Cognitive Symptoms In Patients Research Articles

Hippocampus diffusivity abnormalities in classical trigeminal neuralgia

Abstract Introduction: Patients with chronic pain frequently report cognitive symptoms that affect memory and attention, which are functions attributed to the hippocampus. Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by paroxysmal attacks of unilateral orofacial pain. Given the stereotypical nature of TN pain and lack of negative symptoms including sensory loss, TN provides a unique model to investigate the hippocampal implications of chronic pain. Recent evidence demonstrated that TN is associated with macrostructural hippocampal abnormalities indicated by reduced subfield volumes; however, there is a paucity in our understanding of hippocampal microstructural abnormalities associated with TN. Objectives: To explore diffusivity metrics within the hippocampus, along with its functional and structural subfields, in patients with TN. Methods: To examine hippocampal microstructure, we utilized diffusion tensor imaging in 31 patients with TN and 21 controls. T1-weighted magnetic resonance images were segmented into hippocampal subfields and registered into diffusion-weighted imaging space. Fractional anisotropy (FA) and mean diffusivity were extracted for hippocampal subfields and longitudinal axis segmentations. Results: Patients with TN demonstrated reduced FA in bilateral whole hippocampi and hippocampal body and contralateral subregions CA2/3 and CA4, indicating microstructural hippocampal abnormalities. Notably, patients with TN showed significant correlation between age and hippocampal FA, while controls did not exhibit this correlation. These effects were driven chiefly by female patients with TN. Conclusion: This study demonstrates that TN is associated with microstructural hippocampal abnormalities, which may precede and potentially be temporally linked to volumetric hippocampal alterations demonstrated previously. These findings provide further evidence for the role of the hippocampus in chronic pain and suggest the potential for targeted interventions to mitigate cognitive symptoms in patients with chronic pain.

Association Between Sleep Quality and Cognitive Symptoms in Patients with Major Depressive Disorder.

Cognitive symptoms and sleep disturbance (SD) are common non-mood-related symptoms of major depressive disorder (MDD). In clinical practice, both cognitive symptoms and SD are related to MDD progression. However, there are only a few studies investigating the connection between cognitive symptoms and SD in patients with MDD, and only preliminary evidence suggests a significant association between cognitive symptoms and SD in patients with mood disorders. This study investigates the relationship between cognitive symptoms and sleep quality in patients with major depressive disorder. Patients (n = 20) with MDD were enrolled; their mean Hamilton Depression Scale-17 score was 21.95 (±2.76). Gold standard polysomnography (PSG) was used to assess sleep quality, and the validated THINC-integrated tool (the cognitive screening tool) was used to evaluate cognitive function in MDD patients. Overall, the results showed significant correlations between the cognitive screening tool's total score and sleep latency, wake-after-sleep onset, and sleep efficiency. These findings indicate that cognitive symptoms are associated with poor sleep quality among patients with MDD.

Post-COVID-19 cognitive symptoms in patients assisted by a teleassistance service: a retrospective cohort study.

Four years after the onset of the COVID-19 pandemic, the frequency of long-term post-COVID-19 cognitive symptoms is a matter of concern given the impact it may have on the work and quality of life of affected people. To evaluate the incidence of post-acute COVID-19 cognitive symptoms, as well as the associated risk factors. Retrospective cohort, including outpatients with laboratory-confirmed COVID-19 and who were assisted by a public telehealth service provided by the Telehealth Network of Minas Gerais (TNMG), during the acute phase of the disease, between December/2020 and March/2022. Data were collected through a structured questionnaire, applied via phone calls, regarding the persistence of COVID-19 symptoms after 12 weeks of the disease. Cognitive symptoms were defined as any of the following: memory loss, problems concentrating, word finding difficulties, and difficulty thinking clearly. From 630 patients who responded to the questionnaire, 23.7% presented cognitive symptoms at 12 weeks after infection. These patients had a higher median age (33 [IQR 25-46] vs. 30 [IQR 24-42] years-old, p = 0.042) with a higher prevalence in the female sex (80.5% vs. 62.2%, p < 0.001) when compared to those who did not present cognitive symptoms, as well as a lower prevalence of smoking (8.7% vs. 16.2%, p = 0.024). Furthermore, patients with persistent cognitive symptoms were more likely to have been infected during the second wave of COVID-19 rather than the third (31.0% vs. 21.3%, p = 0.014). Patients who needed to seek in-person care during the acute phase of the disease were more likely to report post-acute cognitive symptoms (21.5% vs. 9.3%, p < 0,001). In multivariate logistic regression analysis, cognitive symptoms were associated with female sex (OR 2.24, CI 95% 1.41-3.57), fatigue (OR 2.33, CI 95% 1.19-4.56), depression (OR 5.37, CI 95% 2.19-13.15) and the need for seek in-person care during acute COVID-19 (OR 2.23, CI 95% 1.30-3.81). In this retrospective cohort of patients with mostly mild COVID-19, cognitive symptoms were present in 23.7% of patients with COVID-19 at 12 weeks after infection. Female sex, fatigue, depression and the need to seek in-person care during acute COVID-19 were the risk factors independently associated with this condition.

Long COVID and its association with neurodegenerative diseases: pathogenesis, neuroimaging, and treatment.

Corona Virus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has presented unprecedented challenges to the world. Changes after acute COVID-19 have had a significant impact on patients with neurodegenerative diseases. This study aims to explore the mechanism of neurodegenerative diseases by examining the main pathways of central nervous system infection of SARS-CoV-2. Research has indicated that chronic inflammation and abnormal immune response are the primary factors leading to neuronal damage and long-term consequences of COVID-19. In some COVID-19 patients, the concurrent inflammatory response leads to increased release of pro-inflammatory cytokines, which may significantly impact the prognosis. Molecular imaging can accurately assess the severity of neurodegenerative diseases in patients with COVID-19 after the acute phase. Furthermore, the use of FDG-PET is advocated to quantify the relationship between neuroinflammation and psychiatric and cognitive symptoms in patients who have recovered from COVID-19. Future development should focus on aggressive post-infection control of inflammation and the development of targeted therapies that target ACE2 receptors, ERK1/2, and Ca2+.

Efficacy of spironolactone as adjunctive therapy to sodium valproate in bipolar-I disorder: A double-blind, randomized, placebo-controlled clinical trial.

Treatment of mood and cognitive symptoms of patients with bipolar disorder is associated with many complications and is generally not associated with therapeutic satisfaction. In this clinical trial, we evaluated the effectiveness of spironolactone in controlling mood and cognitive symptoms, sleep quality, appetite, and body mass index in patients with bipolar disorder in manic episodes. Sixty inpatients with bipolar disorder in manic episodes were treated with spironolactone/placebo in an 8-week randomized, double-blind, placebo-controlled clinical trial. They were evaluated using the Young Mania Rating Scale (YMRS), mini-mental state examination (MMSE), Pittsburgh sleep quality index, Simplified Nutritional Appetite Questionnaire, and body mass index in weeks 1, 4, and 8. For cognitive impairment (MMSE), there were significant interaction effects of group and time at week 8 (B=-1.60, SE=0.69, t=-2.33, p=.021) such that individuals in the spironolactone group experienced more improvement in their cognitive performance. For manic symptoms (YMRS), there were no significant interaction effects of group and time at week 8 (B=-2.53, SE=1.46, t=-1.73, p=.085). Considering the promising findings in this clinical trial, further study of spironolactone as adjunctive therapy in bipolar disorder in manic episodes with larger sample sizes, multicenter settings, and longer follow-ups are recommended.

Low cognitive functioning and depressive symptoms in patients with rheumatoid arthritis and systemic sclerosis: a clinical study

BackgroundRecently, cognitive deficits occurring in rheumatic diseases have attracted scientific attention. Cognitive symptoms in patients with Rheumatoid Arthritis (RA) and Systemic Sclerosis (SSc) have not been thoroughly studied. This study aimed to assess cognitive function and its relationship with depressive symptoms in RA and SSc and compare it to mild neurocognitive disorder due to Alzheimer’s disease (MiND) and to individuals without cognitive impairment.MethodsCognitive function and depressive symptoms were tapped with the Cognitive Telephone Screening Instrument plus (COGTEL+), the Serial Seven Test (SST), the Mini-Mental State Examination (MMSE) and the Geriatric Depression scale-15 (GDS), respectively. Statistical analyses included between groups-, correlation- and regression analyses. Demographic characteristics were considered in the regression models.ResultsThe study included 30 individuals with RA, 24 with SSc, 26 adults without cognitive impairment and 33 individuals with MiND. Lower performance in verbal short-term memory, concentration/attention, verbal fluency and MMSE in patients with RA compared to individuals without cognitive impairment was detected. Of note, performance on verbal fluency, concentration/attention, inductive reasoning and MMSE was lower in RA compared to MiND. Individuals with SSc performed worse in verbal fluency and in MMSE in comparison to adults without cognitive deficits. Verbal fluency deficits in SSc exceeded that in MiND. Performance on MMSE, COGTEL+, prospective memory, working memory, verbal fluency and concentration/attention was related to GDS scores, which did not vary across the groups.ConclusionsPatients with RA and SSc encountered cognitive dysfunction, which partially pertains to depressive symptoms. Of note, the severity of cognitive dysfunction in many cases exceeded that of MiND.

The Effect of Memantine Versus Folic Acid on Cognitive Impairment in Patients with Schizophrenia: A Randomized Clinical Trial.

Objective: Schizophrenia, as one of the most severe psychiatric diseases, has a chronic and debilitating process. The majority of patients with schizophrenia do not respond adequately to treatment with common antipsychotic drugs. Therapeutic problems induced by drug side effects as well as undesired results are major challenging issues regarding this disease. This study aimed at evaluating the effect of memantine supplementation on the improvement of cognitive symptoms in patients with schizophrenia. Method : The present clinical trial was performed on 50 patients with acute schizophrenia who were admitted to Kargarnejad Psychiatric Hospital in Kashan in 2022 and who were diagnosed as schizophrenia cases at least three months ago. Patients were randomly divided into either the intervention group (n = 25) or the placebo group (n = 25). The intervention group received 5 mg of memantine per day for three months. The dose of memantine in this group was increased to the maximum of 20 mg per day. The placebo group received 1 mg of folic acid per day for three months. Moreover, an identical routine schizophrenia therapeutic regimen was administered to all patients. The effectiveness of memantine was evaluated using the Wechsler Adult Intelligence Scale (WAIS-III), which assessed cognitive ability in older adults over a 12-week follow-up period. Results: The WAIS-III score in the 12th week of the study was significantly different between the placebo and intervention groups (P = 0.004), such that the score of the memantine group was higher than that of the placebo group. No significant difference was observed between the two groups in terms of drug side effects. Conclusion: Memantine can be supplemented in the treatment of schizophrenia so as to improve the cognitive symptoms of this disorder. However, subsequent studies involving larger sample sizes and different doses seem to be necessary to provide more accurate results in this respect.

Plasma metabolomics and network pharmacology identified glutamate, glutamine, and arginine as biomarkers of depression under Shuganjieyu capsule treatment

Depression is a psychiatric disorder and confers an enormous burden on society. Mild to moderate forms of depression (MMD) are particularly common. Our previous studies showed that the Shuganjieyu (SGJY) capsule might improve depressive and cognitive symptoms in patients with MMD. However, biomarkers evaluating the efficacy of SGJY and the underlying mechanism remains unclear. The aim of the present study was to discover efficacy biomarkers and explore the underlying mechanisms of SGJY as antidepression treatment. Twenty-three patients with MMD were recruited and administered with SGJY for 8 weeks. Results showed that the content of 19 metabolites changed significantly in the plasma of patients with MMD, among which 8 metabolites improved significantly after SGJY treatment. Network pharmacology analysis showed that 19 active compounds, 102 potential targets, and 73 enzymes were related to the mechanistic action of SGJY. Through a comprehensive analysis, we identified four hub enzymes (GLS2, GLS, GLUL, and ADC), three key differential metabolites (glutamine, glutamate, and arginine), and two shared pathways (alanine, aspartate, and glutamate metabolism; and arginine biosynthesis). Receiver operating characteristic curve (ROC) analysis showed that the three metabolites had a high diagnostic ability. The expression of hub enzymes was validated using RT-qPCR in animal models. Overall, glutamate, glutamine, and arginine may be potential biomarkers for evaluating the efficacy of SGJY. The present study provides a new strategy for pharmacodynamic evaluation and mechanistic study of SGJY, and offers new information for clinical practice and treatment research.

Cognitive issues in patients with IDH mutant gliomas: from neuroscience to clinical neuropsychology.

The understanding of cognitive symptoms in patients with IDH-Mutant gliomas (IDH-Mut) is rapidly developing. In this article, we summarize the neuroscientific knowledge base regarding the influence of IDH-Mut tumors and their treatment on cognition and provide guidance regarding the management of these symptoms in patients. We performed a review of peer reviewed publications relevant to IDH-Mut glioma and cognitive outcomes and provide an overview of the literature as well as a case example to clarify management strategies. At the time of presentation, patients with IDH-Mut gliomas have a favorable cognitive profile as compared with those with IDH-wild type (WT) tumors. The relatively low cognitive burden may reflect the slower growth rate of IDH-Mut tumors, which is less disruptive to both local and widespread neural networks. Human connectomic research using a variety of modalities has demonstrated relatively preserved network efficiency in patients with IDH-Mut gliomas as compared with IDH-WT tumors. Risk of cognitive decline from surgery can potentially be mitigated by careful integration of intra-operative mapping. Longer term cognitive risks of tumor treatment, including chemotherapy and radiation, are best managed by instituting neuropsychological assessment as part of the long-term care of patients with IDH-Mutant glioma. A specific timeline for such integrative care is provided. Given the relative recency of the IDH-mutation based classification of gliomas, as well as the long time course of this disease, a thoughtful and comprehensive strategy to studying patient outcomes and devising methods of cognitive risk reduction is required.

Establishing General Working Population Norms for the Cognitive Symptom Checklist-Work.

The Cognitive Symptom Checklist-Work (CSC-W) is a self-report measure to assess cognitive symptoms (i.e., memory and executive function) in working adults with cancer. To date, general working population norm data are lacking worldwide. We established CSC-W norm values in the general working population, and assessed associations of CSC-W scores with work and health-related factors. This cross-sectional study consisted of 1,000 Dutch working adults, of whom data was collected through an online respondent panel. The sample was stratified for sex and age, and data were weighted. Summary scores of the CSC-W total scale, and memory and executive function symptoms subscales, were determined (e.g., means, percentiles). Z- and T-scores were calculated, and analysis of (co)variance has been applied. Cognitive symptom scores were relatively stable across age groups, but 18-39-year-old respondents reported lower memory and executive function than respondents in other age groups. Symptom scores of memory function (mean 29.1; SD = 16.7) were higher for all age groups and in both sexes compared to executive function (mean 22.1; SD = 16.8). No sex differences in memory and executive function were observed. Higher symptom scores were associated with performing non-manual work only, manual work only, self-reported long-term illness, and higher levels of depressive symptoms and fatigue. The CSC-W norms may enhance the interpretation and facilitate the analysis of self-reported cognitive symptoms in patients with cancer at work. Our findings may support health care professionals in identifying working adults with cancer with cognitive symptoms and in developing personalized treatment.

Vortioxetine improves physical and cognitive symptoms in patients with post-COVID-19 major depressive episodes

Major Depressive Episodes (MDE) following COVID-19 are frequent, can have a characteristic clinical picture, and are associated with immune-inflammatory changes. Vortioxetine is known to improve physical and cognitive performance in patients with depression and shows anti-inflammatory and anti-oxidative activities. This study aimed to retrospectively evaluate the effects of vortioxetine after 1 and 3 months of treatment in 80 patients (44.4% males, 54±17.2 years) with post-COVID-19 MDE. The primary outcome was improvement in physical and cognitive symptoms measured by specific items of Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS), Short Form-36 Health Survey Questionnaire (SF-36), Digit Symbol Substitution Test (DSST), Perceived Deficits Questionnaire for Depression (PDQ-D5). Changes in mood, anxiety, anhedonia, sleep, and quality of life were also investigated, as well as the underlying inflammatory status. Results show that, alongside reduction of depressive symptoms (HDRS, p<0.001), vortioxetine (mean dose: 10.1±4.1 mg/day) significantly improved physical features (all measurements p<0.001) and cognitive functioning (DDST, p=0.02; PDQ-D5, p<0.001) throughout treatment. We also observed significant reductions in inflammatory indexes. Therefore, vortioxetine might be a favorable therapeutic choice in post-COVID-19 patients with MDE because of its beneficial effects on physical complaints and cognition, features that appear to be specifically affected in relation to SARS-CoV-2 infection, and its good safety/tolerability profile. High prevalence and clinical and socioeconomic implications of COVID-19 consequences are a major public health concern and developing tailored, safe interventions is crucial to promote full functional recovery.

A fatal alliance: Glial connexins, myelin pathology and mental disorders

Mature oligodendrocytes are myelin forming glial cells which are responsible for myelination of neuronal axons in the white matter of the central nervous system. Myelin pathology is a major feature of severe neurological disorders. Oligodendrocyte-specific gene mutations and/or white matter alterations have also been addressed in a variety of mental disorders. Breakdown of myelin integrity and demyelination is associated with severe symptoms, including impairments in motor coordination, breathing, dysarthria, perception (vision and hearing), and cognition. Furthermore, there is evidence indicating that myelin sheath defects and white matter pathology contributes to the affective and cognitive symptoms of patients with mental disorders. Oligodendrocytes express the connexins GJC2; mCx47 [human (GJC2) and mouse (mCx47) connexin gene nomenclature according to Söhl and Willecke (2003)], GJB1; mCx32, and GJD1; mCx29 in both white and gray matter. Preclinical findings indicate that alterations in connexin expression in oligodendrocytes and astrocytes can induce myelin defects. GJC2; mCx47 is expressed at early embryonic stages in oligodendrocyte precursors cells which precedes central nervous system myelination. In adult humans and animals GJC2, respectively mCx47 expression is essential for oligodendrocyte function and ensures adequate myelination as well as myelin maintenance in the central nervous system. In the past decade, evidence has accumulated suggesting that mental disorders can be accompanied by changes in connexin expression, myelin sheath defects and corresponding white matter alterations. This dual pathology could compromise inter-neuronal information transfer, processing and communication and eventually contribute to behavioral, sensory-motor, affective and cognitive symptoms in patients with mental disorders. The induction of myelin repair and remyelination in the central nervous system of patients with mental disorders could help to restore normal neuronal information propagation and ameliorate behavioral and cognitive symptoms in individuals with mental disorders.

SAGE‐718 in Patients With Mild Cognitive Impairment or Mild Dementia due to Alzheimer’s Disease: Results From the Phase 2 LUMINARY Study

AbstractBackgroundCognitive impairment has a deleterious impact on patients with AD and their caregivers; new therapies are needed. SAGE‐718, a novel N‐methyl‐D‐aspartate receptor positive allosteric modulator, is being investigated for the treatment of cognitive impairment in patients with neurodegenerative diseases such as Alzheimer’s disease (AD). The LUMINARY Study is designed to evaluate the safety/tolerability of SAGE‐718 and its effects on cognitive symptoms in patients with AD.MethodLUMINARY (NCT04602624) is an open‐label, Phase 2 study evaluating SAGE‐718 (3mg QD for 14 days) in patients with AD. Patients (aged 50‐80 years) with Montreal Cognitive Assessment (MoCA) scores of 15‐24 were included. Treatment‐emergent adverse event (TEAE) incidence through Day 28 (primary endpoint), other safety outcomes (secondary endpoints), and cognitive and functional assessments were analyzed.ResultTwenty‐six patients (69.2% female; mean age 67 years), with a mean±SD MoCA of 20.7±2.61 were enrolled. Most patients (23/26) had a global Clinical Dementia Rating score of 0.5. Eight TEAEs were reported in 7 (26.9%) patients; all were mild/moderate; 6 were treatment related. No serious adverse events or deaths were reported. At Day 14, improvements from baseline were observed on multiple tests of executive functioning (Digit Symbol Substitution, Multitasking, One Touch Stockings, Spatial Working Memory, and 2‐Back tests) and learning and memory (Pattern Recognition Memory and Verbal Recognition Memory tests). Statistically significant MoCA improvement (+2.3 points vs baseline) was observed at Day 28. No changes in attention/psychomotor speed were observed. Functional assessments also captured notable improvement in some patients (Clinical Global Impressions Scales and Amsterdam Instrumental Activities of Daily Living Questionnaire), particularly on items measuring aspects of complex/higher order activities.ConclusionIn this study, SAGE‐718 was generally well tolerated and associated with cognitive and functional improvements in patients with AD. These results support further investigation of SAGE‐718 for the treatment of cognitive impairment associated with AD and other neurodegenerative diseases.

Therapeutic Effects of Low-Level Laser Therapy on Cognitive Symptoms of Patients with Dementia: A Double-Blinded Randomized Clinical Trial.

Objective: To investigate the effects of low-level laser therapy (LLLT) as a new nonpharmaceutical approach to improve cognitive symptoms in patients with dementia. Background: Routine pharmacological treatment of dementia patients is inefficient and has considerable adverse effects. Recent attempts to develop nonpharmaceutical approaches are considered favorable for patients with dementia. Methods: Thirty-two patients with dementia were randomly divided into the same population of LLLT and sham groups. The LLLT group underwent transcranial LLLT, and the sham group received the same protocol with a zero-intensity laser. All patients in the two groups were evaluated using the minimental state examination (MMSE) and clinical dementia rating (CDR) tests at the time of admission as baseline at 2 and 6 weeks postintervention. Results: The rate of change of MMSE scores in sham and LLLT groups was 0.13 ± 0.96 and 2.31 ± 1.81 in week 2 (p = 0.00005) and also -0.25 ± 0.86 and 2.53 ± 1.73 in week 8 (p = 0.000003). In the LLLT group, the mean scores of CDR were 1.28 ± 0.71, 1.28 ± 0.71, and 1.25 ± 0.80 at baseline, week 2, and week 8 (p = 0.605 and p = 0.742), respectively. The mean scores of CDR in the sham group were 1.69 ± 0.73, 1.75 ± 0.68, and 1.72 ± 0.82 at baseline, week 2, and week 8, respectively. Conclusions: These findings suggest that laser therapy could be a promising treatment modality and an adjunct to pharmacotherapy in dementia patients. Clinical Trial Registration: IRCT20191018045148N1 was obtained from the Iranian Registry of Clinical Trials (IRCT.ir).

Discrepancy between subjective and objective memory change after epilepsy surgery: Relation with seizure outcome and depressive symptoms.

Complaints pertaining to memory functioning are among the most often reported cognitive symptoms in patients with epilepsy. However, research suggests a considerable mismatch between patients' perception of memory functioning and the objective performance as measured with standardized neuropsychological tests. Depressive mood might be an important factor in explaining this discrepancy, though other variables have also occasionally been reported as relevant. There are mixed results as to which role these factors play in determining the overall quality of life of patients with epilepsy. The present study aimed to quantify the mismatch between subjective and objective memory functioning by taking into account the dynamic change of these factors as well as depressive symptoms after epilepsy surgery. Moreover, the influencing factors of subjective and objective memory change were investigated as well as their effects on the overall quality of life. Pre- and postoperative data from 78 patients with focal epilepsy were retrospectively analyzed. The results showed that (1) patients with clinically relevant postoperative depressive symptoms underestimate their actual memory performance; (2) for non-seizure-free patients, a postoperative decrease in depressive symptoms was associated with a tendency to underestimate memory decline; (3) the relationship between objective memory change and quality of life is mediated by the factors subjective memory change and depressive mood. Our data demonstrate a quantitative approximation of a pronounced depression-related negative biased self-perception of memory functioning of roughly 1 to 1.5 standard deviations. Moreover, it seems that when patients are relieved of having recurrent epileptic seizures, they may be less influenced by depressive symptoms when judging their memory change. Taken together, our study demonstrates the clinical relevance of incorporating subjective measures of memory functioning and mood that go beyond objective memory performance for the interpretation of how changes in memory functioning may affect patients' quality of life after epilepsy surgery.

Repeated methamphetamine administration produces cognitive deficits through augmentation of GABAergic synaptic transmission in the prefrontal cortex.

Methamphetamine (METH) abuse is associated with the emergence of cognitive deficits and hypofrontality, a pathophysiological marker of many neuropsychiatric disorders that is produced by altered balance of local excitatory and inhibitory synaptic transmission. However, there is a dearth of information regarding the cellular and synaptic mechanisms underlying METH-induced cognitive deficits and associated hypofrontal states. Using PV-Cre transgenic rats that went through a METH sensitization regime or saline (SAL) followed by 7-10 days of home cage abstinence combined with cognitive tests, chemogenetic experiments, and whole-cell patch recordings on the prelimbic prefrontal cortex (PFC), we investigated the cellular and synaptic mechanisms underlying METH-induce hypofrontality. We report here that repeated METH administration in rats produces deficits in working memory and increases in inhibitory synaptic transmission onto pyramidal neurons in the PFC. The increased PFC inhibition is detected by an increase in spontaneous and evoked inhibitory postsynaptic synaptic currents (IPSCs), an increase in GABAergic presynaptic function, and a shift in the excitatory-inhibitory balance onto PFC deep-layer pyramidal neurons. We find that pharmacological blockade of D1 dopamine receptor function reduces the METH-induced augmentation of IPSCs, suggesting a critical role for D1 dopamine signaling in METH-induced hypofrontality. In addition, repeated METH administration increases the intrinsic excitability of parvalbumin-positive fast spiking interneurons (PV + FSIs), a key local interneuron population in PFC that contributes to the control of inhibitory tone. Using a cell type-specific chemogenetic approach, we show that increasing PV + FSIs activity in the PFC is necessary and sufficient to cause deficits in temporal order memory similar to those induced by METH. Conversely, reducing PV + FSIs activity in the PFC of METH-exposed rats rescues METH-induced temporal order memory deficits. Together, our findings reveal that repeated METH exposure increases PFC inhibitory tone through a D1 dopamine signaling-dependent potentiation of inhibitory synaptic transmission, and that reduction of PV + FSIs activity can rescue METH-induced cognitive deficits, suggesting a potential therapeutic approach to treating cognitive symptoms in patients suffering from METH use disorder.

MiR-150-5p and let-7b-5p in Blood Myeloid Extracellular Vesicles Track Cognitive Symptoms in Patients with Multiple Sclerosis.

Cognitive deficits strongly affect the quality of life of patients with multiple sclerosis (MS). However, no cognitive MS biomarkers are currently available. Extracellular vesicles (EVs) contain markers of parental cells and are able to pass from the brain into blood, representing a source of disease biomarkers. The aim of this study was to investigate whether small non-coding microRNAs (miRNAs) targeting synaptic genes and packaged in plasma EVs may reflect cognitive deficits in MS patients. Total EVs were precipitated by Exoquick from the plasma of twenty-six cognitively preserved (CP) and twenty-three cognitively impaired (CI) MS patients belonging to two independent cohorts. Myeloid EVs were extracted by affinity capture from total EVs using Isolectin B4 (IB4). Fourteen miRNAs targeting synaptic genes were selected and measured by RT-PCR in both total and myeloid EVs. Myeloid EVs from CI patients expressed higher levels of miR-150-5p and lower levels of let-7b-5p compared to CP patients. Stratification for progressive MS (PMS) and relapsing-remitting MS (RRMS) and correlation with clinical parameters suggested that these alterations might be attributable to cognitive deficits rather than disease progression. This study identifies miR-150-5p and let-7b-5p packaged in blood myeloid EVs as possible biomarkers for cognitive deficits in MS.

Health-Related Quality of Life Over 6 Months in Patients With Major Depressive Disorder Who Started Antidepressant Monotherapy

ObjectivesMajor depressive disorder (MDD) is increasing worldwide and is associated with impaired quality of life (QOL). This study aimed to assess the QOL and its association with cognitive symptoms in patients with MDD who started antidepressant monotherapy. MethodsData from the PERFORM (Prospective Epidemiological Research on Functioning Outcomes Related to Major Depressive Disorder) study were analyzed. A descriptive epidemiological analysis on EQ-5D-5L utility score, the level of each dimension, and the EuroQoL visual analog scale value was conducted at 4 visits during 6 months’ follow-up. The association between cognitive complaints and changes in QOL measures was analyzed using multivariate linear regression analysis. ResultsThe median EQ-5D-5L utility score improved from 0.67 at baseline to 0.82 at month 6. Although the proportion of patients reporting level 1 (no problem) in every dimension of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression increased over time, less than half of the patients achieved level 1 in pain/discomfort and depression/anxiety, which were closely related to depression and usual activities at month 6. Patients with no cognitive complaints or no history of MDD at baseline showed greater improvement in EQ-5D-5L utility scores and EuroQoL visual analog scale value for measuring QOL than those with these characteristics. ConclusionsTreatment over 6 months improved QOL in patients with MDD although there remained room for improvement in dimensions of usual activities, pain/discomfort, and depression/anxiety. Cognitive complaints or history of MDD at baseline predicted less improvement in QOL at 6 months. Any history of MDD might delay improvement in QOL after treatment.

Translation, Cross-Cultural Adaptation, and Validation to Brazilian Portuguese of the Cerebellar Cognitive Affective/Schmahmann Syndrome Scale.

Cerebellar cognitive affective syndrome (CCAS) is characterized by deficits in executive functions, language processing, spatial orientation, and affect regulation in patients with cerebellar disease. The symptoms can occur isolated or along with motor and coordination symptoms. The aim of our study was to translate and culturally adapt the CCAS scale to Brazilian Portuguese and validate the scale in our population. We performed a cross-sectional study with patients with primary and secondary ataxia. The study included 111 individuals, aged between 20 and 80years, of both genders, 20 without cognitive and/or affective complaints who participated in the pre-test phase, 40 with cerebellar disease (hereditary/neurodegenerative ataxia or acquired/secondary cerebellar ataxia), and 51 healthy controls with no evidence of cognitive impairment and no affective symptoms matched for sex, age, and educational level. The scale was translated, culturally adapted, and validated. Statistical analysis of the data was performed, with association tests, mean comparison, and ROC curve analysis. Based on the analysis of the ROC curve, optimal cutoff values ​were found for each subitem of the scale. The translated and adapted scale has good internal consistency, is reproducible, has good reliability, and has the potential to be a reliable tool for screening cognitive symptoms in patients with cerebellar disease.

Differential Effects of Aripiprazole and Amisulpride on Negative and Cognitive Symptoms in Patients With First-Episode Psychoses.

IntroductionAripiprazole is hypothesized to have an effect on negative and cognitive symptoms in schizophrenia. Likewise, amisulpride is one of the only second-generation antipsychotics with which an effect on negative symptoms is reported. In the present study, we compare the effect of aripiprazole and amisulpride in initially antipsychotic-naïve patients with first-episode psychoses.MethodsPsychopathology and cognitive measures from two consecutive cohorts of antipsychotic-naïve first episode psychotic patients were obtained before and after 6 weeks of antipsychotic monotherapy with either aripiprazole or amisulpride. Matched healthy controls were included to account for retest effects on the cognitive measures. Analyses of variance (repeated-measures ANOVA) were performed to detect effect of time and possible cohort*time interactions.ResultsLongitudinal data was obtained from 47 and 48 patients treated for 6 weeks with amisulpride or aripiprazole, respectively. For the Wallwork negative symptom dimension, there was a cohort*time interaction [F(1, 93) = 4.29, p = 0.041] and a significant effect of time [F(1, 93) = 6.03, p = 0.016], which was driven by an improvement in patients treated with aripiprazole [t(47) = 4.1, p < 0.001] and not observed in patients treated with amisulpride (p > 0.5). For the eight cognitive measures, no cohort*time interaction was found and neither was cognitive improvement in any of the cohorts when accounting for retest effect.ConclusionPatients treated with aripiprazole improved on negative symptoms, which was not the case for patients treated with amisulpride. This may point to a general effect of a partial D2 receptor agonist on negative symptoms in patients with first-episode psychoses. There was, however, no improvement in cognitive functions.