Brain imaging and neuropsychological assessment of individuals recovered from a mild to moderate SARS-CoV-2 infection.

As severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections have been shown to affect the central nervous system, the investigation of associated alterations of brain structure and neuropsychological sequelae is crucial to help address future health care needs. Therefore, we performed a comprehensive neuroimaging and neuropsychological assessment of 223 nonvaccinated individuals recovered from a mild to moderate SARS-CoV-2 infection (100 female/123 male, age [years], mean ± SD, 55.54 ± 7.07; median 9.7 mo after infection) in comparison with 223 matched controls (93 female/130 male, 55.74 ± 6.60) within the framework of the Hamburg City Health Study. Primary study outcomes were advanced diffusion MRI measures of white matter microstructure, cortical thickness, white matter hyperintensity load, and neuropsychological test scores. Among all 11 MRI markers tested, significant differences were found in global measures of mean diffusivity (MD) and extracellular free water which were elevated in the white matter of post-SARS-CoV-2 individuals compared to matched controls (free water: 0.148 ± 0.018 vs. 0.142 ± 0.017, P < 0.001; MD [10-3 mm2/s]: 0.747 ± 0.021 vs. 0.740 ± 0.020, P < 0.001). Group classification accuracy based on diffusion imaging markers was up to 80%. Neuropsychological test scores did not significantly differ between groups. Collectively, our findings suggest that subtle changes in white matter extracellular water content last beyond the acute infection with SARS-CoV-2. However, in our sample, a mild to moderate SARS-CoV-2 infection was not associated with neuropsychological deficits, significant changes in cortical structure, or vascular lesions several months after recovery. External validation of our findings and longitudinal follow-up investigations are needed.

The Network Structure of Cognitive Impairment: From Subjective Cognitive Decline to Alzheimer's Disease.

It was proposed that a reorganization of the relationships between cognitive functions occurs in dementia, a vision that surpasses the idea of a mere decline of specific domains. The complexity of cognitive structure, as assessed by neuropsychological tests, can be captured by exploratory graph analysis (EGA). EGA was applied to the neuropsychological assessment of people (humans) with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD; total N = 638). Both sexes were included. In AD, memory scores detach from the other cognitive functions, and memory subdomains reduce their reciprocal relation. SCD showed a pattern of segregated neuropsychological domains, and MCI showed a noisy and less stable pattern. Results suggest that AD drives a reorganization of cognitive functions toward a less-fractionated architecture compared with preclinical conditions. Cognitive functions show a reorganization that goes beyond the performance decline. Results also have clinical implications in test interpretations and usage.

Brain and cognitive changes in patients with long COVID compared with infection-recovered control subjects.

Between 2.5% and 28% of people infected with SARS-CoV-2 suffer long COVID or persistence of symptoms for months after acute illness. Many symptoms are neurological, but the brain changes underlying the neuropsychological impairments remain unclear. This study aimed to provide a detailed description of the cognitive profile, the pattern of brain alterations in long COVID and the potential association between them. To address these objectives, 83 patients with persistent neurological symptoms after COVID-19 were recruited, and 22 now healthy control subjects chosen because they had suffered COVID-19 but did not experience persistent neurological symptoms. Patients and controls were matched for age, sex and educational level. All participants were assessed by clinical interview, comprehensive standardized neuropsychological tests and structural MRI. The mean global cognitive function of patients with long COVID assessed by Addenbrooke's Cognitive Examination-III screening test [overall cognitive level (OCLz) = -0.39 ± 0.12] was significantly below the infection recovered-controls (OCLz = +0.32 ± 0.16, P < 0.01). We observed that 48% of patients with long COVID had episodic memory deficit, with 27% also with impaired overall cognitive function, especially attention, working memory, processing speed and verbal fluency. The MRI examination included grey matter morphometry and whole brain structural connectivity analysis. Compared to infection recovered controls, patients had thinner cortex in a specific cluster centred on the left posterior superior temporal gyrus. In addition, lower fractional anisotropy and higher radial diffusivity were observed in widespread areas of the patients' cerebral white matter relative to these controls. Correlations between cognitive status and brain abnormalities revealed a relationship between altered connectivity of white matter regions and impairments of episodic memory, overall cognitive function, attention and verbal fluency. This study shows that patients with neurological long COVID suffer brain changes, especially in several white matter areas, and these are associated with impairments of specific cognitive functions.

Chronic Hyponatremia and Brain Structure and Function Before and After Treatment.

RATIONALE & OBJECTIVE: Hyponatremia is the most common electrolyte disorder and is associated with significant morbidity and mortality. This study investigated neurocognitive impairment, brain volume, and alterations in magnetic resonance imaging (MRI)-based measures of cerebral function in patients before and after treatment for hyponatremia. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients with presumed chronic hyponatremia without signs of hypo- or hypervolemia treated in the emergency department of a German tertiary-care hospital. EXPOSURE: Hyponatremia (ie, plasma sodium concentration [Na+]<125mmol/L) before and after treatment leading to [Na+]>130mmol/L. OUTCOMES: Standardized neuropsychological testing (Mini-Mental State Examination, DemTect, Trail Making Test A/B, Beck Depression Inventory, Timed Up and Go) and resting-state MRI were performed before and after treatment of hyponatremia to assess total brain and white and gray matter volumes as well as neuronal activity and its synchronization. ANALYTICAL APPROACH: Changes in outcomes after treatment for hyponatremia assessed using bootstrapped confidence intervals and Cohen d statistic. Associations between parameters were assessed using correlation analyses. RESULTS: During a 3.7-year period, 26 patients were enrolled. Complete data were available for 21 patients. Mean [Na+]s were 118.4mmol/L before treatment and 135.5mmol/L after treatment. Most measures of cognition improved significantly. Comparison of MRI studies showed a decrease in brain tissue volumes, neuronal activity, and synchronization across all gray matter after normalization of [Na+]. Volume effects were particularly prominent in the hippocampus. During hyponatremia, synchronization of neuronal activity was negatively correlated with [Na+] (r=-0.836; 95% CI, -0.979 to-0.446) and cognitive function (Mini-Mental State Examination, r=-0.523; 95% CI, -0.805 to-0.069; DemTect, r=-0.744; 95% CI, -0.951 to-0.385; and Trail Making Test A, r=0.692; 95% CI, 0.255-0.922). LIMITATIONS: Small sample size, insufficient quality of several MRI scans as a result of motion artifact. CONCLUSIONS: Resolution of hyponatremia was associated with improved cognition and reductions in brain volumes and neuronal activity. Impaired cognition during hyponatremia is closely linked to increased neuronal activity rather than to tissue volumes. Furthermore, the hippocampus appears to be particularly susceptible to hyponatremia, exhibiting pronounced changes in tissue volume. PLAIN-LANGUAGE SUMMARY: Hyponatremia is a common clinical problem, and patients often present with neurologic symptoms that are at least partially reversible. This study used neuropsychological testing and magnetic resonance imaging to examine patients during and after correction of hyponatremia. Treatment led to an improvement in patients' cognition as well as a decrease in their brain volumes, spontaneous neuronal activity, and synchronized neuronal activity between remote brain regions. Volume effects were particularly prominent in the hippocampus, an area of the brain that is important for the modulation of memory. During hyponatremia, patients with the lowest sodium concentrations had the highest levels of synchronized neuronal activity and the poorest cognitive test results.

Post-stroke Cognition is Associated with Stroke Survivor Quality of Life and Caregiver Outcomes: A Systematic Review and Meta-analysis.

Disability arising from post-stroke cognitive impairment is a likely contributor to the poor quality of life (QoL) stroke survivors and their carers frequently experience, but this has not been summarily quantified. A systematic literature review and meta-analysis was completed examining the association between general and domain-specific post-stroke cognitive functioning and adult stroke survivor QoL, caregiver QoL, and caregiver burden. Five databases were systematically searched, and eligibility for inclusion, data extraction, and study quality were evaluated by two reviewers using a standardised protocol. Effects sizes (r) were estimated using a random effects model. Thirty-eight studies were identified, generating a sample of 7365 stroke survivors (median age 63.02 years, range 25-93) followed for 3 to 132 months post-stroke. Overall cognition (all domains combined) demonstrated a significant small to medium association with QoL, r = 0.23 (95% CI 0.18-0.28), p < 0.001. The cognitive domains of speed, attention, visuospatial, memory, and executive skills, but not language, also demonstrated a significant relationship with QoL. Regarding caregiver outcomes, 15 studies were identified resulting in a sample of 2421 caregivers (median age 58.12 years, range 18-82) followed for 3 to 84 months post-stroke. Stroke survivor overall cognitive ability again demonstrated a significant small to medium association with caregiver outcomes (QoL and burden combined), r = 0.17 (95% CI 0.10-0.24), p < 0.001. In conclusion, lower post-stroke cognitive performance is associated with significant reductions in stroke survivor QoL and poorer caregiver outcomes. Cognitive assessment is recommended early to identify those at risk and implement timely interventions to support both stroke survivors and their caregivers.

Neuropsychological Changes in Isolated REM Sleep Behavior Disorder: A Systematic Review and Meta-analysis of Cross-sectional and Longitudinal Studies.

The aim of this meta-analysis is twofold: (a) to assess cognitive impairments in isolated rapid eye movement (REM) sleep behavior disorder (iRBD) patients compared to healthy controls (HC); (b) to quantitatively estimate the risk of developing a neurodegenerative disease in iRBD patients according to baseline cognitive assessment. To address the first aim, cross-sectional studies including polysomnography-confirmed iRBD patients, HC, and reporting neuropsychological testing were included. To address the second aim, longitudinal studies including polysomnography-confirmed iRBD patients, reporting baseline neuropsychological testing for converted and still isolated patients separately were included. The literature search was conducted based on PRISMA guidelines and the protocol was registered at PROSPERO (CRD42021253427). Cross-sectional and longitudinal studies were searched from PubMed, Web of Science, Scopus, and Embase databases. Publication bias and statistical heterogeneity were assessed respectively by funnel plot asymmetry and using I2. Finally, a random-effect model was performed to pool the included studies. 75 cross-sectional (2,398 HC and 2,460 iRBD patients) and 11 longitudinal (495 iRBD patients) studies were selected. Cross-sectional studies showed that iRBD patients performed significantly worse in cognitive screening scores (random-effects (RE) model = -0.69), memory (RE model = -0.64), and executive function (RE model = -0.50) domains compared to HC. The survival analyses conducted for longitudinal studies revealed that lower executive function and language performance, as well as the presence of mild cognitive impairment (MCI), at baseline were associated with an increased risk of conversion at follow-up. Our study underlines the importance of a comprehensive neuropsychological assessment in the context of iRBD.

The Iowa Gambling Task: Men and Women Perform Differently. A Meta-analysis.

The Iowa Gambling Task (IGT) was designed to assess decision-making under conditions of complexity and uncertainty; it is currently one of the most widely used tests to assess decision-making in both experimental and clinical settings. In the original version of the task, participants are given a loan of play money and four decks of cards and are asked to maximize profits. Although any single card unpredictably yields wins/losses, variations in frequency and size of gains/losses ultimately make two decks more advantageous in the long term. Several studies have previously suggested that there may be a sex-related difference in IGT performance. Thus, the present study aimed to explore and quantify sex differences in IGT performance by pooling the results of 110 studies. The meta-analysis revealed that males tend to perform better than females on the classic 100-trial IGT (UMD = 3.381; p < 0.001). Furthermore, the significant heterogeneity observed suggests high variability in the results obtained by individual studies. Results were not affected by publication bias or other moderators. Factors that may contribute to differences in male and female performance are discussed, such as functional sex-related asymmetries in the ventromedial prefrontal cortex and amygdala, as well as differences in sensitivity to wins/losses.

The Neurofunctional Correlates of Morphosyntactic and Thematic Impairments in Aphasia: A Systematic Review and Meta-analysis.

Lesion-symptom studies in persons with aphasia showed that left temporoparietal damage, but surprisingly not prefrontal damage, correlates with impaired ability to process thematic roles in the comprehension of semantically reversible sentences (The child is hugged by the mother). This result has led to challenge the time-honored view that left prefrontal regions are critical for sentence comprehension. However, most studies focused on thematic role assignment and failed to consider morphosyntactic processes that are also critical for sentence processing. We reviewed and meta-analyzed lesion-symptom studies on the neurofunctional correlates of thematic role assignment and morphosyntactic processing in comprehension and production in persons with aphasia. Following the PRISMA checklist, we selected 43 papers for the review and 27 for the meta-analysis, identifying a set of potential bias risks. Both the review and the meta-analysis confirmed the correlation between thematic role processing and temporoparietal regions but also clearly showed the involvement of prefrontal regions in sentence processing. Exploratory meta-analyses suggested that both thematic role and morphosyntactic processing correlate with left prefrontal and temporoparietal regions, that morphosyntactic processing correlates with prefrontal structures more than with temporoparietal regions, and that thematic role assignment displays the opposite trend. We discuss current limitations in the literature and propose a set of recommendations for clarifying unresolved issues.

Long term survival in patients with classic infantile Pompe disease reveals a spectrum with progressive brain abnormalities and changes in cognitive functioning.

The aim of this longitudinal cohort study, is to provide more insight into the pattern of brain abnormalities, and possible consequences for cognitive functioning, in patients with classic infantile Pompe disease. We included 19 classic infantile Pompe patients (median age last assessment 8.9 years, range 1.5-22.5 years; 5/19 CRIM negative), treated with ERT. Using MR imaging of the brain (T1, T2, and FLAIR acquisitions), we classified progression of brain abnormalities on a 12-point rating scale at multiple time points throughout follow-up. Additionally we noted specific white matter patterns and examined atrophy. Cognitive development was studied using Wechsler IQ assessments obtained by certified neuropsychologists. The association between age and cognitive functioning, and MRI ratings and cognitive functioning was assessed by linear regression models. All but one patient developed brain abnormalities. The abnormalities progressed in a similar pattern throughout the brain, with early involvement of periventricular white matter, later followed by subcortical white matter, gray matter structures, and juxtacortical U-fibers. We found a significant decline (p < 0.01), with increasing age for full scale IQ, performance IQ and processing speed, but not for verbal IQ (p = 0.17). Each point increment in the 12-point MRI rating scale was associated with a significant decline (3.1-6.0 points) in all the IQ index scores (p < 0.05). The majority of long-term surviving patients in our cohort develop incremental brain MRI abnormalities and decline in cognitive functioning. This highlights the need for new therapies that can cross the blood-brain barrier in order to treat this CNS phenotype.

Neurodevelopmental profiles of 14 individuals with phosphomannomutase deficiency (PMM2-CDG).

PMM2-CDG (formerly CDG-1a), the most common type of congenital disorders of glycosylation, is inherited in an autosomal recessive pattern. PMM2-CDG frequently presents in infancy with multisystemic clinical involvement, and it has been diagnosed in over 1000 people worldwide. There have been few natural history studies reporting neurodevelopmental characterization of PMM2-CDG. Thus, a prospective study was conducted that included neurodevelopmental assessments as part of deep phenotyping. This study, Clinical and Basic Investigations into Known and Suspected Congenital Disorders of Glycosylation (NCT02089789), included 14 participants (8 males and 6 females ages 2-33 years) with a confirmed molecular diagnosis of PMM2-CDG. Clinical features of PMM2-CDG in this cohort were neurodevelopmental disorders, faltering growth, hypotonia, cerebellar atrophy, peripheral neuropathy, movement disorders, ophthalmological abnormalities, and auditory function differences. All PMM2-CDG participants met criteria for intellectual disability (or global developmental delay if younger than age 5). The majority never attained certain gross motor and language milestones. Only two participants were ambulatory, and almost all were considered minimally verbal. Overall, individuals with PMM2-CDG present with a complex neurodevelopmental profile characterized by intellectual disability and multisystemic presentations. This systematic quantification of the neurodevelopmental profile of PMM2-CDG expands our understanding of the range in impairments associated with PMM2-CDG and will help guide management strategies.

Predicting neuropsychological late effects in pediatric brain tumor survivors using the Neurological Predictor Scale and the Pediatric Neuro-Oncology Rating of Treatment Intensity.

OBJECTIVE: The Neurological Predictor Scale (NPS) quantifies cumulative exposure to tumor- and treatment-related neurological risks. The Pediatric Neuro-Oncology Rating of Treatment Intensity (PNORTI) measures the intensity of different treatment modalities, but research is needed to establish whether it is associated with late effects. This study evaluated the predictive validity of the NPS and PNORTI for neuropsychological outcomes in pediatric brain tumor survivors. METHOD: A retrospective chart review was completed of pediatric brain tumor survivors (PBTS) (n = 161, Mage = 13.47, SD = 2.80) who were at least 2 years from the end of tumor-directed treatment. Attention, intellectual functioning, perceptual reasoning, processing speed, verbal reasoning, and working memory were analyzed in relation to the NPS and PNORTI. RESULTS: NPS scores ranged from 1 to 11 (M = 5.57, SD = 2.27) and PNORTI scores ranged from 1 (n = 101; 62.7%) to 3 (n = 18; 11.2%). When controlling for age, sex, SES factors, and time since treatment, NPS scores significantly predicted intellectual functioning [F(7,149) = 12.86, p < .001, R2 = .38] and processing speed [F(7,84) = 5.28, p < .001, R2 = .31]. PNORTI scores did not significantly predict neuropsychological outcomes. CONCLUSIONS: The findings suggest that the NPS has value in predicting IF and processing speed above-and-beyond demographic variables. The PNORTI was not associated with neuropsychological outcomes. Future research should consider establishing clinical cutoff scores for the NPS to help determine which survivors are most at risk for neuropsychological late effects and warrant additional assessment.

Utility of the INECO Frontal Screening and the Frontal Assessment Battery in detecting executive dysfunction in early-onset cognitive impairment and dementia.

OBJECTIVE: The INECO Frontal Screening (IFS) and the Frontal Assessment Battery (FAB) are executive dysfunction (ED) screening tools that can distinguish patients with neurodegenerative disorders from healthy controls and, to some extent, between dementia subtypes. This paper aims to examine the suitability of these tests in assessing early-onset cognitive impairment and dementia patients. METHOD: In a memory clinic patient cohort (age mean = 57.4 years) with symptom onset at ≤65 years, we analyzed the IFS and the FAB results of four groups: early-onset dementia (EOD, n = 49), mild cognitive impairment due to neurological causes (MCI-n, n = 34), MCI due to other causes such as depression (MCI-o, n = 99) and subjective cognitive decline (SCD, n = 14). Data were gathered at baseline and at 6 and 12 months. We also studied the tests' accuracy in distinguishing EOD from SCD patients and ED patients from those with intact executive functioning. Correlations with neuropsychological measures were also studied. RESULTS: The EOD group had significantly (p < .05) lower IFS and FAB total scores than the MCI-o and SCD groups. Compared with the FAB, the IFS showed more statistically significant (p < .05) differences between diagnostic groups, greater accuracy (IFS AUC = .80, FAB AUC = .75, p = .036) in detecting ED and marginally stronger correlations with neuropsychological measures. We found no statistically significant differences in the EOD group scores from baseline up to 6- or 12-months follow-up. CONCLUSIONS: While both tests can detect EOD among memory clinic patients, the IFS may be more reliable in detecting ED than the FAB.

The association between symptom burden and processing speed and executive functioning at 4 and 12 weeks following pediatric concussion.

OBJECTIVES: Symptoms and cognition are both utilized as indicators of recovery following pediatric concussion, yet their interrelationship is not well understood. This study aimed to investigate: 1) the association of post-concussion symptom burden and cognitive outcomes (processing speed and executive functioning [EF]) at 4 and 12 weeks after pediatric concussion, and 2) the moderating effect of sex on this association. METHODS: This prospective, multicenter cohort study included participants aged 5.00-17.99 years with acute concussion presenting to four Emergency Departments of the Pediatric Emergency Research Canada network. Five processing speed and EF tasks and the Post-Concussion Symptom Inventory (PCSI; symptom burden, defined as the difference between post-injury and retrospective [pre-injury] scores) were administered at 4 and 12 weeks post-concussion. Generalized least squares models were conducted with task performances as dependent variables and PCSI and PCSI*sex interaction as the main predictors, with important pre-injury demographic and injury characteristics as covariates. RESULTS: 311 children (65.0% males; median age = 11.92 [IQR = 9.14-14.21 years]) were included in the analysis. After adjusting for covariates, higher symptom burden was associated with lower Backward Digit Span (χ2 = 9.85, p = .043) and Verbal Fluency scores (χ2 = 10.48, p = .033) across time points; these associations were not moderated by sex, ps ≥ .20. Symptom burden was not associated with performance on the Coding, Continuous Performance Test, and Color-Word Interference scores, ps ≥ .17. CONCLUSIONS: Higher symptom burden is associated with lower working memory and cognitive flexibility following pediatric concussion, yet these associations were not moderated by sex. Findings may inform concussion management by emphasizing the importance of multifaceted assessments of EF.

Identification of amnestic mild cognitive impairment among Black and White community-dwelling older adults using NIH Toolbox Cognition tablet battery.

OBJECTIVES: Identify which NIH Toolbox Cognition Battery (NIHTB-CB) subtest(s) best differentiate healthy controls (HC) from those with amnestic mild cognitive impairment (aMCI) and compare the discriminant accuracy between a model using a priori "Norm Adjusted" scores versus "Unadjusted" standard scores with age, sex, race/ethnicity, and education controlled for within the model. Racial differences were also examined. METHODS: Participants were Black/African American (B/AA) and White consensus-confirmed (HC = 96; aMCI = 62) adults 60-85 years old that completed the NIHTB-CB for tablet. Discriminant function analysis (DFA) was used in the Total Sample and separately for B/AA (n = 80) and White participants (n = 78). RESULTS: Picture Sequence Memory (an episodic memory task) was the highest loading coefficient across all DFA models. When stratified by race, differences were noted in the pattern of the highest loading coefficients within the DFAs. However, the overall discriminant accuracy of the DFA models in identifying HCs and those with aMCI did not differ significantly by race (B/AA, White) or model/score type (Norm Adjusted versus Unadjusted). CONCLUSIONS: Racial differences were noted despite the use of normalized scores or demographic covariates-highlighting the importance of including underrepresented groups in research. While the models were fairly accurate at identifying consensus-confirmed HCs, the models proved less accurate at identifying White participants with an aMCI diagnosis. In clinical settings, further work is needed to optimize computerized batteries and the use of NIHTB-CB norm adjusted scores is recommended. In research settings, demographically corrected scores or within model correction is suggested.

Tele-neuropsychology in memory clinic settings: Reliability and usability of videoconference-based neuropsychological testing.

OBJECTIVE: Neuropsychological assessment through VideoTeleConferencing (VTC) can help improve access to diagnostic and follow-up care in memory clinics. This study investigated the stability of performance on VTC assessment in relation to in-person assessment using a test-retest design and explored user experiences of VTC assessment. MATERIALS AND METHODS: Thirty-one patients (62 ± 6.7 years, 45% female, 58% Subjective Cognitive Decline, 42% Mild Cognitive Impairment/dementia diagnosis) were included from the Amsterdam Dementia Cohort between August 2020 and February 2021. Patients underwent a face-to-face neuropsychological assessment followed by a VTC assessment using the same test protocol within 4 months. Reliability coefficients were calculated using intraclass correlation coefficients (ICC). For each test, the proportion of clinically relevant differences in performances between assessment modalities was calculated. User experiences of patients and neuropsychologists were assessed with questionnaires (User Satisfaction and Ease of use [USE] questionnaire and System Usability Scale [SUS]). Neuropsychologists also participated in a focus group. RESULTS: ICC values were moderate to excellent (0.63-0.93) for all test measures in the total sample. On all tests, most patients did not show clinically relevant performance differences between modalities. Patients and neuropsychologists reported overall positive VTC system usability, although neuropsychologists indicated in the focus group that patients without cognitive impairment required less training for the system and were more independent. CONCLUSION: VTC assessment showed adequate to excellent test-retest reliability for a broad range of neuropsychological tests commonly used in practice. Assessment through VTC may be a user friendly method in the memory clinic, especially to monitor individuals at risk for future cognitive decline.

Process approach as a cognitive biomarker related to gray matter volume in mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Process approach is valuable for memory assessment in Alzheimer's disease (AD) and mild cognitive impairment (MCI), yet its underlying mechanisms remain elusive. This study aims to synergize the process approach with brain structure analysis to explore both the discriminative capacity and potential mechanisms underlying the process approach. METHODS: 37 subjects of MCI, 35 subjects of AD and 38 subjects of healthy control (HC) were included. The process approach in Auditory Verbal Learning Test (AVLT), including discriminability (A'), response bias (B"D), semantic clustering (LBCsem) and serial clustering (LBCser) was performed. The gray matter volume (GMV) was analyzed by voxel-based morphometry. Receiver operating characteristic (ROC) analysis and partial correlations were conducted to explore the value of the process approach and investigate the relationship between the process approach, traditional indices of AVLT and GMV. RESULTS: ROC analysis showed the value of A', B"D and LBCser in differentiating MCI and AD. Combining AVLT-Immediately Recall (AVLT-IR) and LBCser showed a higher value in diagnosing MCI. Partial correlations revealed that in the MCI group, A' and B"D were mainly positively associated with GMV of the hippocampus and temporal lobe. CONCLUSION: This study indicated that the process approach is a promising cognitive biomarker to detect MCI and AD.

Cognitive flexibility impairment in temporal lobe epilepsy: The impact of epileptic foci lateralization on executive functions.

INTRODUCTION: Temporal Lobe Epilepsy (TLE) has been associated with memory impairments, which are typically linked to hippocampal and mesial temporal cortex lesions. Considering the presence of extensive bidirectional frontotemporal connections, it can be hypothesized that executive dysfunction in TLE is modulated by the lateralization of the epileptic foci. MATERIAL AND METHODS: A comprehensive neuropsychological executive functions protocol was administered to 63 participants, including 42 individuals with temporal lobe epilepsy (20 with right-TLE and 22 with left-TLE) and 21 healthy controls aged 20-49. RESULTS: The results indicate that TLE patients exhibit poorer executive performance compared to healthy controls in working memory (F(2,60) = 4.18, p <.01), planning (F(2,60) = 4.71, p <.05), set shifting (F(2,60) = 10.1, p <.001), phonetic verbal fluency (F(2,60) = 11.71, p <.01) and semantic verbal fluency (F(2,60) = 9.61, p <.001. No significant differences were found in cognitive inhibition. Furthermore, right-TLE patients showed lower performance than left-TLE in set shifting (F(1,61) = 6.45, p <.05), while no significant differences were observed in working memory, planning, inhibition, and verbal fluency. CONCLUSIONS: This research emphasize the importance of considering the lateralization of the temporal lobe focus to achieve a more accurate neuropsychological characterization. The cognitive differences between left and right TLE patients highlight the need for individualized approaches in their treatment and care.

Cognitive trajectories after surgery: Guideline hints for assessment and treatment.

Elderly patients who undergo major surgery (not-neurosurgical) under general anaesthesia frequently complain about cognitive difficulties, especially during the first weeks after surgical "trauma". Although recovery usually occurs within a month, about one out of four patients develops full-blown postoperative Neurocognitive disorders (NCD) which compromise quality of life or daily autonomy. Mild/Major NCD affect approximately 10% of patients from three months to one year after major surgery. Neuroinflammation has emerged to have a critical role in the postoperative NCDs pathogenesis, through microglial activation and the release of pro-inflammatory cytokines which increase blood-brain-barrier permeability, enhance movement of leukocytes into the central nervous system (CNS) and favour the neuronal damage. Moreover, pre-existing Mild Cognitive Impairment, alcohol or drugs consumption, depression and other factors, together with several intraoperative and post-operative sequelae, can exacerbate the severity and duration of NCDs. In this context it is crucial rely on current progresses in serum and CSF biomarker analysis to frame neuroinflammation levels, along with establishing standard protocol for neuropsychological assessment (with specific set of tools) and to apply cognitive training or neuromodulation techniques to reduce the incidence of postoperative NCDs when required. It is recommended to identify those patients who would need such preventive intervention early, by including them in pre-operative and post-operative comprehensive evaluation and prevent the development of a full-blown dementia after surgery. This contribution reports all the recent progresses in the NCDs diagnostic classification, pathogenesis discoveries and possible treatments, with the aim to systematize current evidences and provide guidelines for multidisciplinary care.

Impact of Neuropsychological Assessment on Subjective Memory Complaints in Patients With Mild Cognitive Impairment.

INTRODUCTION: Patients with Alzheimer's disease (AD), namely at an initial stage like amnestic cognitive impairment (aMCI), typically present with memory complaints. They also have difficulties regarding self-knowledge about their cognitive deficits. In clinical practice, a formal neuropsychological assessment is often done. The present study aimed to understand whether patients with aMCI retain the ability to monitor the success or failure in their performance during the neuropsychological assessment and adjust the report of memory complaints accordingly, as compared to healthy controls. METHODS: Participants were patients with aMCI and healthy controls who were questioned about their own memory abilities using the Subjective Memory Complaints (SMC) scale, applied before and after the neuropsychological assessment protocol. A repeated measures General Linear Model was performed to analyze changes in SMC (within-subjects effects) after the neuropsychological assessment, in patients with aMCI and healthy controls (between-subjects effects). RESULTS: Eighty volunteers, 40 patients with aMCI and 40 healthy controls, participated in the study. Patients with aMCI showed lower MMSE scores, more depressive symptoms, and deficits in memory and learning, language and executive domains. Patients with aMCI had higher SMC scores [9.4(3.6)] than healthy controls [4.4(2.3)] before the neuropsychological assessment. A statistically significant interaction was found between the SMC and the diagnostic group, meaning that healthy controls decreased SMC [3.4(1.9)] after the neuropsychological assessment, whereas patients with aMCI kept high levels of SMC [9.6(3.9)]. In patients with aMCI, an inverse correlation between logical memory and the change in SMC was found, so that patients with lower scores in the logical memory test tended to increase their memory complaints after the assessment. CONCLUSIONS: Both patients with aMCI and healthy controls can monitor and update the impression about their memory abilities following a formal neuropsychological assessment. Patients with aMCI maintain a high SMC level, which is inversely associated with their memory performance. In practical terms, SMC should be measured consistently at a particular moment in time, preferably preceding the objective neuropsychological assessment.

Alcohol-related cognitive impairments in patients with and without cirrhosis.

AIMS: up to 80% of patients with alcohol use disorder display cognitive impairments. Some studies have suggested that alcohol-related cognitive impairments could be worsened by hepatic damage. The primary objective of this study was to compare mean scores on the Brief Evaluation of Alcohol-Related Neurocognitive Impairments measure between alcohol use disorder patients with (CIR+) or without cirrhosis (CIR-). METHODS: we conducted a prospective case-control study in a hepatology department of a university hospital. All patients were assessed using the Evaluation of Alcohol-Related Neuropsychological Impairments test. RESULTS: a total of 82 patients (50 CIR+, 32 CIR-) were included in this study. CIR- patients were significantly younger than CIR+ patients (respectively, 45.5 ± 6.8 vs 60.1 ± 9.0; P < .0001). After adjusting for age and educational level, the mean Evaluation of Alcohol-Related Neuropsychological Impairments total scores in the CIR+ group were significantly lower than in the group of CIR- patients (14.1 ± 0.7 vs 7.8 ± 0.4, respectively, P < .0001). The mean subscores on delayed verbal memory, alphabetical ordination, alternating verbal fluency, visuospatial abilities, and ataxia subtests were also significantly lower in the CIR+ than in the CIR- group (respectively, 1.9 ± 0.2 vs 2.8 ± 0.2; 1.8 ± 0.2 vs 2.7 ± 0.2; 2.2 ± 0.2 vs 3.6 ± 0.2; 0.7 ± 0.2 vs 1.6 ± 0.2; 0.7 ± 0.2 vs 3.1 ± 0.2; P < .0001 for all comparisons). CONCLUSIONS: in the present study, alcohol use disorder patients with cirrhosis presented more severe cognitive impairments than those without cirrhosis. Longitudinal studies are needed to investigate how cirrhosis can influence cognitive impairments.