Cognitive Subdomains Research Articles

The relationship between negative symptoms, social cognition, and social functioning in patients with first episode psychosis

IntroductionSocial functioning is severely affected in psychotic disorders. Negative symptoms and social cognition seem to play an important role in social functioning, although the preponderance and relationship between these three domains is not clear. In this study, we sought to assess the interrelation between social cognition, social functioning, and the expressiveness and experiential factors of negative symptoms in first-episode psychosis (FEP). Sample and methods216 patients, participants in a multicentre study (AGES-CM), comprised our study sample. The WHO Disability Assessment Schedule (WHODAS 2.0) was used to assess functioning, whereas the Positive and Negative Schizophrenia Syndrome Scale (PANSS) was used to measure the severity of negative symptoms, and the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) was applied to assess the emotional processing component of social cognition. Network analyses were conducted with the aim of analysing the patterns of relationships between social cognition, social functioning, and the expressiveness and experiential factors of negative symptoms. ResultsOur findings suggest that there is a direct relationship between social cognition and social functioning (weight = -.077), but also an indirect connection between them, mediated by the experiential (but not the expressiveness) factor of negative symptoms (weight = 0.300). DiscussionThe importance of the affectation of subdomains of social cognition, as well as the role of negative symptoms, specifically the experiential factor, in the functioning of patients with FEP seems to be relevant. The inclusion of these factors in prevention and treatment programs would thus allow us to reduce their impact on the social functioning of these patients.

Cognition in Patients with Sleep-Disordered Breathing: Can Obstructive and Central Apneic Pauses Play a Different Role in Cognitive Impairment?

Background: There are increasing data linking sleep apnea with cognitive impairment. We aimed to clarify the relationship between sleep-disordered breathing (SDB) and cognition. Detailed attention was assigned to the potential role of central versus obstructive apneic pauses in cognitive impairment. Methods: Patients with suspected SDB were prospectively enrolled, and a complex sleep study was performed that included overnight polysomnography. A revised version of Addenbrooke‘s Cognitive Examination (ACE-R) was used to assess cognition, evaluating overall cognition and individual subdomains. Results: A total number of 101 participants were included in the study. In multivariate binary logistic regression analysis, obstructive apnea index ([OAI], 95% CI: 1.009–1.057, p = 0.008) was the only significant contributor to the model predicting attention deficit. The proportion of N1 stage of NREM sleep was the only significant contributor to the model predicting impaired verbal fluency (95% CI: 1.004–1.081, p = 0.029). No significant differences in sleep-related indices were observed in the remaining ACE-R subdomains. Conclusion: Except for verbal fluency and attention, we failed to find any significant association of sleep-related indices with the impairment in different cognitive subdomains. Our data suggest that impairment observed in verbal fluency is associated with a higher proportion of shallow NREM sleep, and attention deficit is associated with higher OAI. Obstructive respiratory episodes seem to play a more important role in cognitive impairment when compared to central ones.

A novel framework to estimate cognitive impairment via finger interaction with digital devices.

Measuring cognitive function is essential for characterizing brain health and tracking cognitive decline in Alzheimer’s Disease and other neurodegenerative conditions. Current tools to accurately evaluate cognitive impairment typically rely on a battery of questionnaires administered during clinical visits which is essential for the acquisition of repeated measurements in longitudinal studies. Previous studies have shown that the remote data collection of passively monitored daily interaction with personal digital devices can measure motor signs in the early stages of synucleinopathies, as well as facilitate longitudinal patient assessment in the real-world scenario with high patient compliance. This was achieved by the automatic discovery of patterns in the time series of keystroke dynamics, i.e. the time required to press and release keys, by machine learning algorithms. In this work, our hypothesis is that the typing patterns generated from user-device interaction may reflect relevant features of the effects of cognitive impairment caused by neurodegeneration. We use machine learning algorithms to estimate cognitive performance through the analysis of keystroke dynamic patterns that were extracted from mechanical and touchscreen keyboard use in a dataset of cognitively normal (n = 39, 51% male) and cognitively impaired subjects (n = 38, 60% male). These algorithms are trained and evaluated using a novel framework that integrates items from multiple neuropsychological and clinical scales into cognitive subdomains to generate a more holistic representation of multifaceted clinical signs. In our results, we see that these models based on typing input achieve moderate correlations with verbal memory, non-verbal memory and executive function subdomains [Spearman’s ρ between 0.54 (P < 0.001) and 0.42 (P < 0.001)] and a weak correlation with language/verbal skills [Spearman’s ρ 0.30 (P < 0.05)]. In addition, we observe a moderate correlation between our typing-based approach and the Total Montreal Cognitive Assessment score [Spearman’s ρ 0.48 (P < 0.001)]. Finally, we show that these machine learning models can perform better by using our subdomain framework that integrates the information from multiple neuropsychological scales as opposed to using the individual items that make up these scales. Our results support our hypothesis that typing patterns are able to reflect the effects of neurodegeneration in mild cognitive impairment and Alzheimer’s disease and that this new subdomain framework both helps the development of machine learning models and improves their interpretability.

Multimethodological validation of the modified fatigue impact scale in a Danish population of people with Multiple Sclerosis

ObjectiveTo provide a multimethodological validation of MFIS in compliance with the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) guidelines using a Danish population of patients with Multiple Sclerosis (pwMS). MethodsFactor analytic and multidimensional Rasch analytic methods were applied to investigate the structural validity of MFIS. We employed measurement and bi-factor models to address divergence and convergence. McDonalds ω was used to assess reliability. Cross-cultural and nomological validity was assessed in relation to relevant external populations and constructs, respectively. Responsiveness was evaluated following one month of multi-disciplinary rehabilitation (MDR). ResultsBased on data from 424 Danish MS patients, the MFIS showed an acceptable fit to both factor analytic and multidimensional Rasch models. MFIS was found to be dominated by a general factor but with considerable substructure present. Sufficient divergence was found between cognitive and physical subdomains, but not the psychosocial subscale. Mc Donald's ωt of 0.96 indicated good reliability of the scale, however, with low specific reliability of the psychosocial subscale. Homogeneity across Danish and European populations of pwMS supported cross-cultural validity. Explorative factor analysis of the nomological network of MFIS revealed expected convergence with cognitive and physical aspects. MFIS showed good responsiveness as indicated by moderate to large effect sizes following MDR. ConclusionThe Danish version of the MFIS showed good reliability, a good structural, cross-cultural, and nomological validity an acceptable fit to a multidimensional Rasch analysis, and a good responsiveness. The psychosocial subscale of the MFIS however should be interpreted with caution.

Associations of Bilateral Vestibulopathy With Cognition in Older Adults Matched With Healthy Controls for Hearing Status

Recent literature suggests there may be a significant effect of the vestibular system on cognition and visuospatial processing. Given the increasing prevalence of dementia and individuals at risk for it, exploring possible modifiable risk factors, including vestibular dysfunction, is vital. To explore the association of bilateral vestibulopathy (BV) with cognitive function in older adults, taking hearing status into account, and to explore multiple vestibular characteristics and their potential associations with cognition in patients with BV. This cross-sectional study assessed older adults (age 55-84 years) with diagnosed BV from a single center using baseline measurements from the Gehoor, Evenwicht en Cognitie (GECKO) study, an ongoing prospective longitudinal cohort study. Each participant was individually matched with a healthy control based on age, sex, and hearing performance. Data were analyzed in January 2022. The primary outcome measure was cognition, measured by the Repeatable Battery for the Assessment of Neuropsychological Status for Hearing-Impaired Individuals (RBANS-H). A total of 68 patients were assessed, including 34 patients with BV (mean [SD] age, 63.3 [6.0] years; 18 [53%] men) matched with 34 control individuals without BV. Overall, participants with BV had a clinically meaningful lower score on the RBANS-H total scale compared with those without BV (mean [SD] score, 98.62 [12.70] vs 105.91 [11.03]). This decline was most pronounced in the subdomains of immediate memory (mean [SD] score, 107.74 [10.66] vs 112.26 [10.66]), visuospatial cognition (mean [SD] score, 90.06 [13.34] vs 100.47 [13.91]), and attention (mean [SD] score, 94.79 [16.39] vs 102.06 [12.97]). There were no differences in language or delayed memory subdomains. Within the BV population, 1 vestibular parameter (the Performance-Oriented Mobility Assessment, in particular the balance subscale) was associated with lower cognitive scores (r32 = 0.51; 95% CI, 0.20 to 0.72; η2 = 0.26). Other vestibular parameters, including measurements of the peripheral vestibular end organ and questionnaires, showed no association. These findings suggest there was an association between vestibular loss and cognitive impairment. Further research on the causal mechanisms underlying this association and the possible impact of vestibular rehabilitation on cognition is needed.

Alteration of Visuospatial System as an Early Marker of Cognitive Decline: A Double-Center Neuroimaging Study.

Amnestic-type mild cognitive impairment (a-MCI) represents the prodromal phase of Alzheimer's disease associated with a high conversion rate to dementia and serves as a potential golden period for interventions. In our study, we analyzed the role of visuospatial (VS) functions and networks in the recognition of a-MCI. We examined 78 participants (32 patients and 46 controls) in a double-center arrangement using neuropsychology, structural, and resting-state functional MRI. We found that imaging of the lateral temporal areas showed strong discriminating power since in patients only the temporal pole (F = 5.26, p = 0.034) and superior temporal gyrus (F = 8.04, p < 0.001) showed reduced cortical thickness. We demonstrated significant differences between controls and patients in various neuropsychological results; however, analysis of cognitive subdomains revealed that the largest difference was presented in VS skills (F = 8.32, p < 0.001). Functional connectivity analysis of VS network showed that patients had weaker connectivity between the left and right frontotemporal areas, while stronger local connectivity was presented between the left frontotemporal structures (FWE corrected p < 0.05). Our results highlight the remarkable potential of examining the VS system in the early detection of cognitive decline. Since resting-state setting of functional MRI simplifies the possible automatization of data analysis, detection of VS system alterations might provide a non-invasive biomarker of a-MCI.

Changes in Cognitive Functioning After Surgical Resection of Language-related, Eloquent-area, High-grade Gliomas Under Awake Craniotomy.

Dominant-hemisphere tumors, especially gliomas, as infiltrative tumors, frequently affect cognitive functioning. Establishing a balance between extensive resection, which is proven to result in longer survival, and less extensive resection, in order to maintain more cognitive abilities, is challenging. To evaluate changes in cognitive functioning before and after surgical resection of language-related, eloquent-area, high-grade gliomas under awake craniotomy. We provided individuals with newly diagnosed high-grade gliomas of the language-related eloquent areas with the same standard of care, including surgical resection of the glioma using intraoperative sensory-motor and cognitive mapping under awake craniotomy, and the same protocol for chemoradiotherapy. Cognitive functioning was assessed using Addenbrooke's Cognitive Examination-Revised (ACE-R) at four time points (preoperatively, early after surgery, and 3 and 6 months postoperatively). The preoperative evaluation revealed a range of cognitive impairments in 70.7% of the individuals, affecting all of the cognitive subdomains (mostly attention and visuospatial abilities). Overall cognitive functioning (ie, ACE-R score) dropped by 13.5% (P = 0.169) early postoperatively. At the 3-month evaluation, an average of 15.3% (P = 0.182) recovery in cognitive functioning was observed (mostly in verbal fluency: 39.1%). This recovery improved further, reaching 29% (P < 0.001) at the 6-month evaluation. The greatest improvement occurred in verbal fluency: 68.8%, P = 0.001. Extensive resection of eloquent-area gliomas with the aid of modern neuroimaging and neuromonitoring techniques under awake craniotomy is possible without significant long-term cognitive sequela.

Copy Number Variant Risk Scores Associated With Cognition, Psychopathology, and Brain Structure in Youths in the Philadelphia Neurodevelopmental Cohort

Psychiatric and cognitive phenotypes have been associated with a range of specific, rare copy number variants (CNVs). Moreover, IQ is strongly associated with CNV risk scores that model the predicted risk of CNVs across the genome. But the utility of CNV risk scores for psychiatric phenotypes has been sparsely examined. To determine how CNV risk scores, common genetic variation indexed by polygenic scores (PGSs), and environmental factors combine to associate with cognition and psychopathology in a community sample. The Philadelphia Neurodevelopmental Cohort is a community-based study examining genetics, psychopathology, neurocognition, and neuroimaging. Participants were recruited through the Children's Hospital of Philadelphia pediatric network. Participants with stable health and fluency in English underwent genotypic and phenotypic characterization from November 5, 2009, through December 30, 2011. Data were analyzed from January 1 through July 30, 2021. The study examined (1) CNV risk scores derived from models of burden, predicted intolerance, and gene dosage sensitivity; (2) PGSs from genomewide association studies related to developmental outcomes; and (3) environmental factors, including trauma exposure and neighborhood socioeconomic status. The study examined (1) neurocognition, with the Penn Computerized Neurocognitive Battery; (2) psychopathology, with structured interviews based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children; and (3) brain volume, with magnetic resonance imaging. Participants included 9498 youths aged 8 to 21 years; 4906 (51.7%) were female, and the mean (SD) age was 14.2 (3.7) years. After quality control, 18 185 total CNVs greater than 50 kilobases (10 517 deletions and 7668 duplications) were identified in 7101 unrelated participants genotyped on Illumina arrays. In these participants, elevated CNV risk scores were associated with lower overall accuracy on cognitive tests (standardized β = 0.12; 95% CI, 0.10-0.14; P = 7.41 × 10-26); lower accuracy across a range of cognitive subdomains; increased overall psychopathology; increased psychosis-spectrum symptoms; and higher deviation from a normative developmental model of brain volume. Statistical models of developmental outcomes were significantly improved when CNV risk scores were combined with PGSs and environmental factors. In this study, elevated CNV risk scores were associated with lower cognitive ability, higher psychopathology including psychosis-spectrum symptoms, and greater deviations from normative magnetic resonance imaging models of brain development. Together, these results represent a step toward synthesizing rare genetic, common genetic, and environmental factors to understand clinically relevant outcomes in youth.

Parsing the Effects of Threat and Deprivation Adverse Childhood Experiences (ACEs) on Multiple Domains of Cognitive Functioning in Two Large-Scale Datasets of Youth

Adverse childhood experiences (ACEs) can impair cognitive development. However, it remains unclear whether specific sub-domains of ACEs (e.g., Threat vs. Deprivation) are associated with impairments in specific sub-domains of cognition. Parsing these associations in large-scale datasets can help clarify heterogeneity in prior literature and represent an essential step toward promoting healthy neurocognitive development.

Reproductive hormone levels, androgen receptor CAG repeat length and their longitudinal relationships with decline in cognitive subdomains in men: The European Male Ageing Study.

ObjectiveIt has been proposed that endogenous sex hormone levels may present a modifiable risk factor for cognitive decline. However, the evidence for effects of sex steroids on cognitive ageing is conflicting. We therefore investigated associations between endogenous hormone levels, androgen receptor CAG repeat length, and cognitive domains including visuoconstructional abilities, visual memory, and processing speed in a large-scale longitudinal study of middle-aged and older men. MethodsMen aged 40-79 years from the European Male Ageing Study (EMAS) underwent cognitive assessments and measurements of hormone levels at baseline and follow-up (mean = 4.4 years, SD ± 0.3 years). Hormone levels measured included total and calculated free testosterone and estradiol, dihydrotestosterone, luteinizing hormone, follicle-stimulating hormone, dehydroepiandrosterone sulphate and sex hormone-binding globulin. Cognitive function was assessed using the Rey-Osterrieth Complex Figure Copy and Recall, the Camden Topographical Recognition Memory and the Digit Symbol Substitution Test. Multivariate linear regressions were used to examine associations between baseline and change hormone levels, androgen receptor CAG repeat length, and cognitive decline. ResultsStatistical analyses included 1,827 and 1,423 participants for models investigating relationships of cognition with hormone levels and CAG repeat length, respectively. In age-adjusted models, we found a significant association of higher baseline free testosterone (β=-0.001, p=0.005) and dihydrotestosterone levels (β=-0.065, p=0.003) with greater decline on Rey-Osterrieth Complex Figure Recall over time. However, these effects were no longer significant following adjustment for centre, health, and lifestyle factors. No relationships were observed between any other baseline hormone levels, change in hormone levels, or androgen receptor CAG repeat length with cognitive decline in the measured domains. ConclusionsIn this large-scale prospective study there was no evidence for an association between endogenous sex hormone levels or CAG repeat length and cognitive ageing in men. These data suggest that sex steroid levels do not affect visuospatial function, visual memory, or processing speed in middle-aged and older men.

Sex Differences in Social Cognition and Association of Social Cognition and Neurocognition in Early Course Schizophrenia.

BackgroundBoth impairment and sex differences in social cognition and neurocognition have been documented in schizophrenia. However, whether sex differences exist in the association between social cognition and neurocognition are not known. We aimed to investigate the contribution of areas of neurocognition to theory of mind (ToM) and hostility bias, representing social cognition, according to sex in early course schizophrenia.MethodsIn this cross-sectional study, we assessed neurocognition using the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS) and assessed the ToM and hostility bias subdomains of social cognition using the Social Cognition Screening Questionnaire (SCSQ) in 131 participants (65 female, 66 male) diagnosed with schizophrenia within 5 years of onset. Sex differences were analyzed using t-tests. The associations of neurocognitive subdomains with ToM and hostility bias according to sex were analyzed using multiple regression analysis. Results were adjusted by age, estimated premorbid intelligence quotient, and symptomatology.ResultsNo sex differences were found in ToM (p = 0.071) or hostility bias (p = 0.057). Higher verbal fluency was significantly associated with higher ToM in females (p < 0.01), whereas higher executive function was significantly associated with higher ToM in males (p < 0.05). Higher verbal fluency was significantly associated with lower hostility bias in females (p < 0.05), whereas neurocognition and hostility bias were not significantly associated in males.ConclusionThe results suggest that neurocognition associated with social cognition differ according to sex. These differences should be considered for more effective treatment of social cognition.

Cognitive remediation in schizophrenia: What happens after 10 years?

Cognitive Remediation Therapy (CRT) represents the gold standard treatment for cognitive impairment in schizophrenia, but the permanence of its effects over time have been poorly investigated. Our study aims to evaluate long lasting cognitive and functional effects of CRT together with standard rehabilitation interventions (SRT) in a group of patients diagnosed with schizophrenia, 10 years after the end of the treatment. Forty patients, previously included in a 5-year follow-up study evaluating the effects of CRT combined with SRT, were revalued 10 years after the complete of the intervention. Results revealed that cognitive and functional improvements of combined CRT/SRT interventions are still preserved 10 years after the end of the treatments, with the only exception of psychomotor speed and coordination cognitive subdomain. Moreover, investigating persistence of the influence of SRT, patients that underwent a shorter SRT following CRT (six months vs one year) showed worsened processing speed abilities.This is the first study confirming that cognitive and functional improvements of joint CRT/SRT interventions are still conserved 10 years after the end of the treatments. Preliminary datas suggest that a longer SRT following CRT may lead to significant benefits, in terms of cognitive gains, in patients affected by schizophrenia.

Occupational therapy for cognitive impairment in stroke patients.

Occupational therapy for cognitive impairment in stroke patients.

Enhancement of Impaired Olfactory Neural Activation and Cognitive Capacity by Liraglutide, but Not Dapagliflozin or Acarbose, in Patients With Type 2 Diabetes: A 16-Week Randomized Parallel Comparative Study

The comparative neuroprotective effects of different antidiabetes drugs have not been characterized in randomized controlled trials. Here, we investigated the therapeutic effects of liraglutide, dapagliflozin, or acarbose treatment on brain functional alterations and cognitive changes in patients with type 2 diabetes. Thirty-six patients with type 2 diabetes inadequately controlled with metformin monotherapy were randomized to receive liraglutide, dapagliflozin, or acarbose treatment for 16 weeks. Brain functional MRI (fMRI) scan and a battery of cognitive assessments were evaluated pre- and postintervention in all subjects. The 16-week treatment with liraglutide significantly enhanced the impaired odor-induced left hippocampal activation with Gaussian random field correction and improved cognitive subdomains of delayed memory, attention, and executive function (all P < 0.05), whereas dapagliflozin or acarbose did not. Structural equation modeling analysis demonstrated that such improvements of brain health and cognitive function could be partly ascribed to a direct effect of liraglutide on left hippocampal activation (β = 0.330, P = 0.022) and delayed memory (β = 0.410, P = 0.004) as well as to the metabolic ameliorations of reduced waist circumference, decreased body fat ratio, and elevated fasting insulin (all P < 0.05). Our head-to-head study demonstrated that liraglutide enhanced impaired brain activation and restored impaired cognitive domains in patients with type 2 diabetes, whereas dapagliflozin and acarbose did not. The results expand the clinical application of liraglutide and provide a novel treatment strategy for individuals with diabetes and a high risk of cognitive decline.

Common perinatal mental disorders and post-infancy child development in rural Ethiopia: A population-based cohort study.

ObjectiveTo investigate whether maternal common mental disorders (CMD) in the postnatal period are prospectively associated with child development at 2.5 and 3.5 years in a rural low‐income African setting.MethodsThis study was nested within the C‐MaMiE (Child outcomes in relation to Maternal Mental health in Ethiopia) population‐based cohort in Butajira, Ethiopia, and conducted from 2005 to 2006. The sample comprised of 496 women who had recently given birth to living, singleton babies with recorded birth weight measurements, who were 15 to 44 years of age, and residing in six rural sub‐districts. Postnatal CMD measurements were ascertained 2 months after delivery. Language, cognitive, and motor development were obtained from the child 2.5 and 3.5 years after birth using a locally adapted version of the Bayley Scales of Infant Development (3rd Ed). Maternal CMD symptoms were measured using a locally validated WHO Self‐Reporting Questionnaire. A linear mixed‐effects regression model was used to analyze the relationship between postnatal CMD and child development.ResultsAfter adjusting for confounders, there was no evidence for an association between postnatal CMD and overall child development or the cognitive sub‐domain in the preschool period. There was no evidence of effect modification by levels of social support, socioeconomic status, stunting, or sex of the child.ConclusionsPrevious studies from predominantly urban and peri‐urban settings in middle‐income countries have established a relationship between maternal CMD and child development, which contrasts with the findings from this study. The risk and protective factors for child development may differ in areas characterized by high social adversity and food insecurity. More studies are needed to investigate maternal CMD’s impact on child development in low‐resource and rural areas.

A systematic review and meta-analysis of transcranial direct-current stimulation effects on cognitive function in patients with Alzheimer's disease.

Transcranial direct-current stimulation (tDCS) appears to enhance cognitive function in Alzheimer's disease (AD). Accordingly, over the last two decades, the number of studies using tDCS for AD has grown. This study aimed to provide a quantitative assessment of the efficacy of tDCS in improving cognitive function in patients with AD. We systematically searched the literature until May 2021 to identify relevant publications for inclusion in our systematic review and meta-analysis. Eligible studies were sham-controlled trials assessing the impacts of anodal or cathodal tDCS on cognitive function in patients with AD. The outcome measure of this study was the effects of tDCS on distinct cognitive domains including memory, attention, and global cognitive function. The initial search yielded a total of 323 records. Five other articles were found using manual search of the databases. Of these, 13 publications (14 different studies) with a total of 211 patients of various degrees of AD severity underwent meta-analysis. Meta-analysis revealed the non-significant effects of tDCS on attention (0.425 SMD, 95% CI, -0.254 to 1.104, p = 0.220), and significant positive impacts on the amelioration ofgeneral cognitive measures (1.640 SMD, 95% CI, 0.782 to 2.498, p < 0.000), and memory (1.031 SMD, 95% CI, 0.688 to 1.373, p < 0.000)dysfunction in patients with AD. However, the heterogeneity of the studies were high in all subdomains of cognition (ϰ2 = 22.810, T2 = 0.552, d.f. = 5, I2 = 78.80%, p < 0.000 for attention, ϰ2 = 96.29, T2 = 1.727, d.f. = 10, I2 = 89.61%, p < 0.000 for general cognition, and ϰ2 = 7.253, T2 = 0.085, d.f. = 5, I2 = 31.06%, p = 0.203 for memory). Improved memory and general cognitive function in patients with AD was shown in this meta-analysis. However, due to the small number of studies and the high heterogeneity of the data, more high-quality studies using standardized parameters and measures are needed before tDCS can be considered as a treatment for AD.

The Assessment of Visuospatial Skills and Verbal Fluency in the Diagnosis of Alzheimer’s Disease

BackgroundIn the diagnosis of Alzheimer’s disease (AD), examining memory is predominant. Our aim was to analyze the potential role of various cognitive domains in the cognitive evaluation of AD.MethodsIn total, 110 individuals with clinically defined AD and 45 healthy control participants underwent neuropsychological evaluation including Addenbrooke’s Cognitive Examination (ACE). Patients with AD were selected in three groups based on disease duration in years (Group 1: ≤2 years, n = 36; Group 2: 2–4 years, n = 44; Group 3: ≥4 years, n = 30). Covariance-weighted intergroup comparison was performed on the global cognitive score and subscores of cognitive domains. Spearman’s rho was applied to study the correlation between cognitive subscores and disease duration. The Wilcoxon signed-rank test was used for within-group analysis among ACE cognitive subscores.ResultsSignificant difference was found between ACE total scores among groups (χ2 = 119.1; p < 0.001) with a high negative correlation (p < 0.001; r = −0.643). With a longer disease duration, all the subscores of ACE significantly decreased (p-values < 0.001). The visuospatial score showed the strongest negative correlation with disease duration with a linear trajectory in decline (r = −0.85). In the early phase of cognitive decline, verbal fluency was the most impaired cognitive subdomain (normalized value = 0.64), and it was significantly reduced compared to all other subdomains (p-values < 0.05).ConclusionWe found that the impairment of verbal fluency is the most characteristic feature of early cognitive decline; therefore, it might have crucial importance in the early detection of AD. Based on our results, the visuospatial assessment might be an ideal marker to monitor the progression of cognitive decline in AD.

The Alzheimer's Disease Prediction Of Longitudinal Evolution (TADPOLE) Challenge: Results after 1 Year Follow-up

Accurate prediction of progression in subjects at risk of Alzheimer's disease is crucial for enrolling the right subjects in clinical trials. However, a prospective comparison of state-of-the-art algorithms for predicting disease onset and progression is currently lacking. We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of patient-specific biomarkers. On a limited, cross-sectional subset of the data emulating clinical trials, performance of the best algorithms at predicting clinical diagnosis decreased only slightly (2 percentage points) compared to the full longitudinal dataset. The submission system remains open via the website https://tadpole.grand-challenge.org, while TADPOLE SHARE (https://tadpole-share.github.io/) collates code for submissions. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.

“Accidental, really?” Attributional bias in patients with Parkinson's disease

IntroductionAmong the cognitive domains impaired in Parkinson's disease (PD), social cognition has received particular attention in recent years. Nevertheless, attributional bias, a social-cognitive subdomain, has not yet been studied in this population, despite its potential relationship with neuropsychiatric symptoms, and despite the possibility that deep-brain stimulation of the subthalamic nucleus, an effective treatment for disabling motor symptoms, worsens cognitive impairment. The present study therefore compared the attributional bias of patients with PD (stimulated and nonstimulated subgroups) with that of controls. It also explored the potential correlations between patients' attributional bias and their clinical scores. MethodsThirty-two patients with PD (12 stimulated and 20 nonstimulated) were recruited and matched with 32 healthy controls. Attributional bias was assessed using the Ambiguous Intentions Hostility Questionnaire, which yields three subscores: Hostility Bias, Aggression Bias, and Blame. Depressive symptoms (Hamilton Rating Scale for Depression), paranoid thoughts (Paranoia Scale), global cognition (Montreal Cognitive Assessment), and social functioning (Social Functioning Questionnaire) were also assessed. ResultsPatients exhibited more hostile and aggressive biases than controls, especially in ambiguous situations. Stimulated patients had greater hostility and aggression biases and a higher blame score than controls in accidental situations. No significant differences were observed between stimulated and nonstimulated patients. ConclusionTo our knowledge, this is the first study to have assessed attributional bias in patients with PD and explored the impact of deep-brain stimulation on this particular subdomain of social cognition. Results suggest that patients exhibit attributional bias, and this impairment may be exacerbated in stimulated patients.

Higher Serum BDNF Levels are Associated with Lower Risk of Cognitive Decline in Older Adults :The Otassha Study

Introduction: There has been growing interest in the use of circulating levels of brain-derived neurotrophic factor (BDNF) in the blood as a biomarker in the context of patients with Alzheimer’s and other neurodegenerative diseases. Prospective data on cognitive decline in the broad older population, however, remain limited. We assessed the relationship of serum BDNF levels with short-term decline in cognitive functioning of community-dwelling older adults. Methods. Prospective study of 405 adults 65-84 years old without dementia in Tokyo, Japan. The Montreal Cognitive Assessment-Japanese version (MoCA-J) and its subscales were used. Linear regression assessed standardized differences in test score differences between baseline (2011) and follow-up (2013) visits, according to baseline serum BDNF quartiles, with adjustment for baseline demographics, disease indicators, and cognitive scores. Results: Among participants who performed on the MoCA-J at baseline (scores in bottom quartile), cognitive decline was .65 (95% CI: .08 - 1.2; p=.025) standard deviations (SD) more pronounced in those with lowest than highest BDNF levels. Decline in executive function, but not in other subdomains, was also most pronounced in those with lowest baseline serum BDNF levels (difference: .32 SD; 95%CI: .08-.55; p=.007) Conclusion: Lower serum BDNF levels were associated with greater 2-year cognitive decline in community-dwelling older Japanese adults. Decline varied among cognitive subdomains, and baseline cognition. Research seeking to evaluate the added-value of serum BDNF for screening and/or health promotion initiatives involving physical activity, which has been linked to increment in BDNF levels, is warranted.