Improvement In Cognitive Symptoms Research Articles

Exploring the Pharmacokinetics and Gut Microbiota Modulation of Hesperidin and Nobiletin from Mandarin Orange Peel in Experimental Dogs: A Pilot Study.

Background/Objectives: Mandarin orange peel (MOP) is recognized for its traditional medicinal properties due to its high flavonoid content. This study aimed to analyze MOP harvested in Japan for specific bioactive compounds and to explore its health applications in dogs, including effects on gut microbiota and cognitive symptoms. Methods: Flavonoid content (particularly hesperidin and nobiletin) of MOP was measured. High-flavonoid MOP was then incorporated into gelatin cubes. In the time-course blood concentration study, experimental beagle dogs received a single oral dose (4 g). For intestinal microbiota analysis and blood biochemical tests, beagle dogs were administered 1 g twice daily. For the Demonstration Test, older dogs (a 14-year-old female Shiba Inu, a 14-year-old female Miniature Dachshund, and a 19-year-old male Miniature Dachshund) were administered 1 g twice daily. Analysis included microbiota profiling via 16S rDNA sequencing and observational assessment of cognitive indicators in a pilot study involving senior dogs with Alzheimer's disease. Results: The MOP powder contained 9.3% hesperidin in early-ripening varieties (October harvest) and 6.9% in ripe varieties (December harvest). Nobiletin content was 41 mg/100 g (0.041%) and 35 mg/100 g (0.035%) for the early and late harvests, respectively. Administration of MOP-enriched gelatin cubes reduced Fusobacteriaceae and increased Eggerthellaceae. Cognitive symptoms like howling and counterclockwise turning showed improvement in senior dogs (n = 3). Conclusions: This study provides preliminary support for the potential health benefits of MOP in canine dietary applications, particularly for gut health and cognitive function. Improvement in cognitive symptoms may be due to the anxiolytic effects of mandarin peel.

Effects of Ketamine and Esketamine on Cognitive Functions in Treatment-Resistant Depression

Major depressive disorder is a public health issue that negatively impacts quality of life and leads to cognitive impairments, causing significant disruptions in work, education, and social life. Treatment-resistant depression is defined as the failure to achieve improvement in depressive symptoms despite the use of at least two different antidepressant medications at adequate doses and durations. Current pharmacological approaches are inadequate for about half of treatment-resistant depression patients, and the effects of these medications on cognitive impairments are limited. Therefore, there is a need for new and effective treatment methods. This review aims to evaluate the effects of ketamine and esketamine on cognitive functions in the treatment of treatment-resistant depression patients. Relevant literature has been reviewed and recent studies have been evaluated. The results of randomized controlled trials indicate that ketamine is effective in treating treatment-resistant depression and can improve specific cognitive domains. Significant improvements in cognitive functions such as visual memory, processing speed, working memory, and attention have been recorded in patients responding to 0.5 mg/kg ketamine infusion. However, long-term use of ketamine may have negative effects on spatial working memory. Esketamine, an NMDA receptor antagonist, has shown rapid and effective antidepressant outcomes, providing stability or improvement in cognitive functions. Additionally, its intranasal administration offers practical advantages. However, findings suggest that high doses of esketamine may have neurotoxic effects and negatively impact cognitive functions. The effects of both drugs on depressive symptoms and cognitive functions vary depending on dose, duration of use, and frequency of administration. In conclusion, while ketamine and esketamine show significant potential in the treatment of treatment-resistant depression and improvement of cognitive symptoms, further research is needed regarding their long-term effects and safety.

Vortioxetine in the Treatment of Major Depressive Disorder Among Working Patients in Routine Clinical Practice: An Analysis of a Post-Marketing Surveillance Study in South Korea.

Patients with major depressive disorder (MDD) experience depressive symptoms such as anhedonia as well as cognitive dysfunction which can subsequently impair their work performance. To assess the effectiveness and safety of vortioxetine in working patients with MDD in South Korea. This was a subgroup analysis of a prospective, multicenter, non-interventional, non-comparative post-marketing surveillance (PMS) study. Vortioxetine-naïve patients aged >18 years who were administered with vortioxetine were followed for up to 24±2weeks. Working patients were defined as those who were working or studying full- (≥6hours/day) or part-time (<6hours/day) at baseline. Effectiveness and adverse events (AEs), assessed by both clinician and patient-reported measured, were analyzed. A total of 1082 working patients (mean age: 39.56 years) were included in the subgroup analysis. Clinically significant improvements in depressive symptoms, including anhedonia, were observed over the 24weeks of follow-up, with mean scores for the total Montgomery-Asberg Depression Rating Scale (MADRS) and anhedonia subscale both significantly decreasing from baseline by mean±standard deviation (SD) of 9.73±9.08 and 5.37±5.24 points, respectively, at 24weeks (both p<0.001 vs baseline). The vast majority of patients (80.01%) treated with vortioxetine also showed improvements in mental health symptoms over the 24weeks, measured using the Clinical Global Impression - Improvement (CGI-I) scores. Significant improvements in cognitive symptoms were also observed over the study period, measured by the Korean Version of the Perceived Deficits Questionnaire-Depression as well as Digit Symbol Substitution Test (all p<0.0001 from baseline at Visits 2 and 3). Vortioxetine was well tolerated in working patients, with the respective rates of any AEs and serious AEs being 18.67% and 1.20%. Working patients treated with vortioxetine had improvements in their depressive symptoms (including anhedonia), cognitive function and performance. Vortioxetine was found to be well tolerated in this study.

Two Cases of Pediatric Leucine-Rich Glioma-Inactivated Protein-1 Encephalitis: Clinical Course, Challenges, and Implications

BackgroundLeucine-rich glioma-inactivated protein 1 (LGI-1) encephalitis is a rare form of autoimmune limbic encephalitis. Although relatively well documented in adults, pediatric cases are rare and remain poorly understood. MethodsWe reviewed two pediatric cases of LGI-1 encephalitis from a single tertiary care facility retrospectively. The detailed analysis included assessment of the initial presentation, clinical progression, diagnostic challenges, treatments, and outcome. To contextualize the differences between pediatric and adult manifestations of disease, we compared these findings with existing literature. ResultsBoth cases illustrate the diagnostic challenges faced at initial presentation due to the rarity of this diagnosis in children and the absence of characteristic faciobrachial dystonic seizures, which is common in adults. The constellation of neuropsychiatric symptoms and refractory focal seizures led to a high clinical suspicion for autoimmune encephalitis, therefore, both cases were treated empirically with intravenous methylprednisolone. The diagnosis in both cases was confirmed with positive serum antibody testing, reinforcing that LGI-1 antibodies are more sensitive in the serum rather than the cerebrospinal fluid (CSF). Seizure control and improvement in cognitive symptoms was achieved through a combination of immunotherapy and antiseizure medications. ConclusionsThis case series underscores the significance of considering LGI-1 encephalitis in the differential diagnosis of pediatric patients exhibiting unexplained neuropsychiatric symptoms and focal seizures and emphasizes the importance of performing both serum and CSF antibody testing. It is necessary to conduct further research to identify the full range of pediatric presentations and to determine the optimal treatment protocol.

The altered volume of striatum: A neuroimaging marker of treatment in first-episode and drug-naïve schizophrenia

Although schizophrenia patients exhibit structural abnormalities in the striatum, it remains largely unknown for the role of the striatum subregions in the treatment response of antipsychotic drugs. The purpose of this study was to investigate the associations between the striatal subregions and improved clinical symptoms in first-episode drug-naïve (FEDN) schizophrenia. Forty-two FEDN schizophrenia patients and 29 healthy controls (HCs) were recruited. At baseline, the Positive and Negative Syndrome Scale (PANSS) was used to assess the clinical symptoms of patients, MRI scanner was used to obtain anatomical images of patients and HCs. After 12-week stable doses of risperidone treatment, clinical symptoms were obtained in 38 patients and anatomical images in 26 patients. After 12 weeks of treatment, the left nucleus accumbens volume decreased, whereas the left pallidum volume increased in schizophrenia patients. The decreased left nucleus accumbens volume was positively correlated with cognitive factor improvement measured by PANSS. Intriguingly, greater left nucleus accumbens volume at baseline predicted greater cognitive improvements. Furthermore, the responders who had >50 % improvement in cognitive symptoms exhibited significantly greater baseline left nucleus accumbens volume compared to non-responders. The left striatum volume at baseline and after treatment predicted the cognitive improvements in FEDN schizophrenia, which could be a potential biomarker for the development of precision medicine approaches targeting cognitive function.

High-definition transcranial direct current stimulation for treating cognitive and negative symptoms in chronic schizophrenia – A sham-controlled proof of concept study

Objectives: Cognitive and negative symptoms are core symptoms of schizophrenia affecting interpersonal and socio-occupational functioning. Impaired dorsolateral prefrontal cortex (DLPFC) function is implicated in negative and cognitive symptoms. Conventional transcranial direct current stimulation (tDCS) to DLPFC has attracted interest as an add-on treatment for these symptoms. High-definition tDCS (HD-tDCS), an optimized form of tDCS, has the potential for more focalized neuromodulation. Studies suggest that an increased number of sessions may increase the effectiveness of stimulation. Hence, we aimed to evaluate the efficacy of 20 sessions of HD-tDCS over the left DLPFC in the improvement of cognitive and negative symptoms in chronic schizophrenia (&gt;2 years continuous illness). Material and Methods: Twenty patients with chronic schizophrenia with predominantly cognitive and negative symptoms were enrolled in this sham-controlled trial. Participants received 20 sessions of HD-tDCS at 2 mA for 20 min, that is, twice daily over 10 days. Montreal cognitive assessment and scale for assessment of negative symptoms were used to assess outcome variables. Assessments were carried out at baseline, 2 weeks, and 6 weeks, respectively. Results: Significant improvement was noted in both active and sham groups across all outcome variables over time. However, a statistically significant decrease in negative symptoms in the active group was noted, which was maintained at the end of 6 weeks, but there was no statistically significant improvement in cognitive symptoms between the active and sham groups at 6 weeks. The stimulation protocol was well tolerated. Conclusion: HD-tDCS has substantial potential in the treatment of negative symptoms; however, its role in cognitive symptoms needs further evaluation.

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.

Cerebrospinal fluid transcripts may predict shunt surgery responses in normal pressure hydrocephalus.

Molecular biomarkers for neurodegenerative diseases are critical for advancing diagnosis and therapy. Normal pressure hydrocephalus (NPH) is a neurological disorder characterized by progressive neurodegeneration, gait impairment, urinary incontinence and cognitive decline. In contrast to most other neurodegenerative disorders, NPH symptoms can be improved by the placement of a ventricular shunt that drains excess CSF. A major challenge in NPH management is the identification of patients who benefit from shunt surgery. Here, we perform genome-wide RNA sequencing of extracellular vesicles in CSF of 42 NPH patients, and we identify genes and pathways whose expression levels correlate with gait, urinary or cognitive symptom improvement after shunt surgery. We describe a machine learning algorithm trained on these gene expression profiles to predict shunt surgery response with high accuracy. The transcriptomic signatures we identified may have important implications for improving NPH diagnosis and treatment and for understanding disease aetiology.

Differential diagnosis of cognitive dysfunction in a multi-morbid patient

IntroductionPatients with systemic lupus erythematosus (SLE) have cognitive dysfunctions as a neuropsychiatric manifestation, associated with disabling symptoms. However, the presence of other medical or psychiatric comorbidities can delay or lead to a misdiagnose.ObjectivesTo present a case of a patient with diagnostic difficulty in the face of multiple medical and neurocognitive comorbidities.MethodsDescription of a case report.Results19-year-old female, Mexican, unemployed, with incomplete high school, with medical history of preterm birth by cesarean at 30 weeks due to placenta previa, history of early puberty, 4 years evolution of focal epilepsy, 1 year evolution of hypothyroidism and mild depression.She began her symptoms 4 years ago, characterized by an abrupt onset of memory disturbances, decreased concentration, poor academic performance, infantile behavior, need for affection, alternated with irritability periods, verbal and physical aggression, repetitive and erratic behavior. She went to multiple specialists with different therapeutic approaches without clinical improvement. In 2020, she was referred to our service for evaluation, evidenciating a mild depressive episode and psychotherapeutic treatment was started.Mental and neurological examination without alterations, normal vital signs, at physical examination: malar rash, oral ulcers, alopecia. Labs: increased erythrocyte sedimentation rate, normocytic anemia, leukopenia, rest normal. An electroencephalogram was requested, without alterations. Simple brain MRI was performed (Figure 1).Psychological (figure 2) and Neuropsychological tests (table 1) were performed, showing alterations in memory recall and inhibitory control. Due to the symptoms presented by the patient, SLE was suspected, and rheumatology evaluation was requested, integrating a diagnosis of incomplete SLE, and started treatment. The patient presented symptomatic improvement in cognitive symptoms and systemic signs. Likewise, a genetic evaluation was requested, without meeting the criteria for a genetic syndrome. The patient continues with symptomatic improvement and multidisciplinary treatment.Total scoresNaturalNormalizedDiagnosisOrbitomedial18083Mild alterationPref-Anterior22106NormalDorsolateral20788NormalBANFE total409104NormalImage:Image 2:ConclusionsNeurocognitive alterations are one of the most frequent manifestations of neurolupus, although its diagnosis and treatment may be delayed in the absence of clinical suspicion, mainly in multi-comorbid patients.In the case, the patient presented multiple diseases that can explain a picture of neurocognitive impairment, such as epilepsy, depression, hypothyroidism. However, in these cases, a multidisciplinary approach is imperative, requiring to rule out the different causes of the patient’s symptoms.Disclosure of InterestNone Declared

Moderate, Little, or No Improvements in Neurobehavioral Symptoms among Individuals with Long COVID: A 34-Country Retrospective Study.

(1) Background: Some people with COVID-19 develop a series of symptoms that last for several months after infection, known as Long COVID. Although these symptoms interfere with people’s daily functioning and quality of life, few studies have focused on neurobehavioral symptoms and the risk factors associated with their development; (2) Methods: 1001 adults from 34 countries who had previously tested positive for COVID-19 completed the Neurobehavioral Symptom Inventory reporting the symptoms before their COVID-19 diagnosis, during the COVID-19 infection, and currently; (3) Results: Participants reported large-sized increases before vs. during COVID-19 in all domains. Participants reported a medium-sized improvement (during COVID-19 vs. now) in somatic symptoms, a small-sized improvement in affective symptoms, and very minor/no improvement in cognitive symptoms. The risk factors for increased neurobehavioral symptoms were: being female/trans, unemployed, younger age, low education, having another chronic health condition, greater COVID-19 severity, greater number of days since the COVID-19 diagnosis, not having received oxygen therapy, and having been hospitalized. Additionally, participants from North America, Europe, and Central Asia reported higher levels of symptoms across all domains relative to Latin America and Sub-Saharan Africa; (4) Conclusions: The results highlight the importance of evaluating and treating neurobehavioral symptoms after COVID-19, especially targeting the higher-risk groups identified. General rehabilitation strategies and evidence-based cognitive rehabilitation are needed in both the acute and Long COVID phases.

The effect of group cognitive behavior therapy on Chinese patients with anorexia nervosa: an open label trial

BackgroundThe high cost of treatment for anorexia nervosa (AN) and lack of trained specialists have resulted in limited accessibility of effective treatment to patients with AN, which is particularly problematic in China. To increase the accessibility of evidence-based treatment and reduce the cost of treatment, this study aimed to explore the feasibility and efficacy of group cognitive behavior therapy (G-CBT) adapted from enhanced cognitive behavior therapy for eating disorders (CBT-E) in Chinese AN patients.MethodA total of 78 patients with AN were assigned to G-CBT or individual outpatient treatment (IOT) and received three months of treatment for AN in each condition. Measures of eating pathology, depression and anxiety were administrated to both intervention groups at three time points: baseline, one month of treatment, and end of treatment; results were compared between groups and over time.ResultsThere were 70 participants included in the final analysis. Both G-CBT and IOT groups showed significant improvement in eating pathology and associated psychopathology (ps < .001) over the course of treatment, but no significant difference in symptom improvement was found between the two groups (ps > .05). G-CBT resulted in additional significant improvement in ED psychopathology over the last two months of treatment, and its overall therapeutic effect was influenced by baseline weight and early symptom improvement.ConclusionPreliminary findings from this open label trial suggest that G-CBT adapted from CBT-E is feasible in an outpatient setting and as effective as IOT in facilitating weight regain and reducing psychopathology in Chinese AN patients with little evidence for the superiority of either intervention.Trial registration: The current study was registered at clinical trials.gov on September 23, 2018 (registration number NCT03684239).Plain English summaryPeople with anorexia nervosa (AN) are known to be unmotivated for treatment and prone to relapse. Recovery from AN often needs intensive, long-term treatment from a specialized multidisciplinary team, which is not accessible for most people in China. Given the increasing incidence of AN and lack of eating disorder (ED) specialists in China, it is important to develop short-term cost-effective treatments for AN. In this study, we explored the feasibility and efficacy of group cognitive behavior therapy (G-CBT) adapted from enhanced cognitive behavior therapy (CBT-E) for people with AN from China. We found that G-CBT was as effective as individual outpatient treatment (IOT) typically provided to AN patients at the research site in facilitating weight regain, improving eating behaviors, and reducing ED and other symptoms. We also found that patients receiving G-CBT made more improvements in cognitive symptoms of the ED, which might help maintain treatment gains and prevent relapse in the long run. This potential long-term advantage of G-CBT needs to be verified in long-term follow-up.

New Pharmacological Targets for the Treatment of Schizophrenia: A Literature Review.

The pharmacological treatment of schizophrenia is currently based on the employment of antipsychotic medications showing an antagonism of dopaminergic and serotoninergic inhibitors. 20-40% of patients are drug-resistant or residually symptomatic in the long-term antipsychotic treatment, and new strategies are needed for improving their functional and cognitive impairment. This systematic review has summarized evidences from the literature regarding the newer pharmacological targets proposed for the treatment of psychosis. We included 128 peer-reviewed articles and 5 other relevant sources published from 2002 to 2020 on PubMed EMBASE, The Cochrane Library, and Google Scholar. The possible role of glutamate and its receptors as targets of the antipsychotic mechanism of action has been described. Glutamatergic neurotransmission and NMDA receptors hypofunction are involved in the neurobiological explanatory model of psychosis and possibly targeted for the successful treatment of cognitive and residual symptoms. Results show an efficacy of D-cycloserine (antagonist at the Glycine site of the NMDA-R) in the treatment of negative symptoms of schizophrenia as well as Memantine (NMDA- Receptor antagonist) for cognition and psychopathology. The putative antipsychotic effect of cannabidiol on positive symptoms and cognition will also be discussed. The action on serotoninergic and GABAergic receptors will be considered as a new pharmacological target, with a possible efficacy of Vabicaserin on symptoms of psychosis. Mynocicline has shown to induce improvements in cognitive symptoms in schizophrenia, as well as Erythropoietin. Oxytocin has been reported to have an antipsychotic-like effect; moreover, COX-2 inhibitors lead to a reduction in positive symptoms of psychosis, specifically in the first episode of illness. This narrative report suggests a promising role of new agents in the treatment of Schizophrenia; however, more research is needed to approve their clinical employment.

Does Phase-Contrast Imaging through the Cerebral Aqueduct Predict the Outcome of Lumbar CSF Drainage or Shunt Surgery in Patients with Suspected Adult Hydrocephalus?

Radiologic imaging plays a key role in diagnosing chronic adult hydrocephalus, but its role in predicting prognosis is still controversial. We sought to evaluate the effectiveness of cardiac-gated phase-contrast MR imaging through the cerebral aqueduct in predicting the clinical response to diagnostic lumbar puncture/lumbar drainage and shunt surgery in suspected adult hydrocephalus. In this retrospective study, the phase-contrast MR imaging of 185 patients with suspected chronic adult hydrocephalus was evaluated using the CSF Flow software package. Decision-making for shunt placement was performed in this cohort on the basis of clinical assessment alone without the availability of quantitative phase-contrast MR imaging results. We recorded the response to lumbar puncture or lumbar drainage and shunt surgery using quantitative tests such as the Tinetti Test, the Timed Up and Go, and the Mini-Mental State Examination and qualitative measures of gait, urinary, and cognitive symptom improvement before and after lumbar puncture/lumbar drainage and shunt surgery. Quantitative analysis of phase-contrast MR imaging was compared with clinical outcome measures. Both CSF stroke volume and flow rate overlapped between lumbar puncture/lumbar drainage responders and nonresponders. There was also a significant overlap between shunt responders and nonresponders. Aqueductal stroke volume or flow rate alone was a poor predictor of lumbar puncture/lumbar drainage and shunt surgery response. Quantitative clinical measures after lumbar puncture/lumbar drainage were better predictors of shunt response. This study suggests that the results of phase-contrast MR imaging through the cerebral aqueduct alone should not be used to select patients for diagnostic or therapeutic CSF diversion.

Does the Presence or Absence of DESH Predict Outcomes in Adult Hydrocephalus?

The DESH (disproportionately enlarged subarachnoid-space hydrocephalus) pattern of "tight high-convexity and medial subarachnoid spaces, and enlarged Sylvian fissures with ventriculomegaly" is used to determine which patients undergo an operation for adult hydrocephalus at many centers. Our aim was to review adult hydrocephalus cases when DESH has not been a criterion for an operation to determine the prevalence of DESH among the cohort and compare the surgical outcomes in the presence or absence of DESH. A retrospective cohort study was conducted at a single institution (Johns Hopkins Hospital) to include patients surgically treated for adult hydrocephalus between 2003 and 2014 drawn from a data base of patients who had undergone standardized hydrocephalus protocol MR imaging. Preoperative imaging was reviewed by 2 blinded neuroradiologists to characterize the presence of DESH. Preoperative and postoperative clinical symptomatology was recorded. Frequencies were compared using the Fisher exact test, and nonparametric means were compared using the Mann-Whitney U Test. One hundred thirty-three subjects were identified and included (96 DESH absent, 37 DESH present). Shunting led to significant improvement in gait and urinary and cognitive symptoms for the overall cohort and for patients with and without DESH (P < .05). The Fisher exact test did not demonstrate any significant differences in either gait or urinary or cognitive symptom improvement between patients with or without DESH (P > .05). The current study demonstrated symptom improvement in patients with adult hydrocephalus following shunting, with no significant differences between subjects with and without DESH. Thus, shunt insertion for patients with adult hydrocephalus should not rely solely on the presence of preoperative DESH findings.

Effects of rTMS on cognitive and negitive symptoms of schizophrenia: A randomized double-blind sham-controlled study

Background Investigators are urgently searching for options to treat cognitive and negative symptoms in schizophrenia because these symptoms are disabling and do not respond adequately to antipsychotic or psychosocial treatment. This study evaluated the efficacy of 20-Hz repetitive transcranial magnetic stimulation (rTMS) applied to the left dorsolateral prefrontal cortex for the treatment of cognitive and negative symptoms in schizophrenia. Methods The study was a randomized double-blind sham-controlled trial for 4 weeks. Seventy patients with schizophrenia were randomly assigned into two treatment groups. After a 2-week pretreatment phase, 34 patients were treated with 20-Hz rTMS applied 5 days per week for 4 weeks to the left dorsolateral prefrontal cortex (added to the ongoing treatment), and 33 patients were subjected to sham rTMS applied similarly. Negative symptoms were assessed with the Scale for the Assessment of Negative Symptoms (SANS), the Positive and Negative symptom scale (PANSS), and Cognitive symptoms were assessed by MATRICS cognitive test battery (MCCB) Chinese version. Results Sixty patients (33 individuals in active group and the other 27 in the sham group) completed the treatment protocol. We found that treatment with 20-Hz rTMS for 4 weeks significantly improved negative symptoms in the active group as compared to the sham group. However, There was no statistically significant difference in improvement in cognitive symptoms between the two groups. Conclusions These findings indicate that application of 20-Hz rTMS to the left dorsolateral prefrontal cortex can effectively improve the negative symptoms, while more optimized parameters are needed to achieve improved therapeutic efficacy for the treatment of cognitive symptoms.

Statins and their effect on cognition: Let's clear up the confusion.

Lipid-lowering drugs, such as statins, rank in the top 5 most frequently used prescription drugs in Canada. In fact, between 2007 and 2011, more than 2.9 million Canadians were taking a lipid-lowering drug.1 With a plethora of robust evidence for secondary prevention of cardiovascular disease, coupled with a well-tolerated adverse effect profile, it is no wonder that statins are prescribed quite often. In the past decade, however, some case reports have suggested a possible increase in the risk of cognitive adverse events, such as memory loss, forgetfulness or feeling “fuzzy,” associated with their use.2 In 2005, Health Canada released a statement in the Canadian Adverse Reaction Newsletter suggesting a possible association between statins and memory loss.3 The onset of these adverse events described in the case reports varied, but most occurred within 1 year of statin initiation. Most of the cases (11/19) reported an improvement in cognitive symptoms once the statin was stopped or the dose reduced. In 2012, the Food and Drug Administration (FDA) issued a safety announcement to health care professionals, warning them about the potential risk of cognitive impairment (memory loss, forgetfulness, amnesia, memory impairment, confusion) with the use of statins for a period of 1 day to years.2 Review of these cases did not reveal an association between cognitive impairment and a specific statin, dose or age of patient. These cases were generally reversible, with symptoms disappearing approximately 3 weeks after statin discontinuation. The FDA also enforced a change in the monograph of statin products to warn health care professionals about this rare, but possible, adverse event. This change in monograph has not been mandated in Canada. On the opposite end of the spectrum, some research evaluated the potential use of statins in the prevention and treatment of Alzheimer disease (AD).4 This article focuses on the effects of statins on cognition and the use of statins for the prevention and treatment of AD.

Lumbar-Peritoneal Shunt followed by Donepezil Administration for Residual Cognitive Impairment in Idiopathic Normal Pressure Hydrocephalus: A Case Report

We often encounter idiopathic normal-pressure hydrocephalus (iNPH) and mild cognitive impairment (MCI) in the same patient. Four iNPH patients whose gait improved following placement of a lumbar-peritoneal shunt (LPS) and whose cognitive function improved after administration of donepezil are reported. LPS is useful for improvement of gait disturbance in iNPH, and donepezil is used to treat impaired memory in dementia of Alzheimer’s type (DAT). These four patients showed improvements in gait disturbances postoperatively, and just after donepezil administration, improvements in cognitive symptoms were recognized in the memory tests of the Mini-Mental State Examination (MMSE). The four patients (two males and two females) ranged in age from 72 to 81 years (mean age: 77 years). In all patients, disproportionately enlarged subarachnoid-space hydrocephalus (DESH) was recognized on imaging examinations, and improvements after the tap test were considered to be indications for surgery. The improvements in the Timed Up and Go Test (TUG) were from 25% to 36%. The patients’ mean MMSE score was 27 points preoperatively, 27 points at 1 week after LPS placement, and 30 points at 3 months after LPS placement. Treatment with donepezil appeared to be effective for residual cognitive impairments after LPS placement.

A randomized placebo-controlled pilot study of pravastatin as an adjunctive therapy in schizophrenia patients: Effect on inflammation, psychopathology, cognition and lipid metabolism

ObjectiveThe aim of this study was to investigate the role of pravastatin, as an adjunctive therapy, on inflammatory markers, lipid and glucose metabolism, psychopathology, and cognition in subjects with schizophrenia and schizoaffective disorder. MethodsSchizophrenia or schizoaffective subjects (N=60) were randomized to receive either a 12-week supply of pravastatin 40mg/day or placebo treatment. Anthropometric measures, lipids and glucose metabolism, inflammatory markers, psychopathology and cognitive performance were assessed at baseline, 6weeks and 12weeks. ResultsPravastatin use was associated with a significant decrease in total cholesterol, low density lipoprotein (LDL) cholesterol and LDL particle number levels, but was not associated with any significant changes in cognition or psychopathology in the participants, except a significant decrease in the Positive and Negative Syndrome Scale (PANSS) positive symptom score from baseline to week 6. However, this decrease failed to remain significant at 12weeks. Interestingly, triglycerides, LDL-cholesterol, total cholesterol, LDL particle number, small LDL particle number, large very low density lipoprotein (VLDL) particle number and C-reactive protein (CRP) followed a similar pattern at 6 and 12weeks as psychopathology. ConclusionsThese results suggest that a randomized trial with a larger sample size and a higher dosage of pravastatin would be helpful in further evaluating the anti-inflammatory properties of pravastatin, its association with improvements in cognitive symptoms, and its potential to reduce positive and negative symptoms associated with schizophrenia or schizoaffective disorders.

Donepezil and Memantine Treatment and Changes in Hippocampal Structure in Dementia of the Alzheimer Type

Previous research has indicated that treatment of Dementia of the Alzheimer Type with donepezil does not affect longitudinal change on hippocampal volume. Despite this, some patients have a clinical response to cholinesterase inhibitors as shown by relative stability or improvement in cognitive symptoms. The same could be said of treatment with the combination of donepezil and memantine. This study aims to examine differences in change in hippocampal structure between those who have clinically responded to treatment with these medications and those who have not.

Effects of sub-chronic donepezil on brain Abeta and cognition in a mouse model of Alzheimer’s disease

Acetylcholinesterase inhibitors (AChEIs) are approved to treat the symptoms of mild to moderate Alzheimer's disease by restoring acetylcholine levels at synapses where the neurotransmitter has been depleted due to neurodegeneration. This assumption is challenged by more recent clinical studies suggesting the potential for disease-modifying effects of AChEIs as well as in vitro studies showing neuroprotective effects. However, few preclinical studies have assessed whether the improvement of cognitive symptoms may be mediated by reductions in Abeta or Tau pathology. The objective of the present study was to determine whether short-duration treatment with donepezil could improve spatial learning and memory in transgenic mice overexpressing mutant human amyloid precursor protein (hAPP) and presenilin 1 (PS1) (Dewachter et al., J Neurosci 20(17):6452-6458, 2000) after amyloid pathology has fully developed, consistent with early stages of Alzheimer'sdisease in humans. In parallel, the effect of donepezil treatment on brain amyloid, Tau, and glial endpoints was measured. This study showed a significant improvement in reference memory in hAPP/PS1 mice along with dose-dependent reductions in brain amyloid-β (Aβ). These results suggest that the observed cognitive improvement produced by donepezil in Alzheimer's disease may be due, at least in part, to reduction of brain Aβ.