Standardized Neuropsychological Assessment Research Articles

Evaluating the Equivalency of Teletesting and the Impact of the COVID-19 Pandemic on Measures of Reading Achievement in a Clinically Referred Sample.

The COVID-19 pandemic highlighted the need to build an evidence base to support teletesting as an equivalent modality for standardized neuropsychological assessment. As such, the purpose of this study was twofold. First, this study evaluated teletesting equivalency of standardized reading achievement measures during COVID-19 in children ages 6-16. Further, to examine the impact of COVID-19 on reading, achievement scores were compared in two samples of children assessed before and during COVID-19. Participants were referred for testing at an outpatient neuropsychology clinic at an urban, academic medical center. Aim one compared assessments administered in-person (n = 1039) versus teletesting (n = 283). A two one-sided test (TOST) was used to determine equivalency. Aim two compared children seen pre-COVID-19 (n = 2125) and during COVID-19 (n = 1322) including a subsample of elementary school-aged children. One-way analyses of covariance were employed, with insurance type and Wechsler Intelligence Scale for Children, Fifth Edition Matrix Reasoning (as a proxy for nonverbal IQ) included as covariates. Results showed equivalence in reading achievement scores administered via teletesting compared to in-person during COVID-19. For aim two, Nonsense Word Decoding scores were significantly higher for the COVID-19 group compared to the pre-COVID-19 group (p = 0.03). No other significant differences in reading scores were found between groups, including no differences among a subsample of elementary school-aged children (ages 6-10; all ps > 0.05). This provides additional support for teletesting equivalency and suggests the negative impact of COVID-19 on foundational reading skills is less than predicted in a clinically referred sample.

Neuronal ceroid lipofuscinoses type 7 (CLN7): a case series reporting cross sectional and retrospective clinical data to evaluate validity of standardized tools to assess disease progression, quality of life, and adaptive skills

BackgroundThis study evaluated the clinical characteristics of neuronal ceroid lipofuscinosis type 7 or CLN7 disease spectrum to characterize the clinical, electrophysiologic and neuroimaging phenotypes.MethodsWe performed a single-center cross sectional data collection along with retrospective medical chart review in patients with a genetic diagnosis of CLN7. This study received ethical approval by the University of Texas Southwestern Medical Center Institutional Review Board. A total of 8 patients were included between the ages of 4 to 6 years. All patients had a genetic diagnosis of CLN7 with homozygous or compound heterozygous mutations in the MFSD8 gene. The information collected includes patient demographics, developmental history, neurological events including seizures and neurodevelopmental regression along with further evaluation of brain magnetic resonance imaging and electrophysiological findings. The clinical phenotype is described through cross sectional and retrospective data collection and standardized tools assessing quality of life and functional skills.ResultsOur findings in this cohort of CLN7 patients indicated that development is initially normal with onset of clinical symptoms as early as two years of age. Language problems were noted prior to or at the onset of seizures in all cases. Gait problems were noted prior to seizure onset in 3 of 8 patients, and at or within 6 months after the onset of seizures in 5 of 8 patients. All patients followed a progressive course of language, motor, and neurocognitive deterioration. Congruent with the medical history, our patients had significantly low scores on adaptive abilities. Natural history data such as this can be used to support future clinical trial designs.ConclusionsThis study provides a comprehensive description of CLN7 disease, highlighting clinical data alongside standardized neuropsychological assessments, neuroimaging, and electrophysiologic data. It emphasizes the value of importance of standardized tools for understanding disease phenotype and their potential use as endpoints in future clinical trials. The findings established can provide a baseline for developing future prospective natural history studies and potential therapeutic clinical trials.

Association of Initial Side of Brain Atrophy With Clinical Features and Disease Progression in Patients With GRN Frontotemporal Dementia.

Pathogenic variants in the GRN gene cause frontotemporal dementia (FTD-GRN) with marked brain asymmetry. This study aims to assess whether the disease progression of FTD-GRN depends on the initial side of the atrophy. We also investigated the potential use of brain asymmetry as a biomarker of the disease. Retrospective examination of data from the prospective Genetic Frontotemporal Initiative (GENFI) cohort study that recruits individuals who carry or were at risk of carrying a pathogenic variant causing FTD. GENFI participants underwent a standardized clinical and neuropsychological assessment, MRI, and a blood sample test yearly. We generated an asymmetry index for brain MRI to characterize brain asymmetry in participants with or at risk of FTD-GRN. Depending on the side of the asymmetry, we classified symptomatic GRN patients as right-GRN or left-GRN and compared their clinical features and disease progression. We generated generalized additive models to study how the asymmetry index evolves in carriers and noncarriers and compare its models with others created with volumetric values and plasma neurofilament light chain. A total of 399 participants (mean age 49.7 years, 59% female) were included (63 symptomatic carriers, 177 presymptomatic carriers, and 159 noncarriers). Symptomatic carriers showed higher brain asymmetry (11.6) than noncarriers (1.0, p < 0.001) and presymptomatic carriers (1.0, p < 0.001), making it possible to classify most of them as right-GRN (n = 21) or left-GRN (n = 36). Patients with right-GRN showed more disease severity at baseline (β = 6.9, 95% CI 2.4-11.0, p = 0.003) but a lower deterioration by year (β = -1.5, 95% CI -2.7 to -0.31, p = 0.015) than patients with left-GRN. Brain asymmetry could be found in GRN carriers 10.4 years before the onset of the symptoms (standard difference 0.85, CI 0.01-1.68). FTD-GRN affects the brain hemispheres asymmetrically and causes 2 anatomical asymmetry patterns depending on the side of the disease onset. We demonstrated that these 2 anatomical asymmetry patterns present different symptoms, severity at the time of the first visit, and different disease courses. Our results also suggest brain asymmetry as a possible biomarker of conversion in GRN carriers.

Advancing Neuro-diagnostics through Virtual Reality (VR) Development of Immersive Tools for the Diagnosis of Neurodegenerative and Cognitive Disorders

This research aims to transform neurodiagnostic methodologies by employing Virtual Reality (VR) as an innovative tool for the early detection, diagnosis, and monitoring of neurodegenerative and cognitive disorders, particularly Alzheimer’s and Parkinson’s disease. The approach leverages VR-based, patient-centric simulations designed to assess cognitive and motor functions within realistic, immersive environments. By integrating machine learning algorithms, these simulations capture detailed motor and cognitive biomarkers, allowing for nuanced analysis and early identification of subtle neurodegenerative indicators. In clinical settings, the VR framework has proven to be a valuable diagnostic tool, offering enhanced engagement and precision over traditional methods. Key advancements include VR-based cognitive testing frameworks that simulate real-life tasks, significantly aiding in assessing memory, spatial orientation, and executive functions, and VR tools for motor function evaluation that incorporate tasks like gait analysis to detect early motor impairment linked to Parkinson's disease. Through interdisciplinary collaborations with neurologists, software engineers, and AI experts, we have clinically validated these VR tools and demonstrated their efficacy in various clinical trials against standard neuropsychological assessments. Ultimately, this research underscores the potential of VR and AI to contribute to a paradigm shift in the early diagnosis and intervention of neurodegenerative disorders.

Long-term neuroplasticity in language networks after anterior temporal lobe resection.

Anterior temporal lobe resection (ATLR) is an effective treatment for drug-resistant temporal lobe epilepsy (TLE), although language deficits may occur after both left and right ATLR. Functional reorganization of the language network has been observed in the ipsilateral and contralateral hemispheres within 12 months after ATLR, but little is known of longer-term plasticity effects. Our aim was to examine the plasticity of language functions up to a decade after ATLR, in relation to cognitive profiles. We examined 24 TLE patients (12 left [LTLE]) and 10 controls across four time points: pre-surgery, 4 months, 12 months, and ~9 years post-ATLR. Participants underwent standard neuropsychological assessments (naming, phonemic, and categorical fluency tests) and a verbal fluency functional magnetic resonance imaging (fMRI) task. Using a flexible factorial design, we analyzed longitudinal fMRI activations from 12 months to ~9 years post-ATLR, relative to controls, with separate analyses for people with hippocampal sclerosis (HS). Change in cognitive profiles was correlated with the long-term change in fMRI activations to determine the "efficiency" of reorganized networks. LTLE patients had increased long-term engagement of the left extra-temporal and contralateral temporal regions, with better language performance linked to bilateral activation. Those with HS exhibited more widespread bilateral activations. RTLE patients showed plasticity in the left extra-temporal regions, with better language outcomes associated with these areas. Both groups of patients achieved cognitive stability over 9 years, with more than 50% of LTLE patients improving. Older age, longer epilepsy duration, and lower pre-operative cognitive reserve negatively affected long-term language performance. Neuroplasticity continues for up to ~9 years post-epilepsy surgery in LTLE and RTLE, with effective language recovery linked to bilateral engagement of temporal and extra-temporal regions. This adaptive reorganization is associated with improved cognitive outcomes, challenging the traditional view of localized surgery effects. These findings emphasize the need for early intervention, tailored pre-operative counseling, and the potential for continued cognitive gains with extended post-ATLR rehabilitation.

Association between a lower T-CD4+ /CD8+ lymphocyte ratio and cognitive impairment in older persons with HIV.

To ascertain the association between the LT-CD4 + /CD8 + ratio and cognitive impairment in older people living with HIV. A cross-sectional study was conducted, including 207 adults aged > 50years with HIV, receiving care at a tertiary-care hospital in Mexico City. Participants underwent a standardized geriatric and neuropsychological assessment to establish the presence of HIV-associated neurocognitive disorder according to the validated Antinori criteria. Multivariate logistic regression models were performed to determine the association between T-CD4 + /CD8 + lymphocyte ratio tercile values (0.57-0.91, and < 0.56; with > 0.91 being the reference category) and cognitive impairment. Participants' median age was 56 (IQR 53-62)years and 173 (83.6%) were men. The prevalence of any kind of cognitive impairment according to the Antinori criteria was 66.2% (n = 137), the highest proportion being asymptomatic neurocognitive impairment (n = 114, 83.2%). Adjusted logistic regression analyses showed that the lowest LT-CD4 + /CD8 + ratio tercile values (< 0.56) were independently associated with the presence of cognitive impairment (OR 3.16; 95% CI 1.22-8.16, p = 0.017). Lower LT-CD4 + /CD8 + ratios are independently associated with cognitively impaired older persons with HIV, which represents another factor that could be addressed to identify individuals at risk and focus on cognitive screening as well as correction of other modifiable risk factors.

Multidomain cognitive improvement in patients with severe aortic valve stenosis undergoing transcatheter aortic valve implantation

Abstract Background Cognitive impairment is prevalent in one third of patients with symptomatic severe aortic valve stenosis scheduled for transcatheter aortic valve implantation (TAVI). How TAVI affects cognitive functioning in these patients remains unknown. Purpose The CAPITA study (CArdiac outPut, cerebral blood flow and cognition In patients with severe aortic valve stenosis undergoing Transcatheter Aortic valve implantation) assessed the effects of TAVI on cerebral lesions and cognitive functioning. Methods CAPITA is a prospective study of cerebral and cognitive outcomes in 148 patients undergoing TAVI. One day before and three months after TAVI, patients underwent a standardized multidomain neuropsychological assessment, and simultaneous brain magnetic resonance imaging. The primary outcome was change in global cognitive functioning as measured with z-scores. Also, we assessed the cognitive subdomains of attention/psychomotor speed, memory, language, and executive functioning. Z-scores for each cognitive domain were constructed as: (test score - mean baseline score) / standard deviation. Global cognitive function was calculated as the mean from the four domain scores. Results Mean age was 80.5±5.7 years, 43% was female and median STS-PROM (Society for Thoracic Surgeons Predicted Risk for 30-day Mortality) was 2.0% (IQR 1.4%-2.9%). MoCA scores improved from 23.3±3.7 to 24.4±3.3, (p&amp;lt;0.001) and MMSE scores from 26.4±2.6 to 26.9±2.4 (p=0.01). There was an overall increase in global cognitive z-scores (0.02±0.52 to 0.15±0.48, p&amp;lt;0.001). Cognitive domains of memory (0.03±0.77 to 0.18±0.80, p=0.003) and language (-0.07±1.07 to 0.20±0.80, p=0.02) significantly improved, whereas executive function (0.01±0.70 to 0.06±0.76, p=0.42) and attention (0.10±0.69 to 0.17±0.69, p=0.06) did not significantly change. Quality of life on the visual analogue scale improved from 66.4±15.9 to 72.9±12.8, (p&amp;lt;0.001). Patients in the lowest tertile of baseline cognitive functioning (i.e., those with worst baseline cognitive functioning), had the largest increase in cognitive functioning, compared with patients in the intermediate or highest tertile of baseline cognitive functioning (0.30±0.55 vs 0.09±0.27 vs 0.01±0.16, p=0.002). Patients with &amp;gt;0.5 SD decline in cognitive functioning (12%), had a higher volume of new white matter hyperintensities on follow-up MRI than patients with stable or improved cognitive functioning (1.26±2.96, vs 0.29±0.45 vs 0.31±0.91 mL, p=0.06). Conclusions In 148 patients who underwent TAVI, there was an overall improvement in cognitive functioning at three months follow-up. This improvement was consistent through different cognitive domains and most prominent in patient with lowest baseline cognitive functioning.Change in cognitive functionin

Self-other voice discrimination task: A potential neuropsychological tool for clinical assessment of self-related deficits

BackgroundDeficits in self are commonly described through different neuro-pathologies, based on clinical evaluations and experimental paradigms. However, currently available approaches lack appropriate clinical validation, making objective evaluation and discrimination of self-related deficits challenging. MethodsWe applied a statistical standardized method to assess the clinical discriminatory capacity of a Self-Other Voice Discrimination (SOVD) task. This task, validated experimentally as a marker for self-related deficits, was administered to 17 patients eligible for neurosurgery due to focal hemispheric brain tumors or epileptic lesions. ResultsThe clinical discriminatory capacity of the SOVD task was evident in three patients who exhibited impairments for self-voice perception that could not be predicted by other neuropsychological deficits. Impairments in other-voice perception were linked to inhibitory neuropsychological deficits, suggesting a potential association with executive deficits in voice recognition. ConclusionsThis exploratory study highlights the clinical discriminatory potential of the SOVD task and suggests that it could complement the standard neuropsychological assessment, paving the way for enhanced diagnoses and tailored treatments for self-related deficits.

A - 15 Convergent Validity between Standard Neuropsychological Assessment and Web-Based Voice-Recognition Neuropsychological Assessment (Intraneuron)

Abstract Objective The prevalence of mild cognitive impairment (MCI) remains high, and often cases may go undetected. The gold standard for detection of cognitive decline is neuropsychological assessment. However, access to neuropsychological assessment can be impacted by geographic and financial limitations. Prior research has determined that electronic-based testing is effective in detecting cognitive change. This study aimed to investigate a convergent validity between standard neuropsychological assessment (SNA) and a web-based, voice-recognition neuropsychological assessment tool (Intraneuron). Method 75 participants from a community-based neurology practice completed SNA and Intraneuron. Intraneuron is comprised of an auditory list learning/recall test and verbal fluency tests (F/A/S, animals). Pearson correlations were conducted to examine the convergent validity between SNA and Intraneuron. A McNemar cross tabulation analysis was utilized to compare the proportions of detected “normal” and “abnormal” screening for SNA (based on clinical diagnosis) and Intraneuron (utilizing 1SD and 1.5SD below the mean as cutoffs). Results There were moderate, positive correlations between the SNA and Intraneuron: animals (r = 0.43, p &amp;lt; 0.001), F/A/S (r = 0.67, p &amp;lt; 0.001), delayed word list recall (r = 0.49, p &amp;lt; 0.001). The McNemar test showed that the classification between SNA and Intraneuron were similar at 1SD and 1.5SD. Conclusions The study demonstrated convergent validity SNA and Intraneuron. Results suggest that the Intraneuron is equivalent in the detection of early cognitive decline compared to SNA. This data provides support for the value of a web-based screening tool and the potential to maximize utilization across multiple settings and improve early detection of cognitive decline.

Higher Number of Children Is Associated With Increased Risk of Generalization Deficits in Older African American Women.

The objectives of this project were to: (1) examine the relationship between the number of biological children and hippocampal-dependent cognitive performance among older African American women and (2) determine the influence of socioeconomic status (i.e., age, education, marital status, median household income), if any, on this relationship. A total of 146 cognitively unimpaired African American women aged 60 and older were recruited from the greater Newark area and reported their number of biological children, marital status, educational level, and age. We retrieved median household income from census tract data based on the participants' addresses. Participants' cognitive performance was assessed using the Rey Auditory Verbal Learning Test (RAVLT) long delay recall and a Rutgers generalization task (Concurrent Discrimination and Transfer Task). As the number of biological children a woman has had increases, the number of generalization errors also increased, indicating poorer hippocampal-dependent cognitive performance when controlling for age, education, marital status, and median household income. There was no significant relationship between the number of children and performance on a standardized neuropsychological measure of episodic memory (RAVLT), although education was a significant covariate. Generalization tasks may better capture early changes in cognitive performance in older African American women who have had children than standardized neuropsychological assessments. This finding may be explained by the fluctuations in estrogen associated with having children. Future studies should explore how these findings can be applied to protecting cognitive function and preventing Alzheimer's disease in older African American women who have had children.

Amygdala TDP-43 pathology is associated with behavioural dysfunction and ferritin accumulation in amyotrophic lateral sclerosis.

Cognitive and behavioural symptoms associated with amyotrophic lateral sclerosis and frontotemporal spectrum disorders (ALSFTSD) are thought to be driven, at least in part, by the pathological accumulation of TDP-43. Here we examine post-mortem tissue from six brain regions associated with cognitive and behavioural symptoms in a cohort of 30 people with sporadic ALS (sALS), a proportion of which underwent standardized neuropsychological behavioural assessment as part of the Edinburgh Cognitive ALS Screen (ECAS). Overall, the behavioural screen performed as part of the ECAS predicted accumulation of pathological phosphorylated TDP-43 (pTDP-43) with 100% specificity and 86% sensitivity in behaviour-associated brain regions. Notably, of these regions, pathology in the amygdala was the most predictive correlate of behavioural dysfunction in sALS. In the amygdala of sALS patients, we show variation in morphology, cell type predominance, and severity of pTDP-43 pathology. Further, we demonstrate that the presence and severity of intra-neuronal pTDP-43 pathology, but not astroglial pathology, or phosphorylated Tau pathology, is associated with behavioural dysfunction. Cases were also evaluated using a TDP-43 aptamer (TDP-43APT), which revealed that pathology was not only associated with behavioural symptoms, but also with ferritin levels, a measure of brain iron. Intra-neuronal pTDP-43 and cytoplasmic TDP-43APT pathology in the amygdala is associated with behavioural symptoms in sALS. TDP-43APT staining intensity is also associated with increased ferritin, regardless of behavioural phenotype, suggesting that ferritin increases may occur upstream of clinical manifestation, in line with early TDP-43APT pathology, representing a potential region-specific imaging biomarker of early disease in ALS.

Validation of the Cognitive Assessment Instrument for Obsessions and Compulsions (CAIOC-13) in an Indian Sample.

Brief self-report measures of cognition are advantageous for flagging significant cognitive dysfunction without extensive neuropsychological assessments. The Cognitive Assessment Instrument for Obsessions and Compulsions (CAIOC-13) is a recently developed self-report that assesses everyday cognitive dysfunction in obsessive-compulsive disorder (OCD), for example, difficulties with reading, slowness, and decision-making. This study was undertaken to validate the CAIOC-13 in an Indian sample of OCD. 75 subjects with OCD and 81 non-clinical controls completed CAIOC-13, Perceived Deficits Questionnaire (PDQ), and Dysfunctional Attitude Scale-Short Form (DAS-SF1). Convergent and divergent validity with PDQ and DAS-SF1 were established with Pearson's correlation; the Receiver Operating Characteristic (ROC) curve was used to analyze discriminant validity; and factorial structure was evaluated using the principal component analysis (PCA). CAIOC-13 scores showed a strong significant correlation (r = 0.56; p < .001) with PDQ and a moderate correlation with DAS-SF1 scores (r = 0.33; p = .003). CAIOC-13 could accurately discriminate between OCD and controls (area under curve = 0.92). PCA revealed strong loading on a single component. CAIOC-13 is a valid tool for briefly assessing OCD-related cognitive dysfunction in Indian samples. Future studies may examine the correlation of CAIOC-13 with standardized neuropsychological assessments.

Go4cognition: Evaluation of a Newly Developed Multicomponent Intervention in Mild Cognitive Impairment.

Cognitive training and physical exercise show positive effects on cognitive decline in subjects with mild cognitive impairment (MCI). Multimodal interventions for MCI patients, combining physical and cognitive training in a social context seem to slow down cognitive decline. Based on a previous study, a new mobile gamification tool (go4cognition; https://www.ontaris.de/go4cognition) has been developed to train cognitive and physical functions simultaneously in a group setting. It involves tasks targeting various cognitive functions (short-term memory, working memory, executive functions). The computer-based setup allows for individual performance analysis. This study evaluated the effects of this tool. 30 participants with MCI, as defined by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) cut-off-score, aged between 66 and 89 years, trained for one hour two days a week for twelve weeks. Additionally, standard neuropsychological assessment of memory and attention was carried out before and after the intervention. The go4cognition device is highly effective in improving various cognitive functions. A significant improvement in the CERAD total score resulting in re-classification of 70% of former MCI patients into non-MCI patients was found. Additionally, an improvement of verbal fluency, verbal memory, spatial memory, and attention was observed. Furthermore, the CERAD total score was significantly correlated with performance in the go4cognition tool. The results of the intervention support the idea of the effectiveness of a combined cognitive and motor intervention by incorporating neuropsychological paradigms in a group setting and suggest a close relation between combined cognitive and physical exercise and cognitive performance.

CSF β-Amyloid and Tau Biomarker Changes in Veterans With Mild Traumatic Brain Injury.

Moderate-to-severe traumatic brain injuries (TBI) have been reported to increase the risk of Alzheimer disease (AD). Whether mild TBI (mTBI) in veterans confers a similar increased risk of AD is less known. This study investigated early AD changes using CSF biomarkers in veterans with blast mTBI. This was a cross-sectional case-control study of veterans with mTBI and non-mTBI veterans and civilians from 2 study sources. Blast-mTBI veterans had at least 1 war zone blast or combined blast/impact mTBI meeting Veterans Affairs (VA) and Department of Defense (DoD) criteria for mTBI. Non-mTBI participants had no lifetime history of TBI. All participants underwent standardized clinical and neuropsychological assessments and lumbar puncture for collection of the CSF. CSF biomarkers were measured using MesoScale Discovery assays for Aβ40 and Aβ42 and INNOTEST ELISAs for phosphorylated tau181 (p-tau181) and total tau (t-tau). Our sample comprised 51 participants with mTBI and 85 non-mTBI participants with mean (SD) ages 34.0 (10.1) and 33.5 years (8.9), respectively. All participants but 1 (99%) were male. Differences in CSF AD biomarkers between mTBI and non-mTBI groups were age dependent and most pronounced at older ages (omnibus test p ≤ 0.08). At age 50 years, the mTBI group had lower mean [95% CI] CSF Aβ42 and Aβ40 than the non-mTBI group by 154 [-12 to 319] and 1864 [610-3,118] pg/mL, respectively. By contrast, CSF p-tau181 and t-tau mean levels remained relatively constant with age in participants with mTBI, while tending to be higher at older ages for the non-mTBI group. The mTBI group also demonstrated poorer cognitive performance at older ages (omnibus p < 0.08): at age 50 years, the mean TMT-B time was higher by 34 seconds [10-58] and the mean CVLT-II short-delay recall was lower by 4.2 points [1.9-6.6]. Poorer verbal memory and verbal fluency performance were associated with lower CSF Aβ42 (p ≤ 0.05) in older participants. CSF Aβ levels decreased in middle-aged veterans with blast-related mTBI. These data suggest that chronic neuropathologic processes associated with blast mTBI share properties in common with pathogenic processes known to portend AD onset, thus raising concern that veterans with blast-related mTBI may develop a dementing disorder later in life.

The Lack of Ad Hoc Neuropsychological Assessment in Adults with Neurofibromatosis: A Systematic Review.

Background: Neurofibromatosis Type 1 (NF1) is a genetic autosomal dominant disorder that affects both the central and peripheral nervous systems. Children and adolescents with NF1 commonly experience neuropsychological, motor, and behavioral deficits. The cognitive profile hallmark of this disorder includes visuospatial and executive function impairments. These cognitive disorders may persist into adulthood. This study aims to analyze previous research studies that have described cognitive dysfunctions in adults with NF1. The purpose of this analysis is to review the neuropsychological and psychological assessment methods used. Methods: A total of 327 articles were identified based on the search terms in their titles and abstracts. The evaluation was conducted by scrutinizing each article's title, abstract, and text. Results: Only 16 articles were found to be eligible for inclusion based on the pre-defined criteria. The selected studies primarily focus on the development of diagnostic protocols for individuals with NF1. Conclusions: The management of NF1 disease requires a multidisciplinary approach to address symptoms, preserve neurological functions, and ensure the best possible quality of life. However, cognitive impairment can negatively affect psychological well-being. This study suggested that cognitive functions in NF1 patients were not tested using specific measures, but rather were evaluated through intelligence scales. Additionally, the findings revealed that there is no standardized neuropsychological assessment for adults with NF1. To address this gap, it would be helpful to create a specific neuropsychological battery to study cognitive function in NF1 patients during clinical studies. This battery could also serve as a tool to design models for cognitive rehabilitation by using reliable and sensitive measures of cognitive outcomes.

Remote digital cognitive assessment reveals cognitive deficits related to hippocampal atrophy in autoimmune limbic encephalitis: a cross-sectional validation study

Autoimmune limbic encephalitis (ALE) is a neurological disease characterised by inflammation of the limbic regions of the brain, mediated by pathogenic autoantibodies. Because cognitive deficits persist following acute treatment of ALE, the accurate assessment of long-term cognitive outcomes is important for clinical assessments and trials. However, evaluating cognition is costly and an unmet need exists for validated digital methods. In this cross-sectional validation study, we investigated whether a remote digital platform could identify previously characterised cognitive impairments in patients with chronic ALE and whether digital metrics would correlate with standard neuropsychological assessment and hippocampal volume. Patients with ALE who had a chronic and stable presentation and received a clinical diagnosis of ALE were recruited for this study. The cognitive performance of 21 patients with ALE and 54 age-matched healthy controls - enrolled via the University of Oxford (UK) Cognitive Neurology Lab testing programme - was assessed with a battery of 12 cognitive tasks from the Cognitron online platform. The platform was optimised with National Institute for Health and Care Research (NIHR) support to be deliverable remotely to elderly and patient groups. The primary outcome measure was behavioural performance and corresponding neuroimaging and neuropsychological assessment metrics. Between February 15, 2021, and April 21, 2022, 21 patients with ALE (mean age 63.01 years, 14 males) and 54 healthy controls (mean age 65.56 years, 23 males) completed the digital cognitive assessment. Patients with ALE performed significantly worse in memory, visuospatial abilities, executive function, and language. No impairments in digit & spatial span, target detection (attention) and emotion discrimination were observed. The global score on the online cognitive tasks correlated significantly with the established Addenbrooke's Cognitive Examination III (ACE) pen-and-paper test. Deficits in visuospatial processing and language were identified in ALE compared to controls using remote digital testing but not using the ACE, highlighting higher sensitivity of computerised testing to residual cognitive impairment. Finally, the hippocampal volumes of patients with ALE and healthy controls correlated with online cognitive scores. These findings demonstrate that subtle cognitive deficits in patients with chronic ALE, who often show full recovery in measures of disability and dependence on daily activities, are detectable using a remote online platform, which also relates to hippocampal atrophy. Such methods may facilitate the characterisation of cognitive profiles in complex neurological diseases. Future longitudinal studies designed to assess the utility of such digital methods for further clinical characterisation are needed. The Wellcome Trust, Medical Research Council, National Institute for Health Research, Rhodes Scholarship, and the Berrow Foundation Scholarship.

Robotic assessment of sensorimotor and cognitive deficits in patients with temporal lobe epilepsy

ObjectiveIndividuals with temporal lobe epilepsy (TLE) frequently demonstrate impairments in executive function, working memory, and/or declarative memory. It is recommended that screening for cognitive impairment is undertaken in all people newly diagnosed with epilepsy. However, standard neuropsychological assessments are a limited resource and thus not available to all. Our study investigated the use of robotic technology (the Kinarm robot) for cognitive screening. Methods27 participants with TLE (17 left) underwent both a brief neuropsychological screening and a robotic (Kinarm) assessment. The degree of impairments and correlations between standardized scores from both approaches to assessments were analysed across different neurocognitive domains. Performance was compared between people with left and right TLE to look for laterality effects. Finally, the association between the duration of epilepsy and performance was assessed. ResultsAcross the 6 neurocognitive domains (attention, executive function, language, memory, motor and visuospatial) assessed by our neuropsychological screening, all showed scores that significantly correlated with Kinarm tasks assessing the same cognitive domains except language and memory that were not adequately assessed with Kinarm. Participants with right TLE performed worse on most tasks than those with left TLE, including both visuospatial (typically considered right hemisphere), and verbal memory and language tasks (typically considered left hemisphere). No correlations were found between the duration of epilepsy and either the neuropsychological screening or Kinarm assessment. SignificanceOur findings suggest that Kinarm may be a useful tool in screening for neurocognitive impairment in people with TLE. Further development may facilitate an easier and more rapid screening of cognition in people with epilepsy and distinguishing patterns of cognitive impairment.

MUSIC CREATIVITY INTERVENTION FOR OLDER ADULTS WITH AND WITHOUT MCI: COGNITIVE BENEFITS AND NEURAL MECHANISMS

Abstract Alzheimer’s and related dementias are debilitating conditions, and at this time, no cure has been identified. Older age is associated with cognitive decline and dementia. Developing and testing innovative non-pharmacological interventions to delay the loss of functional ability and understand the neurobiological mechanisms underlying the intervention’s efficacy is imperative. We conducted a semi-randomized clinical trial evaluating the effects of a novel music creativity curriculum on cognitive and neurological outcomes. Eighty older adults with and without a mild cognitive impairment (MCI) diagnosis were randomized to a 6-week music creativity intervention or a 6-week no-treatment control condition. Before and after the six weeks, both groups participated in a series of self-report and cognitive assessments; they also participated in resting-state fMRI scans to quantify whole-brain network patterns of modularity and flexibility. Those randomized to the music group exhibited improved overall cognitive function and working memory relative to the control group (assessed using standard clinical neuropsychological assessments). The association between being randomized to the music group and increased cognitive function was more robust among those who exhibited greater neural flexibility at baseline. The study shows that music creativity interventions may positively affect cognition, especially among those whose neural network structure is more dynamic or flexible. This study is innovative as it is among the first to identify possible neural mechanisms underlying why music creativity interventions confer a more significant cognitive benefit for some older adults than others.

CSF Alzheimer’s Disease Biomarker Changes in Veterans with Mild Traumatic Brain Injury

AbstractBackgroundTraumatic brain injury (TBI) has been reported to increase risk of Alzheimer’s dementia (AD). It remains unknown whether mild TBI (mTBI) caused by blast in Veterans confers a similar increase of risk. This study investigated early AD changes defined by cerebrospinal fluid (CSF) AD biomarkers in Veterans with blast mTBI.MethodFifty‐one Veterans with mTBI, 34 non‐mTBI Veterans, and 51 non‐mTBI civilians were recruited from Seattle, Washington. Age‐matched Veteran and civilian non‐mTBI participants had no lifetime history of TBI. All blast‐mTBI Veterans had experienced at least one war zone blast or combined blast/impact exposure, with acute symptoms meeting VA/Department of Defense criteria for mTBI. All participants underwent standardized clinical and neuropsychological assessments and lumbar puncture for collection of CSF. CSF biomarkers were measured at the Clinical Neurochemistry Lab in Mölndal, Sweden, using Meso Scale Discovery (MSD) assays for Aβ40 and Aβ42, and Innotest ELISAs for phosphorylated Tau181 (pTau181) and total Tau (tTau).ResultDifferences in all 4 CSF AD biomarkers between participants with and without mTBI were highly age‐dependent and most pronounced in older ages (Figure 1). Both CSF Aβ40 and Aβ42 became lower as age increasing in the mTBI group starting around age 40‐45 years, while they increased with age in the non‐mTBI participants. In contrast, CSF tTau and pTau181 mean levels remained relatively constant with age in participants with mTBI, but increased after age 45 in the non‐mTBI participants. Consequently, for participants aged 50+ years, Veterans with mTBI had lower mean AD biomarkers than the non‐mTBI participants. Similarly, the differences in cognitive performance were age‐dependent, i.e., poorer performance in older Veterans with mTBI than in the non‐mTBI participants. Furthermore, the relationships between CSF Aβ42 and cognitive performance were also age‐dependent; specifically, in participants aged 45+ years, lower CSF Aβ42 level was associated with poorer performance on tests of verbal fluency and memory.ConclusionThe earliest AD biomarker, CSF Aβ42, started to decrease in middle‐aged Veterans with mTBI, more than a decade earlier than those without mTBI in our earlier study, suggesting mTBI may accelerate brain deposition of Aβ and increase risk for AD.

QOL-25. FOR THE LOVE OF WORK: NOVEL STUDY OF VOCATIONAL COGNITIVE REHABILITATION IN PRIMARY BRAIN TUMOR

Abstract BACKGROUND Primary brain cancer survivors live longer, yet experience distress and cognitive impairments that negatively impact their quality of life (QOL), including at work. We present a novel study of vocational tele-cognitive rehabilitation in primary brain cancer survivors. METHODS Retrospective review, post-treatment, radiologically stable adult primary brain cancer patients who completed standardized neuropsychological, psychological, vocational, and QOL assessments. Wilcoxon rank sum and Fisher’s exact or Chi-square tests assessed between-group and within-group comparisons. Tests were two-sided and statistically significant for p &amp;lt; 0.05. RESULTS 79 patients with known baseline work status assessed for between-group comparisons (working versus not). Working (n = 38) and not working (n = 41) subgroups had similar ages, tumor grade/type, and history of radiotherapy. Working had worse executive functioning (p = .05). Not working (n = 41) had worse cognitive function (executive function, attention, verbal learning all p &amp;lt; 0.05) and more engagement in survivorship services (p &amp;lt; 0.04). Of the 79 work-status known patients, 38 underwent vocational tele-cognitive rehabilitation (median 11 sessions) treatment for within-group comparisons. 82% of the treatment group had improved work status compared to 34% in non-treatment. Baseline work status and age were not related to occupational improvements (all p &amp;gt;0.20). Higher dose high radiotherapy dose inversely related to rehab improvements (p&amp;lt; .05). Higher verbal memory (p = 0.05), processing speed (p = .06), executive functioning (p = 0.02), IDH mutation status (p = .06), and motivation for treatment (p = .04) was associated with improvement. Those with depressive symptoms who engaged in clinically indicated psychotherapeutic services significantly improved their work status (p = .01). CONCLUSION Occupational functioning improved after cognitive rehabilitation. Cognitive impairments, IDH mutation status, higher dose radiotherapy, and treatment motivation are important. Not working at baseline, despite more cognitive impairments, improved similar to their working counterparts. Those with depression benefitted from psychotherapeutic support. Vocational tele-cognitive rehabilitation shows promise for improving the work-based abilities of primary brain tumor patients and warrants further investigation.