Cognitive Impairment In Patients Research Articles

Physical activity modifies cognitive impairment-associated mortality risks among chronic kidney disease

BackgroundOlder chronic kidney disease (CKD) patients frequently face unrecognized cognitive impairment and excess mortality. Physical activity (PA) reduces cognitive decline but whether PA modifies cognitive impairment-associated mortality remains unknown. MethodsFrom 2005 to 2011, 30,561 older Taiwanese CKD patients were enrolled. Patients were divided into intact cognition (≥8 scores), mild (6–7 scores), and severe (≤5 scores) cognitive impairment groups by the Short Portable Mental Status Questionnaire (SPMSQ), and were also categorized into high-PA (≥60 min/week of moderate-intensity PA), low-PA (20–60 min/week) or inactive (<20 min/week) groups. Cox regression was conducted to evaluate the individual and joint associations of cognitive impairment and PA on all-cause and cardiovascular mortality. ResultsAfter a median follow-up of 4.52 years, the all-cause mortality were higher in CKD patients with severe (multivariable-adjusted hazard ratio [aHR] 2.31; 95% confidence interval [CI] 2.05–2.60) and mild (aHR 1.74; CI 1.51–1.99) cognitive impairment than cognitively intact ones. Remarkably, decreased PA amount interacted and amplified the cognitive impairment-associated mortality risks. Notably, the high-PA status linked to lower overall mortality risks both in mild (aHR 0.65; CI 0.45–0.93) and severe (aHR 0.73; CI 0.54–0.99) cognitively-impaired patients as compared to inactivity. Survival tree analysis indicated the least mortality in those with high PA and >8 SPMSQ scores. Similar associations were found in the cardiovascular mortality. LimitationsResidual confounding and single ethnicity. ConclusionsCognitive impairment defined by SPMSQ was progressively associated with higher mortality among elderly CKD. Higher PA linked to lower cognitive impairment-associated death risks, and could be promoted for longevity benefits.

Using Dual-Target rTMS, Single-Target rTMS, or Sham rTMS on Post-Stroke Cognitive Impairment.

The clinical application of 10 Hz repetitive transcranil magnetic stimulation (rTMS) remains limited despite its demonstrated effectiveness in enhancing cortical excitability and improving cognitive function. The present study used a novel stimulus target [left dorsolateral prefrontal cortex + primary motor cortex] to facilitate the enhancement of cognitive function through the bidirectional promotion of cognitive and motor functions; Methods: Post-stroke cognitive impairment patients (n = 48) were randomly assigned to receive either dual-target, single-target, or sham rTMS for 4 weeks. Before and after 4 weeks of treatment, participants were asked to complete the Montreal Cognitive Assessment (MoCA) test, the Modified Barthel Index (MBI), the Trail-making Test (TMT), and the Digital Span Test (DST). In addition, the levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in serum were also measured. After adjusting for pre-intervention (baseline) MoCA scores, the post-intervention MoCA scores varied significantly. After post-hoc analysis, differences existed between the post-treatment scores of the dual-target rTMS group and the sham rTMS group (the experimental group scores were significantly higher), and between those of the dual-target rTMS group and the single-target rTMS group (the dual-target rTMS scores were significantly higher). The serum VEGF levels of the dual-target rTMS group were significantly higher those that of the sham rTMS group. The present study presented data showing that a dual-target rTMS therapy is effective for Post-stroke cognitive impairment (PSCI). The stimulation exhibited remarkable efficacy, suggesting that dual-target stimulation (left dorsolateral prefrontal cortex+motor cortex (L-DLPFC+M1)) holds promise as a potential target for TMS therapy in individuals with cognitive impairment after stroke. No: ChiCTR220066184. Registered 26 November, 2022, https://www.chictr.org.cn.

Constipation is associated with emotional and cognitive impairment in patients with Parkinson’s disease: A clinical and brain functional study

ObjectiveConstipation frequently occurs in patients with Parkinson’s disease (PD) and may be related to cognitive and emotional disorders. The aim of this study is to investigate the clinical and brain functional characteristics of patients with PD presenting with constipation. MethodsThe motor and non-motor symptoms of patients with PD were evaluated, and a resting-state functional magnetic resonance imaging (RS-fMRI) study was conducted based on propensity score matching. Alterations in brain function were analyzed using regional homogeneity (ReHo) and functional connectivity (FC). ResultsCompared with patients without constipation (PD-NC group), patients with constipation (PD-C group) had more serious motor and non-motor symptoms (including cognitive and emotional disorders along with visual hallucinations). Further, emotional and cognitive disorders were correlated with the occurrence of constipation in patients with PD. Compared with the PD-NC group, the PD-C group showed a reduced ReHo of the right insula and bilateral orbitofrontal cortex (OFC), increased ReHo of the left postcentral gyrus, and enhanced FC between the right OFC and the left middle temporal gyrus (MTG) and middle occipital gyrus (MOG). Additionally, the activity of the OFC and insula was significantly correlated with the constipation, mood, and cognitive levels of patients with PD. ConclusionsConstipation in patients with PD is closely related to emotional and cognitive impairments, abnormal activity and FC of brain regions such as the right insula and bilateral OFC may play an important role in this.

Cognitive impairment in patients with bipolar disorder alone versus those with bipolar disorder comorbid with borderline personality disorder.

Bipolar disorder (BD) is a severe mental illness. BD often coexists with borderline personality disorders, making the condition more complex. To explore the differences in cognitive impairment between patients with BD and those with BD comorbid with borderline personality disorder. Eighty patients with BD and comorbid borderline personality disorder and 80 patients with BD alone were included in groups A and B, respectively, and 80 healthy volunteers were included as controls. Cognitive function in each group was evaluated using the Chinese version of the repeatable battery for the assessment of neuropsychological status (RBANS), the Stroop color-word test, and the Wechsler intelligence scale-revised (WAIS-RC). The indices of the RBANS, Stroop color-word test, and WAIS-RC in groups A and B were significantly lower than those of the control group (P < 0.05). Group A had significantly longer Stroop color-word test times for single-character, single-color, double-character, and double-color, lower scores of immediate memory, visual breadth, verbal function dimensions and total score of the RBANS, as well as lower scores of verbal IQ, performance IQ, and overall IQ of the WAIS-RC compared with group B (P < 0.05). Compared to group B, group A exhibited significantly longer single-character time, single-color time, double-character time, and double-color time in the Stroop color-word test (P < 0.05). The cognitive function of patients with BD complicated with borderline personality disorder is lower than that of patients with BD.

ARE COGNITIVELY IMPAIRED PATIENTS SUITABLE CANDIDATES FOR HIP ARTHROPLASTY? A PROPENSITY SCORE-MATCHED COHORT STUDY

The growth of life expectancy during the last decades has led to an increment in age-related conditions such as hip arthritis and fractures. On the other hand, these elderly patients will present a higher incidence of mental diseases which, in some studies, have been associated with inferior results.This study aims to evaluate the differences in early complication rates between patients with cognitive impairment compared with those without this condition following total hip replacement for osteoarthritis or fracture in the context of contemporary perioperative care protocols.We conducted a retrospective cohort study where cognitively-impaired patients who required primary hip arthroplasty were compared to a propensity-score matched cohort of patients without cognitive alterations. Early major complications were measured and analyzed in order to determine significant differences.Screening and matching. 1196 patients were identified during the study period. After screening for inclusion and exclusion criteria and matching, two cohorts comprising 65 patients each were compared. After performing the propensity-score match, no significant differences were found in covariates between the two groups.Outcomes. The occurrence of delirium was more frequent in patients with cognitive deficit (27.5%) than in the control group (9%), p&lt;0.001. No significant differences were found among groups regarding myocardial infarction, venous thromboembolism, blood transfusion requirement, 30-day readmission, in-hospital death, 90-days death, dislocation or surgical site infection. The composite outcome of any adverse event did not exhibit a significant difference either.To our knowledge, this is the first study which demonstrates similar outcomes between patients with cognitive impairment and those without these alterations. Our results might indicate that contemporary protocols and implants are bridging the traditional gap between these two populations. These findings support the use of total hip arthroplasty in patients with mental alterations when indicated, especially in those institutions with strict perioperative protocols.

The role of telomere length in predicting cognitive impairments in patients with cerebral atherosclerosis and diabetes mellitus

The role of telomere length in predicting cognitive impairments in patients with cerebral atherosclerosis and diabetes mellitus

The impact of cognitive impairment on patient activation and their value in self-management among COPD patients

ObjectivesTo examine the impact of the interaction between cognitive function and patient activation on self-management behaviors among COPD patients. MethodsWe conducted a study of 331 COPD patients. Cognitive function and patient activation were evaluated at baseline, relevant information on social demography and diseases was collected simultaneously. The primary outcome was self-management behaviors. We performed a multiple logistic regression analysis to evaluate the interaction between cognitive function and patient activation. ResultsWe found the interaction between mild cognitive impairment (MCI) and low patient activation on poor self-management behaviors was multiplicative. The proportion of participants with high patient activation was lower than those with low patient activation among patients with MCI. The incidence of poor self-management behaviors in patients with normal cognition differed significantly between participants with different activation levels (90.2 % vs.31.3 % vs.9.7 %). However, the difference was small in those with MCI (94 % vs. 73.5 % vs. 84.5). Notably, poor self-management behaviors were high among patients with MCI, regardless of their activation level. ConclusionsPatients with COPD are more likely to have poor self-management behaviors when MCI and low patient activation coexist, and it was difficult to be activated for patients with MCI. Practice implicationsThe assessment of cognitive function is crucial for patients with COPD, especially those with low activation.

The Mixed Role of Sleep and Time of Day in Working Memory Performance of Older Adults with Mild Cognitive Impairment.

The importance of night sleep for maintaining good physical and cognitive health is well documented as well as its negative changes during aging. Since Mild Cognitive Impairment (MCI) patients bear additional disturbances in their sleep, this study aimed at examining whether there are potential mixed effects of sleep and afternoon time of day (ToD) on the storage, processing, and updating components of working memory (WM) capacity in older adults with MCI. In particular, the study compared patients' performance in the three working memory components, in two-time conditions: "early in the morning and after night sleep", and "in the afternoon and after many hours since night sleep". The Working Memory Capacity & Updating Task from the R4Alz battery was administered twice to 50 older adults diagnosed with MCI. The repeated measures analysis showed statistically significant higher performance in the morning condition for the working memory updating component (p < 0.001). Based on the findings, it seems that the afternoon ToD condition negatively affects tasks with high cognitive demands such as the WM updating task in MCI patients. These findings could determine the optimal timing for cognitive rehabilitation programs for MCI patients and the necessary sleep duration when they are engaged in cognitively demanding daily activities.

Effects of transcranial direct current stimulation on cognition in MCI with Alzheimer's disease risk factors using Bayesian analysis

Despite the growing interest in precision medicine-based therapies for Alzheimer's disease (AD), little research has been conducted on how individual AD risk factors influence changes in cognitive function following transcranial direct current stimulation (tDCS). This study evaluates the cognitive effects of sequential tDCS on 63 mild cognitive impairment (MCI) patients, considering AD risk factors such as amyloid-beta deposition, APOE ε4, BDNF polymorphism, and sex. Using both frequentist and Bayesian methods, we assessed the interaction of tDCS with these risk factors on cognitive performance. Notably, we found that amyloid-beta deposition significantly interacted with tDCS in improving executive function, specifically Stroop Word-Color scores, with strong Bayesian support for this finding. Memory enhancements were differentially influenced by BDNF Met carrier status. However, sex and APOE ε4 status did not show significant effects. Our results highlight the importance of individual AD risk factors in modulating cognitive outcomes from tDCS, suggesting that precision medicine may offer more effective tDCS treatments tailored to individual risk profiles in early AD stages.

Comparison of the Diagnostic Accuracy of Five Cognitive Screening Tests for Diagnosing Mild Cognitive Impairment in Patients Consulting for Memory Loss.

Objectives: We aimed to evaluate and compare the diagnostic capacity of five cognitive screening tests for the diagnosis of mild cognitive impairment (MCI) in patients consulting by memory loss. Methods: A cross-sectional study involving 140 participants with a mean age of 74.42 ± 7.60 years, 87 (62.14%) women. Patients were classified as MCI or cognitively unimpaired according to a comprehensive neuropsychological battery. The diagnostic properties of the following screening tests were compared: Mini-Mental State Examination (MMSE), Addenbrooke's Cognitive Examination III (ACE-III) and Mini-Addenbrooke (M-ACE), Memory Impairment Screen (MIS), Montreal Cognitive Assessment (MoCA), and Rowland Universal Dementia Assessment Scale (RUDAS). Results: The area under the curve (AUC) was 0.861 for the ACE-III, 0.867 for M-ACE, 0.791 for MoCA, 0.795 for MMSE, 0.731 for RUDAS, and 0.672 for MIS. For the memory components, the AUC was 0.869 for ACE-III, 0.717 for MMSE, 0.755 for MoCA, and 0.720 for RUDAS. Cronbach's alpha was 0.827 for ACE-III, 0.505 for MMSE, 0.896 for MoCA, and 0.721 for RUDAS. Correlations with Free and Cued Selective Reminding Test were moderate with M-ACE, ACE-III, and MoCA, and moderate for the other tests. The M-ACE showed the best balance between diagnostic capacity and time of administration. Conclusions: ACE-III and its brief version M-ACE showed better diagnostic properties for the diagnosis of MCI than the other screening tests. MoCA and MMSE showed adequate properties, while the diagnostic capacity of MIS and RUDAS was limited.

Development and validation of the eMCI-CHD tool: A multivariable prediction model for the risk of mild cognitive impairment in patients with coronary heart disease.

This study aimed to develop and validate an eMCI-CHD tool based on clinical data to predict mild cognitive impairment (MCI) risk in patients with coronary heart disease (CHD). This cross-sectional study prospectively collected data from 400 patients with coronary heart disease (aged 55-90 years, 62% men) from July 2022 to September 2023 and randomized (7:3 ratio) them into training and validation sets. After determining the modeling variables through least absolute shrinkage and selection operator regression analysis, four ML classifiers were developed: logistic regression, extreme gradient boosting (XGBoost), support vector machine, and random forest. The performance of the models was evaluated using area under the ROC curve, accuracy, sensitivity, specificity, and F1 score. Decision curve analysis was used to assess the clinical performance of the established models. The SHapley Additive exPlanations (SHAP) method was applied to determine the significance of the features, the predictive model was visualized with a nomogram, and an online web-based calculator for predicting CHD-MCI risk scores was developed. Of 400 CHD patients (average age 70.86±8.74 years), 220 (55%) had MCI. The XGBoost model demonstrated superior performance (AUC: 0.86, accuracy: 78.57%, sensitivity: 0.74, specificity: 0.84, F1: 0.79) and underwent validation. An online tool (https://mr.cscps.com.cn/mci/index.html) with seven predictive variables (APOE gene typing, age, education, TyG index, NT-proBNP, C-reactive protein, and occupation) assessed MCI risk in CHD patients. This study highlights the potential for predicting MCI risk among CHD patients using an ML model-driven nomogram and risk scoring tool based on clinical data.

Association between angiotensin-converting enzyme gene insertion/deletion polymorphism and cognition impairment in patients with schizophrenia.

Several lines of evidence indicate that an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) gene may be involved in the pathogenesis of schizophrenia and cognitive impairment. However, the relationship between ACE I/D polymorphism and cognitive impairment in patients with schizophrenia remains unclear. The aim of this study was to examine whether ACE gene I/D polymorphism contributed to cognitive impairment in Chinese patients with schizophrenia, and whether the association between clinical symptoms and cognitive impairment depended on different ACE genotypes. The ACE I/D polymorphism was genotyped in 928 schizophrenia patients and 325 healthy controls using a case-control design. The severity of psychopathological symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). Cognitive functioning was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). There were significant differences in genotype and allele frequencies of the ACE I/D polymorphism between patients and healthy controls (both P < 0.01). After controlling for demographic characteristics, patients who are homozygous carriers of D and I performed worse on the RBANS attention index than heterozygous carriers (P = 0.009). In addition, attention index score was negatively correlated with PANSS negative symptom score in patients of all genotypes (all P < 0.05), and positively correlated with positive symptom score only in the I/I genotype (P = 0.005). These findings suggest that ACE I/D gene variants play a role in susceptibility to schizophrenia, specific cognitive impairment and the association between clinical symptoms and cognitive impairment in schizophrenia patients.

Correlations between Immunoinflammatory Factor Levels and Cognitive Functions and Brain Structural Magnetic Resonance Imaging Features among Patients with Primary Schizophrenia.

Schizophrenia is associated with significant cognitive impairment. However, the pathophysiological mechanisms underlying cognitive dysfunction in schizophrenia remain unclear. Based on the latest concept of cognition, immunoinflammatory factors and structural magnetic resonance imaging (sMRI) features of the brain are considered markers of schizophrenia. This study explored the correlations between cognitive function and immunoinflammatory factors and sMRI in primary schizophrenia patients. Non-interventional cross-sectional study was conducted, including 21 patients with primary schizophrenia, who were identified based on the Diagnostic and Statistical Manual, Fifth Edition (DSM-V) and grouped under the observation group. Thirty healthy volunteers with age, gender, hand dominance, and education duration matched with those of the primary schizophrenia patients were recruited to the control group. All subjects underwent sMRI examination. MATRICS consensus cognitive battery (MCCB) was employed to assess the cognitive functions among patients with primary schizophrenia. The levels of serum amyloid A (SAA), monocyte chemoattractant protein 1 (MCP-1), and chitinase-3-like protein 1 (YKL-40) were measured by means of enzyme-linked immunosorbent assay (ELISA). Pearson's correlation analysis was carried out to analyze the correlation between immunoinflammatory factor levels and cognitive functions as well as brain sMRI features. The scores for all MCCB items and the total score for the observation group were apparently lower than those for the control group (p < 0.001), while the YKL-40 and SAA levels were notably higher in the observation group (t = 3.406, p < 0.05; t = 5.656, p < 0.001). Compared to the control group, the observation group exhibited reduced volumes of left and right insular lobes, left and right anterior cingulate cortexes, left and right hippocampi, right parahippocampal gyrus, right amygdala, left inferior occipital lobe, left superior temporal lobe, left temporal pole, and left middle and inferior temporal lobes (p < 0.001). The levels of YKL-40 and SAA were both negatively correlated with MCCB score (r = -0.3668, p = 0.004; r = -0.8495, p < 0.001). The volumes of right insular lobe, left and right anterior cingulate cortexes, right parahippocampal gyrus, right amygdala, and gray matter in left middle temporal lobe were all negatively correlated with the levels of YKL-40 and SAA (p < 0.05). Cognitive impairment in patients with primary schizophrenia is associated with increased serum SAA and YKL-40 levels and decreased gray matter volume.

Association of caffeine consumption with cerebrospinal fluid biomarkers in mild cognitive impairment and Alzheimer's disease: A BALTAZAR cohort study.

We investigated the link between habitual caffeine intake with memory impairments and cerebrospinal fluid (CSF) biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. MCI (N=147) and AD (N=116) patients of the Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk (BALTAZAR) cohort reported their caffeine intake at inclusion using a dedicated survey. Associations of caffeine consumption with memory impairments and CSF biomarkers (tau, p-tau181, amyloid beta 1-42 [Aβ1-42], Aβ1-40) were analyzed using logistic and analysis of covariance models. Adjusted on Apolipoprotein E (APOE ε4), age, sex, education level, and tobacco, lower caffeine consumption was associated with higher risk to be amnestic (OR: 2.49 [95% CI: 1.13 to 5.46]; p=0.023) and lower CSF Aβ1-42 (p=0.047), Aβ1-42/Aβ1-40 (p=0.040), and Aβ1-42/p-tau181 (p=0.020) in the whole cohort. Data support the beneficial effect of caffeine consumption to memory impairments and CSF amyloid markers in MCI and AD patients. We studied the impact of caffeine consumption in the BALTAZAR cohort. Low caffeine intake is associated with higher risk of being amnestic in MCI/AD patients. Caffeine intake is associated with CSF biomarkers in AD patients.

Establishment and evaluation of a clinical prediction model for cognitive impairment in patients with cerebral small vessel disease

BackgroundThere are currently no effective prediction methods for evaluating the occurrence of cognitive impairment in patients with cerebral small vessel disease (CSVD).AimsTo investigate the risk factors for cognitive dysfunction in patients with CSVD and to construct a risk prediction model.MethodsA retrospective study was conducted on 227 patients with CSVD. All patients were assessed by brain magnetic resonance imaging (MRI), and the Montreal Cognitive Assessment (MoCA) was used to assess cognitive status. In addition, the patient’s medical records were also recorded. The clinical data were divided into a normal cognitive function group and a cognitive impairment group. A MoCA score < 26 (an additional 1 point for education < 12 years) is defined as cognitive dysfunction.ResultsA total of 227 patients (mean age 66.7 ± 6.99 years) with CSVD were included in this study, of whom 68.7% were male and 100 patients (44.1%) developed cognitive impairment. Age (OR = 1.070; 95% CI = 1.015 ~ 1.128, p < 0.05), hypertension (OR = 2.863; 95% CI = 1.438 ~ 5.699, p < 0.05), homocysteine(HCY) (OR = 1.065; 95% CI = 1.005 ~ 1.127, p < 0.05), lacunar infarct score(Lac_score) (OR = 2.732; 95% CI = 1.094 ~ 6.825, P < 0.05), and CSVD total burden (CSVD_score) (OR = 3.823; 95% CI = 1.496 ~ 9.768, P < 0.05) were found to be independent risk factors for cognitive decline in the present study. The above 5 variables were used to construct a nomogram, and the model was internally validated by using bootstrapping with a C-index of 0.839. The external model validation C-index was 0.867.ConclusionsThe nomogram model based on brain MR images and clinical data helps in individualizing the probability of cognitive impairment progression in patients with CSVD.

Cognitive impairment in patients awaiting kidney and liver transplantation-A clinically relevant problem?

Cognitive impairment (CI) is common in both end-stage kidney disease (ESKD) and alcohol-related liver cirrhosis. The aim of this study was to assess the prevalence and patterns of CI in patients awaiting kidney and liver transplantation, and to identify its determinants. In this cross-sectional, prospective study, 31 consecutive patients with ESKD and 31 consecutive patients with alcohol-related liver cirrhosis, all currently on transplant waiting lists, were screened for cognitive decline using the Addenbrooke's Cognitive Examination. Medical history, demographics, and laboratory test results were also collected. The prevalence of CI among patients with ESKD and alcohol-related liver cirrhosis was 26% and 90%, respectively. In both groups, memory was the most affected cognitive domain, along with verbal fluency in patients with ESKD, and visuospatial abilities in patients with alcoholic cirrhosis. The most statistically significant increase in the prevalence of CI was found in patients with lower educational attainment, in both alcohol-related liver cirrhosis and ESKD populations as well as in older patients with alcoholic cirrhosis. Furthermore, better cognitive functioning in ESKD patients was associated with higher levels of total lymphocyte count and alanine transaminase (ALT), and in alcohol-related liver cirrhosis patients with higher levels of ALT and aspartate transaminase. A nonsignificant trend toward lower memory domain scores was also observed with increasing ammonia levels and increasing severity of liver disease (higher Child-Pugh scores). Finally, suboptimal performance on the screening test was correlated with the severity of liver disease as assessed by the Model for End-Stage Liver Disease Sodium (MELD-Na), but not at the statistically significant level. The prevalence of CI, especially in patients with alcohol-related liver cirrhosis, is high and can be a significant clinical problem, negatively affecting the transplantation process. Routine screening tests in this group would contribute to the implementation of appropriate management, such as rehabilitation program or psychosocial treatments and facilitate the provision of specialized health care.

Cognitive Impairment and Insomnia in Celiac Disease: A Systematic Review and Meta-Analysis.

Emerging evidence suggests a broader spectrum of celiac disease (CeD) system involvement, including neurological manifestations. We aimed to conduct a systematic review and meta-analysis of the available evidence from studies assessing the association of cognitive impairment and insomnia with CeD. A total of 259 participants with CeD were included in the studies investigating insomnia and 179 were included in studies investigating cognitive impairment. The overall pooled odds ratio for insomnia in patients with CeD was 1.83 (95% confidence interval, 1.38 to 2.42; I2=0.00%). The present study provides valuable insights into the available evidence from studies investigating cognitive impairment in patients with CeD and our systematic review and metaanalysis revealed a significant association between CeD and insomnia.

Characterizing white matter connectome abnormalities in patients with temporal lobe epilepsy using threshold-free network-based statistics.

Emerging evidence illustrates that temporal lobe epilepsy (TLE) involves network disruptions represented by hyperexcitability and other seizure-related neural plasticity. However, these associations are not well-characterized. Our study characterizes the whole brain white matter connectome abnormalities in TLE patients compared to healthy controls (HCs) from the prospective Epilepsy Connectome Project study. Furthermore, we assessed whether aberrant white matter connections are differentially related to cognitive impairment and a history of focal-to-bilateral tonic-clonic (FBTC) seizures. Multi-shell connectome MRI data were preprocessed using the DESIGNER guidelines. The IIT Destrieux gray matter atlas was used to derive the 162×162 structural connectivity matrices (SCMs) using MRTrix3. ComBat data harmonization was applied to harmonize the SCMs from pre- and post-scanner upgrade acquisitions. Threshold-free network-based statistics were used for statistical analysis of the harmonized SCMs. Cognitive impairment status and FBTC seizure status were then correlated with these findings. We employed connectome measurements from 142 subjects, including 92 patients with TLE (36 males, mean age=40.1±11.7 years) and 50 HCs (25 males, mean age=32.6±10.2 years). Our analysis revealed overall significant decreases in cross-sectional area (CSA) of the white matter tract in TLE group compared to controls, indicating decreased white matter tract integrity and connectivity abnormalities in addition to apparent differences in graph theoretic measures of connectivity and network-based statistics. Focal and generalized cognitive impaired TLE patients showcased higher trend-level abnormalities in the white matter connectome via decreased CSA than those with no cognitive impairment. Patients with a positive FBTC seizure history also showed trend-level findings of association via decreased CSA. Widespread global aberrant white matter connectome changes were observed in TLE patients and characterized by seizure history and cognitive impairment, laying a foundation for future studies to expand on and validate the novel biomarkers and further elucidate TLE's impact on brain plasticity.

Ketamine-dependent patients with persistent psychosis have higher neurofilament light chain levels than patients with schizophrenia

ObjectivesKetamine can induce persisting psychosis in a subset of individuals who use it chronically and heavily. Previously, we found that the psychopathology and cognitive impairments in patients with ketamine dependence (KD) exhibiting persistent psychosis (KPP) bear resemblances with schizophrenia, albeit with less severity in those with no persistent psychosis (KNP). Furthermore, we also showed that patients with KD had higher blood levels of neurofilament light chain (NFL), a biomarker for neuroaxonal injury, compared to healthy controls. In this study, we aimed to investigate the differences in NFL levels between patients with KPP and KNP while comparing the levels of individuals with schizophrenia and healthy controls. MethodsWe enrolled 64 treatment-seeking ketamine-dependent patients (53 with KNP and 11 with KPP), 37 medication-free patients with schizophrenia, and 80 healthy controls. Blood NFL levels were measured by single molecule array immunoassay. ResultsNFL levels were highest in the KPP subgroup, followed by the KNP subgroup, and then the schizophrenia and control groups (mean ± SD: 24.5 ± 24.7, 12.9 ± 10.9, 9.2 ± 12.2, and 6.2 ± 2.2 pg/mL, respectively), with no significant difference observed between the schizophrenia and control groups. ConclusionsWe found that KD is associated with higher NFL levels compared to schizophrenia, with the KPP subgroup showing the most consistent alterations. The observation of accentuated neuroaxonal pathology in individuals with KPP implies that this clinical manifestation is associated with a specific neurobiological phenotype, despite prior evidence suggesting syndromal similarity between schizophrenia and KPP.

Identification of profiles associated with conversions between the Alzheimer’s disease stages, using a machine learning approach

BackgroundThe identification of factors involved in the conversion across the different Alzheimer’s disease (AD) stages is crucial to prevent or slow the disease progression. We aimed to assess the factors and their combination associated with the conversion across the AD stages, from mild cognitive impairment to dementia, at a mild, moderate or severe stage and to identify profiles associated with earliest/latest conversion across the AD stages.MethodsIn this study conducted on the real-life MEMORA cohort data collected from January 1, 2013, and December 31, 2019, three cohorts were selected depending on the baseline neurocognitive stage from a consecutive sample of patients attending a memory center, aged between 50 and 90 years old, with a diagnosis of AD during the follow-up, and with at least 2 visits at 6 months to 1 year of interval. A machine learning approach was used to assess the relationship between factors including socio-demographic characteristics, comorbidities and history of diseases, prescription of drugs, and geriatric hospitalizations, and the censored time to conversion from mild cognitive impairment to AD dementia, from the mild stage of dementia to the moderate or severe stages of AD dementia, and from the moderate stage of AD dementia to the severe stage. Profiles of earliest/latest conversion compared to median time to conversion across stages were identified. The median time to conversion was estimated with a Kaplan-Meier estimator.ResultsOverall, 2891 patients were included (mean age 77±9 years old, 65% women). The median time of follow-up was 28 months for mild cognitive impairment (MCI) patients, 33 months for mild AD dementia and 30 months for moderate AD dementia. Among the 1264 patients at MCI stage, 61% converted to AD dementia (median time to conversion: 25 months). Among the 1142 patients with mild AD dementia, 59% converted to moderate/severe stage (median time: 23 months) and among the 1332 patients with moderate AD dementia, 23% converted to severe stage (Q3 time to conversion: 22 months). Among the studied factors, cardiovascular comorbidities, anxiety, social isolation, osteoporosis, and hearing disorders were identified as being associated with earlier conversion across stages. Symptomatic treatment i.e. cholinesterase inhibitors for AD was associated with later conversion from mild stage of dementia to moderate/severe stages.ConclusionThis study based on a machine learning approach allowed to identify potentially modifiable factors associated with conversion across AD stages for which timely interventions may be implemented to delay disease progression.