Improvement In Cognitive Function Research Articles

Effectiveness of dialectical behavior therapy as a transdiagnostic treatment for improving cognitive functions: a systematic review.

Dialectical behavior therapy (DBT) has been found to be an efficacious treatment for disorders characterized by high levels of emotional instability. In view of the multifaceted applications of DBT and the extent to which mental disorders can incapacitate cognitive functions, the current systematic review aimed to investigate the effect of DBT in strengthening cognitive functions across various mental health conditions. Original research studies employing both experimental and quasi-experimental designs were included in the review. The literature search was done using different electronic databases, from the first available literature until June 2022, that covered an approximate period of ten years. Joanna Briggs Institute checklist was used to assess the methodological rigor of the studies. Twelve studies conducted on adolescents with emotional dysregulation, and adults with borderline personality disorder, bipolar disorder, attention deficit hyperactivity disorder, and multiple sclerosis were selected. Results indicate that DBT has the potential to improve key cognitive functions such as attention, memory, fluency, response inhibition, planning, set shifting, tolerance for delayed rewards and time perception, as assessed by neuropsychological tests, self-report of cognitive functions, and neuroimaging techniques. Considering the review's findings that showcase the effectiveness of DBT in fostering improvements in cognitive functions, DBT may possibly be chosen as a preferred treatment to ensure that patients reach optimal levels of cognitive functioning. Limitations include lack of sufficient studies encompassing all the common mental health conditions, usage of neuroimaging techniques as only an indirect measure of cognitive functioning and nuances related to the quality of individual studies.

Aerobic exercise reverses aging-induced depth-dependent decline in cerebral microcirculation.

Aging is a major risk factor for cognitive impairment. Aerobic exercise benefits brain function and may promote cognitive health in older adults. However, underlying biological mechanisms across cerebral gray and white matter are poorly understood. Selective vulnerability of the white matter to small vessel disease and a link between white matter health and cognitive function suggests a potential role for responses in deep cerebral microcirculation. Here, we tested whether aerobic exercise modulates cerebral microcirculatory changes induced by aging. To this end, we carried out a comprehensive quantitative examination of changes in cerebral microvascular physiology in cortical gray and subcortical white matter in mice (3-6 vs. 19-21 months old), and asked whether and how exercise may rescue age-induced deficits. In the sedentary group, aging caused a more severe decline in cerebral microvascular perfusion and oxygenation in deep (infragranular) cortical layers and subcortical white matter compared with superficial (supragranular) cortical layers. Five months of voluntary aerobic exercise partly renormalized microvascular perfusion and oxygenation in aged mice in a depth-dependent manner, and brought these spatial distributions closer to those of young adult sedentary mice. These microcirculatory effects were accompanied by an improvement in cognitive function. Our work demonstrates the selective vulnerability of the deep cortex and subcortical white matter to aging-induced decline in microcirculation, as well as the responsiveness of these regions to aerobic exercise.

THE ROLE OF EMOTIONS IN MUSIC EDUCATION: THEORETICAL INSIGHTS

Emotional expression has been the focus of teachers and educational researchers, as it can result in an improvement in cognitive performance. In specific settings, personal and emotional experiences can provide a steppingstone to developmental and learning processes. Emotions significantly influence learner learning and play a crucial role in quality teaching, educational reform, and learner-teacher interaction. The inherent social and communicative nature of music would make group training an excellent tool for increasing the coordination of behaviour, affect, and mental states among children. This paper aims to explore the literature on various aspects of the concept of emotions in the context of music education with the main focus on opportunities for experiencing and expressing emotion in music education, learners' positive emotion experiences in music education, teaching to generate positive emotion outcomes, and the benefits of a greater emphasis on the emotions in music education. The results of theoretical analysis indicate that music education has a particularly positive effect on identifying emotions, emotion regulation, emotion recognition, improved learning, and self-expression.

Improvement in Cognitive Function and Reducing the Risk of Developing Cardiovascular Events/ Stroke in Homocysteinemia

Improvement in Cognitive Function and Reducing the Risk of Developing Cardiovascular Events/ Stroke in Homocysteinemia

Effectiveness of heartfulness meditation on cognitive and autonomic functions in women with premenstrual syndrome

Background: Heartfulness meditation is heart-based meditation that helps to balance the mental status. The relaxation offered by meditation is so valuable as it not only improves quality but also improves the quantity of life. However, there is a requirement for the long-term practice of these meditations to receive their effects. The relaxation offered by meditation is very promising that it causes improvement in cognitive functions and sleep patterns. Aims and Objectives: The present study was undertaken to observe the effectiveness of heartfulness meditation on cognitive and autonomic functions in women with premenstrual syndrome (PMS). Materials and Methods: The present study was an experimental study. A total of forty females with PMS were part of the study. After recording the baseline values in the pre-menstrual period, the participants were trained in heartfulness meditation for weekdays by an expert. Later, they were asked to practice the heartfulness meditation daily for half an hour for 8 weeks at the meditation center of the college. After 8 weeks of practice of the heartfulness meditation, post-intervention values were recorded. Cognitive parameters were assessed using the spatial and verbal memory tests. Blood pressure and pulse rate were assessed using a diamond digital sphygmomanometer. Results: There was a significant improvement in spatial memory, and verbal memory scores followed by meditation. There was a significant decrease in systolic and diastolic blood pressure and pulse rate followed by the intervention. Conclusion: The study results in support earlier studies as there was a significant improvement in the cognitive scores and a decrease in the autonomic parameters in the participants followed by the practice of the heartfulness meditation. Further detailed studies are recommended to support the incorporation of heartfulness meditation into the routine day lifestyle.

Exercise and Cognition in Elderly

In developed countries, the population is aging. The aging process brings forth a slew of physical and mental changes. There has been a progressive deterioration in the degree of cognitive processes closely tied to the aging process, which is most commonly associated with age-related disorders such as dementia, throughout time. Physical activity and exercise have been identified as a method for promoting older health, as well as encouraging the maintenance of functional ability and acting in the prevention and control of a variety of diseases. The benefits of physical activity in the preservation or even improvement of cognitive performance in both the old without cognitive impairment and the elderly with some degree of cognitive impairment or dementia have piqued researchers’ interest in recent years. The goal of this study was to examine the effects of various types of physical activity and exercise on cognitive function in elderly people with and without prior cognitive impairment, to identify potential mechanisms underlying these effects, and to make exercise prescription recommendations to improve cognitive performance.

A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Therapeutic Effect of Magnesium-L-Threonate Supplementation for Persistent Pain After Breast Cancer Surgery.

Post-mastectomy pain syndrome is a common yet debilitating neuropathic complication after breast cancer procedures, resulting in significantly reduced quality of life. Recently, emerging evidence has supported the therapeutic effect of magnesium administration in chronic pain. However, the role of magnesium supplementation in development of chronic pain after breast cancer surgery remains less known. The aim of this study was to evaluate therapeutic effect of magnesium supplementation on persistent pain after breast cancer procedure. This was a randomized, double-blind, placebo-controlled clinical trial. A total of 109 patients who underwent breast cancer procedure received magnesium-L-threonate (n = 48) or placebo (n = 61) for 12 weeks. Chronic pain incidence, short form of the McGill Pain Questionnaire (SF-MPQ), Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Telephone Interview for Cognitive Status (TICS) were evaluated at 3- and 6-month follow-up. About 31% (15 out of 48) of patients reported chronic pain after magnesium supplementation, and 26% (16 out of 61) of the control group at 6-month follow-up respectively. Total scores of SF-MPQ were significantly increased in the control group 6 months after surgical intervention (mean difference, 1.475; 95% CI, -2.730 to -0.2211), but NOT in the magnesium treated group (mean difference, 1.250; 95% CI, -2.775 to 0.2748). No significant differences were found between two cohorts on SF-MPQ, GAD-7, PHQ-9, PSQI, or TICS at each timepoint. Oral supplementation of magnesium-L-threonate did not effectively prevent the development of persistent pain in breast cancer survivors, nor provide sufficient pain relief over placebo. We did not observe improvement of pain, mood, sleep disorder, or cognitive function after 12-week magnesium supplementation. Future study may focus on magnesium combined with other effective anti-neuropathic pain treatment.

Medium chain triglycerides with a C8:C10 ratio of 30:70 enhances cognitive performance and mitigates the cognitive decline associated with prolonged exercise in young and healthy adults

IntroductionProlonged exercise has been linked to a decline in cognitive function due to a variety of factors, such as a drop in oxygen in the prefrontal cortex and an increase in stress hormones and neurotransmitters. Medium chain triglycerides (MCTs) may possibly offset this decline as they provide energy for the brain via both direct and indirect pathways, alongside promoting chronic physiological adaptations within the brain. MethodsParticipants were divided into two groups; MCT (n = 9) and Placebo (n = 10). The MCT gels contained 6 g of MCT with a C8:C10 ratio of 30:70, whereas the placebo gels contained carbohydrates of similar calorific value to the MCT gels. Participants visited the laboratory on three occasions (familiarisation/fitness test, pre-supplementation, post-supplementation), during which they performed a battery of cognitive tasks assessing domains such as processing speed, working memory, selective attention, decision making and coordination, before and after a prolonged bout of exercise (60 mins at 90% gas exchange threshold (GET). A 2-week supplementation period between visits 2 and 3 involved the ingestion of 2 gels per day. ResultsExercise resulted in detriments in most cognitive tasks pre-supplementation for both groups, and post-supplementation for the Placebo group (main effect ps< 0.05). Post-supplementation, the effect of exercise was mediated in the MCT group for all cognitive tasks (main effect ps< 0.05), except for the Digit and Spatial Span Backwards test phases (main effect ps> 0.05). Furthermore, MCT supplementation enhanced before-exercise cognitive performance and in some measures, such as working memory, this was maintained after-exercise (interaction effect ps> 0.05). ConclusionsChronic MCT supplementation enhanced before-exercise cognitive performance and offset the cognitive decline caused by a prolonged bout of exercise. In some cases, improvements in before-exercise cognitive performance were maintained after-exercise.

Unleashing the potential of dance: a neuroplasticity-based approach bridging from older adults to Parkinson's disease patients.

Parkinson's disease (PD) is a neurodegenerative disorder that affects >1% of individuals worldwide and is manifested by motor symptoms such as tremor, rigidity, and bradykinesia, as well as non-motor symptoms such as cognitive impairment and depression. Non-pharmacological interventions such as dance therapy are becoming increasingly popular as complementary therapies for PD, in addition to pharmacological treatments that are currently widely available. Dance as a sensorimotor activity stimulates multiple layers of the neural system, including those involved in motor planning and execution, sensory integration, and cognitive processing. Dance interventions in healthy older people have been associated with increased activation of the prefrontal cortex, as well as enhanced functional connectivity between the basal ganglia, cerebellum, and prefrontal cortex. Overall, the evidence suggests that dance interventions can induce neuroplastic changes in healthy older participants, leading to improvements in both motor and cognitive functions. Dance interventions involving patients with PD show better quality of life and improved mobility, whereas the literature on dance-induced neuroplasticity in PD is sparse. Nevertheless, this review argues that similar neuroplastic mechanisms may be at work in patients with PD, provides insight into the potential mechanisms underlying dance efficacy, and highlights the potential of dance therapy as a non-pharmacological intervention in PD. Further research is warranted to determine the optimal dance style, intensity, and duration for maximum therapeutic benefit and to determine the long-term effects of dance intervention on PD progression.

Convolvulus prostratus Forssk : A Memory Boosting Herb

Convolvulus prostratus Forssk. aka C. pluricaulis, C. microphyllus commonly known as ‘Shankhpushpi’ has been traditionally used for improvement in memory and cognitive function in cases of dementia, epilepsy, depression, anxiety and central nervous system (CNS) disorders. Studies have shown that this herb has potential to enhance memory recall, increase brain plasticity and boost learning ability. The plant species has several active metabolites including alkaloids, flavonoids, phenolic acids and terpenoids that interacts with protein, neurological signaling pathways and demonstrates pharmacological effects, such as, anti-amnesiac, anti-inflammatory, anxiolytic, analgesic, antioxidant, neuroprotective, memory and learning improving, sedative-hypnotic and anticonvulsant activity, which have been linked to brain health and the prevention of neurodegenerative diseases. In the present study, leaf explant of C. prostratus were cultured on MS (Murashige and Skoog’s medium) medium supplemented with 1mgL-1 2, 4-D shows optimum callus induction. Moreover, several biotechnological approaches could be used for better understanding of its memory enhancing mechanism, such as, phytochemical analysis for active compounds, in vitro and in vivo studies for safety and efficacy, metabolomics for potential health benefits and tissue culture for large scale productionof this medicially potent plant species in controlled environment. At present, there are many commercial medicinal products available in the market consisting Shakhapushpi as an ingredient or whole.

Reducing Target Volumes of Intensity Modulated Radiation Therapy After Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: Long-Term Results of a Prospective, Multicenter, Randomized Trial

The objective of this study was to estimate the long-term survival, late toxicity profile, and quality of life of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with combined induction chemotherapy (IC) and concurrent chemoradiotherapy from a clinical trial focused on reducing the target volume of intensity modulated radiation therapy (IMRT). This prospective, randomized clinical trial was conducted across 6 Chinese hospitals and included 212 patients with stage III-IVB NPC who were randomly allocated to a pre-IC or post-IC group. Eligible patients were treated with 2 cycles of IC+CCRT. All patients underwent radical IMRT. Gross tumor volumes of the nasopharynx were delineated according to pre-IC and post-IC tumor extent in the pre-IC and post-IC groups, respectively. After a median follow-up of 98.4 months, 32 of 97 (32.9%) and 33 of 115 (28.7%) patients experienced treatment failure or died in the pre-IC and post-IC groups, respectively. None of the patients developed grade 4 late toxicity. Late radiation-induced toxicity predominantly manifested as grade 1 to 2 subcutaneous fibrosis, hearing loss, tinnitus, and xerostomia, whereas grade 3 late toxicity included xerostomia and hearing loss. The 5-year estimated overall, progression-free, locoregional recurrence-free, and distant metastasis-free survival rates in the pre-IC and post-IC groups were 78.2% versus 83.3%, 72.0% versus 78.1%, 90.2% versus 93.5%, and 78.1% versus 82.1%, respectively. The pre-IC group had a significantly higher incidence of xerostomia and hearing damage than the post-IC group. In terms of quality of life, compared with the pre-IC group, the post-IC group showed significant improvement in cognitive function (P=.045) and symptoms including dry mouth (P=.004), sticky saliva (P=.047), and feeling ill (P=.041). After long-term follow-up, we confirmed that reducing the target volumes of IMRT after IC in locoregionally advanced NPC showed no inferiority in terms of the risk of locoregional relapse and potentially improved quality of life and alleviated late toxicity.

An Early and Unequal Decline: Life Course Trajectories of Cognitive Aging in the United States.

Objectives: Cognitive aging is a lifelong process with implications for Alzheimer's disease and dementia. This study aims to fill major gaps in research on the natural history of and social disparities in aging-related cognitive decline over the life span. Methods: We conducted integrative data analysis of four large U.S. population-based longitudinal studies of individuals aged 12 to 105 followed over two decades and modeled age trajectories of cognitive function in multiple domains. Results: We found evidence for the onset of cognitive decline in the 4th decade of life, varying gender differences with age, and persistent disadvantage among non-Hispanic Blacks, Hispanics, and those without college education. We further found improvement in cognitive function across 20th century birth cohorts but widening social inequalities in more recent cohorts. Discussion: These findings advance an understanding of early life origins of dementia risk and invite future research on strategies for promoting cognitive health for all Americans.

Efficiency and safety of Vortioxetine in the treatment of depressive disorders in cardiac patients

Importance of the problem. Diseases of the cardiovascular system are in the first place among the causes of death and disability in most industrialized countries, which is undoubtedly an urgent medical and social problem and causes significant economic damage. The prevalence of depressive disorders in modern society, according to WHO estimates, is quite high, and the causes of depressive disorders and methods for their correction in patients with various somatic diseases have been the subject of study by specialists around the world for many decades. The comorbidity of depressive disorders with cardiac pathology is beyond doubt, and the bidirectional relationship of these disorders significantly aggravates the condition of patients, worsens their quality of life and reduces adherence to treatment. The most important conditions for the use of antidepressants in cardiology practice are good tolerability, absence of toxic effect, minimal interaction with other drugs, and relative safety in case of overdose. Vortioxetine, being a modern multimodal antidepressant, demonstrates not only a sufficiently high antidepressant and anti-anxiety activity, but also has a procognitive effect, as well as minimal side effects and undesirable cross-interactions with other drugs, which is confirmed by international randomized placebo-controlled trials. The aim of this work was to evaluate the efficacy and safety of Vortioxetine in the treatment of concomitant depressive disorders in patients with coronary heart disease (CHD), angina pectoris 2-3 functional class (FC) (I 20.8 according to ICD-10), receiving complex therapy for the main (cardiological) diseases at the inpatient and outpatient stages of therapy. Materials and methods. The study included patients with a diagnosis of coronary artery disease, angina pectoris FC 2-3, hypertension 2-3, aged 45 to 66 years (mean age 57.1±1.1 years), receiving complex therapy for the underlying cardiac disease and Vortioxetine at a dose of 10-15 mg/day. within 8 weeks. Anxiety and depressive manifestations were assessed on the HADS scale, the level of cognitive impairment on the PDQ questionnaire, social functioning on the SF-36 questionnaire, the general clinical impression on the CGI-C scale, and the main indicators of the functioning of the cardiovascular system upon admission to the hospital, after 4 weeks of hospitalization. treatment and another 4 weeks after discharge during the period of outpatient observation.The result of the combined therapy of patients with cardiac pathology and concomitant depressive disorder (basic therapy for CVD and Vortioxetine) was not only an improvement in the cardiovascular system (decrease in heart rate, blood pressure, the frequency of anginal pain, an increase in exercise tolerance), but also the relief of depressive manifestations, which contributed to an increase in the adherence of cardiological patients to the implementation of medical recommendations, and, in turn, led to a decrease in the level of end points—mortality, hospitalization rates, progression of chronic heart failure and disability. Conclusions. Appointment of Vortioxetine to cardiac patients with concomitant depressive disorder of moderate severity is quite effective not only in terms of relief of painful manifestations of the CVS, but also leads to a reduction in anxiety-depressive disorders and an improvement in cognitive and social functioning. The good tolerability of the drug makes it possible to recommend it for the treatment of depressive disorders in cardiological patients in a hospital setting and in outpatient practice.

Cognitive function improvement effects of gintonin-enriched fraction in subjective memory impairment: An assessor- and participant-blinded placebo-controlled study

BackgroundGintonin is a new material of ginseng that acts through the ginseng-derived lysophosphatidic acid (LPA) receptor ligand. The gintonin-enriched fraction (GEF) inhibits amyloid plaque accumulation in the cortex and hippocampus, improves cognitive dysfunction by increasing acetylcholine levels, and promoted hippocampal neurogenesis in an animal model of Alzheimer's disease. We evaluated the effect of the GEF on the cognitive performance of subjects with subjective memory impairment (SMI). MethodsIn this eight-week, randomized, assessor- and participant-blinded, placebo-controlled study, participants with SMI were assigned to three groups receiving placebo, GEF 300 mg/day or GEF 600 mg/day. The Korean versions of the Alzheimer's Disease Assessment Scale (K-ADAS), Mini-Mental State Examination (K-MMSE), and Stroop color-word test (K-SCWT) were also evaluated along with the safety profiles. ResultsOne hundred thirty-six participants completed the study. After eight weeks, we analyzed intergroup differences in primary or secondary outcome score changes. When we compared the GEF group with the placebo group, we observed significant improvements in the K-ADAS and K-SCWT scores. The GEF group did not show a significant improvement in K-MMSE and BDI scores compared to the placebo group. No adverse events were observed in the gintonin and placebo groups for eight weeks. ConclusionThe GEF is safe and effective in improving subjective cognitive impairment related to both the K-ADAS and K-SCWT in this study. However, further large-scale and randomized controlled studies are warranted to secure other cognitive function tests besides the K-ADAS and K-SCWT, and to confirm the findings of the current study.

#3961 A COMPARATIVE ANALYSIS OF EMOTIONAL RECOGNITION AND DIFFERENTIATION TWO YEARS FOLLOWING KIDNEY TRANSPLANTATION VERSUS HEMODIALYSIS.

Abstract Background and Aims Cognitive impairment is common in patients with End Stage Kidney Disease. There are conflicting reports regarding the degree and interval of improvement of cognitive functions with the different modalities of renal replacement therapy. Most of the published reports relied on screening tests not covering the emotional aspects of cognition. Also, the timings of assessment are different being at most during the first year of establishing the modality. Method Ninety age, gender, and educational level-matched participants were enrolled in the study. The participants were divided into three equal groups, thirty kidney transplant (KT) patients, thirty hemodialysis patients (HD) for more than two years, and thirty control non-diseased participants. The participants included were below 60 years of age and with no previous history of a neurological defect. All patients were subjected to three Computerized Neurocognitive Battery tests (Age differentiation test, emotional recognition, and differentiation). All the tests were judged for accuracy and the time consumed to answer. Results The median value of transplant duration was 59 months (24- 168), and 66 months (27- 180) of HD duration. Both groups were comparable in age, gender, educational level, socioeconomic, and marital status. KT patients were comparable to controls at all parameters of testing. KT patients' answers were significant of higher accuracy than HD patients (P = 0.04 for age differentiation and emotion recognition, and 0.005 for emotion differentiation). KT and HD had comparable response times. Total correct responses of emotional differentiation tests were negatively correlated with KT duration (rho = −0.348, P = 0.02), and (rho = −0.345, P = 0.01) for HD duration. The cumulative steroid dose was not correlated with any of the tested parameters in the KT group. Conclusion KT offers a much better emotional and social cognitive improvement, an effect that is expected to positively impact the quality of life and involvement in society.

Transferability and sustainability of process-based multi-task adaptive cognitive training in community-dwelling older adults with mild cognitive impairment: a randomized controlled trial

BackgroundCognitive training shows promising effects for improving cognitive domains in individuals with mild cognitive impairment (MCI), including the crucial predictive factor of executive function (EF) for dementia prognosis. Few studies have paid sufficient emphasis on the training-induced effects of cognitive training programs, particularly with regards to targeting EF. A process-based multi-task adaptive cognitive training (P-bM-tACT) program targeting EF is required to examine direct, transfer, and sustainability effects in older adults with MCI.ObjectiveThis study aimed to evaluate the direct effects of a P-bM-tACT program on EF, the transfer effects on untrained cognitive domains, and further explore the sustainability of training gains for older adults with MCI in the community.MethodsIn a single-blind, randomized controlled trial, 92 participants with MCI were randomly assigned to either the intervention group, participating in a P-bM-tACT program (3 training sessions/week, 60 min/session for 10 weeks) or the wait-list control group, accepting a health education program on MCI (1 education session/ twice a week, 40–60 min/session for 10 weeks). The direct and transfer effects of the P-bM-tACT program were assessed at baseline, immediately after 10 weeks of training, and the 3-month follow-up. Repeated measures analysis of variance and a simple effect test were used to compare the direct and transfer effects over the 3-time points between the two groups.ResultsThe P-bM-tACT program yielded a greater benefit of direct and transfer effects in the intervention group participants than in the wait-list control group. Combined with the results of simple effect tests, the direct and transfer effects of participants in the intervention group significantly increased immediately after 10 weeks of training compared to the baseline (F = 14.702 ~ 62.905, p < 0.05), and these effects were maintained at the 3-month follow-up (F = 19.595 ~ 122.22, p < 0.05). Besides, the acceptability of the cognitive training program was established with a high adherence rate of 83.4%.ConclusionsThe P-bM-tACT program exerted positive direct and transfer effects on the improvement of cognitive function, and these effects were sustained for 3 months. The findings provided a viable and potential approach to improving cognitive function in older adults with MCI in the community.Trial registrationThe trial was registered at Chinese Clinical Trials Registry on 09/01/2019 (www.chictr.org.cn; Number Registry: ChiCTR1900020585).

Effectiveness of vortioxetine in patients with major depressive disorder and early-stage dementia: The MEMORY study

BackgroundDepression and dementia are highly prevalent in older adults and often co-occur. This Phase IV study investigated the effectiveness and tolerability of vortioxetine in improving depressive symptoms, cognitive performance, daily and global functioning and health-related quality of life (HRQoL) in patients with major depressive disorder (MDD) and comorbid early-stage dementia. MethodsPatients (n = 82) aged 55–85 years with a primary diagnosis of MDD (onset before age 55 years) and comorbid early-stage dementia (diagnosed ≥6 months before screening and after onset of MDD; Mini-Mental State Examination-2 total score, 20–24) received vortioxetine for 12 weeks (initiated at 5 mg/day and up-titrated to 10 mg/day at day 8, with flexible dosing thereafter [5–20 mg/day]). The primary endpoint was change from baseline in Montgomery–Åsberg Depression Rating Scale (MADRS) total score at week 12. ResultsSignificant improvement in depressive symptom severity was seen from week 1 onwards (P < 0.0001). At week 12, the least-square mean (standard error) change in MADRS total score from baseline was −12.4 (0.78). Significant improvements in cognitive performance were observed (from week 1 for the Digit Symbol Substitution Test and week 4 for the Rey Auditory Verbal Learning Test). Patients also experienced significant improvements in daily and global functioning, and HRQoL. Vortioxetine was well tolerated. From week 4 onwards, more than 50 % of patients were receiving 20 mg/day. LimitationsOpen-label study. ConclusionsVortioxetine demonstrated effectiveness in clinically significantly improving depressive symptoms, cognitive performance, daily and global functioning, and HRQoL in patients with MDD and comorbid early-stage dementia treated for 12 weeks. Trial registrationClinicalTrials.gov/ct2/show/NCT04294654.

Clonal mesenchymal stem cell-derived extracellular vesicles improve mouse model of weight drop-induced traumatic brain injury through reducing cistauosis and apoptosis

ObjectiveTraumatic brain injury (TBI) is a major risk factor for disabilities globally with no effective treatment thus far. Recently, homogenous population of clonal mesenchymal stem cells (cMSC) and their derived extracellular vesicles (cMSC-EVs) have been proposed as a promising TBI treatment strategy. We herein investigated possible therapeutic effect of cMSC-EVs in TBI treatment and the underlying mechanisms considering cis p-tau as an early hallmark of TBI. MethodsWe examined the EVs morphology, size distribution, marker expression, and uptake. Moreover, the EVs neuroprotective effects were studied in both in-vitro and in-vivo model. We also examined the anti-cis p-tau antibody-loading characteristics of the EVs. We treated TBI mouse model with EVs; prepared from cMSC-conditioned media. TBI mice were given cMSC-EVs intravenously and their cognitive functions were analyzed two months of the treatment. We employed immunoblot analysis to study the underlying molecular mechanisms. ResultsWe observed a profound cMSC-EVs uptake by primary cultured neurons. We found a remarkable neuroprotective effect of cMSC-EVs upon nutritional deprivation stress. Furthermore, cMSC-EVs were effectively loaded with an anti-cis p-tau antibody. There was a significant improvement in cognitive function in TBI animal models treated with cMSC-EVs compared to the saline-treated group. There was a decreased cis p-tau and cleaved caspase3 as well as increased p-PI3K in all treated animals. ConclusionsThe results revealed that cMSC-EVs efficiently improved animal behaviors after TBI by reducing cistauosis and apoptosis. Moreover, the EVs can be employed as an effective strategy for antibody delivery during passive immunotherapy.

Real world evidence of improved attention and cognition during physical therapy paired with neuromodulation: a brain vital signs study.

Non-invasive neuromodulation using translingual neurostimulation (TLNS) has been shown to advance rehabilitation outcomes, particularly when paired with physical therapy (PT). Together with motor gains, patient-reported observations of incidental improvements in cognitive function have been noted. Both studies in healthy individuals and case reports in clinical populations have linked TLNS to improvements in attention-related cognitive processes. We investigated if the use of combined TLNS/PT would translate to changes in objective neurophysiological cognitive measures in a real-world clinical sample of patients from two separate rehabilitation clinics. Brain vital signs were derived from event-related potentials (ERPs), specifically auditory sensation (N100), basic attention (P300), and cognitive processing (N400). Additional analyses explored the attention-related N200 response given prior evidence of attention effects from TLNS/PT. The real-world patient sample included a diverse clinical group spanning from mild-to-moderate traumatic brain injury (TBI), stroke, Multiple Sclerosis (MS), Parkinson's Disease (PD), and other neurological conditions. Patient data were also acquired from a standard clinical measure of cognition for comparison. Results showed significant N100 variation between baseline and endpoint following TLNS/PT treatment, with further examination showing condition-specific significant improvements in attention processing (i.e., N100 and N200). Additionally, CogBAT composite scores increased significantly from baseline to endpoint. The current study highlighted real-world neuromodulation improvements in neurophysiological correlates of attention. Overall, the real-world findings support the concept of neuromodulation-related improvements extending beyond physical therapy to include potential attention benefits for cognitive rehabilitation.

Improvement of synaptic plasticity and cognitive function in RASopathies—a monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (SynCoRAS)

BackgroundCognitive impairment is a common medical issue in rat sarcoma (RAS) pathway disorders, so-called RASopathies, like Neurofibromatosis type 1 (NF1) or Noonan syndrome (NS). It is presumed to be caused by impaired synaptic plasticity. In animal studies, pathway-specific pharmacological interventions with lovastatin (LOV) and lamotrigine (LTG) have been shown to improve synaptic plasticity as well as cognitive function. The aim of this clinical trial is to translate the findings of animal studies to humans and to probe the effect of lovastatin (NS) and lamotrigine (NS and NF1) on synaptic plasticity and cognitive function/alertness in RASopathies.MethodsWithin this phase IIa, monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (syn. SynCoRAS), three approaches (approaches I–III) will be carried out. In patients with NS, the effect of LTG (approach I) and of LOV (approach II) is investigated on synaptic plasticity and alertness. LTG is tested in patients with NF1 (approach III). Trial participants receive a single dose of 300 mg LTG or placebo (I and III) and 200 mg LOV or placebo (II) daily for 4 days with a cross-over after at least 7 days. Synaptic plasticity is investigated using a repetitive high-frequency transcranial magnetic stimulation (TMS) protocol called quadri-pulse theta burst stimulation (qTBS). Attention is examined by using the test of attentional performance (TAP). Twenty-eight patients are randomized in groups NS and NF1 with n = 24 intended to reach the primary endpoint (change in synaptic plasticity). Secondary endpoints are attention (TAP) and differences in short interval cortical inhibition (SICI) between placebo and trial medication (LTG and LOV).DiscussionThe study is targeting impairments in synaptic plasticity and cognitive impairment, one of the main health problems of patients with RASopathies. Recent first results with LOV in patients with NF1 have shown an improvement in synaptic plasticity and cognition. Within this clinical trial, it is investigated if these findings can be transferred to patients with NS. LTG is most likely a more effective and promising substance improving synaptic plasticity and, consecutively, cognitive function. It is expected that both substances are improving synaptic plasticity as well as alertness. Changes in alertness may be a precondition for improvement of cognition.Trial registrationThe clinical trial is registered in ClinicalTrials.gov (NCT03504501; https://www.clinicaltrials.gov; date of registration: 04/11/2018) and in EudraCT (number 2016–005022-10).