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As the most common chromosomal disorder compatible to life, Down syndrome (DS) is caused by an extra copy of chromosome 21. Almost all DS patients have cognitive dysfunction. Therefore, it is important to study the underlying pathogenetic mechanism to elucidate its molecular basis. This article has provided a review for the molecular mechanisms of NRIP1 and DYRK1A genes, which have been closely associated with the cognitive dysfunctions of DS patients. It has also summarized the research progress on the mechanism of DS and development of new therapeutic strategies based on such studies, with an aim to provide insights into the prevention and treatment for the cognitive dysfunctions in DS patients.

Introduction: Children with focal epilepsy often present with executive functions (EFs) deficits. EFs deficits can contribute to adaptive challenges and have a negative impact on academic achievement. The purpose of this study was to investigate the EFs profiles of children diagnosed with frontal lobe epilepsy or temporal lobe epilepsy. Also, we aimed to examine the impact of medical and sociodemographic features on executive functioning and to compare the results of performance-based tests and ratings measures., Method: EFs were assessed using performance based-tests and rating scales. The Child Executive Functions Battery (CEF-B) and the Behavior Rating Inventory of Executive Function (BRIEF) for parents and teachers were used., Results: Fifty children aged 6-16 years participated in the study, 28 diagnosed with frontal lobe epilepsy and 22 diagnosed with temporal lobe epilepsy. Results showed that approximately 30 % of both groups of epilepsy patients had significant deficits in EFs compared to normative data. Deficits were observed across various domains of EFs (inhibition, working memory, flexibility and planning). Most patients exhibited deficits in one or two of the 4 domains. Worse executive performances were significantly associated with older age at assessment time, longer duration of epilepsy, higher seizure frequency, earlier age at onset and higher number of anti-seizure medication. Additionally, correlation and congruence analyses showed significant discrepancies between the performance-based and rating measures of executive functioning., Conclusion: Our findings provide substantial evidence of significant executive deficits in children with FLE and TLE and support the clinical validity of the CEF-B battery in this population. The low level of agreement between performance tests and daily life questionnaires suggests that the two methods are complementary for understanding children's executive functioning. Comprehensive assessment and targeted interventions to address EFs difficulties are recommended for this particular population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The development of malaria-induced neurocognitive and behavioral sequelae is not entirely understood. We hypothesize that liver dysfunction caused by Plasmodium infection is responsible for malaria-induced neurocognitive and behavioral sequelae. Our metabolic hypothesis not only explains neurocognitive sequelae after cerebral malaria (CM) but also after other severe, non-severe, and asymptomatic malaria infections., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Impairments in mathematics have been found in children with Genetic Generalized Epilepsy (GGE), yet little is known about the underpinnings of these difficulties. The aim of this study was to investigate basic numeracy and secondary mathematics skills in GGE and explore cognitive and clinical correlates that relate to those skills. Nineteen children with GGE and 22 typically developing controls aged 8-16 years completed a neuropsychological battery which assessed: (i) basic numeracy skills: non-symbolic and symbolic magnitude comparison; (ii) secondary mathematics skills: calculation, reasoning, and fluency; and (iii) cognitive skills: intelligence, fluid reasoning, processing speed, and working memory. Epilepsy clinical factors (age of epilepsy onset, duration of epilepsy, number of anti-seizure medications) were also recorded. Children with GGE were impaired in select basic numeracy skills (non-symbolic magnitude comparison), and all secondary mathematics skills compared to controls. In children with GGE, the visuo-spatial central executive correlated with both basic numeracy skills. The verbal central executive correlated with mathematics reasoning. Non-verbal intelligence was related to symbolic magnitude comparison and mathematics reasoning. Fluid reasoning was correlated with non-symbolic magnitude comparison and mathematics problems solving. Epilepsy variables did not relate to mathematics outcomes. Overall, we found that children with GGE experience significant difficulties in select basic numeracy and all secondary mathematics skills. Risk factors for mathematics difficulties included reduced working memory capacity, lower intelligence and fluid reasoning. Our findings suggest that children with GGE may require accommodation for limited central executive working memory capacity in combination with academic supports for poor mathematics skills., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The study of One Million U.S. Radiation Workers and Veterans, the Million Person Study (MPS), examines the health consequences, both cancer and non-cancer, of exposure to ionizing radiation received gradually over time. Recently the MPS has focused on mortality patterns from neurological and behavioral conditions, e.g., Parkinson's disease, Alzheimer's disease, dementia, and motor neuron disease such as amyotrophic lateral sclerosis. A fuller picture of radiation-related late effects comes from studying both mortality and the occurrence (incidence) of conditions not leading to death. Accordingly, the MPS is identifying neurocognitive diagnoses from fee-for-service insurance claims from the Centers for Medicare and Medicaid Services (CMS), among Medicare beneficiaries beginning in 1999 (the earliest date claims data are available). Linkages to date have identified ∼540,000 workers with available health information. Such linkages provide individual information on important co-factor and confounding variables such as smoking, alcohol consumption, blood pressure, obesity, diabetes and many other health and demographic characteristics. The total person-level set of time-dependent variables, outcomes, organ-specific dose measures, co-factors, and demographics will be massive and much too large to be evaluated with standard software. Thus, development of specialized open-source software designed for large datasets (Colossus) is nearly complete. The wealth of information available from CMS claims data, coupled with individual dose reconstructions, will thus greatly enhance the quality and precision of health evaluations for this new field of low-dose radiation and neurocognitive effects., (© 2024 by Radiation Research Society. All rights of reproduction in any form reserved.)

Alzheimer's disease (AD) is a progressive neurodegenerative disease of age with no effective preventative or treatment approaches. Deeper understanding of the mechanisms underlying the accumulation of toxic β-amyloid oligopeptides and the formation of amyloid plaque in AD has the potential to identify new therapeutic targets. Prior research links the insulin-like growth factor (IGF) system to pathologic mechanisms underlying AD. Suppression of local IGF-I receptor (IGFIR) signaling in AD mice has been shown to reduce plaque formation in the brain and delay neurodegeneration and behavioral changes. However, direct inhibitors of IGFIR signaling are not a viable treatment option for AD due to the essentiality of the IGFIR in physiological growth and metabolism. We have previously demonstrated a more selective means to reduce local IGFIR signaling through inhibition of PAPP-A, a novel zinc metalloprotease that regulates local IGF-I bioavailability through cleavage of inhibitory IGF binding proteins. Here we tested if deletion of PAPP-A in a mouse model of AD provides protection against pathology and behavioral changes. We show that compared to AD mice, AD/PAPP-A KO mice had significantly less plaque burden, reduced astrocytic activation, decreased IGF-IR activity, and improved cognition. Human senile AD plaques showed specific immunostaining for PAPP-A. Thus, inhibition of PAPP-A expression or activity may represent a novel treatment strategy for AD., Competing Interests: Declaration of competing interest DJB has a potential conflict related to his research. He is co-inventor on patents held by Mayo Clinic, patent applications licensed or to be filed by Unity Biotechnology and is a Unity Biotechnology shareholder. Research in the Baker laboratory has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo conflict of interest policies. The other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) is a prevalent problem with survivors suffering from chronic cognitive impairments. Following TBI there is a series of neuropathological changes including neurogenesis. It is well established that neurogenesis in the dentate gyrus (DG) of the hippocampus is important for hippocampal dependent learning and memory functions. Following TBI, injury-enhanced hippocampal neurogenesis is believed to contribute to post-injury cognitive recovery. Behavioral function is connected to synaptic plasticity and neuronal dendritic branching is critical for successful synapse formation. To ascertain the functional contribution of injury-induced DG new neurons in post-TBI cognitive recovery, it is necessary to study their dendritic morphological development and the molecular mechanisms controlling this process. Utilizing transgenic mice with tamoxifen-induced GFP expression and Notch1 knock-out in nestin+ neural stem cells, this study examined dendritic morphology, the role of Notch1 in regulating dendritic complexity of injury-induced DG new neurons, and their association to post-TBI cognitive recovery. We found that at 8 weeks after a moderate TBI, injury-induced DG new neurons in the injured control mice displayed a similar dendritic morphology as the cells in non-injured mice accompanied with cognitive recovery. In comparison, in Notch1 conditional knock-out mice, DG new neurons in the injured mice had a significant reduction in dendritic morphological development including dendritic arbors, volume span, and number of branches in comparison to the cells in non-injured mice concomitant with persistent cognitive dysfunction. The results of this study confirm the importance of post-injury generated new neurons in cognitive recovery following TBI and the role of Notch1 in regulating their maturation process., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background and Aims: The association between white matter abnormalities (WMA) and cognitive decline previously reported in poststroke patients has been mainly documented using visual scales. However, automated segmentation of WMA provides a precise determination of the volume of WMA. Nonetheless, it is rarely used in the stroke population and its potential advantage over visual scales is still unsettled. The objective of this study was to examine whether automated segmentation of WMA provides a better account than the visual Fazekas and Wahlund scales of the decline in executive functions and processing speed in stroke patients., Methods: The analyses were conducted on the 358 patients of the GRECogVASC cohort with an MRI performed at six months poststroke in the Amiens center. WMA were visually analyzed using the Fazekas (subcortical abnormalities) and Wahlund scales. Segmentation was performed using LST (3.0.3). Following preliminary studies to determine the optimal segmentation threshold, we examined the relationship between cognitive status and WMA volume computed at each threshold using receiver operating characteristic (ROC) curves. Finally, we assessed the ability of both Fazekas and Wahlund visual scores and WMA volume to account for cognitive scores by using a bivariate Pearson correlation analysis, comparing correlation coefficients with the Fisher transformation and repeating correlation analysis after adjustment for the lesion volume., Results: Increasing the threshold led to an underestimation of WMA (P=0.0001) (significant for a threshold ≥0.2) and an improvement in correct rejection of signal changes in the stroke cavity (P=0.02) (significant for a threshold ≤0.5), susceptibility artifacts (P=0.002) (significant for a threshold ≤0.6), and corticospinal degeneration (P=0.03) (significant for a threshold ≤0.5). WMA volume decreased with increasing threshold (P=0.0001). Areas under the curve (AUC) did not differ according to the threshold (processing speed: P=0.85, executive cognitive functions: P=0.7). Correlation coefficients between cognitive scores and WMA were higher for WMA volume than the Fazekas (processing speed: Z=-3.442, P=0.001; executive functions: Z=-2.751, P=0.006) and Wahlund scores (processing speed: Z=-3.615, P=0.0001; executive functions: Z=-2.769, P=0.006). Adjustment for lesion volume did not alter the correlations with WMA volume (processing speed: r=-0.327 [95%CI: -0.416; -0.223], P=0.0001; executive functions: r=-0.262 [95%CI: -0.363; -0.150], P=0.0001)., Conclusion: This study shows that WMA volume assessed by automated segmentation provides a better account of cognitive disorders than visual analysis. This should favor its wider use to refine imaging determinants of poststroke cognitive disorders., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objective: Cognitive problems in idiopathic intracranial hypertension (IIH) is generally overlooked in the presence of disabling headache and threat to visual function. The aim of this study was to search for cognitive deficits in patients with IIH using neuropsychologic tests in addition to P300 potential recordings to assess cognition related brain activity., Methods: Fifty IIH patients were examined using Montreal Cognitive Assessment Test, Stroop Test and Visual Aural Digit Span Test to measure different domains of cognition at the time of diagnosis. P300 potentials were recorded by using an oddball paradigm. Hospital Anxiety and Depression Scale was used to determine anxiety and depression. Quality of life (QoL) was assessed by SF-36. The results were compared with fifty healthy controls with matching age, gender and body mass index., Results: Neuropsychologic tests revealed wide cognitive impairment including attention, working memory, executive function, naming, language, delayed recall and orientation in IIH patients. In addition, quality of life was affected in the sub-parameters of general health perceptions, emotional role functioning, vitality, mental health and bodily pain. P300 potential latencies were long and the amplitudes were reduced indicating deficits in attention and working memory. Anxiety scores were high, and health-related QoL was low mainly involving vitality, emotional and mental health. Cognitive dysfunction was not correlated with the levels of anxiety and the correlation with headache severity was mild., Conclusion: A multidomain cognitive decline mainly involving attention and working memory was recorded in IIH patients. It was not correlated with anxiety and only a mild correlation with headache severity was present which may indicate a casual relationship between raised intracranial pressure and cognitive deficits. Screening is important as neuropsychological rehabilitation might be relevant in these patients., Competing Interests: Declarations. Conflict of interest: None. Ethical approval: The study protocol was approved by the Manisa Celal Bayar University Medical School Ethics Committee (reference number: 11/ 08 / 2021 / 20.478.486 / 898) and was performed under the ethical standards outlined in the Declaration of Helsinki. Written informed consent was obtained from all participants. Informed consent: Applicable., (© 2024. The Author(s) under exclusive licence to Belgian Neurological Society.)

Purpose: To preliminarily investigate the reliability and validity of the Chinese version of the Cerebellar Cognitive Affective Syndrome Scale (CCAS scale) in the cerebellar injury population., Methods: In this study, 40 patients with cerebellar injury and 39 normal individuals hospitalized in a stroke center were assessed using the Chinese version of the CCAS scale A, MMSE, and PHQ2, and the results were analyzed using content validity, structural validity, internal consistency, inter- rater agreement, and test-retest reliability., Results: The correlation coefficients of semantic fluency, phonemic fluency, category switching, digit span forward, digit span backward, cube, verbal recall, similarities and Go No-Go subscores in the Chinese version of the CCAS scale A were 0.586-0.831 (P ≤ 0.05) with the total score, but there was no significant correlation between the affect and the total score (P = 0.110). The total cognitive score of the Chinese version of the CCAS scale A was correlated with the (r = 0.807, P ≤ 0.01), and the total score of the Chinese version of the CCAS scale A affect was correlated with the total score of PHQ2 (r = 0.884, P ≤ 0.01). The 2 factors were extracted using principal component analysis, and the cumulative variance contribution rate was 59.633%. The factor loadings of each of the corresponding factors were > 0.5, indicating good structural validity of the Chinese version of the CCAS scale A. Cronbach α = 0.827 indicated good internal consistency, and inter-rater reliability (ICC > 0.95) and test-retest reliability (ICC = 0.717-0.895)indicated that the Chinese version of the CCAS scale A had good inter-rater reliability and test-retest reliability., Conclusion: The Chinese version of the CCAS scale A has good reliability and validity in the cerebellar injury population and is useful for screening cerebellar cognitive-emotional syndrome., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the First People's Hospital of Changzhou, Jiangsu Province, China.Ethics number is (2020) 科第146号. Informed consent: Informed consent was obtained from all individual participants included in the study.The participant has consented to the submission of the case report to the journal., (© 2024. The Author(s).)

Background: The association between the pattern of cortical thickness (CT) and executive dysfunction (ED) in mild cognitive impairment (MCI) and subjective cognitive complaints (SCC) is still poorly understood. We aimed to investigate the association between CT and ED in a large French cohort (MEMENTO) of 2323 participants with MCI or SCC., Methods: All participants with available CT and executive function data (verbal fluency and Trail Making Test [TMT]) were selected (n=1924). Linear regressions were performed to determine relationships between executive performance and the brain parenchymal fraction (BPF) and CT using FreeSurfer., Results: The global executive function score was related to the BPF (sß: 0.091, P<0.001) and CT in the right supramarginal (sß: 0.060, P=0.041) and right isthmus cingulate (sß: 0.062, P=0.011) regions. Literal verbal fluency was related to the BPF (sß: 0.125, P<0.001) and CT in the left parsorbitalis region (sß: 0.045, P=0.045). Semantic verbal fluency was related to the BPF (sß: 0.101, P<0.001) and CT in the right supramarginal region (sß: 0.061, P=0.042). The time difference between the TMT parts B and A was related to the BPF (sß: 0.048, P=0.045) and CT in the right precuneus (sß: 0.073, P=0.019) and right isthmus cingulate region (sß: 0.054, P=0.032)., Conclusions: In a large clinically based cohort of participants presenting with either MCI or SCC (a potential early stage of Alzheimer's disease [AD]), ED was related to the BPF and CT in the left pars orbitalis, right precuneus, right supramarginal, and right isthmus cingulate regions. This pattern of lesions adds knowledge to the conventional anatomy of ED and could contribute to the early diagnosis of AD., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background and Objectives: Moyamoya disease (MMD) is a rare noninflammatory disorder involving progressive intracranial vasculopathy and impaired cerebral blood flow in the anterior circulation, resulting in stroke and cognitive impairment. We aimed to characterize cognitive impairment and the possible predictive value of sociodemographic and clinical characteristics of adults with MMD., Methods: This cross-sectional study examined neurocognitive performance in a group of 42 consecutive adult patients (mean age = 40.52 years; 69% female) referred for a presurgical neuropsychological evaluation. Neuropsychological functioning was assessed with a comprehensive battery, and cognitive dysfunction was defined as 1.5 SDs below the mean. Neurocognitive performance correlated with clinical/demographic characteristics and disease markers., Results: Most patients (91%) had a history of stroke, and 45% had cognitive deficits, most notably on measures of attention/speed (48%), executive functioning (47%), visuoconstruction (41%), and memory (31%-54%). Only higher educational attainment and poor collateral blood flow in the right hemisphere differentiated cognitively impaired (n = 19) and intact groups (n = 23), and MMD-related characteristics (eg, disease duration, stroke history) did not differentiate the 2 groups., Conclusion: Consistent with previous work, frontal-subcortical cognitive deficits (eg, deficits in mental speed, attention, executive functioning) were found in nearly half of patients with MMD and better cognitive performance was associated with factors related to cognitive reserve. Angiographic metrics of disease burden (eg, Suzuki rating, collateral flow) and hemodynamic reserve were not consistently associated with poorer cognitive outcomes, suggesting that cognition is a crucial independent factor to assess in MMD and has relevance for treatment planning and functional status., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

It has been more than three years since COVID-19 impacted the lives of millions of people, many of whom suffer from long-term effects known as long-haulers. Notwithstanding multiorgan complaints in long-haulers, signs and symptoms associated with cognitive characteristics commonly known as "brain fog" occur in COVID patients over 50, women, obesity, and asthma at excessive. Brain fog is a set of symptoms that include cognitive impairment, inability to concentrate and multitask, and short-term and long-term memory loss. Of course, brain fog contributes to high levels of anxiety and stress, necessitating an empathetic response to this group of COVID patients. Although the etiology of brain fog in COVID-19 is currently unknown, regarding the mechanisms of pathogenesis, the following hypotheses exist: activation of astrocytes and microglia to release pro-inflammatory cytokines, aggregation of tau protein, and COVID-19 entry in the brain can trigger an autoimmune reaction. There are currently no specific tests to detect brain fog or any specific cognitive rehabilitation methods. However, a healthy lifestyle can help reduce symptoms to some extent, and symptom-based clinical management is also well suited to minimize brain fog side effects in COVID-19 patients. Therefore, this review discusses mechanisms of SARS-CoV-2 pathogenesis that may contribute to brain fog, as well as some approaches to providing therapies that may help COVID-19 patients avoid annoying brain fog symptoms., Competing Interests: Declarations. Ethics Approval and Consent to Participate: Not applicable Consent for Publication: Not applicable Competing Interests: The author declares no competing interests., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: Declarations. Ethics Approval: N/A. Consent to Participate: N/A. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: Black populations show increased incidences of diagnosis, worse disease severity, and earlier likelihood of mortality due to MS. Clinical outcomes are also linked to biological sex and as with Black individuals, MS characteristics between sexes have also shifted overtime. This study examined whether clinical disease progression differed by race and sex for patients with MS., Design: "Black" (N = 47) and "White" (N = 58) participants with MS (82 % female) were recruited from a longitudinal examination of the impact of race and sex on the cognition and disease duration of patients in the gulf south region of the United States., Results: Black participants had shorter disease durations [F (1,103) = 4.70, p = .03], (MDiff = [-3.96]) and were younger [F (1, 103) = 14.25, p < .001], (MDiff = [-9.04]). Despite this, Black individuals had worse SDMT t-scores [F (1, 103) = 5.22, p = .024], (MDiff = [-4.62])]. Women exhibited higher MSSS scores [F (1, 96) = 5.59, p = .02], (MDiff = [-2.15]). Specifically, Black women were younger than White women [F (1, 84) = 14.47, p < .001], (MDiff = [-9.15])] and had shorter disease durations [F (1, 84) = 6.04, p = .016], (MDiff = [-4.57])] yet scored lower on the SDMT T-scores [F (1, 84) = 6.11, p = .015], (MDiff = [-5.51])]., Conclusion: Findings suggest an interaction between race and sex may influence clinical progression in MS. Despite being younger and having shorter disease durations Black participants with MS, specifically Black women exhibited worse clinical outcomes., Summary: For women and men, MS incidence among Black Americans has become similar to White Americans. However, Black individuals experience greater disease severity and earlier mortality. Clinical impairment often accompanies MS. We examined the influence of race and sex on clinical status using the Symbol Digit Modalities Test t-scores (SDMT T-scores) and Multiple Sclerosis Severity Scores (MSSS) in Black (N = 47) and White (N = 58) patients with MS. Women exhibited higher MSSS scores than men [F (1, 96) = 5.59, p = .02], (MDiff = [-2.15]). Black participants had shorter disease durations [F (1, 103) = 4.70, p = .03], (MDiff = [-3.96]) and were younger [F (1, 103) = 14.25, p < .001], (MDiff = [-9.04]). Despite this, Black individuals had worse SDMT T-scores [F (1, 103) = 5.22, p = .024], (MDiff = [-4.62])]. Specifically, Black women were younger than White women [F (1, 84) = 14.47, p < .001], (MDiff = [-9.15])] and had shorter disease durations [F (1, 84) = 6.04, p = .016], (MDiff = [-4.57])] yet scored lower on the SDMT T-scores [F (1, 84) = 6.11, p = .015], (MDiff = [-5.51])]. These findings suggest that an interaction between race and sex may influence clinical progression in MS., Competing Interests: Declaration of competing interest The authors have no competing interest nor relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Memory and affective processing were compared in young adults with a remote mild traumatic brain injury (mTBI), to healthy younger and older adults. We evaluated memory performance when encoding was done under multi-tasking (divided attention) conditions, likely to exacerbate cognitive and psychological symptoms in mTBI., Methods: Participants studied pairs of unrelated words under either full or divided attention conditions. Memory for single words (item memory) and for pairs of words (associative memory) was then assessed in sequential independent recognition tests, under full attention., Results: Associative memory was poorer than item memory, and worse when encoding was done under divided than full attention. The decline in recognition accuracy from full to divided attention conditions on the associative memory test was significantly greater in mTBI compared to young adults and was similar in magnitude to that observed in older adults under full attention. Self-reported mental and total fatigue increased significantly as performance on the memory tests, following the divided attention condition, decreased, but only in the mTBI group., Conclusions: Results show lingering memory deficits, and suggest that cognitive tasks may be experienced as psychologically more demanding in those with a mTBI, even months or years after injury.

Deficits in rhythm perception and production have been reported in a variety of psychiatric, neurodevelopmental and neurologic disorders. Since correlations between rhythmic abilities and cognitive functions have been demonstrated in neurotypical individuals, we here investigate whether and how rhythmic abilities are associated with cognitive functions in 35 participants with neurocognitive deficits due to acquired brain lesions. We systematically assessed a diverse set of rhythm perception and production abilities including time and beat perception and finger-tapping tasks. Neuropsychological tests were applied to assess separable cognitive functions. Using multiple regression analyses we show that lower variability in aligning movements to a pacing sequence was predicted by better inhibitory control and better working memory performance. Working memory performance also predicted lower variability of rhythmic movements in the absence of an external pacing sequence and better anticipatory timing to sequences with gradual tempo changes. Importantly, these predictors remained significant for all regression models when controlling for other cognitive variables (i.e., cognitive flexibility, information processing speed, and verbal learning ability) and potential confounders (i.e., age, symptom strength of depression, manual dexterity, duration of illness, severity of cognitive impairment, and musical experience). Thus, all rhythm production abilities were significantly predicted by measures of executive functions. In contrast, rhythm perception abilities (time perception/beat perception) were not predicted by executive functions in this study. Our results, enhancing the understanding of cognitive underpinnings of rhythmic abilities in individuals with neurocognitive deficits, may be a first mandatory step to further potential therapeutic implications of rhythm-based interventions in neuropsychological rehabilitation., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The purpose of this study was to identify patterns of structural disconnection and multivariate lesion-behaviour relationships associated with post-stroke deficits across six commonly impacted cognitive domains: executive function, language, memory, numerical processing, praxis, and visuospatial attention., Methods: Stroke survivors (n = 593) completed a brief domain-specific cognitive assessment (the Oxford Cognitive Screen (OCS)) during acute hospitalisation. Network-level and multivariate (sparce canonical correlation) lesion mapping analyses were conducted to identify focal neural correlates and distributed patterns of structural disconnection associated with impairment on each of the 16 OCS measures., Results: Network-level and multivariate lesion mapping analyses identified significant correlates for 12/16 and 10/16 OCS measures, respectively which were largely consistent with correlates reported in past work. Language impairments were reliably localised to network- and voxel-level correlates centred in left fronto-temporal regions. Memory impairments were associated with disconnection in a large network of left hemisphere regions. Number processing deficits were associated with damage to voxels centred in the left insular/opercular cortex, as well as disconnection within the surrounding white matter tracts. Within the domain of attention, different subtypes of visuospatial neglect were linked to distinct but partially overlapping patterns of disconnection and voxel-level damage. Praxis impairment was not linked to any voxel-level regions but was significantly associated with disconnection within the left hemisphere dorsal attention network., Conclusion: These results highlight the utility of routine, domain-specific cognitive assessment and imaging data for theoretically-driven lesion mapping analyses, while providing novel insight into the complex anatomical correlates of common and debilitating post-stroke cognitive impairments., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Neurocognition can be severely affected in pediatric brain tumor survivors. We analyzed the association of cognitive functioning with radiotherapy dose, postoperative cerebellar mutism syndrome (pCMS), hydrocephalus, intraventricular methotrexate (MTX) application, tumor localization, and biology in pediatric survivors of a posterior fossa tumor., Methods: Subdomain-specific neurocognitive outcome data from 279 relapse-free survivors of the HIT-2000 trial (241 medulloblastoma and 38 infratentorial ependymoma) using the Neuropsychological Basic Diagnostic tool based on Cattell-Horn-Carroll's model for intelligence were analyzed., Results: Cognitive performance 5.14 years (mean; range = 1.52-13.02) after diagnosis was significantly below normal for all subtests. Processing speed and psychomotor abilities were most affected. Influencing factors were domain-specific: CSI-dose had a strong impact on most subtests. pCMS was associated with psychomotor abilities (β = -0.25 to -0.16) and processing speed (β = -0.32). Postoperative hydrocephalus correlated with crystallized intelligence (β = -0.20) and short-term memory (β = -0.15), age with crystallized intelligence (β = 0.15) and psychomotor abilities (β = -0.16 and β = -0.17). Scores for fluid intelligence (β = -0.23), short-term memory (β = -0.17) and visual processing (β = -0.25) declined, and scores for selective attention improved (β = 0.29) with time after diagnosis., Conclusions: The dose of CSI was strongly associated with neurocognitive outcomes. Low psychomotor abilities and processing speed both in patients treated with and without CSI suggest a strong contribution of the tumor and its surgery on these functions. Future research therefore should analyze strategies to both reduce CSI dose and toxicity caused by other treatment modalities., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Neuropsychology is important in differential diagnosis, treatment planning, surgical work-up, and support of patients with movement disorders and their families. The cognitive profiles of several movement disorders are reviewed here. The authors also review relevant neuropsychologic literature related to neurosurgic intervention and cognitive-enhancing medication for patients with movement disorders., Competing Interests: Disclosure Preparation of this article was supported in part by a grant from Barrow Neurological Foundation, United States to AIT (AN 455003032626)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Neuropsychological evaluation is an essential component of clinical care for people with epilepsy and also has a specialized role in predicting cognitive outcome after epilepsy surgery. Neuropsychological research in the field of epilepsy has had a significant impact on our knowledge regarding memory and language systems, lateralization of cognitive functions, and the heterogeneity in cognitive phenotypes among people with epilepsy. Interventions that consider the impact of health disparities, cognition, psychological functioning, individual risk and resilience factors, and modifiable lifestyle factors, are critical for optimizing cognitive functioning, psychological health, and quality of life for people with epilepsy., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Encephalopathy is part of the clinical triad of Susac syndrome, but a detailed understanding of the neurocognitive and neuropsychiatric profile of this condition is lacking. Existing literature indicates that cognitive deficits range in severity from subtle to profound. Executive function and short-term recall are affected frequently. Psychiatric manifestations may be absent or may include anxiety, mood disorders or psychosis. If psychiatric phenomena develop during the disease course, it can be hard to disentangle whether symptoms directly relate to the pathology of Susac syndrome or are secondary to treatment-related side effects. In this article, we review what is known about the cognitive and psychiatric morbidity of Susac syndrome and identify areas where knowledge is deficient. Importantly, we also provide a framework for future research, arguing that better phenotyping, understanding of pathophysiology, evaluation of treatments on cognitive and psychiatric outcomes, and longitudinal data capture are vital to improving patient outcomes., (© 2024. Crown.)

Background: This study aimed at preliminarily assessing, in a cohort of non-demented amyotrophic lateral sclerosis (ALS) patients, the ecological validity, and more specifically the veridicality, of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and the ALS Cognitive Behavioral Screen (ALS-CBS™), by relating their scores to caregiver-report ratings of cognitive changes., Methods: N = 147 patient-caregiver dyads were recruited. Patients were administered the ECAS and ALS-CBS™, whilst caregiver the Caregiver Behavioral Questionnaire (CBQ) and Beaumont Behavioural Inventory (BBI). An Ecological Cognitive Functioning Index (ECFI) was derived from those items of the CBQ and BBI that tap on executive and language changes. Ecological validity was assessed via both correlational and predictive analyses net of caregiver-rated behavioural changes (as assessed by the ECAS-Carer Interview)., Results: The ECFI was associated with the total scores on both the ECAS (p = .014) and ALS-CBS™ (p = .017). When looking at ECAS and ALS-CBS™ subscales, those assessing verbal fluency were selectively associated with the ECFI. The ECFI was higher in patients performing defectively on the ECAS (p = .004) and on the ALS-CBS™ (p = .027)., Discussion: This study suggests that both the ECAS and the ALS-CBS™ represent a valid estimate of non-demented ALS patients' cognitive status in the real world, also highlighting the clinical relevance of cognitive changes reported by caregivers., (© 2024. Fondazione Società Italiana di Neurologia.)

Purpose of Review: The risk of cognitive impairment is higher in people with CKD than in the general population. The complex relationship between CKD and cognitive dysfunction has not been extensively characterized. Here, we review epidemiological associations, specific patterns of CKD-related cognitive impairment, the underlying mechanisms, and recently published data on relevant biomarkers., Recent Findings: Despite some discrepancies, recent published studies have confirmed that CKD is associated with cognitive function (e.g. incident cognitive events). Although patients with CKD often exhibit impairments in executive functions and attention, it is noteworthy that other cognitive functions (e.g. memory) can be preserved. The key mechanisms described recently include vascular damage, genetic factors, the accumulation of uremic toxins, disruption of the blood-brain barrier, glymphatic system dysfunction, and changes in the gut-brain axis. Kidney function is increasingly seen as a game changer in the interpretation of biomarkers of cognitive impairment and, especially, hallmarks of Alzheimer disease., Summary: The data reviewed here highlight the need for interdisciplinary collaboration between nephrologists and neurologists in the care of patients with CKD at risk of cognitive impairment. In order to further improving diagnosis and therapy, future research must elucidate the mechanisms underlying the CKD-cognitive impairment association and confirm the value of biomarkers., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Alzheimer's disease (AD) is characterized by disorders in brain energy. The lack of sufficient energy for nerve function leads to cognitive dysfunction and massive neuronal loss in AD. Ketone bodies are an alternative to glucose as a source of energy in the brain, and alternate-day fasting (ADF) promotes the production of the ketone body β-hydroxybutyric acid (βOHB). In this study, 7-month-old male WT mice and 3xTg mice underwent dietary control for 20 weeks. We found that ADF increased circulating βOHB concentrations in 3xTg mice, improved cognitive function, reduced anxiety-like behaviors, improved hippocampal synaptic plasticity, and reduced neuronal loss, Aβ oligomers and tau hyperphosphorylation. In addition, ADF improved mitochondrial bioenergetic function by promoting brain ketone metabolism and rescued brain energy deficits in 3xTg mice. A safety evaluation showed that ADF improved exercise endurance and liver and kidney function in 3xTg mice without negatively affecting muscle motor and heart functions. This study provides a theoretical basis and strong support for the application of ADF as a non-drug strategy for preventing and treating brain energy defects in the early stage of AD., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: This study investigated whether cognitive screening tools used for people with amyotrophic lateral sclerosis (pwALS) are affected by the screen being administered face-to-face or remotely online. It also investigated whether demographic variables predicted total cognitive screen scores., Methods: The cognitive component of the Edinburgh Cognitive and Behavioural ALS Screen (ECASc), the cognitive component of the ALS Cognitive Behavioural Screen (ALS-CBSc), and the Mini Addenbrooke's Cognitive Examination (Mini-ACE) were administered to 41 pwALS and 41 controls face-to-face. Versions of the cognitive screens designed to be administered remotely were administered to 57 pwALS and 44 controls via videoconferencing methods. Backwards stepwise linear regressions were conducted to assess whether total scores on the ECASc, ALS-CBSc, and Mini-ACE scores were predicted by administration mode (face-to-face or remote) or demographic variables., Results: Mode of administration significantly affected scores on the ECASc and ALS-CBSc; remote administration was associated with better total scores. Administration mode did not significantly affect Mini-ACE scores. All cognitive screens were significantly affected by IQ scores; higher IQ scores predicted better screening tool scores. Only ECASc scores were significantly affected by age, with older age predicting poorer scores. Being female was associated with better Mini-ACE scores; sex did not predict ECASc and ALS-CBSc scores., Conclusions: Our results suggest that videoconferencing versions of the ECASc and ALS-CBSc may function differently to the original, face-to-face versions. There are advantages to using remote versions of cognitive screening tools but clinicians and researchers who use them should consider that they may not yield equivalent scores., (© 2024. The Author(s).)

Serotonin is a monoamine neurotransmitter that plays a main role in regulating physiological and cognitive functions. Serotonergic system dysfunction is involved in the etiology of various psychiatric and neurological disorders. Therefore, the present study was designed to investigate the effects of early-life serotonin depletion on cognitive disorders caused by sleep deprivation. Serotonin was depleted by para-chlorophenylalanine (PCPA, 100 mg/kg, s.c.) at postnatal days 10-20, followed by sleep deprivation-induced through the multiple platform apparatus for 24 h at PND 60. After the examination of the novel object recognition and passive avoidance memories, the hippocampi and prefrontal cortex were dissected to examine the brain-derived neurotrophic factor (BDNF) mRNA expression by PCR. Our findings showed that postnatal serotonin depletion and sleep deprivation impaired the novel object recognition and passive avoidance memories and changed the BDNF levels. In the same way, the serotonin depletion in early life before sleep deprivation exacerbated the harmful effects of sleep deprivation on cognitive function and BDNF levels. It can be claimed that the serotonergic system plays a main role in the modulation of sleep and cognitive functions., (© 2024 International Society for Developmental Neuroscience.)

Background and Hypothesis: It remains unclear whether the relation of chronic kidney disease (CKD) with cognitive dysfunction is independent of blood pressure (BP). We evaluated kidney function in relation to premorbid BP measurements, cerebral small vessel disease (CSVD), and incident mild cognitive impairment (MCI) and dementia in Framingham Offspring Cohort participants., Methods: We included Framingham Offspring participants free of dementia, attending an examination during midlife (exam cycle 6, baseline) for ascertainment of kidney function status, with brain magnetic resonance imaging late in life (exam cycles 7-9), cognitive outcome data, and available interim hypertension and BP assessments. We related CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2) and albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g) to CSVD markers and cognitive outcomes using multivariable regression analyses., Results: Among 2604 participants (mean age 67.4 ± 9.2, 64% women, 7% had CKD, and 9% albuminuria), albuminuria was independently associated with covert infarcts [adjusted OR, 1.55 (1.00-2.38); P = 0.049] and incident MCI and dementia [adjusted hazard ratio (HR), 1.68 (1.18-2.41); P = 0.005 and 1.71, (1.11-2.64); P = 0.015, respectively]. CKD was not associated with CSVD markers but was associated with a higher risk of incident dementia [HR, 1.53 (1.02-2.29); P = 0.041]. While albuminuria was predictive of the Alzheimer's disease subtype [adjusted HR = 1.68, (1.03-2.74); P = 0.04), CKD was predictive of vascular dementia [adjusted HR, 2.78 (1.16-6.68); P = 0.023]., Conclusions: Kidney disease was associated with CSVD and cognitive disorders in asymptomatic community dwelling participants. The relation was independent of premorbid BP, suggesting that the link between kidney and brain disease may involve additional mechanisms beyond BP-related injury., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Obstructive sleep apnea (OSA) affects quality of life and health in nearly 1 billion patients all over the world. With aging society, OSA increases the risk of Alzheimer's disease and leads to severe cognitive impairment. Chronic intermittent hypoxia (CIH), the core pathological mechanism of OSA, may induce synaptic plasticity damage and cognitive impairment, and decrease learning and memory and attention ability. However, the molecular mechanism underlying OSA is still not fully understood. And, there is no targeted treatment strategy for cognitive impairment in patients with OSA. Firstly, the correlation between OSA and cognitive dysfunction was summarized in this review. Secondly, the molecular mechanism of CIH-induced cognitive impairment was elucidated from the perspectives of synaptic plasticity damage, oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, mitochondrial dysfunction and autophagy. Finally, the current treatment strategy for cognitive impairment in patients with OSA was summarized.

Objective: This study investigated the weight of different cognitive disorders on patient behaviour influencing the risk of falls after recent stroke., Design: Survey and retrospective monocentric study., Subjects/patients: 74 professionals/108 patients., Methods: Survey of professionals to ask for their thoughts concerning the weight of different cognitive disorders on the risk of falls and a retrospective study of patients post-stroke to determine whether these cognitive deficits could distinguish fallers from non-fallers. Univariate and multivariate logistic regression analyses were conducted., Results: In part 1, major cognitive disorders identified were anosognosia, confusion, inattention, precipitation, and unilateral spatial neglect. In part 2, 25 patients (23%) were fallers. After adjustment for length of rehabilitation stay and disease severity, on multivariate analysis, the cognitive disorders significantly associated with risk of falls were anosognosia (odds ratio 16), precipitation (13.3), inattention (8.3), and perseveration (4.9). Unilateral spatial neglect was not independently associated. Aphasia did not play a role., Conclusion: Some cognitive disorders, easily identified before any neuropsychological assessment, strongly modify patient behaviour in terms of risk of falls. It is proposed that these disorders should not be considered as an additional factor along with physical and general factors but rather as a multiplying factor applied to the others.

White matter microvascular alterations in temporal lobe epilepsy (TLE) may be relevant to acquired neurodegenerative processes and cognitive impairments associated with this condition. We quantified microvascular changes, myelin, axonal, glial and extracellular-matrix labelling in the gyral core and deep temporal lobe white matter regions in surgical resections from 44 TLE patients with or without hippocampal sclerosis. We compared this pathology data with in vivo pre-operative MRI diffusion measurements in co-registered regions and neuropsychological measures of cognitive impairment and decline. In resections, increased arteriolosclerosis was observed in TLE compared to non-epilepsy controls (greater sclerotic index, p < 0.001), independent of age. Microvascular changes included increased vascular densities in some regions but uniformly reduced mean vascular size (quantified with collagen-4, p < 0.05-0.0001), and increased pericyte coverage of small vessels and capillaries particularly in deep white matter (quantified with platelet-derived growth factor receptorβ and smooth muscle actin, p < 0.01) which was more marked the longer the duration of epilepsy (p < 0.05). We noted increased glial numbers (Olig2, Iba1) but reduced myelin (MAG, PLP) in TLE compared to controls, particularly prominent in deep white matter. Gene expression analysis showed a greater reduction of myelination genes in HS than non-HS cases and with age and correlation with diffusion MRI alterations. Glial densities and vascular size were increased with increased MRI diffusivity and vascular density with white matter abnormality quantified using fixel-based analysis. Increased perivascular space was associated with reduced fractional anisotropy as well as age-accelerated cognitive decline prior to surgery (p < 0.05). In summary, likely acquired microangiopathic changes in TLE, including vascular sclerosis, increased pericyte coverage and reduced small vessel size, may indicate a functional alteration in contractility of small vessels and haemodynamics that could impact on tissue perfusion. These morphological features correlate with white matter diffusion MRI alterations and might explain cognitive decline in TLE., (© 2024. The Author(s).)

Cognitive impairment is a typical symptom of both neurodegenerative and certain other diseases. In connection with these different pathologies, the etiology and neurological and metabolic changes associated with cognitive impairment must differ. Until these characteristics and differences are understood in greater detail, pharmacological treatment of the different forms of cognitive impairment remains suboptimal. Neurotransmitter receptors, including neuronal nicotinic acetylcholine receptors (nAChRs), dopamine receptors, and glutamine receptors, play key roles in the functions and metabolisms of the brain. Among these, the role of nAChRs in the development of cognitive impairment has attracted more and more attention. The present review summarizes what is presently known concerning the structure, distribution, metabolism, and function of nAChRs, as well as their involvement in major cognitive disorders such as Alzheimer's disease, Parkinson's disease, vascular dementia, schizophrenia, and diabetes mellitus. As will be discussed, the relevant scientific literature reveals clearly that the α4β2 and α7 nAChR subtypes and/or subunits of the receptors play major roles in maintaining cognitive function and in neuroprotection of the brain. Accordingly, focusing on these as targets of drug therapy can be expected to lead to breakthroughs in the treatment of cognitive disorders such as AD and schizophrenia., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Worldwide, around 50 million people live with dementia, and this number is projected to triple by 2050. It has been estimated that 20% of all dementia cases have a predominant cerebrovascular pathology, while perhaps another 20% of vascular diseases contribute to a mixed dementia picture. Therefore, the vascular contribution to dementia affects 20 million people currently and will increase markedly in the next few decades, particularly in lower- and middle-income countries.In this review, we discuss the mechanisms of vascular cognitive impairment (VCI) and review management. VCI refers to the spectrum of cerebrovascular pathologies that contribute to any degree of cognitive impairment, ranging from subjective cognitive decline, to mild cognitive impairment, to dementia. While acute cognitive decline occurring soon after a stroke is the most recognized form of VCI, chronic cerebrovascular disease, in particular cerebral small-vessel disease, can cause insidious cognitive decline in the absence of stroke. Moreover, cerebrovascular disease not only commonly co-occurs with Alzheimer's disease (AD) and increases the probability that AD pathology will result in clinical dementia, but may also contribute etiologically to the development of AD pathologies.Despite its enormous health and economic impact, VCI has been a neglected research area, with few adequately powered trials of therapies, resulting in few proven treatments. Current management of VCI emphasizes prevention and treatment of stroke and vascular risk factors, with most evidence for intensive hypertension control. Reperfusion therapies in acute stroke may attenuate the risk of VCI. Associated behavioral symptoms such as apathy and poststroke emotionalism are common. We also highlight novel treatment strategies that will hopefully lead to new disease course-modifying therapies. Finally, we highlight the importance of including cognitive endpoints in large cardiovascular prevention trials and the need for an increased research focus and funding for this important area., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cerebellar pathology engenders the disturbance of movement that characterizes Friedreich ataxia (FRDA), yet the impact of cerebellar pathology on cognition in FRDA remains unclear. Numerous studies have unequivocally demonstrated the role of the cerebellar pathology in disturbed cognitive, language and affective regulation, referred to as Cerebellar Cognitive Affective Syndrome (CCAS), and quantified by the CCAS-Scale (CCAS-S). The presence of dysarthria in many individuals with ataxia, particularly FRDA, may confound results on some items of the CCAS-S resulting in false-positive scores. This study explored the relationship between performance on the CCAS-S and clinical metrics of disease severity in 57 adults with FRDA. In addition, this study explored the relationship between measures of intelligibility and naturalness of speech and scores on the CCAS-S in a subgroup of 39 individuals with FRDA. We demonstrated a significant relationship between clinical metrics and performance on the CCAS-S. In addition, we confirmed the items that returned the greatest rate of failure were based on Verbal Fluency Tasks, revealing a significant relationship between these items and measures of speech. Measures of speech explained over half of the variance in the CCAS-S score suggesting the role of dysarthria in the performance on the CCAS-S is not clear. Further work is required prior to adopting the CCAS-S as a cognitive screening tool for individuals with FRDA., (© 2024. The Author(s).)

Objective: Low health literacy is common among people with epilepsy (PWE) and may play an important role in disease management and outcomes. The current study evaluated whether health literacy is related to cognition, health, and everyday functioning in PWE., Methods: This cross-sectional, correlational study included 25 demographically comparable healthy adults retrospectively matched to a consecutive series of 89 PWE presenting for neuropsychological evaluation in a surgical setting and who completed the Newest Vital Sign and Brief Health Literacy Screener. The PWE also completed a comprehensive neuropsychological battery and measures of quality of life and everyday functioning., Results: PWE had significantly lower health literacy as compared to healthy adults (ps < 0.05) at a medium-to-large effect size. In analyses covarying for education and oral word reading literacy in the PWE sample, lower health literacy was independently associated with bilateral seizure onsets, greater antiseizure medication burden, poorer performance on measures of memory and information processing speed, and difficulties with self-care (ps < 0.05)., Significance: Findings suggest that PWE are at risk for low health literacy, which may be partly attributable to disrupted brain-behavior relationships and contribute to poorer everyday functioning. Future studies are needed to identify effective methods to support and improve health literacy in PWE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Awareness of cognitive deficits is related to executive functions and may, therefore, be sensitive to the effects of lumbar puncture (LP) in idiopathic normal pressure hydrocephalus (iNPH). Although a reduction in awareness of cognitive deficits (RACD) has been previously described in iNPH, there is a lack of systematic, psychometrically validated reports. In this study, we investigated RACD and its LP-related changes in iNPH patients and compared them with those in clinical and healthy control groups., Methods: RACD was assessed before and after lumbar puncture (LP) in 24 patients (14 iNPH, 10 other age-associated cognitive syndromes; AACS) and compared with 23 healthy controls (HC), employing two RACD measures alongside cognitive examination. Local metacognition was measured using a visual percentile-based rating system and operationalized as the t-scaled distance between the participants' task-specific performance estimations and their objective test performance (ΔTSPE). Global metacognition, targeting broader estimates of cognitive functioning (ECF), was quantified by subtracting self- from informant-obtained sum scores on a questionnaire evaluating participants' dysexecutive problems (DEX-DS). Within-group and between-group differences in ΔTSPE and DEX-DS scores were compared non-parametrically, focusing on post-LP changes., Results: Averaged ΔTSPE was higher in the patient groups and mirrored the groups' lower objective test performance, while averaged DEX-DS showed no group difference. Following LP, group comparisons revealed iNPH-specific decrease in both RACD measures., Conclusion: Our study revealed LP-related RACD changes in iNPH patients compared to those in AACS and HC participants. The results suggest a mitigation of impaired metacognitive abilities in iNPH, possibly resulting from LP-induced improvements in (local) metacognitive performance, facilitating ECF adjustment alongside a metacognitively stimulating testing procedure., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cognitive impairment represents one of the core features of schizophrenia, involves both neurocognition and social cognition domains, and has a significant negative impact on real-world functioning. The present review provides a framework for the conceptualization and characterization of "primary" and "secondary" cognitive impairment in schizophrenia. In this conceptualization, primary cognitive impairment can be defined as a consequence of the neurobiological alterations that underlie psychopathological manifestations of the disorder, while secondary cognitive impairment can be defined as the results of a source issue that has a negative impact on cognitive performance. Sources of secondary cognitive impairment are frequent in people with schizophrenia and include several different factors, such as positive and negative symptoms, depressive symptoms, autistic symptoms, pharmacotherapy, substance abuse, metabolic syndrome, social deprivation, and sleep disorders. It can be hypothesized that secondary cognitive impairment may be improved by effectively resolving the source issue, while primary cognitive impairment may benefit from dedicated treatment. Further research is required to confirm this hypothesis, to better characterize the distinction between primary and secondary cognitive impairment in a clinical and in a neurobiological perspective, and to evaluate the impact of systematically assessing and treating secondary cognitive impairment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Early prediction of poststroke motor recovery is challenging in clinical settings. The Prediction recovery potential (PREP2) algorithm is the most accurate approach for prediction of Upper Limb function available to date but lacks external validation., Objectives: (i) To externally validate the PREP2 algorithm in a prospective cohort, (ii) to study the characteristics of patients misclassified by the algorithm, and (iii) to compare the performance according to the presence of cognitive syndromes (aphasia, neglect, cognitive disorders)., Methods: We enrolled 143 patients with stroke and upper extremity weakness persistent at Day 3. Evaluation to predict the recovery status according to the PREP2 algorithm included age, SAFE and NIHSS scores at Day 3 and transcranial magnetic stimulation to determine the presence of the motor-evoked potential before day seven. Actual recovery (excellent, good, limited, or poor) was defined based on the Action Research Arm test score at 3 months. Accuracy was computed by comparing the predictions of the PREP2 and the actual category of the patient. Additionally, to investigate misclassifications and the impact of cognitive syndromes, we recorded SAFE and NIHSS scores at Day 7, the Montreal Cognitive Assessment (MoCA) score, the presence of aphasia and neglect and Magnetic Resonance Imaging was used to evaluate the corticospinal tract lesion load., Results: The PREP2 algorithm showed a very good predictive value with 78% accuracy [95% CI: 71.2%-86.1%], especially for the extreme categories of recovery (EXCELLENT 87.5% [95% CI: 78.9%-96.2%] and POOR 94.9% [95% CI: 87.9%-100%]), and only 46.5% [95% CI: 19.05%-73.25%] for the GOOD category and even worse than chance for the LIMITED category 0%. Pessimistic predictions (false-negative cases) had a drastic improvement in the SAFE score acutely compared to that of well-predicted patients with unfavorable recovery ( P  < 001). The predictive value of PREP2 decreased significantly when patients had cognitive disorders (MoCA score <24) versus not (69.4% [95% CI: 52.8%-86.1%] vs 93.1% [95% CI: 83.9%-100%], P  = .01)., Conclusion: Our study provides an external validation of the PREP2 algorithm in a prospective population and underlines the importance of taking into account cognitive syndromes in motor recovery prediction., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A growing body of research suggested that there was a link between poor periodontal health and systemic diseases, particularly with the early development of cognitive disorders, dementia, and depression. This is especially true in cases of changes in diet, malnutrition, loss of muscular endurance, and abnormal systemic inflammatory response. Our study aimed to determine the extent of these associations to better target the multi-level healthy aging challenge investigating the impact of periodontal disease on cognitive disorders (cognitive impairment and cognitive decline), dementia, and depression. We conducted a comprehensive literature search up to November 2023 using six different electronic databases. Two independent researchers assessed the eligibility of 7363 records against the inclusion criteria and found only 46 records that met the requirements. The study is registered on PROSPERO (CRD42023485688). We generated random effects pooled estimates and 95% confidence intervals (CI) to evaluate whether periodontal disease increased the risk of the investigated outcomes. The quality assessment revealed moderate quality of evidence and risk of bias. Periodontal disease was found to be associated with both cognitive disorders (relative risk (RR) 1.25, 95% CI 1.11-1.40, in the analysis of cross-sectional studies); cognitive impairment (RR 3.01, 95% CI 1.52-5.95 for longitudinal studies, cognitive decline); and dementia (RR 1.22, 95% CI 1.10-1.36). However, no significant increased risk of depression among subjects with periodontal disease was found (RR 1.07, 95% CI 0.95-1.21). Despite the association with two of the three explored outcomes, the available evidence on periodontal diseases and dementia, cognitive disorders, and depression is controversial due to several limitations. Therefore, further investigations involving validated and standardized tools are required., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

In addition to well-known symptoms such as sleepiness and cataplexy, many people with narcolepsy have impaired cognition, reporting inattention, poor memory, and other concerns. Unfortunately, research on cognition in narcolepsy has been limited. Strong evidence demonstrates difficulties with sustained attention, but evidence for executive dysfunction and impaired memory is mixed. Animal research provides some insights into how loss of the orexin neurons in narcolepsy type 1 may give rise to impaired cognition via dysfunction of the prefrontal cortex, and cholinergic and monoaminergic systems. This paper reviews some of these clinical and preclinical findings, provides a neurobiological framework to understand these deficits, and highlights some of the many key unanswered questions., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The cerebellar cognitive affective syndrome is a neuropsychiatric syndrome composed of affective (anxiety, depression, euphoria, and emotional lability) and cognitive symptoms (executive, attentional, and visuospatial deficits) that was described in the 1990s. We present the case of a 49-year-old woman with a history of an acute neurological episode at the age of 28, after which she reported a change in personality, brief and alternating periods of depression, hypomania, and mixed episodes, and cognitive impairment that had a major impact on her personal and occupational level of functioning. She was initially diagnosed with bipolar disorder, but a clinical, neuropsychological, and imaging re-evaluation prompted a diagnostic reconsideration in favor of a cerebellar cognitive affective syndrome. This enabled therapeutical and prognostic refinement. Here, we discuss the diagnostic challenges of this syndrome and the implications that an accurate diagnosis has for patients.

Fetal alcohol spectrum disorders (FASDs) refer to a group of clinical conditions that occur in a person exposed to alcohol before birth. Neuroimaging shows abnormalities in brain structure, cortical development, white matter microstructure, and functional connectivity in individuals with FASD. These abnormalities modify the normal developmental trajectories resulting in deficits in cognition and behavior across several domains, including general intelligence, memory, language, attention, learning, visuospatial abilities, executive functioning, fine and gross motor skills, and social and adaptive functioning. This paper provides a review of the cognitive and behavioral outcomes of prenatal alcohol exposure. Updates data on FASD-specific neurobehavioral profile and its potential as a diagnostic tool will then be presented.

Background: Non-suicidal self-injury (NSSI) may be related to serious cognitive impairment in patients with major depressive disorder (MDD), but the specific mechanism is still unclear. This study attempts to identify the neurobiological process alterations of cognitive impairment in MDD patients with NSSI by examining the functional connectivity of the frontotemporal cortex in MDD patients with or without NSSI., Method: Thirty MDD patients with NSSI, 36 MDD patients without NSSI, and 35 healthy controls (HC) were included in the study. The MATRICS Consensus Cognitive Battery (MCCB) was used to comprehensively assess the cognitive function of the subjects and functional near-infrared spectroscopy (fNIRS) was used to detect the functional connectivity of the frontotemporal cortex and its brain regions of interest., Results: MDD patients with or without NSSI had multi-domain cognitive impairments. MDD patients with NSSI showed the lowest score in performance of attention/alertness and the weakest functional connectivity of frontotemporal when compared with the MDD patients without NSSI and the HC. In addition, the functional connectivity of the bilateral frontotemporal cortex was positively correlated with verbal learning and working memory in MDD patients with NSSI., Conclusion: In MDD patients, the appearance of NSSI is often accompanied by further impairment of attention/alertness and a decline in functional connectivity of the frontotemporal cortex. The impairment of verbal learning and working memory was associated with decreased functional connectivity of the frontotemporal cortex in MDD patients with NSSI., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Given the frequency of stroke worldwide, tools for neuropsychological assessment of patients with acute stroke are needed to identify cognitive impairments, guide rehabilitation efforts and allow for a prognosis of outcome. However, requirements for assessment tools for acute cognitive deficits differ substantially from tests for chronic neuropsychological impairments and screening tools for suspected dementia. The Oxford Cognitive Screen (OCS) has been developed as a quick to administer neurocognitive screening for acute neurological patients providing information on various cognitive domains. It is available in different languages. The present study reports cut-off scores, parallel-test reliability and concurrent validity of the German version (D-OCS). Following standardized language adaptation and translation, the D-OCS was administered to 100 healthy individuals to generate cut-off scores (5th percentile). Subsequently, 88 neurological patients were assessed with both versions of the D-OCS as well as other tests to evaluate reliability and validity of the D-OCS subscales. In a further study, the D-OCS was compared to the MoCA test in 65 acute stroke patients revealing comparable sensitivity but also differences between both tools. The cut-off scores were comparable to other international versions of the OCS. Intraclass correlations were highly significant and document reliability of the D-OCS subtests. Scores on subtests correlated significantly with independent tests securing validity. Comparison with the MoCA revealed comparable sensitivity and specificity. The D-OCS is a reliable and valid assessment tool well suited for patients with acute stroke. Differences to the MoCA test are discussed., (© 2024 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

Objectives: Electroconvulsive therapy (ECT) is an effective somatic treatment, but it may be limited by cognitive adverse effects. The existing cognitive screening instruments often lack specificity to ECT-associated cognitive deficits. The ElectroConvulsive Therapy Cognitive Assessment was developed and validated in a clinical setting, but the reliability and validity of the Chinese version of ElectroConvulsive Therapy Cognitive Assessment (ECCA-C) have not been studied in a large clinical sample., Methods: The ECCA-C and the Montreal Cognitive Assessment (MoCA) were administered to patients with major depressive disorder (MDD) undergoing ECT at 3 time points: pretreatment (baseline), before the fifth treatment, and 1 week posttreatment. The instruments were also administered to a sample of healthy subjects., Results: Sixty-five patients with MDD and 50 age- and sex-matched healthy controls were recruited in this study. Overall, the patient group had statistically significantly lower MoCA and ECCA-C scores than the control group (both P values <0.001). The Cronbach α of the ECCA-C was 0.88 at baseline. Statistically significant decreases over time were observed in ECCA-C: pre-ECT (23.9 ± 4.0) > mid-ECT (21.3 ± 3.4) > post-ECT (18.7 ± 4.8) (all P values <0.001), whereas no statistically significant changes in MoCA scores were found at these 3 time points ( F = 1.86, P = 0.165). A cutoff score of 26.5 on the ECCA-C was found to best differentiate between MDD patients and healthy controls., Conclusions: The ECCA-C showed satisfactory psychometric properties and may be a more sensitive instrument than the MoCA to assess cognitive impairment associated with ECT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This study was supported by the Beijing Anding Hospital, Capital Medical University (YJ2021-05)., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Impaired self-awareness (SA) after acquired brain injury (ABI) has traditionally been linked to deficits in executive functions. However, conflicting findings about this relationship have been reported in the literature. This inconsistency is probably due to the multicomponent nature of both constructs, as not all aspects of executive functions may be equally relevant to all components of self-awareness. This study explored whether offline SA (i.e. metacognitive knowledge) and online SA (i.e. error detection) relate to a less studied executive component, conflict monitoring/resolution., Method: Twenty-six patients with ABI performed the Three-Conflict Cognitive Control Task (3CCT), an experimental task that allowed to measure the ability to monitor and solve three different types of conflicts (Distractors-filtering, Spatial Stroop and Simon). Measures of SA were collected: offline SA was based on self-informant discrepancy about patient's everyday functional difficulties, and online SA was based on error detection abilities during a performance-based naturalistic task (The Breakfast Conflict Task)., Results: After controlling for global cognition, the conflict monitoring measure of 3CCT demonstarted incremental validity in predicting offline and online SA measured in naturalistic tasks., Conclusions: Conflict monitoring/resolution seems to be an important component of SA. This finding contributes to further understand the relationship between executive functions and SA. In addition, conflict monitoring/resolution is an executive component that should be considered when designing assessment and intervention strategies to deal with ISA.

Objectives: Sensitivity to moral and conventional rules (SMCR) is supported by bilateral brain networks and psychosocial input both of which may be altered in temporal lobe epilepsy (TLE). This study evaluated the components of SMCR in patients with TLE, aiming to clarify their preservation and link to psychopathological and cognitive aspects., Methods: Adult patients with unilateral TLE and healthy controls were evaluated using neuropsychological tests for SMCR, memory, language, and executive functions, the Empathy Questionnaire (EQ), and the Symptom Checklist-90-R (SCL-90-R)., Results: The SMCR test items showed good reliability and validity, yielding the Severity and Rules factors distinct from the Executive, Lexical and Memory factors. Patients with right TLE scored worse in moral rules recognition than controls, but this difference was nullified by a significant influence for age and sex. The Severity and Rules factors related to semantic fluency and age and, respectively, TLE side and psychoticism. However, these factors did predict TLE membership., Conclusions: In adult patients with TLE, the SMCR test reflects a distinct cognitive domain. Conventional rules are well-retained, while moral reasoning may be only affected in right TLE if unfavorable demographics coexist. Although age, TLE side, semantic abilities, and psychoticism cooperate to determine SMCR, impairment of such domain is not a distinctive feature of TLE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Little is known about amyotrophic lateral sclerosis (ALS)-nonspecific cognitive deficits - most notably memory disturbance - and their biological underpinnings. We investigated the associations of the Alzheimer's disease (AD) genetic risk factor APOE and cerebrospinal fluid (CSF) biomarkers Aβ and tau proteins with cognitive and motor phenotype in ALS., Methods: APOE haplotype was determined in 281 ALS patients; for 105 of these, CSF levels of Aβ42, Aβ40, total tau (T-tau), and phosphorylated tau (P-tau181) were quantified by chemiluminescence enzyme immunoassay (CLEIA). The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was employed to evaluate the neuropsychological phenotype., Results: APOE-E4 allele was associated with worse ECAS memory score (median, 14.0 in carriers vs. 16.0 in non-carriers) and lower CSF Aβ42 (-0.8 vs. 0.1, log-transformed values) and Aβ42/40 ratio (-0.1 vs. 0.3). Some 37.1% of ALS patients showed low Aβ42 levels, possibly reflecting cerebral Aβ deposition. While lower Aβ42/40 correlated with lower memory score (β = 0.20), Aβ42 positively correlated with both ALS-specific (β = 0.24) and ALS-nonspecific (β = 0.24) scores. Although Aβ42/40 negatively correlated with T-tau (β = -0.29) and P-tau181 (β = -0.33), we found an unexpected positive association of Aβ42 and Aβ40 with both tau proteins. Regarding motor phenotype, lower levels of Aβ species were associated with lower motor neuron (LMN) signs (Aβ40: β = 0.34; Aβ42: β = 0.22)., Conclusions: APOE haplotype and CSF Aβ biomarkers are associated with cognitive deficits in ALS and particularly with memory impairment. This might partly reflect AD-like pathophysiological processes, but additional ALS-specific mechanisms could be involved., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Aaron T. Beck's cognitive model of depression became the basis for the analysis of cognitive factors as significant correlates and predictors of depression. Psychological mechanisms of depression related to the depressive cognitive triad, the specificity of cognitive schemas and errors in cognitive processing determined the directions of further research on depression. The presented analysis of selected studies confirms and extends Beck's assumptions about the role of cognitive factors in the development and maintenance of depressive symptoms. The analysis of psychological, neuroimaging and biochemical studies provides a broader perspective of understanding both the etiology and mechanisms that sustain the symptoms of depression. The development of neuroimaging research has broadened the knowledge about the brain mechanisms of depression - the presented research combine the theoretical constructs of the cognitive concept of depression with the characteristics of the activity of brain structures and their functional connections. The following conclusions seem to be particularly important for clinical practice: 1) impairment of the cognitive inhibition function in depression reduces the control of negative automatic thoughts - strengthening working memory is important; 2) different brain mechanisms for processing rewards and punishments in people suffering from depression and in healthy people explain the formation of self-esteem - this knowledge can be an important element of psychoeducation in therapeutic work; 3) neuroimaging studies indicate neuronal correlates of cognitive distortions observed in depression - for further research on depression, it would be particularly important to monitor changes in brain activity in the course of its treatment.