Impairment In Cognitive Domains Research Articles

Cognitive Impairment in Patients with Immune Thrombocytopenia

Background Immune thrombocytopenia (ITP) is an autoimmune condition characterized by a low platelet count (<100 x 109/L). Patients with ITP have an increased risk of bruising and bleeding (mainly skin and mucosal). A study by Cooper et al published in 2020 showed that 43% of adult ITP patients have occult cerebral microbleeds (CMBs) on susceptibility-weighted magnetic resonance imaging (SW-MRI). The clinical and prognostic significance of CMBs has not been established but some studies have shown they are associated with cognitive impairment. ITP was believed to be an isolated blood disease, but more recent studies demonstrate impaired quality of life with symptoms including fatigue, memory and concentration problems. This may be suggestive of cognitive impairment. There is only one study by Frith et al that has reported cognitive impairment in adult patients with ITP. The findings of this study are important, although cognitive impairment was measured using a self-reported cognitive failures questionnaire, which may be less robust. Aims The primary objectives of the study were to establish the prevalence of cognitive impairment and which cognitive domains are impaired in patients with ITP. The secondary objective was to investigate any link between ITP disease parameters, presence of CMBs and cognitive impairment. Methods Ethical approval was granted by the London-Surrey Borders Health Research Authority (reference number: 13/LO/1365). Patients with ITP who attend the Imperial College Healthcare NHS ITP center and who had a nadir platelet count ≤ 30 x 109/L at any time during their disease course were recruited to the study. Patients underwent cognitive testing using an automated neuropsychological test battery (CANTAB), completion of SMOG (skin, mucosae, organs) bleeding questionnaire, cerebral SW-MRI to identify CMBs and a full blood count. CANTAB is a validated and automated software tool used in clinical practice and research to assess cognitive impairment. Five key cognitive domains (episodic memory, executive function, processing speed, working memory and attention) were assessed using different tasks. Z-scores standardized for age, sex and education level were generated. Based on the z-scores, the patients' cognitive performance was categorized as impaired or not impaired. Clinical data (including date of diagnosis, nadir platelet count, number of ITP treatments received and co-morbidities) was collected from medical records. One sample T-Tests were used for continuous data while Pearson's Chi Square Test and Fisher's Exact Test were used for categorical data. Multiple comparisons corrections were not performed. Results A total of 69 patients completed CANTAB cognitive testing and MRI. The median age was 40 years (range 19-88), median age at diagnosis was 31 years (range 4-83), median duration of disease was 69 months (range 5-535), median nadir platelet count was 5 x 109/L (range 0-30), median platelet count at time of test was 95 x 109/L (range 4-653) and median ITP treatments received were 4 (range 0-14). Forty-six percent of patients had other co-morbidities, 65% were female and 52% of patients were receiving ITP treatment at the time of cognitive testing. Of the 69 patients tested, 50% (95% CI [37, 62]) had at least one impaired cognitive domain (Figure 1a). The percentage of patients with impairment per domain were 22% episodic memory, 19% executive function, 16% processing speed, 13% working memory and 3% attention. Two patients could not finish the episodic memory CANTAB task; therefore, their score for this domain could not be generated. Higher organ bleeding score was associated with impaired episodic memory (p=0.048) (Figure 1b). Older age at diagnosis, age at time of cognitive test and number of ITP treatments received were associated with impaired episodic memory (p=0.03, p=0.08 and p=0.04 respectively). There was no correlation between the presence or number of CMBs and impaired cognition. Conclusion This is the first study to objectively measure cognitive impairment in patients with ITP. It showed that a significant proportion (50%) of patients with ITP suffer from cognitive impairment, with episodic memory being most affected. These results suggest that ITP is not just a 'low platelet' disease. Correlation between ITP disease parameters and impaired cognition requires further investigation in a larger cohort. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impact and Risk Factors of Limbic Predominant Age-Related TDP-43 Encephalopathy Neuropathologic Change in an Oldest-Old Cohort.

Limbic predominant age-related TAR DNA binding protein 43 (TDP-43) encephalopathy neuropathologic change (LATE-NC) is a prevalent degenerative pathology in the oldest-old who are the fastest-growing segment of our population with the highest rates of dementia. We aimed to determine the relationship between LATE-NC and cognitive impairment and to identify its potential risk factors by studying its relationship with common past medical histories in an oldest-old cohort. Participants from The 90+ Study with longitudinal evaluations and autopsy data were included. Dementia status and impairment in 5 main cognitive domains were determined at postmortem conferences leveraging all clinical and neuropsychological data blind to neuropathologic diagnosis. Medical history information was obtained from patients and their informants. LATE-NC and Alzheimer disease neuropathologic change (ADNC) were considered present in those with TDP-43 pathology in the hippocampus and/or neocortex and those with high likelihood of ADNC according to NIA-AA guidelines, respectively. We examined the association of degenerative pathologies with cognitive outcomes and multiple comparisons-adjusted relationship of medical history variables with LATE-NC and ADNC using logistic regressions adjusted for age at death, sex, and education. Three hundred twenty-eight participants were included in this study. LATE-NC was present in 32% of the participants. It had a significant association with the presence of dementia (OR 2.8, 95% CI 1.7-4.6) and impairment in memory (OR 3.0, 95% CI 1.8-5.1), language (OR 2.6, 95% CI 1.6-4.3), and orientation (OR 3.5, 95% CI 2.1-5.9). The association with impaired orientation was unique to LATE-NC, and the strength and significance of the other associations were comparable to ADNC. Furthermore, we found that history of osteoarthritis (OR 0.37, adjusted 95% CI 0.21-0.66) and hypertension (OR 0.52, adjusted 95% CI 0.28-0.98) were associated with a reduced likelihood of LATE-NC, but not ADNC. Our results suggest that LATE-NC is a prevalent degenerative pathology in the oldest-old and has significant associations with dementia and impairment in cognitive domains with magnitudes that are comparable to ADNC. We also found that past medical histories of hypertension and osteoarthritis were associated with a lower likelihood of LATE-NC. This might help identify upstream mechanisms leading to this important pathology.

Theory of mind and facial emotion recognition in adults with temporal lobe epilepsy: A meta-analysis.

BackgroundMounting studies have investigated impairments in social cognitive domains (including theory of mind [ToM] and facial emotion recognition [FER] in adult patients with temporal lobe epilepsy (TLE). However, to date, inconsistent findings remain.MethodsA search of PubMed, Web of Science, and Embase databases was conducted until December 2021. Hedges g effect sizes were computed with a random-effects model. Meta-regressions were used to assess the potential confounding factors of between-study variability in effect sizes.ResultsThe meta-analysis included 41 studies, with a combined sample of 1,749 adult patients with TLE and 1,324 healthy controls (HCs). Relative to HCs, adult patients with TLE showed large impairments in ToM (g = −0.92) and cognitive ToM (g = −0.92), followed by medium impairments in affective ToM (g = −0.79) and FER (g = −0.77). Besides, no (statistically) significant differences were observed between the magnitude of social cognition impairment in adult with TLE who underwent and those who did not undergo epilepsy surgery. Meta-regressions exhibited that greater severity of executive functioning was associated with more severe ToM defects, and older age was associated with more severe FER defects.ConclusionsResults of this meta-analysis suggest that adult patients with TLE show differential impairments in the core aspects of social cognitive domains (including ToM and FER), which may help in planning individualized treatment with appropriate cognitive and behavioral interventions.

Freezing of gait is a risk factor for cognitive decline in Parkinson’s disease

BackgroundsFreezing of gait (FOG) and cognitive impairment are serious symptoms of Parkinson’s disease (PD). Understanding the association between FOG and cognition may help formulate specific interventions for PD individuals.ObjectivesWe aimed to investigate the associations of cognitive impairment in different domains with FOG status using multiple neuropsychological tests.MethodsTwo cohorts including 691 and 104 participants were recruited from Parkinson’s progression markers initiative (PPMI) and central China, respectively. All participants underwent FOG assessment and neuropsychological tests, and 595 individuals from PPMI and 51 from central China were enrolled for longitudinal observation. Cross-sectional and longitudinal associations between cognition and FOG status were evaluated using multivariable-adjusted models.ResultsWorse cognitive performances were observed in patients with FOG compared to those without FOG in both cohorts (β = − 0.020, p < 0.001) using multivariate-adjusted models. Moreover, patients with progressive FOG during follow-up manifested more serious cognitive declines (HR = 1.40, 95% CI = 1.07–1.80). The FOG was mainly associated with the decline of executive, attention, and orientation. Furthermore, FOG was associated with higher levels of cognition-related biomarkers including T-tau, P-tau, and NfL in cerebrospinal fluid (p < 0.050).ConclusionsFOG is a risk factor for cognitive decline in PD, which emphasizes the need for early detection and monitoring of cognitive changes and interventions on cognitive impairments in PD patients with FOG.

A comprehensive assessment of neurocognitive and psychological functioning in adults with early-treated phenylketonuria.

Relative to youth with early-treated phenylketonuria (ETPKU), much less is known regarding the cognitive profile of adults with ETPKU. The present study aimed to address this gap by providing a comprehensive assessment of neuropsychological functioning among adults with ETPKU. A sample of 40 adults with ETPKU (ages 18 - 36) and a demographically matched group of 32 healthy individuals without PKU participated. Participants completed a comprehensive neuropsychological battery including the NIH Toolbox, Wechsler Abbreviated Scale of Intelligence - Second Edition (WASI-II), Conners' Continuous Performance Test (CPT-3), select subtests from the Weschler Adult Intelligence Scale - Fourth Edition (WAIS-IV) as well as several self-report measures of cognitive and psychoemotional functioning. Scores from these tests were combined to create cognitive composites reflecting overall task performance in the areas of verbal ability, visuospatial skills, executive functioning, motor skills, and processing speed. No group differences were observed for full scale IQ or verbal ability. However, individuals with ETPKU demonstrated poorer performance on measures of executive functioning, processing speed, motor skills, and visuospatial skills as compared to the non-PKU group. Within the ETPKU group, recent blood phenylalanine levels (an indicator of metabolic control) were significantly correlated with performance across most cognitive domains and aspects of psychological functioning. Present findings suggest that the neuropsychological profile of adult ETPKU is characterized by circumscribed impairments in select cognitive domains. In addition, the results underscore the importance of maintaining metabolic control across the lifespan in individuals with ETPKU.

Executive Dysfunction in Patients With Alcohol Use Disorder: A Systematic Review.

A medical condition known as alcohol use disorder (AUD) is defined as an impaired capacity to reduce or regulate alcohol consumption despite negative social, occupational, or health effects. According to studies, habitual drinkers experience a reduction in their capacity to process new information, gain new skills, and formulate plans. Studies indexed in PubMed, PubMed Central, Google Scholar, ResearchGate, and ScienceDirect, published from 2012 to 2022, were identified through the search terms “alcohol use disorder” and “executive function.” A total of 2242 abstracts were identified through the initial search terms. Full texts were reviewed for 61 articles, out of which nine articles met the criteria for inclusion. This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The current systematic review primarily focuses on the following issues: clinical neuropsychological tests of executive dysfunction, specific brain regions most affected by alcohol neurotoxic effects, and alcohol-related dementia. This review concluded that chronic alcohol dependence syndrome causes impairments in several cognitive function domains. Study shows frontal lobe damage is caused by chronic alcohol consumption. A faulty interaction among large-scale networks underlies patients' executive dysfunction in AUD, which is suggested by changes in prefrontal white-matter pathways. The goal of this systematic review is to improve the ability to recognize alcoholics who are particularly at risk of functional impairments to tailor therapeutic therapy to maximize the chance of maintaining abstinence and neuropsychology concerning this complex disease.

P01.05.A Working memory performance is associated with functional connectivity between the right dlPFC and DMN in glioma patients

Abstract Background Patients with primary brain tumors frequently suffer from cognitive impairments in multiple domains, leading to serious consequences for socio-professional functioning and quality of life. The functional-anatomical basis of these impairments is still poorly understood. The study of correlated BOLD activity in the brain (i.e. functional connectivity) has greatly contributed to our understanding of how brain activity supports cognitive function. In particular, activity observed during the execution of specific tasks can be related to various distributed functional networks, stressing the importance of interactions between remote brain regions. Among these networks, the Default Mode Network (DMN) and the Fronto-Parietal Network (FPN) have consistently been associated with working memory performance. Recently, using task-fMRI in glioma patients, poor performance in a working memory task was associated with less deactivation of the DMN during this task and to a lack of task-evoked changes in the DMN-FPN structure. In this study, we investigated whether these effects are reflected in the resting-state (RS) functional connectivity of the same patient group, i.e. when no task was performed during fMRI. We additionally zoomed in on the part of the FPN located in the dorsolateral Prefrontal Cortex (dlPFC), since this region is believed to be mainly responsible for DMN deactivation. Material and Methods Resting-state functional MRI data were acquired pre-operatively from 45 brain tumor patients (20 low- and 25 high-grade glioma patients). Results of a pre-operative in-scanner N-back working memory fMRI task were used to assess working memory performance. Patient brains were parcellated into ROIs using both the Gordon and Yeo atlas, which have the FPN and DMN network identities readily available. The dlPFC was defined based on masks retrieved from NeuroSynth. To measure DMN-FPN functional connectivity the average Pearson correlation between the activation time series in the regions belonging to the FPN and the DMN was calculated. Functional connectivity between the DMN and the dlPFC was calculated in a similar way. Results The average correlation between the resting-state fMRI activity in the right dlPFC and in the DMN was negatively associated with working memory performance for both the Gordon atlas (p &amp;lt; 0.003) and Yeo atlas (p &amp;lt; 0.007). No association was found for the correlation between activity in the left dlPFC and the DMN, nor for the correlation between the activity in the whole FPN and the DMN. Conclusion Our findings show that working memory performance of glioma patients is related to interactions between networks that can be measured with resting-state fMRI. Furthermore, the results provide further evidence that not only specific brain regions are important for cognitive performance, but that also the interactions between large-scale networks should be considered.

Executive Dysfunction, Social Cognition Impairment, and Gray Matter Pathology in Myotonic Dystrophy Type 2: A Pilot Study.

In contrast to myotonic dystrophy type 1, the cognitive and radiologic profile of myotonic dystrophy type 2 (DM2) is relatively poorly characterized. To conduct a pilot study to systematically evaluate cognitive and radiologic features in a cohort of Greek individuals with DM2. Eleven genetically confirmed individuals with DM2 and 26 age- and education-matched healthy controls were administered the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS) to screen for impairment in multiple cognitive domains. MRI data were evaluated by morphometric analyses to identify disease-specific gray and white matter alterations. The following statistical thresholds were used for cognitive comparisons: PFDR < 0.05 and Bayes factor (BF 10 ) >10. The DM2 group exhibited cognitive impairment (ECAS Total score; PFDR = 0.001; BF 10 = 108.887), which was dominated by executive impairment ( PFDR = 0.003; BF 10 = 25.330). A trend toward verbal fluency impairment was also identified. No significant impairments in memory, language, or visuospatial function were captured. The analysis of subscores revealed severe impairments in social cognition and alternation. Voxel-based morphometry identified widespread frontal, occipital, and subcortical gray matter atrophy, including the left superior medial frontal gyrus, right medial orbitofrontal gyrus, right operculum, right precuneus, bilateral fusiform gyri, and bilateral thalami. DM2 may be associated with multifocal cortical and thalamic atrophy, which is likely to underpin the range of cognitive manifestations mostly characterized by executive impairment and specifically by impaired social cognition.

Plasma β-amyloid, tau, neurodegeneration biomarkers and inflammatory factors of probable Alzheimer's disease dementia in Chinese individuals.

BackgroundPlasma-derived β-amyloid, tau, and neurodegeneration (ATN) biomarkers can accurately diagnose Alzheimer’s disease (AD) and predict its progression. Few studies have investigated the relationship between plasma biomarkers and changes in plasma inflammatory markers in clinically diagnosed AD.MethodsSeventy-four participants were recruited, including 30 mild-to-moderate AD dementia patients and 44 normal controls (NC). All participants underwent neuropsychological testing and blood sampling for biomarker testing. AD was clinically diagnosed according to the National Institute on Aging-Alzheimer’s Association (NIA-AA) core criteria and required age-mismatched hippocampal atrophy. We performed Single Molecule Array (Simoa), an ultra-sensitive enzyme-linked immunosorbent assay (ELISA), to examine plasma ATN markers, including β-amyloid (Aβ) 40, Aβ42, p-tau181, total (t)-tau, neurofilament protein light chain (NfL), and inflammatory factors (TNF-α, IL-1β, IL-6, and IL-8).ResultsThe level of the plasma Aβ42/Aβ40 ratio was significantly declined and the levels of the plasma p-tau181, NfL and TNF-α were significantly higher in the AD group than the NC group, but there was no significant difference in the levels of plasma t-tau, IL-1β, IL-6, and IL-8 between the AD and NC groups. The levels of plasma p-tau181, NfL, Aβ42/Aβ40 ratio, and TNF-α were all associated with impairments in multiple cognitive domains. Among them, the plasma Aβ42/Aβ40 ratio, and the p-tau181 and TNF-α levels were associated with impairments in global cognition, memory, and visuospatial abilities, but not with executive function, only plasma NfL level was associated with executive function. Plasma NfL showed higher diagnostic performance in AD than in NC individuals (AUC = 0.833). A combined diagnostic prediction model of plasma Aβ42/Aβ40 ratio, p-tau 181, and NfL had the highest value than each factor alone (AUC = 0.902),with a sensitivity and specificity of 0.867 and 0.886, respectively.ConclusionThe levels of plasma ATN biomarkers (Aβ42/Aβ40 ratio, p-tua181, and NfL) were significantly changed in clinically diagnosed AD patients and they all associated with different domains of cognitive impairment. Plasma ATN biomarkers better differentiate mild-to-moderate AD dementia from NC when they are incorporated into diagnostic models together rather than individually. Plasma ATN biomarkers have the potential to be a screening tool for AD. However, the expression of inflammatory factors in AD patients requires further research.

A-137 Cortical Vision Impairment: A Case Study of Associated Neurodevelopmental Disorders and Neuropsychological Findings

Abstract Objective: Cortical Visual Impairment (CVI) is characterized by a decreased visual response, related to a neurological lesion. It is the most common cause of permanent visual impairment in children. CVI is not attributed to the functioning of the eyes, but instead to visual processing centers and pathways. Deficits due to CVI may lead to impairment in cognitive, learning, and social domains. The objective of the case study is to examine neuropsychological findings of a child with CVI. Method: The subject was a 10-year, 2-month old male with a history of seizure activity. Based on decreased corpus callosum and PVL, a diagnosis of CVI was made. He evidenced significant visual latencies and difficulties with visual novelty. Continuing behavioral and academic concerns resulted in a referral for evaluation. Results: Assessment revealed extremely low cognitive ability. Relative strengths were evident in nonverbal skills. Academic skills fell at the pre-K to early K level. Neurocognitive functions ranged from the low to the very-low range with relative strengths in rapid naming, symbol recognition, semantic memory, and social intent. Findings on the SRS-2 and the ADOS-2 revealed difficulties with social awareness and communication but were not consistent with an ASD. Conclusions: CVI is a prevalent cause of visual impairment in children. Children often display multiple developmental disorders and features of autism and low cognitive ability are not uncommon. Disentangling the role of CVI in early cognitive, social, and adaptive development remains an important area for research. Assessment to identify strengths and weakness to facilitate social, academic and adaptive development is necessary.

Automated Early Detection of Alzheimer's Disease by Capturing Impairments in Multiple Cognitive Domains with Multiple Drawing Tasks.

Background:Automatic analysis of the drawing process using a digital tablet and pen has been applied to successfully detect Alzheimer’s disease (AD) and mild cognitive impairment (MCI). However, most studies focused on analyzing individual drawing tasks separately, and the question of how a combination of drawing tasks could improve the detection performance thus remains unexplored.Objective:We aimed to investigate whether analysis of the drawing process in multiple drawing tasks could capture different, complementary aspects of cognitive impairments, with a view toward combining multiple tasks to effectively improve the detection capability.Methods:We collected drawing data from 144 community-dwelling older adults (27 AD, 65 MCI, and 52 cognitively normal, or CN) who performed five drawing tasks. We then extracted motion- and pause-related drawing features for each task and investigated the associations of the features with the participants’ diagnostic statuses and cognitive measures.Results:The drawing features showed gradual changes from CN to MCI and then to AD, and the changes in the features for each task were statistically associated with cognitive impairments in different domains. For classification into the three diagnostic categories, a machine learning model using the features from all five tasks achieved a classification accuracy of 75.2%, an improvement by 7.8% over that of the best single-task model.Conclusion:Our results demonstrate that a common set of drawing features from multiple drawing tasks can capture different, complementary aspects of cognitive impairments, which may lead to a scalable way to improve the automated, reliable detection of AD and MCI.

Lower Preoperative Verbal Memory Performance Is Associated with Delirium after Coronary Artery Bypass Graft Surgery: A Prospective Cohort Study.

Cognitive impairment constitutes one of the major risk factors of delirium after coronary artery bypass graft (CABG) surgery; however, it is unclear whether only patients with global cognitive decline are at increased risk for delirium or if individuals with preserved global cognitive functions but impairments in specific cognitive domains are also more vulnerable to developing delirium. Thus, this study aimed to analyze the neurocognitive status of patients scheduled for CABG surgery with the use of an advanced computerized cognitive battery (CNS Vital Signs) and to investigate possible associations between impaired performance in selective cognitive areas and the risk of postoperative delirium development. The study enrolled 127 participants with a median age of 67years (IQR: 63-71). Postoperative delirium developed in 32 (25%) patients.Before surgery, the patients were screened for global cognitive impairment with the use of the Mini-Mental State Examination Test, and the individuals were asked to perform the CNS Vital Signs battery to investigate 12 specific cognitive domains. The Confusion Assessment Method and the Memorial Delirium Assessment Scale were used to screen for a diagnosis of delirium postoperatively. In multivariate models, a lower score of verbal memory-assessed preoperatively was independently associated with the risk of postoperative delirium development. Other independent predictors of delirium included more advanced age, gender female, depression, postoperative pyrexia, and the presence of extracorporeal circulation. As decreased verbal memory constitutes an independent risk factor for postoperative delirium, a verbal memory test may be a useful predictor of postoperative delirium development.

Biomarkers of Frailty: miRNAs as Common Signatures of Impairment in Cognitive and Physical Domains.

Simple SummaryA growing number of studies have focused their attention on the potential role of microRNAs (miRNA) as biomarkers for several diseases. However, very few evaluated the role of miRNAs in the aetiogenesis of frailty, a multidimensional geriatric syndrome, characterized by an individual and dynamic state of impairments in one or more domains, such as physical, cognitive, psychological, and social. In this review, we first provided an overview on the different frailty domains, current assessment tools and plasma/blood biomarkers. Then, we collected the evidence linking changes of miRNAs expression to impairment of frailty in physical and cognitive domains, with the ultimate aim of finding those that are common. In silico analyses prioritized ten top-ranked miRNAs and their targets, the three most significant regulating processes involved in inflammation and energy homeostasis pathway. Such miRNAs, through the integration with existing markers, may be useful for an early and accurate diagnosis of frailty in the elderly population.The past years have seen an increasing concern about frailty, owing to the growing number of elderly people and the major impact of this syndrome on health and social care. The identification of frail people passes through the use of different tests and biomarkers, whose concerted analysis helps to stratify the populations of patients according to their risk profile. However, their efficiency in prognosis and their capability to reflect the multisystemic impairment of frailty is discussed. Recent works propose the use of miRNAs as biological hallmarks of physiological impairment in different organismal districts. Changes in miRNAs expression have been described in biological processes associated with phenotypic outcomes of frailty, opening intriguing possibilities for their use as biomarkers of fragility. Here, with the aim of finding reliable biomarkers of frailty, while considering its complex nature, we revised the current literature on the field, for uncovering miRNAs shared across physical and cognitive frailty domains. By applying in silico analyses, we retrieved the top-ranked shared miRNAs and their targets, finally prioritizing the most significant ones. From this analysis, ten miRNAs emerged which converge into two main biological processes: inflammation and energy homeostasis. Such markers, if validated, may offer promising capabilities for early diagnosis of frailty in the elderly population.

Trail Making Test Could Predict Impairment in Cognitive Domains in Patients with Multiple Sclerosis: A Study of Diagnostic Accuracy.

Cognitive impairment (CI) and executive dysfunction (ED) are prevalent in patients with multiple sclerosis (PwMS). The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) is the gold standard neuropsychological battery (NPB) for detecting CI. Delis-Kaplan Executive Function System (DKEFS) NPB evaluates ED. We aimed to find practical test(s) from DKEFS with acceptable diagnostic utility for early detection of impairment in cognitive and executive domains. Cognitive and executive tasks, physical disability, and depression scores of 30 PwMS were assessed (17 women, age: 38.1). Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Controlled Oral Word Association Test (COWAT) from MACFIMS and Trail Making Test (TMT), Design Fluency Test (DFT), and Verbal Fluency Test (VFT) from DKEFS were selected. The association between patients' characteristics and performance in tests, and diagnostic accuracy of DKEFS tests in detecting impairment in cognitive tasks were evaluated, using Pearson correlation and receiver operator characteristic curve analyses, respectively. A significant correlation was found between disease duration and SDMT and TMT subtests. Expanded Disability Status Scale was significantly related to SDMT, VFT-switching, and TMT subtests. Beck Depression Inventory was significantly related to DFT. TMT-switching detected abnormalities in SDMT and PASAT with 100% sensitivity, 93.3% (for SDMT), and 85.7% specificity (for PASAT). TMT-letter showed 100% sensitivity and 90% specificity in identifying abnormalities in COWAT. TMT, particularly the switching condition, is a practical paper-based test that could predict impairment in cognitive tasks. Clinicians may use TMT as a screening tool among PwMS.

The association of cognitive impairment with quality of life and functional impairment in Ugandan first-episode psychosis patients: a cross sectional study

IntroductionCognitive impairment is common in first-episode psychosis patients and often associated with poor quality of life and functional impairment. However, most literature on this association is from high income countries and not low resource countries like Uganda. We aimed to determine the association between cognitive impairment with quality of life and functional impairment in Ugandan first-episode psychosis patients.MethodsAt Butabika national psychiatric hospital of Uganda, we enrolled 94 first-episode psychosis patients aged 18–60 years with a confirmed first-episode of psychosis and no previous treatment with antipsychotic medication. Neuropsychological assessment was performed using the MATRICS consensus cognitive battery (MCCB). Quality of life and functional impairment were assessed using the brief version of the World Health Organisation Quality of Life scale (WHOQOL-BREF) and the MINI International Neuropsychiatric Inventory (MINI) respectively. Linear regression analyses determined the association between impairment in different cognitive domains with various quality of life and functional impairment domains while controlling for age, gender and level of education.ResultsHigh scores in the reasoning and problem solving cognitive domain were associated with better quality of life in the psychological domain of WHOQOL-BREF (p = 0.029). For functional impairment, high cognitive scores in the domains of speed of processing (p = 0.018), reasoning and problem solving (p = 0.015), working memory (p = 0.017) and visual learning and memory (p = 0.002) were associated with psychosis “having a greater impact on other members of the family” on the MINI. Higher scores in the social cognition domain were associated with “less aggressive and disruptive behaviour” (p = 0.003).ConclusionCognitive impairment in Ugandan first-episode psychotic patients is associated with both poorer quality of life and functional impairment. Remediation of cognitive function may be a plausible intervention to improve outcomes in Ugandan first-episode psychosis patients.

Ankle-Brachial Index and Cardio-Ankle Vascular Index as Predictors of Cognitive Decline Over Time After Carotid Endarterectomy.

Objective: Patients with carotid stenosis risk cognitive impairment even after carotid endarterectomy (CEA) because of the long-term presence of vascular risk factors. Early prediction of cognitive decline is useful because early appropriate training for impaired cognitive domains can improve their functions. Ankle-brachial index (ABI) and cardio-ankle vascular index (CAVI) are frequently used as general indicators of systemic atherosclerosis and are associated with cognitive function in the general population. This study aimed to evaluate the utility of those vascular biomarkers for predicting cognitive decline in patients after CEA.Methods: Patients who had undergone both CEA at our institute and cognitive evaluations between March 2016 and January 2022 were invited to participate in this study. Associations between ABI or CAVI three years before baseline and cognitive function at baseline were assessed retrospectively in 94 patients, and associations between ABI or CAVI at baseline and three-year changes in cognitive functions were assessed prospectively in 24 patients. Cognitive functions were assessed using the Frontal Assessment Battery (FAB) and Neurobehavioral Cognitive Status Examination (Cognistat).Results: Low ABI three years before baseline was associated with poor performances on Cognistat and FAB at baseline. ABI, as a continuous measure, three years before baseline, showed positive linear associations with total Cognistat score and subscores for naming, construction, and judgment at baseline. The Wilcoxon signed-rank test showed that the total Cognistat score, total FAB score, and subscores for attention and inhibitory control declined after three years. CAVI at baseline was negatively associated with three-year changes in total Cognistat score and subscores for naming, construction, and memory.Conclusion: Cognitive function can decline over time in patients with carotid stenosis even after CEA. ABI and CAVI might be useful to predict cognitive function and its decline among patients who have undergone CEA.

Clinical Features and Potential Mechanisms Relating Neuropathological Biomarkers and Blood-Brain Barrier in Patients With Alzheimer's Disease and Hearing Loss.

BackgroundThe aim of this study was to explore clinical features and potential mechanisms relating neuropathological biomarkers and blood-brain barrier (BBB) in Alzheimer’s disease (AD) and hearing loss (HL).Materials and MethodsA total of 65 patients with AD were recruited and auditory function was assessed by threshold of pure tone audiometry (PTA). Patients were divided into AD with HL (AD-HL) and AD with no HL (AD-nHL) groups based on the standard of World Health Organization. Clinical symptoms were assessed by multiple rating scales. The levels of neuropathological biomarkers of β amyloid1-42 (Aβ1–42) and multiple phosphorylated tau (P-tau), and BBB factors of matrix metalloproteinases (MMPs), receptor of advanced glycation end products, glial fibrillary acidic protein, and low-density lipoprotein receptor related protein 1 were measured.Results(1) Compared with AD-nHL group, AD-HL group had significantly impaired overall cognitive function and cognitive domains of memory, language, attention, execution, and activities of daily living (ADL) reflected by the scores of rating scales (P < 0.05). PTA threshold was significantly correlated with the impairments of overall cognitive function and cognitive domains of memory and language, and ADL in patients with AD (P < 0.05). (2) P-tau (S199) level was significantly increased in CSF from AD-HL group (P < 0.05), and was significantly and positively correlated with PTA threshold in patients with AD. (3) MMP-3 level was significantly elevated in CSF from AD-HL group (P < 0.05), and was significantly and positively correlated with PTA threshold in patients with AD (P < 0.05). (4) In AD-HL group, P-tau (S199) level was significantly and positively correlated with the levels of MMP-2 and MMP-3 in CSF (P < 0.05).ConclusionAD-HL patients have severely compromised overall cognitive function, multiple cognitive domains, and ADL. The potential mechanisms of AD-HL involve elevations of AD neuropathological biomarker of P-tau (S199) and BBB factor of MMP-3, and close correlations between P-tau (S199) and MMP-2/MMP-3 in CSF. Findings from this investigation highly suggest significance of early evaluation of HL for delaying AD progression, and indicate new directions of drug development by inhibiting neuropathological biomarkers of AD and protecting BBB.

Executive Functions in Overweight and Obese Treatment-Seeking Patients: Cross-Sectional Data and Longitudinal Perspectives.

Background: Recent evidence suggests that a higher body weight may be linked to cognitive impairment in different domains involving executive/frontal functioning. However, challenging results are also available. Accordingly, our study was designed to verify whether (i) poor executive functions are related to a higher body weight and (ii) executive functioning could contribute to weight loss in treatment-seeking overweight and obese patients. Methods: We examined general executive functioning, inhibitory control, verbal fluency, and psychomotor speed in a sample including 104 overweight and obese patients. Forty-eight normal-weight subjects participated in the study as controls. Results: Univariate Analysis of Variance showed that obese patients obtained lower scores than overweight and normal-weight subjects in all executive measures, except for errors in the Stroop test. However, when sociodemographic variables entered the model as covariates, no between-group difference was detected. Furthermore, an adjusted multiple linear regression model highlighted no relationship between weight loss and executive scores at baseline. Conclusions: Our results provide further evidence for the lack of association between obesity and the executive domains investigated. Conflicting findings from previous literature may likely be due to the unchecked confounding effects exerted by sociodemographic variables and inclusion/exclusion criteria.

Abnormal Functional Connectivity of Thalamic Subdivisions in Alzheimer’s Disease: A Functional Magnetic Resonance Imaging Study

Alzheimer’s disease (AD) is characterized by global cognitive impairment in multiple cognitive domains. Thalamic dysfunction during AD progression has been reported. However, there are limited studies regarding dysfunction in the functional connectivity (FC) of thalamic subdivisions and the relationship between such dysfunction and clinical assessments. This study examined dysfunction in the FC of thalamic subdivisions and determined the relationship between such dysfunction and clinical assessments. Forty-eight patients with AD and 47 matched healthy controls were recruited and assessed with scales for multiple cognitive domains. Group-wise comparisons of FC with thalamic subdivisions as seed points were conducted to identify abnormal cerebral regions. Moreover, correlation analysis was conducted to evaluate the relationship between abnormal FC and cognitive performance. Decreased FC of the intralaminar and medial nuclei with the left precuneus was observed in patients but not in heathy controls. The abnormal FC of the medial nuclei with the left precuneus was correlated with the Mini Mental State Examination score in the patient group. Using the FC values showing between-group differences, the linear support vector machine classifier achieved quite good in accuracy, sensitivity, specificity and area under the curve. Dysfunction in the FC of the intralaminar and medial thalamus with the precuneus may comprise a potential neural substrate for cognitive impairment during AD progression, which in turn may provide new treatment targets.

Early alterations in cortical morphology after neoadjuvant chemotherapy in breast cancer patients: A longitudinal magnetic resonance imaging study.

There is growing evidence that chemotherapy may have a significant impact on the brains of breast cancer patients, causing changes in cortical morphology. However, early morphological alterations induced by chemotherapy in breast cancer patients are unclear. To investigate the patterns of those alterations, we compared female breast cancer patients (n = 45) longitudinally before (time point 0, TP0) and after (time point 1, TP1) the first cycle of neoadjuvant chemotherapy, using voxel‐based morphometry (VBM) and surface‐based morphometry (SBM). VBM and SBM alteration data underwent correlation analysis. We also compared cognition‐related neuropsychological tests in the breast cancer patients between TP0 and TP1. Reductions in gray matter volume, cortical thickness, sulcal depth, and gyrification index were found in most brain areas, while increments were found to be mainly concentrated in and around the hippocampus. Reductions of fractal dimension mainly occurred in the limbic and occipital lobes, while increments mainly occurred in the anterior and posterior central gyrus. Significant correlations were found between altered VBM and altered SBM mainly in the bilateral superior frontal gyrus. We found no significant differences in the cognition‐related neuropsychological tests before and after chemotherapy. The altered brain regions are in line with those associated with impaired cognitive domains in previous studies. We conclude that breast cancer patients showed widespread morphological alterations soon after neoadjuvant chemotherapy, despite an absence of cognitive impairments. The affected brain regions may indicate major targets of early brain damage after chemotherapy.