Mendelian Randomization Analysis to Assess Whether Magnetic Resonance Imaging Signs of Cerebral Small Vessel Disease Can Cause Cognitive Decline and Dementia.

OBJECTIVE: Cognitive decline and dementia have been linked to cerebral small vessel disease, so we explored using Mendelian randomization whether cerebral small vessel disease visible as 10 neuroimaging signs may cause cognitive decline and dementia. METHODS: We analyzed publicly available data from genome-wide association studies using two-sample Mendelian randomization involving inverse variance weighting, weighted median, MR-Egger, and MR-PRESSO approaches. RESULTS: Mendelian randomization suggested that cognitive decline can be caused by lacunar stroke (inverse variance weighting, ß = -0.012, 95% CI -0.024 to -0.001, P = 0.033). Furthermore, an elevated burden of white matter hyperintensities was associated with an increased risk of Dementia due to Parkinson's disease (inverse variance weighting, OR 2.035, 95% CI 1.105 to 3.745, P = 0.023). Notably, no significant associations were observed between neuroimaging markers of Cerebral Small Vessel Disease and other types of dementia. CONCLUSION: This Mendelian randomization study provides evidence that lacunar stroke and white matter lesions can cause cognitive decline, and that white matter hyperintensity may increase risk of dementia due to Parkinson's disease. These results underscore the need for further investigations into the neurocognitive effects of cerebral small vessel disease.

Later-Life Cognitive Trajectories and Risk of Death: Results from a 6-Year Longitudinal Study of 7082 Chinese.

BACKGROUND AND OBJECTIVES: To identify cognitive decline trajectories in a Chinese elderly population, explore the associations between these trajectories and mortality, and further identify risk factors related to certain trajectories of cognitive decline. DESIGN: Prospective cohort study. SETTING: The group-based trajectory modeling and Cox proportional hazards models were conducted to explore the association between cognitive trajectory groups and mortality, while multinomial logistic regression models were constructed to estimate potential risk factors. PARTICIPANTS: We included 7082 participants aged 65 years or above in three consecutive but non-overlapping cohorts of the Chinese Longitudinal Healthy Longevity Survey with the Chinese version of the Mini-Mental State Examination up to 6 years. Participants were subsequently followed for a median (IQR) of 2.89 (1.38-3.12) years to obtain their survival status and date of death. MEASUREMENTS: Chinese version of the Mini-Mental State Examination was used to measure participants' cognitive function. RESULTS: Through use of group-based trajectory modeling, we determined three cognitive trajectory groups. Then, after adjusting for confounding factors, we found a monotonic and positive association between cognitive decline and mortality risk. Meanwhile, the association varied among elderly populations in different age groups and BMI categories, but did not differ by sex, smoking, drinking and exercising. Older seniors, females and those with poorer baseline cognitive function and less social participation tended to be more likely to be in the unfavorable trajectory groups. CONCLUSION: We found that the faster the cognitive decline, the higher the mortality, especially among those aged 65-79 years and those overweight. Our findings suggested the importance of implement better monitoring of the cognitive function of the elderly population.

Alteration of dynamical degree centrality in brain functional network and its association with metabolic disorder in minimal hepatic encephalopathy.

PURPOSE: To investigate dynamical degree centrality (dDC) alteration and its association with metabolic disturbance and cognitive impairment in minimal hepatic encephalopathy (MHE). METHODS: Fifty-eight cirrhotic patients (22 with MHE, 36 without MHE [NHE]) and 25 healthy controls underwent resting-state functional magnetic resonance imaging, 1H-magnetic resonance spectroscopy, and neurocognitive examination based on the Psychometric Hepatic Encephalopathy Score (PHES). We obtained metabolite ratios in the bilateral posterior cingulate cortex and precuneus, including glutamate and glutamine (Glx)/total creatine (tCr), myo-inositol (mI)/tCr, total choline/tCr, and N-acetyl aspartate/tCr. For each voxel, degree centrality was calculated as the sum of its functional connectivity with other voxels in the brain; and sliding-window correlation was used to calculate dDC per voxel. RESULTS: We observed a stepwise increase in Glx/tCr and a decrease in mI/tCr from NHE to MHE. The intergroup dDC differences were observed in the bilateral posterior cingulate cortex and precuneus (region of interest [ROI1]), bilateral superior-medial frontal gyrus and anterior cingulate cortex (ROI2), and left caudate head. The dDC in ROI2 (r = 0.450, P < 0.001) and mI/tCr (r = 0.297, P = 0.024) was correlated with PHES. Significant correlations were found between dDC in ROI1 and Glx/tCr (r = - 0.413, P = 0.001) and mI/tCr (r = 0.554, P < 0.001). The dDC in ROI2, Glx/tCr, and mI/tCr showed potential for distinguishing NHE from MHE (areas under the curve = 0.859, 0.655, and 0.672, respectively). CONCLUSION: Our findings suggested dynamic brain network disorganization in MHE, which was associated with metabolic derangement and neurocognitive impairment.

Neurotoxicity of the antineoplastic drugs: "Doxorubicin" as an example.

There is an increased prevalence of cancer, and chemotherapy is widely and routinely utilized to manage the majority of cancers; however, administration of chemotherapeutic drugs has faced limitations concerning the "off-target" cytotoxicity. Chemobrain and impairment of neurocognitive functions have been observed in a significant fraction of cancer patients or survivors and reduce their life quality; this could be ascribed to the ability of chemotherapeutic drugs to alter the structure and function of the brain. Doxorubicin (DOX), an FDA-approved chemotherapeutic drug with therapeutic effectiveness, is commonly used to treat several carcinomas clinically. DOX-triggered neurotoxicity is the most serious adverse reaction after DOX-induced cardiotoxicity which greatly limits its clinical application. DOX-induced neurotoxicity is a net of multiple mechanisms that have been verified in pre-clinical and clinical studies, such as oxidative stress, neuroinflammation, mitochondrial disruption, apoptosis, autophagy, disruption of neurotransmitters, and impairment of neurogenesis. There is a massive need for developing novel therapeutics for both cancer and DOX-associated neurotoxicity; therefore investigating the implicated mechanisms of DOX-induced chemobrain will reveal multi-targets for novel curative strategies. Recently, various neuroprotective mechanisms were employed to mitigate DOX-mediated neurotoxicity. For this purpose, therapeutic interventions using pharmacological compounds were developed to protect healthy "off-target" tissues from DOX-induced toxicity. In addition, nanoplatforms were used to enable target delivery of DOX; to prevent its deposition in non-cancerous tissues. The aim of the current review is to provide some reference value for the future management of DOX-induced neurotoxicity and to summarize the underlying mechanisms of DOX-mediated neurotoxicity and the potential therapeutic interventions.

Multidisciplinary approach to optimizing long-term outcomes in pediatric kidney transplant recipients: multifaceted needs, risk assessment strategies, and potential interventions.

The post-transplant course of pediatric kidney transplant recipients is marked by a myriad of challenges, encompassing medical complications, recurrent hospitalizations, physical and dietary restrictions, and mental health concerns such as depression, anxiety, and post-traumatic stress disorder. Moreover, pediatric recipients are at risk of neurodevelopmental impairment, which may result in neurocognitive deficits and pose significant psychosocial obstacles. Addressing these multifaceted demands necessitates a multidisciplinary approach to pediatric kidney transplant care. However, the existing literature on the effective implementation of such a model remains scarce. This review examines the psychosocial and neurodevelopmental challenges faced by pediatric kidney transplant recipients and their families, discussing their impact on long-term transplant outcomes. Furthermore, it provides insights into risk assessment strategies and potential interventions within a multidisciplinary framework, aiming to enhance patient care and optimize post-transplant outcomes.

Effects of cognitive training and group psychotherapy on cognitive performance of post COVID-19 patients: an exploratory and non-randomized clinical trial.

Cognitive complaints are common signs of the Post COVID-19 (PC) condition, but the extent and type of cognitive impairment may be heterogeneous. Little is known about neuropsychological treatment options. Preliminary evidence suggests cognitive symptoms may improve with cognitive training and naturally over time. In this clinical trial, we examined whether participation in a weekly group consisting of cognitive training and group psychotherapy is feasible and would exert beneficial effects on cognitive performance in PC and whether improvements were associated with intervention group participation or represented a temporal improvement effect during syndrome progression. 15 PC patients underwent an 8-week intervention. Cognitive performance was assessed before and after each intervention group participation. A control group of 15 PC patients with subjective neurocognitive or psychiatric complaints underwent two cognitive assessments with comparable time intervals without group participation. To attribute changes to the intervention group participation, interaction effects of group participation and time were checked for significance. This is an exploratory, non-randomized, non-blinded controlled clinical trial. Within the intervention group, significant improvements were found for most cognitive measures. However, significant time x group interactions were only detected in some dimensions of verbal memory and visuo-spatial construction skills. Significant time effects were observed for attention, concentration, memory, executive functions, and processing speed. The intervention setting was feasible and rated as helpful and relevant by the patients. Our results suggest that cognitive symptoms of PC patients may improve over time. Patients affected by both neurocognitive impairments and mental disorders benefit from group psychotherapy and neurocognitive training. The present study provides evidence for a better understanding of the dynamic symptomatology of PC and might help to develop further studies addressing possible therapy designs. The main limitations of this exploratory feasibility trial are the small sample size as well as the non-randomized design due to the clinical setting.

Safety of Prior Propranolol Therapy for Infantile Hemangioma.

Propranolol has been the primary treatment for infantile hemangioma (IH) since 2008. Prior studies have investigated the effects in late childhood of propranolol therapy given in infancy for IH, including neurocognitive dysfunction, sleep disorders, and hypoglycemia. However, few studies have determined the risk of these adverse effects later in life. Using the TrinetX database, we studied the risk of growth impairment, sleep disorders, learning disabilities, and diabetes mellitus in children aged 10-17 years who had received propranolol for IH in infancy. The maximum age of 17 years was chosen for the study, as propranolol was established as a treatment for IH in 2008. The results showed no statistically significant risk of growth impairment, sleep disorders, learning disabilities, or diabetes mellitus in IH patients treated with propranolol. These findings support existing evidence that propranolol therapy given in infancy for IH is not associated with long-term adverse effects up to age 17 years in the studied patient population.

Inhibitory control and working memory predict rhythm production abilities in patients with neurocognitive deficits.

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

Cerebrovascular pulsatility indicates preoperative subcortical cognitive impairment and an increased risk for postoperative delirium in elderly patients undergoing elective spine surgery.

Introduction: Advances in spine surgery enable safe interventions in elderly patients, but perioperative neurocognitive disorders (pNCD), such as post-operative delirium (POD) and cognitive dysfunction (POCD), remain a serious concern. Pre-operative cognitive impairment is a major risk factor for pNCD. Comprehensive pre-operative cognitive assessments are not feasible in clinical practice, making effective screening methods desirable. This study investigates whether pre-operative cerebrovascular duplex sonography can assess subcortical (vascular) cognitive impairment and the risk for POD. Methods: This prospective single-center study recruited patients aged ≥60 years scheduled for elective spine surgery at a German university hospital. Patients underwent pre-operative assessments including cognitive abilities (CERAD test battery), structural MRI, and cerebrovascular duplex sonography. POD screening was conducted three times daily for at least 3 days. The primary hypothesis, that the mean pulsatility index (PI) of both internal carotid arteries (ICA) predicts POD risk, was tested using logistic regression. Secondary analyses examined the association between POD risk and ICA flow (time-averaged peak velocities, TAPV) and correlations with cognitive profiles and MRI characteristics. Results: POD occurred in 22% of patients (n = 22/99) within three postoperative days. Patients with POD were significantly older (75.9 ± 5.4 vs. 70.0 ± 6.9 years, p < 0.01) but did not differ by gender (p = 0.51). ICA PI significantly predicted POD risk (OR = 5.46 [95%CI: 1.81-16.49], p = 0.003), which remained significant after adjustment for age and duration of surgery (ORadj = 6.38 [95% CI: 1.77-23.03], p = 0.005). TAPV did not inform the POD risk (p = 0.68). ICA PI Pre-operative cognitive scores were significantly associated with ICA PI (mean CERAD score: r = -0.32, p < 0.001). ICA PI was also significantly associated with total white matter lesion volume (τ = 0.19, p = 0.012) and periventricular white matter lesion volume (τ = 0.21, p = 0.007). Discussion: This is the first study to demonstrate that cerebrovascular duplex sonography can assess the risk for POD in elderly spine surgery patients. Increased ICA PI may indicate subcortical impairment, larger white matter lesion load, and lower white matter volume, predisposing factors for POD. Pre-operative cerebrovascular duplex sonography of the ICA is widely available, easy-to-use, and efficient, offering a promising screening method for POD risk. Increased ICA PI could supplement established predictors like age to adjust surgical and peri-operative procedures to individual risk profiles.

Early region-specific impact of adjuvant radiation therapy on cognition and quality of life in adult patients with primary brain tumors.

PURPOSE: While treatments for primary brain tumors increase survival, they have cognitive sequelae. Neurocognition's anatomical distribution makes it susceptible to brain damage. This study aims to evaluate the contribution of radiotherapy on short-term cognitive impairment. METHODS/PATIENTS: Using a prospective database of cognitive rehabilitation in adults operated on for primary brain tumors, a retrospective sub-analysis of the contribution of radiotherapy was performed. Thirty-four subdivisions of 12 neurocognitive regions were delineated in 48 irradiated patients and 30 non-irradiated patients. In the first group, the correlation between radiation dose and deterioration was evaluated. In all patients, the impact of tumor and surgical changes on dysfunction was calculated and compared with dose-dependent response. RESULTS: The correlation between cognitive status and radiation dose is especially strong and significant in the left hemisphere and in specific subdivisions such as the posterior hippocampus or the dorsolateral prefrontal cortex, with the left prevailing over posterior dominance. Memory is the most affected domain 1 month after radiotherapy, as attention is three months later. The hippocampus is involved in various cognitive domains in addition to memory. The prefrontal subregions and the genu of the corpus callosum are more affected by the relationship with disease and surgical changes than by radiation exposure. Patients ongoing a course of radiotherapy do not benefit from concurrent cognitive rehabilitation. CONCLUSIONS: There is a correlation between the dose of radiation received by several encephalic regions and degree of short-term domain-specific cognition decline, considering other factors of risk and cognitive rehabilitation.

Postoperative Delirium and Neurocognitive Disorders: A Comprehensive Review of Pathophysiology, Risk Factors, and Management Strategies.

Postoperative delirium (POD) and neurocognitive disorders (NCDs) are common and serious complications that can occur after surgery, particularly in older adults and those with preexisting cognitive impairments. These conditions are associated with significant morbidity, increased healthcare costs, and reduced quality of life. Understanding the underlying mechanisms, risk factors, and effective management strategies for POD and NCDs is critical for improving patient outcomes and reducing the burden on healthcare systems. This comprehensive review aims to synthesize current knowledge on the pathophysiology, risk factors, and management strategies for POD and NCDs. It explores the neurobiological and molecular mechanisms contributing to these conditions, identifies the patient-related, surgical, and environmental factors that increase risk, and evaluates pharmacological and non-pharmacological approaches to prevention and treatment. A thorough literature review was conducted using recent studies, clinical guidelines, and expert consensus to provide a detailed overview of the pathophysiology, risk factors, clinical presentation, prevention, and management of POD and NCDs. The pathophysiology of POD and NCDs involves complex interactions between neuroinflammatory processes, neurotransmitter imbalances, and brain network disruptions. Risk factors include advanced age, preexisting cognitive impairment, type and duration of surgery, and perioperative complications. Management strategies emphasize a multidisciplinary approach, incorporating preoperative optimization, careful intraoperative management, and postoperative interventions. Pharmacological treatments, such as antipsychotics, and non-pharmacological approaches, including environmental modifications and cognitive rehabilitation, play crucial roles in management. Postoperative delirium and NCDs are multifactorial conditions with significant impacts on surgical outcomes. Effective management requires a comprehensive understanding of their pathophysiology and risk factors and the implementation of targeted prevention and treatment strategies. Future research should focus on personalized approaches to prevention and treatment, further elucidation of mechanisms, and developing predictive models to enhance care for patients at risk of these neurocognitive complications.

Hydrocephalus: A Review of Etiology-Driven Treatment Strategies.

Hydrocephalus is a broad term usually understood as cerebrospinal fluid (CSF) accumulation resulting in cerebral ventricular system expansion. The production of CSF is by the choroid plexus in lateral ventricles, flowing between the third and fourth ventricles and eventually to the subarachnoid space. It is critical for proper neuronal function. Hydrocephalus is a neurological pathology linked to high morbidity from neurocognitive and motor impairment. It is classified as either communicating or non-communicating. Communicating hydrocephalus is understood as a deficit at cranial arachnoid villi and granulation absorption sites. However, there has been evidence that extracranial lymphatic vessels in the ethmoid bone region also play a role, as indicated by decreased lymphatic absorption in rat models of hydrocephalus. Treatment typically involves surgical shunt placement or endoscopic third ventriculostomy (ETV) technique with or without choroid plexus cauterization (CPC). These surgical interventions have high failure risks and complications that require re-intervention, further increasing morbidity and mortality risks. To date, there are few nonsurgical treatment strategies, but many have proved limited benefit, and many patients still require surgery. This analysis lays out the typical treatments and explores new, innovative interventions by highlighting the active role of brain parenchymal tissue in the pathogenesis of hydrocephalus.

"Navigating moyamoya: bridging gaps in neurocognitive outcomes through STA-ACA bypass".

With its bimodal age distribution, higher prevalence in Far East Asian populations, and significant risk of ischemic stroke, Moyamoya disease (MMD) poses a distinctive clinical challenge. In a recently published study by Sho Tsunoda et al., the neurocognitive results of patients with MMD undergoing revascularization surgery were assessed, highlighting the potential advantages of superficial temporal artery to anterior cerebral artery (STA-ACA) direct bypass in ameliorating neuropsychological impairment. Despite its propitious findings, the study's limitations-including a small sample size, single-center design, and lack of long-term follow-up-underscore the need for further research. Future multicenter, prospective trials with larger patient cohorts and comprehensive neurocognitive assessments are essential to validate these results and enhance the generalizability of the findings. This letter emphasizes the importance of robust study designs in advancing our understanding of MMD treatment and ensuring better patient outcomes.

Refining the standard of care in immune thrombotic thrombocytopenic purpura.

Acute immune thrombotic thrombocytopenic purpura (iTTP) is a medical emergency. In the setting of any thrombotic microangiopathy (TMA), blood should be drawn to measure ADAMTS13 activity and inhibitor levels, and an assessment should be made of TTP risk before receiving ADAMTS13 results. This can include the use of PLASMIC and French scores. Plasma exchange (PE) is then initiated. Upon confirmation of iTTP, with ADAMTS13 less than 10% in the presence of an inhibitor, interventions targeting all facets of iTTP pathophysiology should be instituted: replenishing ADAMTS13 via continued PE; suppressing anti-ADAMTS13 autoantibodies with glucocorticoids and rituximab; and inhibiting the thrombotic process-uncontrolled formation of platelet/Von Willebrand factor (VWF) microthrombi-with caplacizumab. The latter, an addition to existing standards of care, is based on International Society on Thrombosis and Haemostasis guidelines and emphasizes tracking of ADAMTS13 activity. In HERCULES, a pivotal randomized controlled trial, caplacizumab use resulted in fewer recurrent iTTP episodes, decreased PE, and shortened hospital stay. In settings of high suspicion for iTTP, clinicians should consider the administration of caplacizumab before receiving ADAMTS13 results because the greatest benefits of caplacizumab accrued starting it within 3 days of TMA recognition. In HERCULES, serious bleeding events occurred among 11% of those in the caplacizumab group vs 1% in the placebo group, but all resolved, most without intervention. iTTP survivors receiving PE and immunosuppression alone are at a heightened risk for stroke, other cardiovascular disorders, neurocognitive impairment, and kidney disease. Whether rapid prevention of VWF multimer/platelet formation with caplacizumab can suppress such long-term sequelae, and whether caplacizumab can replace PE in initial therapy, are under investigation.

Cardiovascular Disease, Brain Glucose Metabolism, and Neurocognitive Decline in People With Human Immunodeficiency Virus.

Background: Cardiovascular disease (CVD) and neuroinflammation are thought to exacerbate neurocognitive dysfunction in treated people with human immunodeficiency virus (PWH). Here, we longitudinally measured brain glucose metabolism as a measure of neuronal integrity in treated PWH using [18F]Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in correlation with atherosclerotic cardiovascular disease (ASCVD) scores, cerebrospinal fluid (CSF) neuroinflammatory markers, neurocognitive outcomes, and other clinical and laboratory variables (CLVs). Methods: Well-controlled PWH (n = 36) underwent baseline and follow-up FDG PET/CT obtained 3.5 years apart on average. Longitudinal changes in whole brain and regional relative FDG uptake, brain volumes, CLVs, CSF cytokines, and neuropsychological measures were measured. A variable selection model identified baseline variables related to future brain metabolic changes while multivariable models explored neuropsychological implications of brain metabolism and volumetrics. Results: High ASCVD scores predicted future decreased thalamic uptake (slope = -0.0068, P = .027) and decreasing thalamic uptake correlated with worsening cognition (slope = 15.80, P = .020). Despite longitudinal greater than expected gray matter loss, whole brain FDG uptake did not change over the follow-up period. Most CSF cytokines decreased longitudinally but were not predictive of FDG changes. Conclusions: We found that high ASCVD scores in a group of treated PWH were related to thalamic hypometabolism, which in turn correlated with neurocognitive decline. Our findings support the contribution of CVD to neurocognitive dysfunction. More proactive CVD management may have a role in mitigating progression of cognitive impairment. Lack of change in global brain glucose metabolism despite documented accelerated gray matter volume loss over the same period suggests that FDG PET might underestimate neuronal injury in PWH compared to structural magnetic resonance imaging.

Development and Validation of an Automatic Computerized Neurocognitive Battery in Chinese.

OBJECTIVES: Neuropsychological test batteries, which accurately and comprehensively assess cognitive functions, are a crucial approach in the early detection of and interventions for cognitive impairments. However, these tests have yet to gain wide clinical application in China owing to their complexity and time-consuming nature. This study aimed to develop the Computerized Neurocognitive Battery for Chinese-Speaking participants (CNBC), an autorun and autoscoring cognitive assessment tool to provide efficient and accurate cognitive evaluations for Chinese-Speaking individuals. METHODS: The CNBC was developed through collaboration between clinical neurologists and software engineers. Qualified volunteers were recruited to complete CNBC and traditional neurocognitive batteries. The reliability and validity of the CNBC were evaluated by analyzing the correlations between the measurements obtained from the computerized and the paper-based assessment and those between software-based scoring and manual scoring. RESULTS: The CNBC included 4 subtests and an autorun version. Eighty-six volunteers aged 51-82 years with 7-22 years of education were included. Significant correlations (0.256-0.666) were observed between paired measures associated with attention, executive function, and episodic memory from the CNBC and the traditional paper-based neurocognitive batteries. This suggests a strong construct validity of the CNBC in assessing these cognitive domains. Furthermore, the correlation coefficients between manual scoring and system scoring ranged from 0.904-1.0, indicating excellent inter-rater reliability for the CNBC. INTERPRETATION: A novel CNBC equipped with automated testing and scoring features was developed in this study. The preliminary results confirm its strong reliability and validity, indicating its promising potential for clinical utilization.

Association between cerebral blood flow variation and cognitive decline in older patients undergoing hemodialysis.

Background: The mechanism of cognitive impairment in hemodialysis patients is multifactorial. The relationship between cerebral blood flow and the decline of cognitive function is poorly understood. Objective: To investigate the association between cerebral blood flow variation and decline of cognitive function in older patients undergoing hemodialysis. Methods: In this prospective observational cohort study of 121 older patients undergoing hemodialysis, we used transcranial Doppler ultrasound (TCD) to measure cerebral arterial mean flow velocity (MFV) throughout dialysis, assessed cognitive function at baseline and 12-month follow-up, and then analyzed associations between MFV and changes on cognitive scores. Results: TCD recordings demonstrated a significant reduction in MFV throughout dialysis, which were significantly correlated with cumulative ultrafiltration volume (rho 0.356, p < 0.001), ΔSBP (rho 0.251, p = 0.005), and ΔMAP (rho 0.194, p = 0.032). Compared with the baseline assessments, cognitive scores of participants at the 12-month follow-up were significantly worsened in global cognition (MOCA), some tests of memory (CFT-memory), executive function (TMT-B, SCWT-C, and SCWT-T), attention/processing speed (SDMT), and visuospatial function (CFT-copy) (p < 0.05). The worsening scores in global cognition (MOCA) (ß = 0.066, 95% CI 0.018-0.113, p = 0.007) and some tests of memory (AVLT5) (ß = 0.050, 95% CI 0.004-0.097, p = 0.035) and executive function (TMT-B, SCWT-C, SCWT-T) (ß = 1.955, 95% CI 0.457-3.453, p = 0.011; ß = 0.298, 95% CI 0.112-0.484, p = 0.002 and ß = 1.371, 95% CI 0.429-2.303, p = 0.004, respectively) were significantly associated with the reduction of MFV. Conclusion: Hemodialysis may significantly reduce cerebral blood flow in older patients; Repetitive intradialytic decreases in CBF may be one of the mechanisms underlying the decline of cognitive function. Clinical trial registration: https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000C5B5&selectaction=Edit&uid=U0003QEL&ts=4&cx=-djoi2.

Uncovering neural substrates across Alzheimer's disease stages using contrastive variational autoencoder.

Alzheimer's disease is the most common major neurocognitive disorder. Although currently, no cure exists, understanding the neurobiological substrate underlying Alzheimer's disease progression will facilitate early diagnosis and treatment, slow disease progression, and improve prognosis. In this study, we aimed to understand the morphological changes underlying Alzheimer's disease progression using structural magnetic resonance imaging data from cognitively normal individuals, individuals with mild cognitive impairment, and Alzheimer's disease via a contrastive variational autoencoder model. We used contrastive variational autoencoder to generate synthetic data to boost the downstream classification performance. Due to the ability to parse out the nonclinical factors such as age and gender, contrastive variational autoencoder facilitated a purer comparison between different Alzheimer's disease stages to identify the pathological changes specific to Alzheimer's disease progression. We showed that brain morphological changes across Alzheimer's disease stages were significantly associated with individuals' neurofilament light chain concentration, a potential biomarker for Alzheimer's disease, highlighting the biological plausibility of our results.

Neuroprotective impact of glycitin on memory impairment in a pentylenetetrazol-induced chronic epileptic rat model: insights into hippocampal histology, oxidative stress, and inflammation.

Epilepsy, characterized by recurrent seizures, often accompanies neurocognitive impairments and is associated with increased oxidative stress and inflammation. This study investigates the possible neuroprotective properties of glycitin, a soy isoflavone, on memory impairment, its impact on oxidative stress responses, and inflammatory gene expression in a chronic epileptic rat model induced by pentylenetetrazol (PTZ). Glycitin was administered at varying doses to evaluate its potential neuroprotective impact on memory, oxidative stress, and inflammation in this model. Behavioural assessments, memory retention and recall capabilities, histopathological examinations, measurements of oxidative stress biomarkers, and molecular assessments were employed for comprehensive evaluation. The results demonstrated that glycitin significantly improved memory impairment and reduced oxidative stress in epileptic rats. Additionally, glycitin treatment decreased the expression of tumor necrosis factor-α (TNF-α) and nuclear factor kappa B (NF-κB), indicating its potential to modulate the inflammatory response associated with epilepsy. These observations underscore the potential of glycitin as a therapeutic candidate for mitigating memory impairments linked to chronic epilepsy due to its antioxidant and anti-inflammatory properties, offering insights into novel avenues for the development of targeted interventions aimed at preserving cognitive function and ameliorating oxidative damage and inflammation in epileptic conditions.

Neuroanatomical profiles of cognitive phenotypes in patients with primary brain tumors.

Background: Patients with brain tumors demonstrate heterogeneous patterns of cognitive impairment, likely related to multifactorial etiologies and variable tumor-specific factors. Cognitive phenotyping offers a patient-centered approach to parsing heterogeneity by classifying individuals based on patterns of impairment. The aim of this study was to investigate the neuroanatomical patterns associated with each phenotype to gain a better understanding of the mechanisms underlying impairments. Methods: Patients with primary brain tumors were recruited for a prospective, observational study. Patients were cognitively phenotyped using latent profile analysis in a prior study, revealing 3 distinct groups: generalized, isolated verbal memory, and minimal impairment. Whole brain cortical thickness (CT), fractional anisotropy, and mean diffusivity (MD) were compared across phenotypes, and associations between imaging metrics and cognitive scores were explored. Results: Neurocognitive, structural MRI, and diffusion MRI data were available for 82 participants at baseline. Compared to the minimal impairment group, the generalized impairment group showed a widespread, bi-hemispheric pattern of decreased CT (P-value range: .004-.049), while the verbal memory impairment group showed decreased CT (P-value range: .006-.049) and increased MD (P-value range: .015-.045) bilaterally in the temporal lobes. In the verbal memory impairment group only, increased parahippocampal MD was associated with lower verbal memory scores (P-values < .01). Conclusions: Cognitive phenotypes in patients with brain tumors showed unique patterns of brain pathology, suggesting different underlying mechanisms of their impairment profiles. These distinct patterns highlight the biological relevance of our phenotyping approach and help to identify areas of structural and microstructural vulnerability that could inform treatment decisions.