Neuropsychological Performance Research Articles

Ketogenic diet modifies ribosomal protein dysregulation in KMT2D Kabuki syndrome

BackgroundKabuki syndrome (KS) is a genetic disorder caused by DNA mutations in KMT2D, a lysine methyltransferase that methylates histones and other proteins, and therefore modifies chromatin structure and subsequent gene expression. Ketones, derived from the ketogenic diet, are histone deacetylase inhibitors that can ‘open’ chromatin and encourage gene expression. Preclinical studies have shown that the ketogenic diet rescues hippocampal memory neurogenesis in mice with KS via the epigenetic effects of ketones. MethodsSingle-cell RNA sequencing and mass spectrometry-based proteomics were used to explore molecular mechanisms of disease in individuals with KS (n=4) versus controls (n=4). FindingsPathway enrichment analysis indicated that loss of function mutations in KMT2D are associated with ribosomal protein dysregulation at an RNA and protein level in individuals with KS (FDR <0.05). Cellular proteomics also identified immune dysregulation and increased abundance of other lysine modification and histone binding proteins, representing a potential compensatory mechanism. A 12-year-old boy with KS, suffering from recurrent episodes of cognitive decline, exhibited improved cognitive function and neuropsychological assessment performance after 12 months on the ketogenic diet, with concomitant improvement in transcriptomic ribosomal protein dysregulation. InterpretationOur data reveals that lysine methyltransferase deficiency is associated with ribosomal protein dysfunction, with secondary immune dysregulation. Diet and the production of bioactive molecules such as ketone bodies serve as a significant environmental factor that can induce epigenetic changes and improve clinical outcomes. Integrating transcriptomic, proteomic, and clinical data can define mechanisms of disease and treatment effects in individuals with neurodevelopmental disorders. FundingThis study was supported by the Dale NHMRC Investigator Grant (APP1193648) (R.D), Petre Foundation (R.D), and The Sydney Children’s Hospital Foundation/Kids Research Early and Mid-Career Researcher Grant (E.T).

Neuropsychological profiles in first-episodes psychosis and their relationship with clinical, metacognition and social cognition variables.

An increasing interest in the assessment of neuropsychological performance variability in people with first-episode psychosis (FEP) has emerged. However, its association with clinical and functional outcomes requires further study. Furthermore, FEP neuropsychological subgroups have not been characterized by clinical insight or metacognition and social cognition domains. The aim of this exploratory study was to identify specific groups of patients with FEP based on neuropsychological variables and to compare their sociodemographic, clinical, metacognition and social cognition profiles. A sample of 149 FEP was recruited from adult mental health services. Neuropsychological performance was assessed by a neuropsychological battery (WAIS-III; TMT; WSCT; Stroop Test; TAVEC). The assessment also included sociodemographic characteristics, clinical, functional, metacognition and social cognition variables. Two distinct neuropsychological profiles emerged: one neuropsychological impaired cluster (N = 56) and one relatively intact cluster (N = 93). Significant differences were found between both profiles in terms of sociodemographic characteristics (age and level of education) (p = 0.001), clinical symptoms (negative, positive, disorganized, excitement and anxiety) (p = 0.041-0.001), clinical insight (p = 0.038-0.017), global functioning (p = 0.014), as well as in social cognition domains (emotional processing and theory of mind) (p = 0.001; p = 0.002). No significant differences were found in metacognitive variables (cognitive insight and 'jumping to conclusions' bias). Relationship between neurocognitive impairment, social cognition and metacognition deficits are discussed. Early identifying of neuropsychological profiles in FEP, characterized by significant differences in clinical and social cognition variables, could provide insight into the prognosis and guide the implementation of tailored early-intervention.

Examining the role of depression on the relationship between performance-based and self-reported cognitive functioning after sport-related concussion.

Little is known about the relationship between neuropsychological test performance, cognitive symptom reporting, and depressive symptoms after sport-related concussion. Accordingly, this cross-sectional study examined these relationships in collegiate athletes. It was hypothesized that depressive symptoms would moderate and mediate the relationship between performance-based and self-reported cognitive functioning after concussion. After sustaining a sport-related concussion, 110 collegiate athletes completed a neuropsychological battery, the Post-Concussion Symptoms Scale, and the Beck Depression Inventory-Fast Screen. Neuropsychological test performance, depressive symptoms, and their interactions were entered into distinct hierarchical linear regression analyses with self-reported cognition as the dependent variable to assess moderation. Mediation was analyzed using the PROCESS macro with 5000 bootstrap samples and a 95% confidence interval. There was a significant interaction between the mean memory composite and depressive symptoms when predicting cognitive symptom reporting, p = 0.047. Simple effects tests revealed that for athletes who had a lower memory composite score, an increase in depressive symptoms led to an increase in self-reported cognitive dysfunction, p < 0.001, ηp2 = 0.11. Depressive symptoms partially mediated the relationship between the memory composite and cognitive symptom reporting, indirect effect = -0.26, 95%CI[-0.58,0.001], but this relationship was not found for any other neurocognitive domain. For tests of memory, depressive symptoms moderated and partially mediated the relationship between performance-based and self-reported cognitive functioning after sport-related concussion. Athletes reporting high depressive symptoms and cognitive dysfunction may need more comprehensive evaluations to inform return-to-play decisions, and depression could be a treatment target for athletes who report high levels of cognitive dysfunction after concussion.

Increased anterior insula connectivity associated with cognitive maintenance in amnestic mild cognitive impairment: a longitudinal study.

The insula, a crucial hub of the human brain network, can be divided into anterior and posterior regions. Previous studies have reported that different insula subregions play various roles in amnestic mild cognitive impairment (aMCI). However, the longitudinal changes in the functional connectivity (FC) of each insula subregion in aMCI patients over time remain unclear. Twenty aMCI patients and 20 healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging (fMRI) scans and neuropsychological assessments at baseline and at the 15-month follow-up. FMRI data were preprocessed using SPM 12 and the CONN toolbox. Two-way analysis of covariance was used to compare longitudinal changes in the FC of each insula subregion with covariates including sex, age, education, follow-up interval, volume of gray matter, and global correlation (GCOR). Pearson's correlation was used to evaluate the relationship between insula subregional FC and neuropsychological performance in aMCI patients. In aMCI patients, the right anterior insula exhibited significantly increased FC with the left anterior cingulate cortex, whereas the left posterior insula exhibited decreased FC with the right precuneus compared with HCs. Furthermore, FC between the right anterior insula and left anterior cingulate cortex was significantly correlated with global cognition at follow-up. The current findings revealed different functional alterations in the insula subregions and provided new insights into the neurodegenerative process in aMCI patients.

Similarities and differences of neuropsychological functions, metacognitive abilities and resilience in Cognitive Disengagement Syndrome (CDS) and Attention Deficit/Hyperactivity Disorder (ADHD)

It was aimed to evaluate the relationships between neuropsychological functions, self-reported metacognitive abilities, and resilience levels among children with Attention Deficit Hyperactivity Disorder (ADHD) and those with Cognitive Disengagement Syndrome (CDS) compared to healthy controls. This cross-sectional, case-control study was consisted of 36 children with CDS only, 36 with ADHD only, 33 with CDS and ADHD and 39 control children were enrolled for a total sample of 144 children. The intellectual and neuropsychological functioning of the participating children was evaluated using the WISC-IV. Metacognitive Awareness Inventory for Children(MAI-C), Emotional Resilience Scale(ERS), and Revised Child Anxiety and Depression Scale(RCADS) were used. In both Processing Speed Index (PSI) and Perceptual Reasoning Index (PRI), children with CDS had significantly lower scores compared to those with ADHD, while those with ADHD and ADHD + CDS were similar to each other and controls. Children with CDS had greater metacognitive awareness than those with ADHD only and those with ADHD + CDS, whereas controls had the greatest level of metacognitive awareness. The emotional sensitivity of children with CDS was similar to that of children with ADHD + CDS and significantly greater than that of children with ADHD and controls, while control children had the lowest levels. The results of this study suggest that metacognitive abilities and emotional resilience may be targeted in rehabilitation/therapy of children with CDS ± ADHD and that interventions targeting processing speed and perceptual reasoning in younger children with CDS symptoms may be beneficial.

Longitudinal neuropsychological performance of post-stroke adults with and without rehabilitation

This study compared the neuropsychological performance of two post-stroke groups, one undergoing rehabilitation and the other not receiving any intervention, on the acute and chronic stroke phases, and explored sociodemographic and neurological variables associated with changes in performance over time. Sixty-three adults underwent neuropsychological assessment with the Cognitive Screening Instrument (TRIACOG) less than thirty days after having a stroke and were reassessed three to six months after stroke. Thirty-eight participants did not undertake rehabilitation and twenty-five did physiotherapy and/or speech therapy between the two time points. The frequency of cognitive deficits (between groups) and the range of cognitive assessment scores over time (between and within groups) were analyzed. There was a significant decrease in the frequency of neuropsychological deficits and improvement on neuropsychological assessment scores over time only in the group undergoing rehabilitation. Severity of the neurological condition, years of education and being in rehabilitation explained the longitudinal changes in several cognitive domains measured by TRIACOG. Engaging in rehabilitation within three to six months post-stroke is crucial for enhancing the recovery of neuropsychological deficits. Cognitive screening instruments like TRIACOG can be used by health professionals to identify stroke-related neuropsychological changes and plan interventions.

Deep brain stimulation in Parkinson's disease: A scientometric and bibliometric analysis, trends, and research hotspots.

Parkinson disease (PD), a prevalent neurodegenerative ailment in the elderly, relies mainly on pharmacotherapy, yet deep brain stimulation (DBS) emerges as a vital remedy for refractory cases. This study performs a bibliometric analysis on DBS in PD, delving into research trends and study impact to offer comprehensive insights for researchers, clinicians, and policymakers, illuminating the current state and evolutionary trajectory of research in this domain. A systematic search on March 13, 2023, in the Scopus database utilized keywords like "Parkinson disease," "PD," "Parkinsonism," "Deep brain stimulation," and "DBS." The top 1000 highly cited publications on DBS in PD underwent scientometric analysis via VOS Viewer and R Studio's Bibliometrix package, covering publication characteristics, co-authorship, keyword co-occurrence, thematic clustering, and trend topics. The bibliometric analysis spanned 1984 to 2021, involving 1000 cited articles from 202 sources. The average number of citations per document were 140.9, with 31,854 references. "Movement Disorders" led in publications (n = 98), followed by "Brain" (n = 78) and "Neurology" (n = 65). The University of Oxford featured prominently. Thematic keyword clustering identified 9 core research areas, such as neuropsychological function and motor circuit electrophysiology. The shift from historical neurosurgical procedures to contemporary focuses like "beta oscillations" and "neuroethics" was evident. The bibliometric analysis emphasizes UK and US dominance, outlining 9 key research areas pivotal for reshaping Parkinson treatment. A discernible shift from invasive neurosurgery to DBS is observed. The call for personalized DBS, integration with NIBS, and exploration of innovative avenues marks the trajectory for future research.

Neuropsychological functioning of adults with PTEN hamartoma tumor syndrome.

PTEN hamartoma tumor syndrome (PHTS) might be associated with a distinct cognitive and psychological profile. However, previous studies are limited, predominantly based on small and pediatric cohorts, likely affected by selection bias, and show a broad range of findings. We aimed to characterize the neuropsychological functioning of adults with PHTS. A total of 40 participants, with intellectual disability as exclusion criterium, completed an extensive clinical neuropsychological assessment including cognitive tasks, questionnaires, and a clinical diagnostic interview. The cognitive tasks and questionnaire data were categorized as below and above average based on 1.5 SD. About 80% of participants showed an average level of intelligence. In addition, 30% and 24% of participants scored below average on immediate memory recall and speed of information processing, respectively. Furthermore, about 25% reported above average scores on the majority of the questionnaires, indicating psychological distress, signs of alexithymia, and cognitive complaints. Personality of participants was characterized by inflexibility, social withdrawal, and difficulties in recognizing and describing their own emotions. Adults with PHTS demonstrate a heterogeneous yet distinct neuropsychological profile that is characterized by slower information processing, psychological problems, and specific personality traits. These findings provide directions on how to optimize the care and daily lives of adults with PHTS.

Single-value brain activity scores reflect both severity and risk across the Alzheimer's continuum.

Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional magnetic resonance imaging (fMRI) activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive aging. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer's disease (AD) and risk states like mild cognitive impairment (MCI) or subjective cognitive decline (SCD). To this end, we analyzed subsequent memory fMRI data from individuals with SCD, MCI, and AD dementia as well as healthy controls (HC) and first-degree relatives of AD dementia patients (AD-rel) who participated in the multi-center DELCODE study (N = 468). Based on the individual participants' whole-brain fMRI novelty and subsequent memory responses, we calculated the FADE and SAME scores and assessed their association with AD risk stage, neuropsychological test scores, CSF amyloid positivity, and ApoE genotype. Memory-based FADE and SAME scores showed a considerably larger deviation from a reference sample of young adults in the MCI and AD dementia groups compared to HC, SCD and AD-rel. In addition, novelty-based scores significantly differed between the MCI and AD dementia groups. Across the entire sample, single-value scores correlated with neuropsychological test performance. The novelty-based SAME score further differed between Aβ-positive and Aβ-negative individuals in SCD and AD-rel, and between ApoE ε4 carriers and non-carriers in AD-rel. Hence, FADE and SAME scores are associated with both cognitive performance and individual risk factors for AD. Their potential utility as diagnostic and prognostic biomarkers warrants further exploration, particularly in individuals with SCD and healthy relatives of AD dementia patients.

Cognition and Functional Capacity: An Initial Comparison of Veteran and Non-Veteran Older Adults.

The U.S. Military Veterans aged 65 and older comprise an estimated 43% of the 22 million living Veterans in the United States. Veterans have high rates of physical, psychiatric, and social challenges, but it is not known whether Veteran status confers additional risk for cognitive or functional impairments in later life. Thus, this investigation specifically compared older Veterans with their non-Veteran peers in cognitive functioning and performance-based functional capacity. Participants (N = 110; 29 Veterans and 81 non-Veterans) were part of a larger longitudinal study on biopsychosocial functioning in independently living older adult residents of a Continuing Care Senior Housing Community. The University of California San Diego Institutional Review Board approved the study and all participants provided written informed consent. Participants provided demographic and mental health information and were administered a comprehensive neuropsychological battery. Functional capacity was assessed using the UCSD Performance-Based Skills Assessment-Brief (UPSA-B), which uses financial and communication role-plays to assess everyday functioning skills. Neuropsychological scores were appropriately normed prior to analysis. Multivariate Analyses of Variances with post hoc t-tests and an Analysis of Covariance were used to examine neuropsychological and functional capacity differences, respectively, between Veterans and non-Veterans. Veterans did not differ from non-Veterans in educational attainment (16.4 years versus 15.5 years, P = 0.110), but they were significantly older (mean age 86.9 years ± 5.7, versus 81.74 years ± 6.53; P < 0.001) and were more likely to be male (X2 [1, N = 110] = 62.39, P < 0.001). Thus, though neuropsychological norms already accounted for demographic differences in our participants, age and sex were controlled in the Analysis of Covariance predicting UPSA-B score from Veteran status. Results suggested that, compared to non-Veterans, Veterans had significantly worse performance in the list learning portion of a test of verbal memory (Hopkins Verbal Learning Test-Revised, Total Recall; t = 2.56, P = 0.012, d = 0.56). Veterans and non-Veterans did not significantly differ in performance on the delayed recall portion of the verbal learning test and did not differ on a cognitive screening test (Montreal Cognitive Assessment) or on measures of premorbid intellectual functioning (Wide Range Achievement Test-4 Reading), language (Boston Naming Test, Verbal Fluency), visual memory (Brief Visuospatial Memory Test-Revised), attention/working memory (WAIS-IV Digit Span), processing speed (WAIS-IV Digit Symbol Coding), executive function (Delis-Kaplan Executive Function System Trails and Color-Word Test), or functional capacity (UPSA-B). Because our examination of multiple outcomes might have inflated Type I error, we performed a post hoc adjustment of P values using Benjamini-Hochberg procedures and the group difference in verbal learning remained significant. Despite largely similar function in most domains, Veterans performed significantly more poorly in verbal list learning than their non-Veteran peers. Additional attention should be given to the understanding, assessment, and possible treatment of learning and memory differences in older Veterans, as this may be an area in which Veteran status confers additional risk or vulnerability to decline. This is the first study to compare objective neuropsychological and functional performance between older (age 65+) US Veterans and non-Veterans.

Veterans Aging Cohort Study Index 2.0 Shows Improved Discrimination of Neurocognitive Impairment and Frailty in People with HIV

Objective: This study examined whether the revised VACS2.0 index (including serum albumin, body mass index (BMI), and white blood cell (WBC) count) had stronger correlations with cognitive function, brain volume, and frailty in PWH ≥ 50 years compared to the VACS1.0. Design and Methods: Neuropsychological performance (NP) Z-scores (learning, retention, executive functioning (EF), psychomotor function/processing speed (PM/PS), language, and global cognition), and neuroimaging measures (brain volumetrics) were analyzed in PWH (n = 162). A subset of the sample (n = 159) was defined as either frail (n = 18) or non-frail (n = 141) according to the Fried phenotype criteria. Brain volumes, NP scores, and frailty subgroups were analyzed with both VACS scores, albumin, BMI, and WBC count using Pearson's significance tests and independent T-tests. Results: Higher VACS scores significantly correlated with lower brain volumes. Higher VACS2.0 scores were associated with lower NP in the EF and PM/PS domains and were primarily driven by albumin. VACS1.0 scores did not correlate with cognition Z-scores. There was no relationship between frailty status and VACS1.0. PWH who were frail had significantly greater VACS2.0 scores than non-frail PWH. Conclusions: The addition of albumin to the VACS index improved its correlations with NP and frailty in PWH. While low albumin levels may contribute to cognitive decline or frailty, the reverse causality should also be considered. These findings suggest that the VACS2.0 index (especially albumin) is a valuable measure for clinicians to improve outcomes in PWH.

Neuropsychological Profile of 25 Brazilian Patients with 22q11.2 Deletion Syndrome: Effects of Clinical and Socioeconomic Variables.

The 22q11.2 deletion syndrome (22q11.2DS) is associated with a heterogeneous neurocognitive phenotype, which includes psychiatric disorders. However, few studies have investigated the influence of socioeconomic variables on intellectual variability. The aim of this study was to investigate the cognitive profile of 25 patients, aged 7 to 32 years, with a typical ≈3 Mb 22q11.2 deletion, considering intellectual, adaptive, and neuropsychological functioning. Univariate linear regression analysis explored the influence of socioeconomic variables on intellectual quotient (IQ) and global adaptive behavior. Associations with relevant clinical conditions such as seizures, recurrent infections, and heart diseases were also considered. Results showed IQ scores ranging from 42 to 104. Communication, executive functions, attention, and visuoconstructive skills were the most impaired in the sample. The study found effects of access to quality education, family socioeconomic status (SES), and caregiver education level on IQ. Conversely, age at diagnosis and language delay were associated with outcomes in adaptive behavior. This characterization may be useful for better understanding the influence of social-environmental factors on the development of patients with 22q11.2 deletion syndrome, as well as for intervention processes aimed at improving their quality of life.

Pituitary dysfunction following mild traumatic brain injury in female athletes: neuropsychological and psychological functioning

Pituitary dysfunction following mild traumatic brain injury in female athletes: neuropsychological and psychological functioning

Deep brain stimulation of the amygdala for treatment-resistant combat post-traumatic stress disorder: Long-term results

Deep brain stimulation (DBS) holds promise for neuropsychiatric conditions where imbalance in network activity contributes to symptoms. Treatment-resistant Combat post-traumatic stress disorder (TR-PTSD) is a highly morbid condition and 50% of PTSD sufferers fail to recover despite psychotherapy or pharmacotherapy. Reminder-triggered symptoms may arise from inadequate top-down ventromedial prefrontal cortex (vmPFC) control of amygdala reactivity. Here, we report long-term data on two TR-PTSD participants from an investigation utilizing high-frequency amygdala DBS. The two combat veterans were implanted bilaterally with quadripolar electrodes targeting the basolateral amygdala. Following a randomized staggered onset, patients received stimulation with adjustments based on PTSD symptom severity for four years while psychiatric and neuropsychiatric symptoms, neuropsychological performance, and electroencephalography were systematically monitored. Evaluation of vmPFC-Amygdala network engagement was assessed with 18FDG positron emission tomography (PET). CAPS-IV scores varied over time, but improved 55% from 119 at baseline to 53 at 4-year study endpoint in participant 1; and 44%, from 68 to 38 in participant 2. Thereafter, during 5 and 1.5 years of subsequent clinical care respectively, long-term bilateral amygdala DBS was associated with additional, clinically significant symptomatic and functional improvement. There were no serious stimulation-related adverse psychiatric, neuropsychiatric, neuropsychological, neurological, or neurosurgical effects. In one subject, symptomatic improvement was associated with an intensity-dependent reduction in amygdala theta frequency power. In our two participants, FDG-PET findings were inconclusive regarding the hypothesized mechanism of suppression of amygdala hyperactivity. Our findings encourage further research to confirm and extend our preliminary observations.

INTRAVENOUS IMMUNOGLOBULINS LEAD TO FUNCTIONAL VASCULAR AMELIORATION IN LONG-COVID

Objective: The Long-COVID syndrome constitutes a major physical and psychological challenge for many patients after the recovery from COVID-19. We have previously shown positive effects of intravenous immunoglobulins (IVIG) on multiple symptoms. The effect of this therapeutical approach on vascular function and different levels of disease burden remains elusive. Design and method: We performed a prospective study, enrolling 21 patients with diagnosed Long-COVID, who received 3 monthly courses of IVIG (0.5 g/kg Privigen, CSL Behring, Austria) alongside supportive therapy (group 1). The control group (group 2; n=29) was addressed by supportive therapy, only. The study population was homogeneous for age, comorbidities and time since SARS-CoV-2 infection. We assessed vascular endothelial function by flow mediated dilation (FMD). Long-COVID associated fatigue intensity, related disability and quality of life were assessed by Short Form Health Survey-36, Chalder and Bell scale. Neuropsychological assessments utilized the German version of the ’Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery’ (CERAD-Plus). Results: The median FMD at baseline in group 1 was 5.0% (interquartile range [IQR] 4.2-6.1%). We saw a substantial amelioration (+27%) of FMD after IVIG, reaching a median of 6.6% (IQR 4.5-9.4%; p=0.039). Baseline FMD in the comparison group was 5.2% (IQR 3.5-7.6%), supportive treatment resulting in unsignificant increase (FMD 6.1% [IQR 4.6-7.7%; p=0.177). Baseline CERAD-Plus scores were comparable between groups (p=0.280). Only treatment with IVIG resulted in a relevant amelioration of neurocognition (p=0.05; group 2 p=0.430). Furthermore, less Fatigue (Chalder Fatigue scale bimodal and Likert p=0.002, each) and disability was seen after 3 months of IVIG (Bell Score, p=0.008), supportive treatment did not ameliorate this burden (Chalder Fatigue Scale bimodal p=0.086 and Likert p=0.952; Bell Score p=0.121). Health related quality of life (SF-36) increased for both groups (group 1 p=0.003, group 2 p=0.017). Conclusions: Using a broad test battery, addressing neuropsychological function, fatigue, related disability and health related quality of life as well as vascular function, we were able to confirm the potential beneficial effect of IVIG in Long-COVID. IVIG might be a candidate approach in this context, that requires further evaluation in randomized controlled trials.

Data-driven decomposition and staging of flortaucipir uptake in Alzheimer's disease.

Previous approaches pursuing in vivo staging of tau pathology in Alzheimer's disease (AD) have typically relied on neuropathologically defined criteria. In using predefined systems, these studies may miss spatial deposition patterns which are informative of disease progression. We selected discovery (n=418) and replication (n=132) cohorts with flortaucipir imaging. Non-negative matrix factorization (NMF) was applied to learn tau covariance patterns and develop a tau staging system. Flortaucipir components were also validated by comparison with amyloid burden, gray matter loss, and the expression of AD-related genes. We found eight flortaucipir covariance patterns which were reproducible and overlapped with relevant gene expression maps. Tau stages were associated with AD severity as indexed by dementia status and neuropsychological performance. Comparisons of flortaucipir uptake with amyloid and atrophy also supported our model of tau progression. Data-driven decomposition of flortaucipir uptake provides a novel framework for tau staging which complements existing systems. NMF reveals patterns of tau deposition in AD. Data-driven staging of flortaucipir tracks AD severity. Learned flortaucipir patterns overlap with AD-related gene expression.

Back from the sideline, but back to baseline? A pediatric case study examining neuropsychological functioning after sustaining multiple sport-related concussions

ABSTRACT Most individuals recover quickly from a concussion; however, youth who sustain multiple concussions may be at risk for long-term cognitive impairments. This case study examines the neuropsychological performance of a 13-year-old malewith five head injuries. After his first concussion during study participation (fourth injury overall), several improvements were observed, likely due to practice effects, yet after sustaining another concussion <2 years later,declines were observed in visuoconstruction, verbal memory, and intellectual functioning. Across serial re-evaluation, his vocabulary knowledge declined, and fewer improvements were observed than anticipated when accounting for serial practice effects, highlighting the possible cumulative impact of multiple concussions.

Cognitive and brain connectivity trajectories in critically ill COVID-19 patients.

Multiple Organ failure (MOF) is one of the main causes of admission to the Intensive Care Unit (ICU) of patients infected with COVID-19 and can cause short- and long-term neurological deficits. To compare the cognitive functioning and functional brain connectivity at 6-12 months after discharge in two groups of individuals with MOF, one due to COVID-19 and the other due to another cause (MOF-group), with a group of Healthy Controls (HC). Thirty-six participants, 12 from each group, underwent a neuropsychological and neuroimaging assessment at both time-points. Functional connectivity of the resting state networks was compared between COVID-19 and HC while controlling for the effect of MOF. The association between functional connectivity and neuropsychological performance was also investigated. Compared to the HC, COVID-19 group demonstrated hypoconnectivity between the Default Mode Network and Salience Network. This pattern was associated with worse performance on tests of attention and information processing speed, at both time-points. The study of the association between cognitive function and brain functional connectivity in COVID-19 allows the understanding of the short- and long-term neurological alterations of this disease and promotes the development of intervention programs to improve the quality of life for this understudied population.

GBA moderates cognitive reserve's effect on cognitive function in patients with Parkinson's disease.

Cognitive reserve (CR) involves an individual's ability to maintain cognitive vitality over their lifespan. Glucocerebrosidase (GBA) gene mutations contribute to additional effects on cognitive function in Parkinson's disease (PD) patients, but the interplay between GBA mutations and CR remains unclear. We investigated the interactions among CR, GBA, and diseases, aiming to examine whether the CR established at different stages interacts with specific genotypes to affect cognitive function. Three hundred and eighteen participants' CR indicators (i.e., education, occupation, and social function) and comprehensive neuropsychological function (i.e., tests for executive function, attention/working memory, visuospatial function, memory, and language) were evaluated. We found that CR established in a specific life stage influences the individual's cognitive function, particularly in PD, based on their distinct GBA rs9628662 genotypes. Attention/working memory and memory performance are affected by occupational complexity in midlife in PD patients with the GG genotype (q < 0.0001; q < 0.0001) and healthy adults with the T genotype (q = 0.0440; q < 0.0001). Language is influenced by early education and occupation, and the effects of occupation are also observed in PD patients with the GG genotype (q = 0.0040) and in healthy adults carrying the T genotype (q = 0.0040). CR, established at different life stages, can be influenced by the GBA rs9628662 genotype, impacting later-life cognition. Validating genotypes and incorporating genotype information when assessing cognitive reserve effects is crucial and can enhance targeted cognitive training.

Long-term neuropsychological trajectories in children with epilepsy: does surgery halt decline?

Neuropsychological impairments are common in children with drug-resistant epilepsy. It has been proposed that epilepsy surgery may alleviate these impairments by providing seizure freedom; however, findings from prior studies have been inconsistent. We mapped long-term neuropsychological trajectories in children before and after undergoing epilepsy surgery, to measure the impact of disease course and surgery on functioning. We performed a retrospective cohort study of 882 children who had undergone epilepsy surgery at Great Ormond Street Hospital (1990-2018). We extracted patient information and neuropsychological functioning - obtained from IQ tests (domains: Full-Scale IQ, Verbal IQ, Performance IQ, Working Memory, and Processing Speed) and tests of academic attainment (Reading, Spelling and Numeracy) - and investigated changes in functioning using regression analyses. We identified 500 children (248 females) who had undergone epilepsy surgery (median age at surgery = 11.9 years, interquartile range = [7.8,15.0]) and neuropsychology assessment. These children showed declines in all domains of neuropsychological functioning in the time leading up to surgery (all p-values ≤ 0.001; e.g., βFSIQ = -1.9, SEFSIQ = 0.3, pFSIQ < 0.001). Children lost on average one to four points per year, depending on the domain considered; 27-43% declined by 10 or more points from their first to their last preoperative assessment. At the time of presurgical evaluation, most children (46-60%) scored one or more standard deviations below the mean (<85) on the different neuropsychological domains; 37% of these met the threshold for intellectual disability (Full-Scale IQ < 70). On a group level, there was no change in performance from pre- to postoperative assessment on any of the domains (all p-values > 0.128). However, children who became seizure-free through surgery showed higher postoperative neuropsychological performance (e.g., rrb-FSIQ = 0.37, p < 0.001). These children continued to demonstrate improvements in neuropsychological functioning over the course of their long-term follow-up (e.g., βFSIQ = 0.9, SEFSIQ = 0.3, pFSIQ = 0.004). Children who had discontinued antiseizure medication (ASM) treatment at one-year follow-up showed an eight-to-13-point advantage in postoperative Working Memory, Processing Speed, and Numeracy, and greater improvements in Verbal IQ, Working Memory, Reading, and Spelling (all p-values < 0.034) over the postoperative period compared to children who were seizure-free and still receiving ASMs. In conclusion, by providing seizure freedom and the opportunity for ASM cessation, epilepsy surgery may not only halt but reverse the downward trajectory that children with drug-resistant epilepsy display in neuropsychological functioning. To halt this decline as soon as possible, or potentially prevent it from occurring in the first place, children with focal epilepsy should be considered for epilepsy surgery as early as possible after diagnosis.