEMI for GAD might entail specifically boosting inhibition plausibly by augmenting it with dialectical behavioral therapy, encouraging high-intensity physical exercises, and targeting negative emotional contrast avoidance.

The Parkinson's Disease Composite of Executive Functioning: A Measure for Detecting Cognitive Decline in Clinical Trials.

Executive functioning is one of the first domains to be impaired in Parkinson disease (PD), and the majority of patients with PD eventually develop dementia. Thus, developing a cognitive endpoint measure specifically assessing executive functioning is critical for PD clinical trials. The objective of this study was to develop a cognitive composite measure that is sensitive to decline in executive functioning for use in PD clinical trials. We used cross-sectional and longitudinal follow-up data from PD participants enrolled in the PD Cognitive Genetics Consortium, a multicenter setting focused on PD. All PD participants with Trail Making Test, Digit Symbol, Letter-Number Sequencing, Semantic Fluency, and Phonemic Fluency neuropsychological data collected from March 2010 to February 2020 were included. Baseline executive functioning data were used to create the Parkinson's Disease Composite of Executive Functioning (PaCEF) through confirmatory factor analysis. We examined the changes in the PaCEF over time, how well baseline PaCEF predicts time to cognitive progression, and the required sample size estimates for PD clinical trials. PaCEF results were compared with the Montreal Cognitive Assessment (MoCA), individual tests forming the PaCEF, and tests of visuospatial, language, and memory functioning. A total of 841 participants (251 no cognitive impairment [NCI], 480 mild cognitive impairment [MCI], and 110 dementia) with baseline data were included, of which the mean (SD) age was 67.1 (8.9) years and 270 were women (32%). Five hundred forty five PD participants had longitudinal neuropsychological data spanning 9 years (mean [SD] 4.5 [2.2] years) and were included in analyses examining cognitive decline. A 1-factor model of executive functioning with excellent fit (comparative fit index = 0.993, Tucker-Lewis index = 0.989, and root mean square error of approximation = 0.044) was used to calculate the PaCEF. The average annual change in PaCEF ranged from 0.246 points per year for PD-NCI participants who remained cognitively unimpaired to -0.821 points per year for PD-MCI participants who progressed to dementia. For PD-MCI, baseline PaCEF, but not baseline MoCA, significantly predicted time to dementia. Sample size estimates were 69%-73% smaller for PD-NCI trials and 16%-19% smaller for PD-MCI trials when using the PaCEF rather than MoCA as the endpoint. The PaCEF is a sensitive measure of executive functioning decline in PD and will be especially beneficial for PD clinical trials.

A - 23 Interpretation Consideration: Serial Baseline Performances on Core Executive Function Measures in Healthy Youth Athletes

Abstract Purpose Sports participation in youth has demonstrated better core executive function (EF) abilities compared to those who do not participate (Contreras-Osorio et al., 2021). However, previous research has not observed a pattern of improvement across all EF abilities (M√∂hring et al., 2022), indicating EF development in childhood is not linear (Anderson, 2002). The present study compared baseline scores of cognitive flexibility, working memory, and inhibition at two timepoints among youth athletes. Method Data from the Delis-Kaplan Executive Function System Trail Making Letter-Number Sequencing (cognitive flexibility), Wechsler Intelligence Scale for Children Fourth Edition Working Memory Index, and Golden Stroop Color-Word Inhibition test were analyzed in a sample of youth athletes (n = 32), aged 8–16 years. Mean age difference between time 1 and 2 was 1.86 years. Paired-samples t-test examined the difference in core EF scores at two timepoints. Results Performance on a measure of inhibition significantly improved over time (p = 0.02; effect size [d] = 0.43). Performances on measures of working memory and cognitive flexibility did not significantly differ over time (p = 0.16 and p = 0.61, respectively). Conclusions Healthy youth athletes performed significantly better only on a measure of inhibition at baseline two than baseline one, suggesting clinicians should anticipate variation in scores when re-examining core EF abilities after two years. Further, clinicians should exercise caution when interpreting variation in baseline scores because it could be due to sports participation. Future research should investigate whether inhibition continues to improve overtime and whether significant changes are observed in other core EFs.

Assessment tools for cognitive performance in Parkinson's disease and its genetic contributors.

We have shown that genetic factors associating with motor progression of Parkinson's disease (PD), but their roles in cognitive function is poorly understood. One reason is that while cognitive performance in PD can be evaluated by various cognitive scales, there is no definitive guide indicating which tool performs better. Data were obtained from the Parkinson's Progression Markers Initiative, where cognitive performance was assessed using five cognitive screening tools, including Symbol Digit Modalities Test (SDMT), Montreal Cognitive Assessment, Benton Judgment of Line Orientation, Modified Semantic Fluency Test, and Letter Number Sequencing Test, at baseline and subsequent annual follow-up visit for 5 years. Genetic data including ApoE and other PD risk genetic information were also obtained. We used SPSS-receiver operating characteristic and ANOVA repeated measures to evaluate which cognitive assessment is the best reflecting cognitive performance in PD at early stage and over time. Logistic regression analyses were used to determine the genetic associations with the rapidity of cognitive decline in PD. SDMT performed better in detecting mild cognitive impairment at baseline (AUC = 0.763), and SDMT was the only tool showing a steady cognitive decline during longitudinal observation. Multigenetic factors significantly associated with cognitive impairment at early stage of the disease (AUC = 0.950) with IP6K2 rs12497850 more evident, and a significantly faster decline (AUC = 0.831) within 5 years after motor onset, particularly in those carrying FGF20 rs591323. SDMT is a preferable cognitive assessment tool for PD and genetic factors synergistically contribute to the cognitive dysfunction in PD.

Relationships between cognitive flexibility performance and adaptive behavior outcomes in survivors of pediatric brain tumor

Objective: Survivors of pediatric brain tumors are at increased risk of executive function (EF) and adaptive behavior difficulties. While previous research suggests that executive dysfunction impacts suboptimal adaptive outcomes, the specific elements of EF influencing this relationship remain unexplored. This study examines the relationship between cognitive flexibility and adaptive behavior in survivors compared to healthy controls. Methods: 86 survivors (M age(SD)=23.41(4.24), 44 females) and 86 controls (M age(SD)=23.09(4.50), 44 females) completed the Delis-Kaplan Executive Function System Trail Making Test (TMT) and Verbal Fluency Test (VFT). The Letter-Number Sequencing (LNS) and Category Switching (CS) conditions were isolated as measures of cognitive flexibility. Informants provided responses to obtain adaptive behavior ratings using the Scales of Independent Behavior-Revised (SIB-R). Linear regressions explored relationships between cognitive flexibility and SIB-R scores in survivors compared to controls. Results: For both TMT and VFT, the relationship between cognitive flexibility and adaptive behavior was significantly different between survivors and controls for SIB-R scores in Social Communication, Community Living, and Personal Living Skills (p<.0125). Survivors’ better LNS performance predicted greater SIB-R scores across the same 3 domains (all p= <.001, r 2semipartial=.08). Similarly, survivors’ better CS performance predicted greater SIB-R scores across the same 3 domains (p = 0.002 to .02, r 2semipartial =.03 to .04). No significant relationships were found in controls (all p >.05). After adjusting for working memory and inhibitory control, most relationships remained significant in survivors (p= <.001 to .046, r 2semipartial=.02 to .08). Conclusion: These findings reveal a robust, positive relationship between cognitive flexibility performance and adaptive behaviors specific to survivors.

White matter alterations and their associations with biomarkers and behavior in subjective cognitive decline individuals: a fixel-based analysis.

Subjective cognitive decline (SCD) is an early stage of dementia linked to Alzheimer's disease pathology. White matter changes were found in SCD using diffusion tensor imaging, but there are known limitations in voxel-wise tensor-based methods. Fixel-based analysis (FBA) can help understand changes in white matter fibers and how they relate to neurodegenerative proteins and multidomain behavior data in individuals with SCD. Healthy adults with normal cognition were recruited in the Northeastern Taiwan Community Medicine Research Cohort in 2018-2022 and divided into SCD and normal control (NC). Participants underwent evaluations to assess cognitive abilities, mental states,physical activity levels, and susceptibility to fatigue. Neurodegenerative proteins were measured usingan immunomagnetic reduction technique. Multi-shell diffusion MRI data were collected and analyzed using whole-brain FBA, comparing results between groups and correlating them with multidomain assessments. The final enrollment included 33 SCD and 46 NC participants, with no significant differences in age, sex, or education between the groups. SCD had a greater fiber-bundle cross-section than NC (pFWE < 0.05) at bilateral frontal superior longitudinal fasciculus II (SLFII). These white matter changes correlate negatively with plasma Aβ42 level (r = -0.38, p = 0.01) and positively with the AD8 score for subjective cognitive complaints (r = 0.42, p = 0.004) and the Hamilton Anxiety Rating Scale score for the degree of anxiety (Ham-A, r = 0.35, p = 0.019). The dimensional analysis of FBA metrics and blood biomarkers found positive correlations of plasma neurofilament light chain with fiber density at the splenium of corpus callosum (pFWE < 0.05) and with fiber-bundle cross-section at the right thalamus (pFWE < 0.05). Further examination of how SCD grouping interacts between the correlations of FBA metrics and multidomain assessments showed interactions between the fiber density at the corpus callosum with letter-number sequencing cognitive score (pFWE < 0.01) and with fatigue to leisure activities (pFWE < 0.05). Based on FBA, our investigation suggests white matter structural alterations in SCD. The enlargement of SLFII's fiber cross-section is linked to plasma Aβ42 and neuropsychiatric symptoms, which suggests potential early axonal dystrophy associated with Alzheimer's pathology in SCD. The splenium of the corpus callosum is also a critical region of axonal degeneration and cognitive alteration for SCD.

Comparing embedded performance validity indicators within the WAIS-IV Letter-Number sequencing subtest to Reliable Digit Span among adults referred for evaluation of attention-deficit/hyperactivity disorder

Objectives: This study investigated the Wechsler Adult Intelligence Scale-Fourth Edition Letter-Number Sequencing (LNS) subtest as an embedded performance validity indicator among adults undergoing an attention-deficit/hyperactivity disorder (ADHD) evaluation, and its potential incremental value over Reliable Digit Span (RDS). Method: This cross-sectional study comprised 543 adults who underwent neuropsychological evaluation for ADHD. Patients were divided into valid (n = 480) and invalid (n = 63) groups based on multiple criterion performance validity tests. Results: LNS total raw scores, age-corrected scaled scores, and age- and education-corrected T-scores demonstrated excellent classification accuracy (area under the curve of .84, .83, and .82, respectively). The optimal cutoff for LNS raw score (≤16), age-corrected scaled score (≤7), and age- and education-corrected T-score (≤36) yielded .51 sensitivity and .94 specificity. Slightly lower sensitivity (.40) and higher specificity (.98) was associated with a more conservative T-score cutoff of ≤33. Multivariate models incorporating both LNS and RDS improved classification accuracy (area under the curve of .86), and LNS scores explained a significant but modest proportion of variance in validity status above and beyond RDS. Chaining LNS T-score of ≤33 with RDS cutoff of ≤7 increased sensitivity to .69 while maintaining ≥.90 specificity. Conclusions: Findings provide preliminary evidence for the criterion and construct validity of LNS as an embedded validity indicator in ADHD evaluations. Practitioners are encouraged to use LNS T-score cutoff of ≤33 or ≤36 to assess the validity of obtained test data. Employing either of these LNS cutoffs with RDS may enhance the detection of invalid performance.

Does Including Facebook Training Improve the Effectiveness of Computerized Cognitive Training? A Randomized Controlled Trial.

To determine whether implementing a Facebook training program improves the effectiveness of computerized cognitive training (CCT) in older adults. Randomized, controlled, double single-blind trial with parallel groups. Community centers. Eighty-six adults between 60 and 90 years old. Nine face-to-face 60-min sessions of CCT with VIRTRAEL for all participants. The experimental group received an additional 30 min of Facebook training per session. Attention (d2 Test of Attention); learning and verbal memory (Hopkins Verbal Learning Test-Revised); working memory (Letter-Number Sequencing test), semantic and abstract reasoning (Similarities and Matrix Reasoning tests); and planning (Key Search test). There was a significant Group*Time interaction in the Hopkins Verbal Learning Test-Revised-Trial 3, Letter-Number sequencing, and Matrix tests. Between groups, post-hoc analyses showed a difference in Matrix reasoning (p < .001; d = 0.893) at post-intervention in favor of the experimental group. Significant main effects of time were found in the CCT group between baseline and 3-month follow-up for Concentration (F = 26.431, p ≤ .001), Letters and Numbers (F = 30.549, p ≤ .001), Learning (F = 38.678, p ≤ .001), Similarities (F = 69.885, p ≤ .001), Matrix (F = 90.342, p ≤ .001), and Key Search (F = 7.904, p = .006) tests. The utilization of CCT with VIRTRAEL, a freely accessible tool with broad applicability, resulted in enhanced attention, verbal learning, working memory, abstract and semantic reasoning, and planning among older adults. These improvements were sustained for at least three months post-training. Additional training in Facebook did not enhance the effectiveness of CCT.

3-Year test-retest reliability in Parkinson’s disease and healthy older adults: The Parkinson’s progression markers initiative study

Repeated neuropsychological assessments are often conducted in clinical and research settings to track cognitive changes over single or multiple intervals in patients with Parkinson’s disease (PD). Yet few studies have documented test-retest reliability in PD. To address this gap, we used data from the Parkinson’s Progression Markers Initiative (PPMI) to investigate the reliability of five well-known neuropsychological tests over a 3-year follow-up assessment in early-stage PD with either normal (PD-NC; N = 158) or abnormal (PD-AC; N = 39) cognitive screening, categorized based on recommended cutoffs for the Montreal Cognitive Assessment (MoCA), and healthy older adults (HOA; N = 102). All participants analyzed maintained the same cognitive status category across the assessment points. Intraclass correlation coefficients (ICCs) estimated reliability. The overall ICCs calculated across time points were as follows: Judgment of Line Orientation (PD-NC = .47, PD-AC = .50, HOA = .59); Letter-Number Sequencing (PD-NC = .64, PD-AC = .64, HOA = .65); Semantic Fluency (PD-NC = .69, PD-AC = .89, HOA = .77); Symbol Digit Modalities Test (PD-NC = .67, PD-AC = .83, HOA = .71). For the two primary components of the Hopkins Verbal Learning Test-Revised, we found the following ICCs: immediate recall (PD-NC = .46, PD-AC = .57, HOA = .58); delayed recall (PD-NC = .42, PD-AC = .57, HOA = .54). Findings from this study provide useful information for clinicians and researchers toward selecting suitable neuropsychological tests to monitor cognition at two or more time points among newly diagnosed individuals with PD and HOA.

Effect of mindfulness-based cognitive therapy vs. psychoeducational intervention on plasma brain-derived neurotrophic factor and cognitive function in bipolar patients: a randomized controlled trial.

Few controlled trials have assessed the benefits of Mindfulness Based Cognitive Therapy (MBCT) on cognitive functions and brain-derived neurotrophic factor (BDNF) in bipolar disorder (BD). This study aims to evaluate the impact of MBCT adjunctive treatment on these variables. Main hypothesis was that MBCT would improve cognitive functioning and BDNF more than Psychoeducation and TAU. Randomized, multicenter, prospective and single-blinded trial. Included BD outpatients randomly assigned to three treatment arms: MBCT plus treatment as usual (TAU), Psychoeducation plus Tau and TAU. Cognitive functions were assessed with Continuous Performance Test-III, Stroop Test, Trail Making Test, Digit Span and Letter-Number Sequencing from Wechsler Adult Intelligence Scale III, Face Emotion Identification Task and Face Emotion Discrimination Task. BDNF serum level was measured with ELISA. Patients were assessed at baseline, 8 weeks and 6 months. Eighty-four patients were recruited (TAU = 10, Psychoeducation = 34, MBCT = 40). No significant differences between treatment groups were found. MBCT does not achieve better results than Psychoeducation or TAU. Being Psychoeducation and TAU efficient interventions, as well as the scarce duration of a more complex intervention, such as MBCT, are suggested as explanatory variables of these results. ClinicalTrials.gov: NCT02133170. Registered 04/30/2014.

Ab. No. 16 Exercises and Pain Education Improves Clinical Outcomes in a Subgroup of Patients With Chronic Low Back Pain Positive for Central Sensitization

Introduction: Exercises have been found to decrease pain and the overall sensitivity of the central nervous system through the activation of exercise-induced endogenous analgesia and spinal inhibitory mechanisms. Despite the recommendations of many reviews that exercise programs reduce pain and disability in persons with chronic pain, the overall confidence is considered ‘critically low’. This study aimed to evaluate the effect of different exercises (aerobic, motor control, and superficial strengthening) relative to patient education on pain sensitivity and clinical outcomes in patients with chronic non-specific low back pain (NSCLBP) positive for central sensitization. Methods: The trial is a randomized controlled study with concealed allocation and blinding of assessors with four experimental groups (n=172) and one healthy control group (n=43). Participants were engaged in moderately intense treadmill walking sessions, activities for trunk stabilization, and strengthening exercises for the trunk and abdominal muscles along with patient education as per their group allocation. The control group received only patient education. The primary outcome was the cold pressor test. The secondary outcomes were pain intensity, disability, letter-number sequencing subtest, Stroop neurophysiological test, quality of life, and isometric muscle strength of the spine and hip muscles. Measures were taken at baseline and 12 and 24 weeks. Result: The results showed that patients with CLBP exhibit impaired CPM relative to healthy volunteers even after the intervention period. The overall results of the study showed improvement with time, and there was no difference between the groups in improving outcomes (p &gt; 0.05). There was a small effect size in favor of groups that received exercise and patient education (&lt;0.15) over the control group. Conclusion: Considering the comparable effects on clinical outcomes in patients with NSCLBP, this population may be encouraged to undertake exercises of moderate intensity of their preference.

Emotion Comprehension and Socio-cognitive Skills in Children with High Functioning Autism Spectrum Disorders.

This study aimed to compare socio-cognitive skills and emotion comprehension between children with Autism Spectrum Disorder (ASD) and children with neurotypical development. This quantitative, cross-sectional, controlled study involved 19 children in each group, matched by age (6-12 years) and sex. The assessments examined cognitive aspects (Intelligence Quotient was assessed using the Vocabulary and Matrix Reasoning subtests; working memory using the digit span and letter-number sequencing subtests; attention using the Continuous Performance Test - Identical Pairs; and executive functions using the Trail Making Test), social functions (Children's Social Skills, Behavior Problems, and Academic Competence Inventory), and emotion comprehension (language was assessed using the Strange Stories Test; emotional facial expressions using the digital emotion comprehension test; emotional/affective prosody using the Profiling Elements of Prosody in Speech-Communication - Brazilian Portuguese adapted version). The group with ASD exhibited better performance in executive functions (p=0.02). However, they lagged the control group in social skills (p=0.04), behavior problems (p=0.03), and emotion comprehension (language, facial expressions, and prosody) (all p<0.05). The findings indicate that children with ASD have diminished performance in social skills and emotion comprehension compared to children with neurotypical development. Therefore, the development of technologies and/or therapeutic interventions that address these deficits among children with ASD is recommended.

The Effect of Web-Based Telerehabilitation Programs on Children and Adolescents With Brain Injury: Systematic Review and Meta-Analysis.

Acquired brain injury (ABI) in children and adolescents can lead to motor and executive impairments that often require long-term treatment. The implementation of web-based telerehabilitation therapy at home is a method to improve the functional status of patients. Therefore, we performed a systematic review of the effects of web-based telerehabilitation programs on functional outcomes in children and adolescents with brain injury and supplemented the findings with a meta-analysis. This study evaluated the therapeutic effect of web-based telerehabilitation training on children and adolescents with brain injury to determine whether web-based telerehabilitation therapy improved motor function, executive function, physical activity level, lower limb strength, hand and upper limb function, visual processing skills, and occupational functional performance in children and adolescents with brain injury. PubMed, Embase, Scopus, Web of Science, and the Cochrane Library were searched for randomized controlled trials on web-based telerehabilitation programs in children and adolescents with brain injury until December 2022, and the risk of bias was evaluated using the Cochrane Collaboration Tool. Relevant data were extracted, and a meta-analysis was performed using RevMan5.3 software. Overall, 17 studies involving 848 patients were included. Web-based telerehabilitation therapy improved the motor function (standardized mean difference [SMD] 0.29, 95% CI 0.01-0.57; P=.04), physical activity level (SMD 0.42, 95% CI 0.11-0.73; P=.007), lower limb strength (SMD 0.52, 95% CI 0.13-0.90; P=.009), and visual processing skills (SMD 0.26, 95% CI 0.02-0.50; P=.04) of children and adolescents with brain injury. It also improved executive function in letter-number sequencing (SMD 1.26, 95% CI 0.26-2.26; P=.01), attention (SMD 0.38, 95% CI 0.09-0.66; P=.009), and symbol search (SMD 1.18, 95% CI 0.43-1.93, P=.002). Web-based telerehabilitation therapy improved motor function, physical activity level, lower limb strength, letter-number sequencing, attention, and symbol search, which improved the quality of life in children and adolescents with brain injury. Web-based telerehabilitation programs provide great convenience for children and adolescents with ABI who need long-term treatment and allow them to exercise at home for rehabilitation training. The widespread implementation of remote interventions also provides children and adolescents in remote areas with better access to rehabilitation services. This review provides evidence for the effectiveness of web-based telerehabilitation therapy, but there was heterogeneity in some of the results because of different disease types and intervention programs. Future studies can expand the sample size according to disease type and increase follow-up time according to different exercise prescriptions to further refine the long-term effects of this intervention on various functions of children and adolescents with ABI. PROSPERO CRD42023421917; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=421917.

BIOLOGICAL AGE AND COGNITIVE PERFORMANCE AMONG LATE MID-LIFE WOMEN

Abstract Older biologic age, indicated by accelerated epigenetic aging, may place women at risk for poorer cognitive performance as they age. However, findings are inconsistent and based upon limited neuropsychological batteries. Studies of midlife women are few, yet women comprise two thirds of those with Alzheimer’s disease, and midlife is a critical transition and potential window for early intervention. We tested whether greater epigenetic age would be associated with poorer cognitive performance among late midlife women. 224 MsBrain study participants (average age=59 years, 82% White, 14% Black, 4% other ethnicities) underwent phlebotomy, including epigenetic aging clock estimates (GrimAge, DunedinPACE, PCPhenoAGE), and a neuropsychological battery assessing global cognitive function (Montreal Cognitive Assessment), verbal learning and memory (California Verbal Learning Test), working memory and attention (Letter Number Sequencing), letter fluency (P, R, W); semantic fluency (animal task), spatial ability (Card Rotations), processing speed (Symbol Digit Modalities Test), and perceptual speed (Finding A’s). In linear regression models controlling for age, race, and education, older PCPhenoAge was associated with poorer global cognitive performance [B(SE)=-.07(.03), p=.01], verbal memory [B(SE)=-.09(.03), p=.006], working memory [B(SE)=-.12(.03), p=.0001], attention [B(SE)=-.10(.04), p=.02], spatial ability [B(SE)=-.77(.34), p=.02], processing speed [B(SE)=-.24(.09), p=.007], and somewhat lower letter fluency [B(SE)=-.23(.13), p=.07]. GrimAge and DunedinPACE showed similar yet less consistent patterns. Interactions by race (p’s&amp;lt;.05) indicate that associations between older biologic age and poorer cognitive performance (verbal learning, verbal memory, processing speed) was particularly pronounced among Black women in the sample. Older biologic age is associated with poorer cognitive performance across multiple domains among late midlife women, particularly for Black women. Biologic age may serve as an early indicator of risk that could help identify women warranting early intervention to help maintain cognitive function. Supported by NIH RF1AG053504, R01AG053504, K24HL123565

Association of liver fibrosis with cognitive decline in Parkinson’s disease

BackgroundCognitive decline is a common but variable non-motor manifestation of Parkinson’s disease. Chronic liver disease contributes to dementia, but its impact on cognitive performance in Parkinson’s disease is unknown. We assessed the effect of liver fibrosis on cognition in Parkinson’s disease. MethodsWe conducted a retrospective cohort study using data from the Parkinson’s Progression Markers Initiative. Our exposure was liver fibrosis at baseline, based on the validated Fibrosis-4 score. Our primary outcome was the Montreal Cognitive Assessment, and additional outcome measures were the Symbol Digit Modalities Test, the Benton Judgement of Line Orientation, the Letter-Number Sequencing Test, and the Modified Semantic Fluency Test. We used linear regression models to assess the relationship between liver fibrosis and scores on cognitive assessments at baseline and linear mixed models to evaluate the association between baseline Fibrosis-4 score with changes in each cognitive test over five years. Models were adjusted for demographics, comorbidities, and alcohol use. ResultsWe included 409 participants (mean age 61, 40 % women). There was no significant association between liver fibrosis and baseline performance on any of the cognitive assessments in adjusted models. However, over the subsequent five year period, liver fibrosis was associated with more rapid decline in scores on the Montreal Cognitive Assessment (interaction coefficient, −0.07; 95 % CI, −0.12, −0.02), the Symbol Digit Modalities Test, the Benton Judgement of Line Orientation, and the Modified Semantic Fluency Test. ConclusionIn people with Parkinson’s disease, the presence of comorbid liver fibrosis was associated with more rapid decline across multiple cognitive domains.

Associations of Orthostatic Hypotension and Orthostatic Intolerance with Domain-Specific Cognitive Decline in Patients with Early Parkinson Disease: An 8-Year Follow-up

ObjectiveAlthough orthostatic hypotension (OH) and orthostatic intolerance (OI) are prevalent in patients with Parkinson disease (PD), it remains unclear how these conditions primarily affect the trajectory of decline in specific cognitive domains. This study aimed to explore the effects of OH and OI on longitudinal domain-specific cognitive changes in patients with PD. DesignAn 8-year follow-up of the Parkinson Progression Markers Initiative cohort study. Setting and ParticipantsA total of 403 patients with early, untreated PD and 195 matched healthy controls were included. They were classified into OH, OI, and normal groups. OH was defined according to the international consensus, and OI was defined as the presence of orthostatic symptoms without meeting the criteria for OH. MethodsThe patients underwent detailed neuropsychological testing annually for up to 8 years of follow-up. Linear mixed effects models were used to investigate the associations between OH, OI, and longitudinal cognitive changes. ResultsThe prevalence of both OH and OI in patients with PD was significantly higher than that in controls (13.4% vs 7.2%, P = .002, for OH, and 29.3% vs 14.4%, P < .001, for OI). The OH group in patients with PD showed a faster decline in Letter-Number Sequencing (LNS) (β = −0.11, 95% CI −0.20 to −0.02, t = −2.44, P = .015) and Semantic Fluency Test (SFT) (β = −0.44, 95% CI –0.81 to −0.08, t = −2.42, P = .016) scores than the normal group. Similarly, the OI group showed a steeper decline in LNS (β = −0.08, 95% CI –0.14 to −0.01, t = −2.20, P = .028) and SFT (β = −0.36, 95% CI –0.63 to −0.08, t = −2.55, P = .011) scores compared to the normal group. There were no significant longitudinal changes in the other neuropsychological test scores between the groups. Conclusions and ImplicationsBoth OH and OI may be associated with a faster decline in executive function among cognitive domains of patients with PD. These findings may highlight the potential importance of orthostatic blood pressure control in PD patients with OH and even those with orthostatic symptoms without OH.

4 Relationships Between Task-Switching Performance and Adaptive Behavior Outcomes in Survivors of Pediatric Brain Tumor

Objective:Survivors of pediatric brain tumor (BT) experience impaired executive function (EF) and adaptive behavior (i.e. the ability to complete daily living tasks independently). The literature hypothesizes that executive dysfunction contributes to suboptimal adaptive behavior outcomes in BT survivors; however, the aspects of EF that drive this relationship remain unexplored. Task-switching is an EF component that involves switching between concurrently presented tasks. This skill is critical for many day-to-day activities and may therefore contribute to observed adaptive functioning difficulties. This study investigates relationships between performance on two task-switching measures and adaptive behavior outcomes in BT survivors compared to healthy controls.Participants and Methods:86 survivors of pediatric BT (Mage(SD)= 23.42(4.24), 44 females) and 86 age- and sex-matched controls (Mage(SD) = 23.09(4.40), 44 females) from the Atlanta area completed the Delis-Kaplan Executive Function System Trail Making Test (TMT) and Verbal Fluency Test (VFT). Respectively, the Letter-Number Sequencing (LNS) and Category Switching (CS) conditions were isolated as measures of task-switching. Baseline conditions, representing the foundational skills needed to perform these timed task-switching measures rapidly (TMT: Letter Sequencing, Number Sequencing; VFT: Category Fluency), were included as covariates in all regressions. Informants familiar with the participants’ daily living were interviewed with the Scales of Independent Behavior-Revised (SIB-R) to measure adaptive behavior in four domains (Motor Skills, Social Communication, Personal Living, Community Living). Linear regressions and t-tests confirmed group differences on task-switching performance and on adaptive functioning outcomes, respectively. Then, linear regressions investigated relationships between performance on each task-switching measure (LNS, CS) and SIB-R scores for survivors. A group by task-switching interaction was added to directly explore group differences in these relationships. α=.0125 was used due to Bonferroni correction for the four SIB-R comparisons within each task-switching measure.Results:BT survivors were more impaired than controls on LNS, CS, and SIB-R scores (p&lt;.05, except Personal Living p=.058). For TMT, decreased performance on LNS predicted lower SIB-R scores in Social Communication (p=.001, r2semipartial=.14), Personal Living (p=.002, r2semipartial=.13), and Community Living (p=.003, r2semipartial =.11), but not Motor Skills (p=.184) in BT survivors. Strength of significant relationships was greater for survivors than controls (all p&lt;.002). For VFT, decreased performance on CS predicted lower SIB-R scores in Personal Living (p=.036, r2semipartial =.06) and Community Living (p=.04, r2semipartial =.05), but not in Motor Skills (p=.716) or Social Communication (p=.14) in BT survivors. Positive relationships between CS and SIB-R scores for all 4 domains were greater in survivors than controls (p&lt;.0125).Conclusions:These findings reveal a robust, positive relationship between task-switching performance and independent, daily behaviors that is specific to BT survivors. The relationship between LNS and Motor Skills may have been weakened by covariates involving baseline motor abilities; however, CS results suggest that task-switching is important for motor skills in survivors relative to controls. Community living skills were impaired in survivors and consistently related to task-switching performance. This work may inform interventions to target task-switching abilities and consequently, promote everyday living skills. Interventions aimed at vulnerabilities in adaptive behavior may help increase independence and quality-of-life as survivors transition to adulthood.

55 Hoarding Behaviors in Late Life Depression are Associated with Increased Burden of Executive Dysfunction, Disability, and Poorer Response to Depression Treatment

Objective:Late Life Major Depressive Disorder (LLD) and Hoarding Disorder (HD) are common in older adults with prevalence estimates up to 29% and 7%, respectively. Both LLD and HD are characterized by executive dysfunction and disability. There is evidence of overlapping neurobiological dysfunction in LLD and HD suggesting potential for compounded executive dysfunction and disability in the context of comorbid HD and LLD. Yet, prevalence of HD in primary presenting LLD has not been examined and potential compounded impact on executive functioning, disability, and treatment response remains unknown. Thus, the present study aimed to determine the prevalence of co-occurring HD in primary presenting LLD and examine hoarding symptom severity as a contributor to executive dysfunction, disability, and response to treatment for LLD.Participants and Methods:Eighty-three adults ages 65-90 participating in a psychotherapy study for LLD completed measures of hoarding symptom severity (Savings Inventory-Revised: SI-R), executive functioning (WAIS-IV Digit Span, Letter-Number Sequencing, Coding; Stroop Interference; Trail Making Test-Part B; Letter Fluency), functional ability (World Health Organization Disability Assessment Schedule-II-Short), and depression severity (Hamilton Depression Rating Scale) at post-treatment. Pearson's Chi-squared tests evaluated group differences in cognitive and functional impairment rates and depression treatment response between participants with (HD+LLD) and without (LLD-only) clinically significant hoarding symptoms. Linear regressions were used to examine the association between hoarding symptom severity and executive function performance and functional ability and included as covariates participant age, years of education, gender, and concurrent depression severity.Results:At post-treatment, 24.1% (20/83) of participants with LLD met criteria for clinically significant hoarding symptoms (SI-R.41). Relative to LLD-only, the LLD+HD group demonstrated greater impairment rates in Letter-Number Sequencing (χ2(1)=4.0, p=.045) and Stroop Interference (χ2(1)=4.8, p=.028). Greater hoarding symptom severity was associated with poorer executive functioning performance on Digit Span (t(71)=-2.4, β=-0.07, p=.019), Letter-Number Sequencing (t(70)=-2.1, β=-0.05, p=.044), and Letter Fluency (t(71)=-2.8, β=-0.24, p=.006). Rates of functional impairment were significantly higher in the LLD+HD (88.0%) group compared to the LLD-only (62.3%) group, (χ2(1)=5.41, p=.020). Additionally, higher hoarding symptom severity was related to greater disability (t(72)=2.97, β=0.13, p=.004). Furthermore, depression treatment response rates were significantly lower in the LLD+HD group at 24.0% (6/25) compared to 48.3% (28/58) in the LLD-only group, χ2(1)=4.26, p=.039.Conclusions:The present study is among the first to report prevalence of clinically significant hoarding symptoms in primary presenting LLD. The findings of 24.1% co-occurrence of HD in primary presenting LLD and increased burden on executive functioning, disability, and depression treatment outcomes have important implications for intervention and prevention efforts. Hoarding symptoms are likely under-evaluated, and thus may be overlooked, in clinical settings where LLD is identified as the primary diagnosis. Taken together with results indicating poorer depression treatment response in LLD+HD, these findings underscore the need for increased screening of hoarding behaviors in LLD and tailored interventions for this LLD+HD group. Future work examining the course of hoarding symptomatology in LLD (e.g., onset age of hoarding behaviors) may provide insights into the mechanisms associated with greater executive dysfunction and disability.