Significant Cognitive Deficits Research Articles

Exploring the Neurocognitive Correlates of Suicidal Ideation in Major Depressive Disorder: The Role of Frontoparietal and Default Mode Networks

Suicidal ideation (SI) is a common symptom of major depressive disorder (MDD), often accompanied by cognitive alterations and emotional dysregulation. However, it is unclear whether cognitive dysfunction in patients with MDD is related to the presence or absence of SI and impaired connectivity within or between large-scale neurocognitive networks. Previous studies have shown that the frontoparietal network (FPN) and default mode network (DMN) are critical for cognitive control and emotional regulation. Participants were 51 MDD patients with suicidal ideation (MDDSI), 52 MDD patients without suicidal ideation (MDDNSI), and 55 healthy controls (HC). Using areas located within FPN and DMN networks as regions of interest (ROIs), we compared the cognitive performance of the three groups and the strength of the resting state functional connections (RSFC) within and between the FPN and DMN networks. Additionally, we examined the correlation between the strength of FC within the FPN and cognitive function in the SI group. Furthermore, network-based statistics (NBS) were used to correct for the strength of FPN and DMN functional connections. The study identified significant cognitive deficits in MDD patients. Reduced strength of FC was observed within the FPN and DMN networks in the SI group compared to the NSI group. In the SI group, the strength of FC within the FPN network was positively correlated with attention/vigilance. These insights underscore the critical roles of the FPN and DMN in the suicidal ideation, shedding light on the cognitively relevant neurobiological characteristics of MDDSI, providing new insights into the neural mechanisms of MDDSI.URL: https://www.chictr.org.cn/bin/project/edit?pid=131537Registration number: ChiCTR2100049646

Unraveling the Prefrontal Cortex-Basolateral Amygdala Pathway's Role on Schizophrenia's Cognitive Impairments: A Multimodal Study in Patients and Mouse Models.

This study investigated the role of the medial prefrontal cortex (mPFC)-basolateral amygdala (BLA) pathway in schizophrenia (SCZ)-related cognitive impairments using various techniques. This study utilized clinical scales, magnetic resonance imaging, single-cell RNA sequencing, and optogenetics to investigate the mPFC-BLA pathway in SCZ patients. In the mouse model, 6-week-old methylazoxymethanol acetate-induced mice demonstrated significant cognitive deficits, which were addressed through stereotaxic injections of an adeno-associated viral vector to unveil the neural connection between the mPFC and BLA. Significant disparities in brain volume and neural activity, particularly in the dorsolateral prefrontal cortex (DLPFC) and BLA regions, were found between SCZ patients and healthy controls. Additionally, we observed correlations indicating that reduced volumes of the DLPFC and BLA were associated with lower cognitive function scores. Activation of the mPFC-BLA pathway notably improved cognitive performance in the SCZ model mice, with the targeting of excitatory or inhibitory neurons alone failing to replicate this effect. Single-cell transcriptomic profiling revealed gene expression differences in excitatory and inhibitory neurons in the BLA of SCZ model mice. Notably, genes differentially expressed in the BLA of these model mice were also found in the blood exosomes of SCZ patients. Our research provides a comprehensive understanding of the role of the PFC-BLA pathway in SCZ, underscoring its significance in cognitive impairment and offering novel diagnostic and therapeutic avenues. Additionally, our research highlights the potential of blood exosomal mRNAs as noninvasive biomarkers for SCZ diagnosis, underscoring the clinical feasibility and utility of this method.

Melatonin Ameliorates Post-Stroke Cognitive Impairment in Mice by Inhibiting Excessive Mitophagy.

Post-stroke cognitive impairment (PSCI) remains the most common consequence of ischemic stroke. In this study, we aimed to investigate the role and mechanisms of melatonin (MT) in improving cognitive dysfunction in stroke mice. We used CoCl2-induced hypoxia-injured SH-SY5Y cells as a cellular model of stroke and photothrombotic-induced ischemic stroke mice as an animal model. We found that the stroke-induced upregulation of mitophagy, apoptosis, and neuronal synaptic plasticity was impaired both in vivo and in vitro. The results of the novel object recognition test and Y-maze showed significant cognitive deficits in the stroke mice, and Nissl staining showed a loss of neurons in the stroke mice. In contrast, MT inhibited excessive mitophagy both in vivo and in vitro and decreased the levels of mitophagy proteins PINK1 and Parkin, and immunofluorescence staining showed reduced co-localization of Tom20 and LC3. A significant inhibition of mitophagy levels could be directly observed under transmission electron microscopy. Furthermore, behavioral experiments and Nissl staining showed that MT ameliorated cognitive deficits and reduced neuronal loss in mice following a stroke. Our results demonstrated that MT inhibits excessive mitophagy and improves PSCI. These findings highlight the potential of MT as a preventive drug for PSCI, offering promising therapeutic implications.

Ganoderma lucidum spore extract improves sleep disturbances in a rat model of sporadic Alzheimer's disease.

Introduction: Ganoderma lucidum (G. lucidum, Lingzhi) has long been listed as a premium tonic that can be used to improve restlessness, insomnia, and forgetfulness. We previously reported that a rat model of sporadic Alzheimer's disease (sAD) that was induced by an intracerebroventricular injection of streptozotocin (ICV-STZ) showed significant learning and cognitive deficits and sleep disturbances. Treatment with a G. lucidum spore extract with the sporoderm removed (RGLS) prevented learning and memory impairments in sAD model rats. Method: The present study was conducted to further elucidate the preventive action of RGLS on sleep disturbances in sAD rats by EEG analysis, immunofluorescence staining, HPLC-MS/MS and Western blot. Results: Treatment with 720mg/kg RGLS for 14days significantly improved the reduction of total sleep time, rapid eye movement (REM) sleep time, and non-REM sleep time in sAD rats. The novelty recognition experiment further confirmed that RGLS prevented cognitive impairments in sAD rats. We also found that RGLS inhibited the nuclear factor-κB (NF-κB)/Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammatory pathway in the medial prefrontal cortex (mPFC) in sAD rats and ameliorated the lower activity of γ-aminobutyric acid (GABA)-ergic neurons in the parabrachial nucleus (PBN). Discussion: These results suggest that inhibiting the neuroinflammatory response in the mPFC may be a mechanism by which RGLS improves cognitive impairment. Additionally, improvements in PBN-GABAergic activity and the suppression of neuroinflammation in the mPFC in sAD rats might be a critical pathway to explain the preventive effects of RGLS on sleep disturbances in sAD.

Neurocognition and social cognition in youth and young adults at ultra-high-risk for psychosis and bipolar disorder

BackgroundSchizophrenia and bipolar disorder are associated with significant deficits in neurocognition and social cognition. Unlike the studies in chronic stages of these disorders, very limited information is available regarding neurocognitive and social-cognitive impairment before the onset of bipolar disorder. Our main aim was to investigate the differences in neurocognition and social cognition between individuals at ultra-high risk for psychosis (UHR-P) and bipolar disorder (UHR-BD). MethodsThis study included 152 help-seeking individuals identified as UHR-P (n = 78) and UHR-BD (n = 74), who were compared with a healthy control group (n = 43). A comprehensive neuropsychological battery was administered to all participants. ResultsUHR-P was associated with widespread deficits in all neurocognitive and social-cognitive domains. Effect sizes (Cohen's d) of these deficits ranged from −0.57 to −1.34. UHR-BD was associated with significant deficits in processing speed, executive functions, sustained attention and social cognition (d = −0.48 to-0.70, p < 0.05). UHR-P performed significantly worse than UHR-BD in social cognition, processing speed, verbal memory and executive function domains (d = −0.39 to-0.64, p < 0.05). Negative symptoms were associated with impaired social cognition in the UHR-P group and verbal memory deficits in the UHR-BD group. Cognitive impairment was associated with functional impairment in both groups. ConclusionsWhile UHR-P is associated with more widespread cognitive impairment, deficits in processing speed, executive functions, sustained attention and social cognition might be common features of both UHR groups. In early intervention services, cognition should be considered as a target for assessment and intervention not only for individuals at high risk for psychosis but also for bipolar disorder.

Integrated Psychological Rehabilitation Program on Neurocognition, Social Skill, and Functional Disability in Persons with Schizophrenia: A Pilot Study

Abstract Introduction: Schizophrenia, a chronic and severe mental disorder, is characterized by disruptions in thinking, perception, emotions, and behavior. These disturbances are accompanied by significant cognitive and social skill deficits that affect their functional outcomes encompassing employment, independent living, social interactions, and community integration. To address these issues, the development of psychological rehabilitation programs addressing cognitive and social skill deficits becomes pivotal in schizophrenia care. Objective: The study was designed to develop modules for the integrated psychological rehabilitation program (IPRP) that focus on neurocognitive functions, social skills, and functional disability and evaluate its feasibility among schizophrenia patients. Materials and Methods: The present study made use of a pre- and posttest research design and used purposive sampling to recruit patients diagnosed with schizophrenia. Twelve participants completed the 1-month IPRP along with the pre- and posttest evaluations encompassing cognitive functions, social skills, and disability using the Bender Gestalt Test, Social Skills Assessment Screening Scale, NIMHANS neuropsychology battery, Postgraduate Institute Memory Scale, and WHO Disability Assessment Schedule II. IPRP consisted of psychoeducation, cognitive retraining, and social skills training. Results: The majority of the participants were college educated (91.7%), unemployed (83.3%), single (75%), males (75%), residing in urban areas (66.7%), and living in joint family (66.7%). Wilcoxon signed-rank test was used to compare pre- and posttest means. The results found significant improvements in various cognitive domains, including visuospatial ability (Z = 2.43, P = 0.015), remote (Z = 2.12, P = 0.034) and immediate memory (Z = 2.04, P = 0.042), verbal retention for similar (Z = 2.26, P = 0.024) and dissimilar pairs (Z = 2.82, P = 0.005), recognition (Z = 2.14, P = 0.032), total memory (Z = 3.06, P = 0.002), mental speed in terms of time taken (Z = 2.98, P = 0.003) and errors made (Z = 2.26, P = 0.024) on the digit symbol substitution test, comprehension (Z = 2.84, P = 0.004), social skills (Z = 2.807, P = 0.005), and overall disability (Z = 2.94, P = 0.003). Conclusion: The findings from the study underscore the potential of the IPRP in mitigating cognitive deficits, enhancing social skills, and reducing overall disability among schizophrenia patients.

Cognitive impairment following sedative overdose

Introduction Patients with sedative overdose may have residual cognitive impairment at the time they are deemed medically cleared for discharge. Impairment could affect the performance of high-risk activities, including driving. The Trail Making Test is an alpha-numeric assessment that can be performed at the bedside to assess cognitive function. We examined whether there were differences in cognitive function when medically cleared between patients that overdosed on sedative and non-sedative drugs. Methods A prospective, observational study assessed cognitive function using the Trail Making Test between 2018 and 2021. Patients (16 years and greater) completed testing upon medical clearance if they spoke English and had no previous neurological injury. Continuous covariates were compared using t-tests or Mann–Whitney U tests and multiple linear regression; binary variables were modelled using logistic regression. Results Of 171 patients enrolled, 111 (65 per cent) had sedative overdose; they were older (median 32.1 versus 22.2 years) and more likely to be male (58.6 per cent versus 36.7 per cent). Benzodiazepines and paracetamol were the commonest drug overdoses. Patients with sedative overdose performed worse on Trail Making Test part A (37.0 versus 33.1 seconds, P = 0.017) and Trail Making Test part B (112.4 versus 81.5 seconds, P = 0.004). Multiple linear regression analysis indicated that patient age (P < 0.001, 1.7 seconds slower per year, 95 per cent confidence interval: 0.9–2.6 seconds) and perception of recovery (P = 0.006, 36.4 seconds slower if perceived not recovered, 95 per cent confidence interval: 10.8–62.0 seconds) were also associated with Trail Making Test part B times. Patients with sedative overdose were more likely to be admitted to the intensive care unit (Odds Ratio: 4.9, 95 percent confidence interval: 1.1–22.0; P = 0.04). Discussion Our results are broadly in keeping with previously published work, but include a wider range of drug overdose scenarios (polypharmacy and recreational drugs). While patients demonstrated some perception of their cognitive impairment, our model could not reliably be used to provide individual discharge advice. The study design did not allow us to prove causation of cognitive impairment, or to make comparison between the strength of an overdose to the trail making test time. Conclusions Trail Making Test results suggested that patients who had sedative drug overdoses may have significant cognitive deficits even when medically cleared. Risk of harm may be minimised with advice to avoid high-risk activities such as driving. More profound impacts seen on the Trail Making Test part B than A may mean higher-order thinking is more affected than simple cognitive function.

Systemic treatment with ubiquitin carboxy terminal hydrolase L1 TAT protein ameliorates axonal injury and reduces functional deficits after traumatic brain injury in mice

Traumatic brain injury (TBI) is often associated with axonal injury that leads to significant motor and cognitive deficits. Ubiquitin carboxy terminal hydrolase L1 (UCHL1) is highly expressed in neurons and loss of its activity plays an important role in the pathogenesis of TBI. Fusion protein was constructed containing wild type (WT) UCHL1 and the HIV trans-activator of transcription capsid protein transduction domain (TAT-UCHL1) that facilitates transport of the protein into neurons after systemic administration. Additional mutant proteins bearing cysteine to alanine UCHL1 mutations at cysteine 152 (C152A TAT-UCHL1) that prevents nitric oxide and reactive lipid binding of C152, and at cysteine 220 (C220A TAT-UCHL1) that inhibits farnesylation of the C220 site were also constructed. WT, C152A, and C220A TAT-UCHL1 proteins administered to mice systemically after controlled cortical impact (CCI) were detectable in brain at 1 h, 4 h and 24 h after CCI by immunoblot. Mice treated with C152A or WT TAT-UCHL1 decreased axonal injury detected by NF200 immunohistochemistry 24 h after CCI, but C220A TAT-UCHL1 treatment had no significant effect. Further study indicated that WT TAT-UCHL1 treatment administered 24 h after CCI alleviated axonal injury as detected by SMI32 immunoreactivity 7 d after CCI, improved motor and cognitive deficits, reduced accumulation of total and K48-linked poly-Ub proteins, and attenuated the increase of the autophagy marker Beclin-1. These results suggest that UCHL1 activity contributes to the pathogenesis of white matter injury, and that restoration of UCHL1 activity by systemic treatment with WT TAT-UCHL1 after CCI may improve motor and cognitive deficits. These results also suggest that farnesylation of the C220 site may be required for the protective effects of UCHL1.

Change in Cognitive Function over the Course of Major Depressive Disorder: A Systematic Review and Meta-analysis.

Major depressive disorder (MDD) is associated with significant cognitive deficits during the acute and remitted stages. The aim of this systematic review and meta-analysis was to examine the course of cognitive function whilst considering demographic, treatment, or clinical features of MDD that could moderate the extent of cognitive change. Databases were searched to identify studies that reported on cognitive function in MDD with a ≥12-week test-retest interval. Relevant studies were pooled using random effects modelling to generate an inverse-variance, weighted, mean effect size estimate (Hedges' g) of cognitive change for each cognitive variable and for an overall composite cognitive domain. Of 6898 records, 99 eligible studies were identified from which 69 were meta-analysed, consisting of 4639 MDD patients (agemean = 40.25years, female% = 64.62%) across 44 cognitive variables. In over 95% of cognitive variables, improvements were either of non-significant, negligible, or of a small magnitude, and when compared to matched healthy controls, the possibility of practice effects could not be precluded. Depressive symptom improvement and the number of previous depressive episodes moderated the extent of cognitive change, demonstrating state- and scar-like features for one-quarter of the cognitive domains. Further longitudinal studies are required to elucidate the MDD cognitive trajectory from initial onset. Findings nonetheless suggest that following pharmacological and non-pharmacological treatment, cognitive change in MDD is typically small, but the capacity for change may be less with episode recurrence. Targeting cognition early in the course of illness may facilitate better prognosis and support a more complete functional recovery.

Social cognition and social motivation in schizophrenia and bipolar disorder: are impairments linked to the disorder or to being socially isolated?

People with schizophrenia on average are more socially isolated, lonelier, have more social cognitive impairment, and are less socially motivated than healthy individuals. People with bipolar disorder also have social isolation, though typically less than that seen in schizophrenia. We aimed to disentangle whether the social cognitive and social motivation impairments observed in schizophrenia are a specific feature of the clinical condition v. social isolation generally. We compared four groups (clinically stable patients with schizophrenia or bipolar disorder, individuals drawn from the community with self-described social isolation, and a socially connected community control group) on loneliness, social cognition, and approach and avoidance social motivation. Individuals with schizophrenia (n = 72) showed intermediate levels of social isolation, loneliness, and social approach motivation between the isolated (n = 96) and connected control (n = 55) groups. However, they showed significant deficits in social cognition compared to both community groups. Individuals with bipolar disorder (n = 48) were intermediate between isolated and control groups for loneliness and social approach. They did not show deficits on social cognition tasks. Both clinical groups had higher social avoidance than both community groups. The results suggest that social cognitive deficits in schizophrenia, and high social avoidance motivation in both schizophrenia and bipolar disorder, are distinct features of the clinical conditions and not byproducts of social isolation. In contrast, differences between clinical and control groups on levels of loneliness and social approach motivation were congruent with the groups' degree of social isolation.

Epigenetic studies in children at risk of stunting and their parents in India, Indonesia and Senegal: a UKRI GCRF Action Against Stunting Hub protocol paper

IntroductionIn 2020, an estimated 150 million children under the age of 5 years were stunted. Stunting results from early-life adversity and it is associated with significant physical and cognitive deficit,...

The relationship between serum prolactin levels and cognitive function in drug-naïve schizophrenia patients: a cross-sectional study.

This study aimed to investigate the association between serum prolactin levels and psychiatric symptoms and cognitive function in drug-naïve schizophrenia patients. The study recruited 91 drug-naïve schizophrenia patients and 67 healthy controls. Sociodemographic and clinical data were collected, and cognitive function was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). Serum prolactin levels were measured, and statistical analyses were performed to examine the relationship between prolactin levels, clinical symptoms, and cognitive function. The study found that drug-naïve schizophrenia patients had severe cognitive deficits compared to healthy controls across all seven domains of the MCCB. However, no correlation was found between these patients' serum prolactin levels and clinical severity or cognitive function. The drug-naïve schizophrenia patients had significant cognitive deficits compared to healthy controls. However, there was no significant relationship between prolactin levels and symptomatology and cognition in drug-naïve schizophrenia patients.

The relationship between performance validity testing, external incentives, and cognitive functioning in long COVID

ABSTRACT Introduction Performance validity test (PVT) failures occur in clinical practice and at higher rates with external incentives. However, little PVT research has been applied to the Long COVID population. This study aims to address this gap. Methods Participants were 247 consecutive individuals with Long COVID seen for neuropsychological evaluation who completed 4 PVTs and a standardized neuropsychological battery. The sample was 84.2% White and 66% female. The mean age was 51.16 years and mean education was 14.75 years. Medical records were searched for external incentive (e.g., disability claims). Three groups were created based on PVT failures (Pass [no failures], Intermediate [1 failure], and Fail [2+ failures]). Results A total of 8.9% participants failed 2+ PVTs, 6.4% failed one PVT, and 85% passed PVTs. From the full sample, 25.1% were identified with external incentive. However, there was a significant difference between the rates of external incentives in the Fail group (54.5%) compared to the Pass (22.1%) and Intermediate (20%) groups. Further, the Fail group had lower cognitive scores and higher frequency of impaired range scores, consistent with PVT research in other populations. External incentives were uncorrelated with cognitive performance. Conclusions Consistent with other populations, results suggest Long COVID cases are not immune to PVT failure and external incentives are associated with PVT failure. Results indicated that individuals in the Pass and Intermediate groups showed no evidence for significant cognitive deficits, but the Fail group had significantly poorer cognitive performance. Thus, PVTs should be routinely administered in Long COVID cases and research.

Effects of Vitamin B 12 Supplementation on Cognitive Function in Survivors of Hemorrhagic Stroke

Background: Hemorrhagic stroke often leads to significant cognitive deficits in survivors. Vitamin B12 plays a crucial role in neurological functions, suggesting its potential in cognitive recovery post-stroke. This retrospective cohort study explored the impact of Vitamin B12 supplementation on cognitive function in hemorrhagic stroke survivors, a subject that holds substantial importance in stroke rehabilitation and patient care. Objective: The primary objective was to evaluate the effectiveness of Vitamin B12 supplementation in improving cognitive function, as measured by MMSE and MoCA scores, in adults who have recently survived a hemorrhagic stroke. Methods: The study included 75 adults diagnosed with hemorrhagic stroke within the last six months. Participants were administered a daily oral dose of 1000 mcg of Vitamin B12 for three months. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at the start and end of the supplementation period. Additionally, Vitamin B12 levels were measured at baseline and after three months to gauge the physiological uptake of the supplement. Results: The study observed significant improvements in cognitive function, with the MMSE score increasing by an average of 2.2 (p=0.0463) and the MoCA score by 5.8 (p=0.0410). There was also a notable average increase of 400 pg/mL in Vitamin B12 levels (p&lt;0.05). The supplementation was generally well-tolerated, with only 8% of participants reporting minor adverse effects, a rate not statistically significant (p&gt;0.05). Conclusion: The study provides preliminary evidence that Vitamin B12 supplementation may positively impact cognitive function in survivors of hemorrhagic stroke. However, due to the study's limitations, further extensive research is necessary to corroborate these findings and to deepen our understanding of the role of Vitamin B12 in post-stroke cognitive recovery.

Dichotomous interpretations and a stroke of luck: A case of silent cerebral hemorrhage

“Silent Cerebral Hemorrhage” in a young alcohol-dependent individual can pose a significant challenge to the treating physician. The neuroimaging and clinical presentation maybe dichotomous to a critical extent.Our aim was to explore the scientific understanding of “Silent Cerebral Hemorrhage” and share the wisdom gathered about the diagnosis and management of this rare entity. A 32-year-old male presented with fever and episodes of vomiting alongwith urinary incontinence, in the backdrop of heavy alcohol abuse. Detailed neurological assessment revealed no abnormal findings. MMSE indicated towards no significant cognitive deficits. On MRI, an extensive intracerebral hemorrhage was observed.The I.C.H. score was 2/6 and the FUNC score was 8/11; which was in stark contrast to NIH Stroke Scale score of 0/42.Blood-panel showed deranged liver enzymes. Patient was managed conservatively. Irritability was controlled using Haloperidol. Prophylactic antiepileptics were also started.Upon follow-up, patient showed drastic improvement. Patient was started on Acamprosate for maintenance of abstinence.Through this case report we have tried to highlight that “Silent Cerebral Hemorrhage” can present as a curve-ball for clinicians and psychiatrists. The dichotomy in interpretation of stroke-related scales may cause a dilemma about the course of management.“In this case, the absence of neurological deficits was indeed a stroke of luck for the patient.”: “Silent Cerebral Hemorrhage” can present as a curve-ball for clinicians and psychiatrists. Hence, we should be vigilant about it in our clinical practice. The dichotomy in interpretation of stroke-related scales may cause a dilemma about the course of management.

Cognitive deficits profiles in the first-episode of schizophrenia, clinical high risk of psychosis, and genetically high-risk of psychosis.

Cognitive deficits are core characteristics of schizophrenia, presenting before the emergence of psychotic symptoms. Individuals with a clinical high-risk for psychosis (CHR) and those with genetically high-risk of psychosis (GHR) also exhibit cognitive impairments. Nonetheless, it remains uncertain in which domains of cognitive impairments in these two groups were more similar to those of schizophrenia patients. Moreover, it is unclear which domains of impairment are caused by quality factors and which are more related to the state of disease. This research initiative aimed to extensively examine the distinct cognitive impairment profiles among the CHR, GHR, and first-episode schizophrenia (FES) cohorts. We compared the cognitive functions of the three groups and a healthy control group (HCs) using the MATRICS Consensus Cognitive Battery (MCCB). The participants for this study were recruited from the Beijing Anding Hospital of Capital Medical University. Our sample consisted of 56 patients with FES, 42 with CHR, 26 with GHR, and 62 HCs. The participants across all groups were matched in terms of gender, age, and level of education. Individuals with FES, GHR, and CHR showed significant impairment across the majority of MCCB domains, with the exception of visual learning, in comparison to HCs. None of the MCCB domains demonstrated a discerning ability to accurately differentiate between individuals with CHR and those with GHR. In the speed of processing and attention/vigilance domains, individuals with GHR and CHR exhibited scores between those of FES and HCs, with all group differences reaching statistical significance. This pattern of results indicates an intermediate level of cognitive function in individuals with GHR and CHR. Conversely, the levels of impairment observed in working memory and verbal learning were relatively consistent across all three groups: FES, CHR, and GHR. Notably, individuals in the CHR group exhibited performance akin to that of the HCs in the reasoning/problem-solving domain, while showing significant differences from the FES group, with the CHR individuals demonstrating better performance. Additionally, individuals with GHR displayed performance in social cognition similar to that of the HCs, while also demonstrating significant distinctions from the FES group, with the GHR individuals demonstrating better performance. Significant cognitive deficits exist in individuals with CHR, GHR, and FES, and these deficits vary across domains. Processing speed and attention/vigilance could potentially serve as robust biomarkers for identifying individuals at a risk of psychosis. The impairment observed in reasoning/problem-solving abilities might signify a qualitative trait, whereas deficits in social recognition could indicate a state characteristic specific to schizophrenia.

Quality of life in patients with subjective cognitive impairment compared with those diagnosed with mild cognitive impairment or dementia referred to a rural and remote memory clinic

AbstractBackgroundPerceived cognitive decline is a significant source of anxiety for many patients, especially as awareness of dementia grows. We sought to compare whether quality of life (QOL) in patients with subjective cognitive impairment (SCI) who performed normally on a neuropsychological battery significantly differed from those diagnosed with mild cognitive impairment (MCI), Alzheimer’s disease (AD), or non‐Alzheimer’s dementia (non‐AD) at initial assessment in a rural and remote memory clinic.Method610 patients referred to our Rural and Remote Memory Clinic (RRMC) between 2004‐2019 were included in this study. As part of their RRMC assessment, each patient and their caregiver independently rated the patient’s QOL using the Quality of Life of the Patient (QOLPT) scale. We compared self‐reported and caregiver‐reported patient QOL scores in those with SCI (n = 166) to those diagnosed with MCI (n = 98), AD (n = 228), and non‐AD (n = 118).ResultPatients with SCI self‐reported significantly lower QOL compared to patients with AD (mean 34.55 vs 35.96, p&lt;0.05). Interestingly, the reverse was seen in caregivers: SCI caregivers rated patient QOL higher than AD caregivers (mean 34.61 vs 31.72, p&lt;0.001). Patients with SCI also reported lower QOL than patients with MCI (mean 35.55 vs 36.97, p&lt;0.05). SCI caregivers reported higher patient QOL than their non‐AD counterparts (mean 34.61 vs 31.17, p&lt;0.001). Caregiver‐rated patient QOL was higher in those with MCI compared to AD (mean 34.52 vs 31.72, p&lt;0.001). Patients with MCI self‐reported higher QOL scores compared to patients with non‐AD (mean 36.97 vs 34.81, p&lt;0.05). Similarly, MCI caregivers reported higher patient QOL than non‐AD caregivers (mean 34.52 vs 31.72, p&lt;0.001). No other comparisons were statistically significant.ConclusionAlthough they lacked clinically significant cognitive deficits, patients with SCI self‐reported significantly lower QOL than patients with MCI and AD, although patients with MCI self‐reported higher QOL than patients with non‐AD. Conversely, caregiver‐reported patient QOL was higher for patients with SCI than patients with AD and non‐AD. MCI caregivers also reported higher patient QOL compared to AD and non‐AD caregivers. This shows that SCI seriously impacts QOL. More work needs to be done on how we can better support patients with SCI to improve their QOL.

Glial changes are associated with cerebrovascular integrity in hyperhomocysteinemia‐induced VCID in mouse and human brain

AbstractBackgroundWith the aged population estimated to double by 2050 and the rate of dementia expected to triple, it is critical to identify treatments for dementia. One of the leading causes of dementia is vascular contributions to cognitive impairment and dementia (VCID), and is frequently found co‐morbidly with Alzheimer’s disease, the other leading cause of dementia. A modifiable risk factor for VCID is hyperhomocysteinemia (HHcy), which is defined as elevated levels of plasma homocysteine (a non‐protein‐forming amino acid), and most late‐life HHcy is caused by impaired B vitamin absorption. Although HHcy is a risk factor for VCID, the mechanism through which it induces cognitive impairment remains unclear.MethodWe used human and mouse brain tissue to determine glial and vascular changes associated with HHcy. Wild‐type (C57Bl6J) mice were placed on a HHcy or control diet for 6, 10, 14, or 18 weeks. Using qPCR, we investigated pro‐ and anti‐inflammatory cytokines. We also determined changes in microglia (IBA‐1) and identified the number of microhemorrhages and cognitive changes. In humans, we identified 31 autopsied research volunteers with antemortem homocysteine levels; 13 cases had normal plasma homocysteine levels (&lt;14µmol/L) and 18 had high plasma homocysteine levels (&gt;14µmol/L). We determined whether the level of plasma homocysteine was associated with microglia (IBA‐1) and astrocytes (GFAP) as well as microhemorrhages and atherosclerosis severity in the frontal and occipital cortices. Both gene expression and protein inflammatory markers were measured to determine associations with plasma homocysteine.ResultIn our mouse model of HHcy, we identified a time course of glial changes that first begins with an increase in pro‐inflammatory cytokines and increases in microglial staining at 6 weeks on diet. This is followed by cognitive changes at 10 weeks on diet. Finally, at 14 weeks on diet, we see significant cognitive deficits due to HHcy. In human tissue, HHcy was associated with more microglia but fewer astrocytes, a significant decrease in inflammation and increased microhemorrhages in the frontal cortex.ConclusionTaken together, this data shows that in both mouse and human tissue, HHcy induces significant glial and vascular pathology that could be driven by inflammatory effects.

Cortical thickness alterations and systemic inflammation define long-COVID patients with cognitive impairment

As the heterogeneity of symptoms is increasingly recognized among long-COVID patients, it appears highly relevant to study potential pathophysiological differences along the different subtypes. Preliminary evidence suggests distinct alterations in brain structure and systemic inflammatory patterns in specific groups of long-COVID patients.To this end, we analyzed differences in cortical thickness and peripheral immune signature between clinical subgroups based on 3 T-MRI scans and signature inflammatory markers in n = 120 participants comprising healthy never-infected controls (n = 30), healthy COVID-19 survivors (n = 29), and subgroups of long-COVID patients with (n = 26) and without (n = 35) cognitive impairment according to screening with Montreal Cognitive Assessment. Whole-brain comparison of cortical thickness between the 4 groups was conducted by surface-based morphometry.We identified distinct cortical areas showing a progressive increase in cortical thickness across different groups, starting from healthy individuals who had never been infected with COVID-19, followed by healthy COVID-19 survivors, long-COVID patients without cognitive deficits (MoCA ≥ 26), and finally, long-COVID patients exhibiting significant cognitive deficits (MoCA < 26). These findings highlight the continuum of cortical thickness alterations associated with COVID-19, with more pronounced changes observed in individuals experiencing cognitive impairment (p < 0.05, FWE-corrected). Affected cortical regions covered prefrontal and temporal gyri, insula, posterior cingulate, parahippocampal gyrus, and parietal areas. Additionally, we discovered a distinct immunophenotype, with elevated levels of IL-10, IFNγ, and sTREM2 in long-COVID patients, especially in the group suffering from cognitive impairment.We demonstrate lingering cortical and immunological alterations in healthy and impaired subgroups of COVID-19 survivors. This implies a complex underlying pathomechanism in long-COVID and emphasizes the necessity to investigate the whole spectrum of post-COVID biology to determine targeted treatment strategies targeting specific sub-groups.

Cognitive-Behavioral Therapy (CBT) Versus Cognitive Retraining (CR) in Depression

Mood disorders are recurrent or episodic with significant cognitive deficits and incomplete recovery. Cognitive behavior therapy (CBT) has been a well-established evidence-based intervention, and Cognitive retraining (CR) is emerging to reduce cognitive deficits by application of techniques that improve attention, memory, and/or executive functions that enhance psychosocial functioning. Method: The present study compared CBT and CR delivered as independent interventions as well as combined with medicines employing pre-post intervention and experimental research design. Outcome measures were Beck Depression Inventory (BDI-II), Metacognitive Questionnaire (MCQ30), World Health Organization Quality of Life- Brief (WHOQOLBref), and Global Assessment of Functioning (GAF). Results: CBT group statistically had highest QOL supported by environment and global functioning. The change in mean scores on outcome measures was greater for CR groups. Conclusion: CR with or without medicine is a feasible treatment option when CBT promulgation is inhibited by patient, therapist, or environmental variables.