Changes In Cognitive Function Research Articles

Transcranial direct current stimulation in the management of epilepsy: a meta-analysis and systematic review

BackgroundTranscranial direct current stimulation (tDCS) has recently become a novel and non-invasive treatment option for refractory epilepsy. Previous systematic reviews have suggested that tDCS may be effective in treating epilepsy, this study presents the first meta-analysis on its effectiveness.MethodsWe searched PubMed, Embase, Cochrane Library, and Web of Science for relevant randomized controlled trials (RCTs) from database inception to May 2024. The Cochrane risk of bias tool RoB2.0 was used to assess the risk of bias. Primary outcomes included changes in seizure frequency from baseline and the proportion of patients with a ≥50% reduction in seizure frequency.ResultsOf the 608 studies initially identified, 14 were finally included. The pooled results from the random-effects model indicated that tDCS significantly reduced seizure frequency (WMD 0.41, 95% CI 0.24, 0.59). Further subgroup analysis revealed that tDCS significantly reduced seizure frequency in temporal lobe epilepsy, and seizure frequency was more alleviated in studies that had treatment sessions of fewer than 5 times, and followed up within 2 months' post-treatment. Only four studies provided data on patients with a ≥50% reduction in seizure frequency, showing no significant difference (RR 2.96, 95% CI 0.85, 10.32). In the systematic review, three studies analyzed cognitive function changes after tDCS treatment, but none reported significant improvements. The most common side effect during tDCS treatment was transient tingling, and no patients required additional life-support measures due to side effects.ConclusionThe current meta-analysis on available trials indicates that tDCS can effectively reduce seizure frequency in the short term and is well-tolerated. However, its impact on cognitive improvement in epilepsy patients requires further investigation.Systematic review registrationhttps://inplasy.com/inplasy-2024-6-0033/, identifier INPLASY202460033.

Role of Cardiovascular Risk in Associations of Brain-Derived Neurotrophic Factor with Longitudinal Brain and Cognitive Trajectories in Older Adults

ABSTRACT Background Higher levels of brain-derived neurotrophic factor (BDNF) have been associated with better neurocognitive outcomes. BDNF is present in cardiovascular tissue, and some evidence suggests it may benefit cardiovascular function. The current study assessed whether there is a mediating and/or moderating role of cardiovascular health in the relationship between BDNF and brain and cognitive outcomes. Method We examined longitudinal data from 397 older adults (aged 54–89;164 females, 233 males) enrolled in the Alzheimer’s Disease Neuroimaging Initiative with available plasma BDNF, medical, neuroimaging, and cognitive assessments. We used path analysis and linear regression to estimate the mediating and moderating roles of two measures of cardiovascular health, the Framingham Risk Score (FRS) and pulse pressure, in the relationships between BDNF and longitudinal changes in brain structure (white matter hyperintensity volume, hippocampal volume, and primary visual cortex volume) and cognitive function (executive function, episodic memory, and language). Results There was no significant association of plasma BDNF with FRS or pulse pressure (ps > 0.31), precluding mediation. There were no robust associations between BDNF and longitudinal change in any brain structural or cognitive measures (ps > .12). Higher FRS was significantly associated with greater increases in WMH volume (ps < .01). FRS and pulse pressure were not associated with any other brain structural or cognitive outcomes (ps > .07). Conclusion These results suggest that cardiovascular health may not play an important role in the influence of BDNF on neurocognitive health in older adults.

Cognotoxemia: endotoxemia and gender predict changes in working memory performance in healthy adults

IntroductionExamining the contribution of peripheral systems to cognitive function under healthy circumstances may improve our understanding of the systems that confer risk or resilience in diseased states. Endotoxemia—a pro-inflammatory response to the translocation of bacteria that reside in the gut on other sources (e.g., respiratory tract; infection) into the blood—was hypothesized to relate to worsened cognitive functioning. Gender was explored as a moderator.MethodsA sample of 162 healthy adults (25–65 years old) provided plasma, from which a measure of endotoxemia was determined [i.e., the ratio of lipopolysaccharide binding protein (LBP) to soluble cluster of differentiation 14 receptors (sCD14)]. Participants performed an array of laboratory and ambulatory cognitive tasks at three timepoints, each separated by 9 months. Two sets of multilevel models were used: Prospective models, linking endotoxemia at baseline with changes in cognition across time, and coupling models, which examine correlations of endotoxemia with cognition across time.ResultsA prospective model indicated lower levels of endotoxemia at baseline predicted improvements in working memory across the three timepoints; higher levels were associated with no change in cognitive performance. Gender was not found to modulate this finding. Interestingly, a coupling analysis of endotoxemia and gender across time showed that in men, those with higher endotoxemia performed better at the working memory task overall; in women, working memory performance was similar regardless of endotoxemia level.ConclusionThis work provides initial evidence that endotoxemia may be associated with a dampening of improvement in working memory, improvement consistent with practice effects, which should be expected in a sample of healthy, relatively young adults. The findings also provide preliminary evidence that, at least for men, higher degrees of endotoxemia are not inherently negative, and may link with short term positive outcomes for working memory.

Assessing the state of cognitive performance of employees and determining the range of thermal comfort of different genders in Ilam hospitals

Introduction: Thermal comfort is essential for a productive work environment and affects the well-being and performance of employees, so maintaining optimal levels of satisfaction, productivity, and efficiency, especially in indoor spaces, is essential. Therefore, the present study's aim is to evaluate the state of cognitive performance. Employees and determination of the thermal comfort range of different genders of employees in the hospitals of Ilam city were done. Methods and Materials: This research was conducted by survey and field method to identify the state of thermal comfort and cognitive performance of people in the real conditions of therapeutic spaces. For this purpose, the responses of 400 employees of five hospitals in Ilam City were recorded by simple sampling from the beginning of August to November 1402. The reliability status of the questionnaires was confirmed using Cronbach's alpha, and the thermal comfort status of the people was determined through the regression model. Linearity and correlation analysis between measured variables were analyzed through SPSS27 software. Results: The analysis of the linear regression model showed that the range of thermal comfort between men and women differs by 1.79 degrees Celsius, and this difference is a tendency for warmer temperatures in men and a tendency for colder temperatures in women, the average scores obtained at Zagros Hospital In the visual-spatial/executive component (7.00), attention (4.34), memory (3.08) has the best performance, Imam Khomeini Hospital (RA) has the best performance in the verbal component (2.95), Hazrat Qaim Hospital (A) In the abstraction component (2.02), it has the best performance and awareness of time and place in all hospitals equal to 6.00. Conclusion: The level of coverage and activity rate among women significantly affects the feeling of thermal comfort, cognitive performance, and productivity of employees at work. The results of this research show the need to revise the current standards of workplace clothing, attendance time, and employee activity rate. Moreover, changes in cognitive performance among hospital staff highlight the need to consider targeted cognitive enhancement strategies to increase staff efficiency.

Double negative T cells promote surgery-induced neuroinflammation, microglial engulfment and cognitive dysfunction via the IL-17/CEBPβ/C3 pathway in adult mice

CD3(+) CD4(−) CD8(−) double negative T cells (DNTs) manifest themselves in autoimmune diseases and associated inflammation. In the central nervous system, the increased presence of DNTs is associated with the progression of neurological conditions and brain injury. Active DNTs that produce IL-17 have been regarded as a pro-inflammatory phenotype. The IL-17 signaling pathway mediates neuroinflammatory responses by inducing glial activation and producing inflammatory factors. Neuroinflammation is considered integral to the pathogenesis of perioperative neurocognitive disorders (PNDs), commonly developed after surgery in susceptible patients. We and others have demonstrated a significant role for complement C3 in surgery-induced neuroinflammation and cognitive impairment but the regulatory mechanisms for this remain unexplored. We hypothesized that surgery induces DNT infiltration into the CNS that in turn upregulate complement C3 expression and this causes changes that contribute to cognitive impairment. Using an adult murine abdominal surgery model, we investigated perioperative changes in cognitive performance, quantifying the presence of T cell subsets and phenotype, IL-17 signaling pathway activation, glial cell activation and C3 expression in the brain. Postoperative IL-17 specific inhibitor GSK2981278 administration or preoperatively conditional CEBPβ knock-down by AAV9 viral vector were then applied to evaluate the effect of inhibiting IL-17 signaling pathway on postoperative C3 expression and cognitive performance. The results showed an increased hippocampus infiltration of DNTs with augmented IL-17 production, along with C3 upregulation and cognitive impairment. Both inhibition of IL-17 or knock-down of CEBPβ significantly suppressed C3 expression, synaptic engulfment by microglia and attenuated cognitive impairment. These findings indicate that DNTs promote postoperative neuroinflammation and cognitive impairment via the IL-17/CEBPβ/C3 pathway and targeting this IL-17 axis could be a potential therapeutic strategy to ameliorate postoperative neuroinflammation and cognitive impairment.

Associations between white matter microstructure and cognitive decline in major depressive disorder versus controls in Germany: a prospective case-control cohort study

Cognitive deficits are a key source of disability in individuals with major depressive disorder (MDD) and worsen with disease progression. Despite their clinical relevance, the underlying mechanisms of cognitive deficits remain poorly elucidated, hampering effective treatment strategies. Emerging evidence suggests that alterations in white matter microstructure might contribute to cognitive dysfunction in MDD. We aimed to investigate the complex association between changes in white matter integrity, cognitive decline, and disease course in MDD in a comprehensive longitudinal dataset. In the naturalistic, observational, prospective, case-control Marburg-Münster Affective Disorders Cohort Study, individuals aged 18-65 years and of Caucasian ancestry were recruited from local psychiatric hospitals in Münster and Marburg, Germany, and newspaper advertisements. Individuals diagnosed with MDD and individuals without any history of psychiatric disorder (ie, healthy controls) were included in this subsample analysis. Participants had diffusion-weighted imaging, a battery of neuropsychological tests, and detailed clinical data collected at baseline and at 2 years of follow-up. We used linear mixed-effect models to compare changes in cognitive performance and white matter integrity between participants with MDD and healthy controls. Diffusion-weighted imaging analyses were conducted using tract-based spatial statistics. To correct for multiple comparisons, threshold free cluster enhancement (TFCE) was used to correct α-values at the family-wise error rate (FWE; ptfce-FWE). Effect sizes were estimated by conditional, partial R2 values (sr2) following the Nakagawa and Schielzeth method to quantify explained variance. The association between changes in cognitive performance and changes in white matter integrity was analysed. Finally, we examined whether the depressive disease course between assessments predicted cognitive performance at follow-up and whether white matter integrity mediated this association. People with lived experience were not involved in the research and writing process. 881 participants were selected for our study, of whom 418 (47%) had MDD (mean age 36·8 years [SD 13·4], 274 [66%] were female, and 144 [34%] were male) and 463 (53%) were healthy controls (mean age 35·6 years [13·5], 295 [64%] were female, and 168 [36%] were male). Baseline assessments were done between Sept 11, 2014, and June 3, 2019, and after a mean follow-up of 2·20 years (SD 0·19), follow-up assessments were done between Oct 6, 2016, and May 31, 2021. Participants with MDD had lower cognitive performance than did healthy controls (p<0·0001, sr2=0·056), regardless of timepoint. Analyses of diffusion-weighted imaging indicated a significant diagnosis × time interaction with a steeper decline in white matter integrity of the superior longitudinal fasciculus over time in participants with MDD than in healthy controls (ptfce-FWE=0·026, sr2=0·002). Furthermore, cognitive decline was robustly associated with the decline in white matter integrity over time across both groups (ptfce-FWE<0·0001, sr2=0·004). In participants with MDD, changes in white matter integrity (p=0·0040, β=0·071) and adverse depressive disease course (p=0·0022, β=-0·073) independently predicted lower cognitive performance at follow-up. Alterations of white matter integrity occurred over time to a greater extent in participants with MDD than in healthy controls, and decline in white matter integrity was associated with a decline in cognitive performance across groups. Our findings emphasise the crucial role of white matter microstructure and disease progression in depression-related cognitive dysfunction, making both priority targets for future treatment development. German Research Foundation (DFG).

Effects of variation in exercise training load on cognitive performances and neurotrophic biomarkers in patients with coronary artery disease.

This study compared the effects of linear (LP) and nonlinear (NLP) training periodization on cognitive functions, neurotrophic biomarkers [plasma brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1)], and cathepsin-B in patients with coronary artery disease (CAD). Forty-four patients with CAD reported to our laboratory on two occasions to undergo testing procedures before and after training sessions, and were then blindly randomized to NLP or LP for 36 training sessions. Visit 1 included blood samples and a maximal cardiopulmonary exercise testing to get maximal oxygen uptake (V̇o2peak). Visit 2 included cognitive functions assessment. Thirty-nine patients completed the study (LP: n = 20, NLP: n = 19), with no observed changes in cognitive performances after the training intervention in either group. IGF-1 concentration decreased in both groups (time-effect: P < 0.001), whereas BDNF concentration increased (time-effect: P < 0.05) without group interaction, and cathepsin-B did not change after the intervention. Associations were found between ΔV̇o2peak and ΔBDNF (R2 = 0.18, P = 0.04), and ΔIGF-1 and Δshort-term/working memory (R2 = 0.17, P = 0.01) in the pooled sample, with ΔIGF-1 and ΔBDNF accounting for 10% of the variance in Δshort-term/working memory. In the LP group, associations were found between ΔV̇o2peak and ΔBDNF (R2 = 0.45, P = 0.02), ΔBDNF and Δshort-term/working memory (R2 = 0.62, P = 0.004), ΔIGF-1 and Δshort-term/working memory (R2 = 0.31, P = 0.01), and ΔIGF-1 and Δexecutive function (R2 = 0.22, P = 0.04). This study indicates that linear and nonlinear training periodization led to an increase in BDNF, and a decrease in IGF-1, without change in cognitive function in individuals with stable CAD.NEW & NOTEWORTHY We used a novel and supervised iso-energetic training, integrating both moderate- and high-intensity aerobic exercises. Our findings indicate that greater variation in training load did not yield cognitive enhancements, although both protocols exhibited positive effects on brain-derived neurotrophic factor (BDNF) levels. Moreover, this study establishes a clear positive association between short-term and working memory and neurotrophic biomarkers. In addition, the independent predictive value of change in insulin-like growth factor-1 (IGF-1) on improvement in short-term and working memory highlight the close relationship between neurotrophic markers and cognition. Consequently, our results advocate for exercise training interventions targeting neurotrophic biomarkers to enhance cognitive function among individuals with coronary artery disease.

Cannabis Use and Age‐Related Changes in Cognitive Function From Early Adulthood to Late Midlife in 5162 Danish Men

ABSTRACTIntroductionCannabis is by far the most widely used and abused drug listed on the Drug Enforcement Administration's Schedule I, which includes drugs with a high potential for abuse. There is evidence of short‐term negative effects of cannabis use on cognition, but only a limited number of studies have explored the association between cannabis use and age‐related cognitive decline. The aim of the present study was to investigate the relationship between cannabis use and age‐related cognitive decline from early adulthood to late midlife.MethodsThe study population consisted of 5162 men who had participated in Danish follow‐up studies on cognitive aging. These studies included scores on the military intelligence test Børge Prien's Prøve from both the conscription assessment (mean age = 20 years; p1 and p99: 18 and 26 years) and from the follow‐up (mean age = 64 years; p1 and p99: 55 and 72 years) as well as extensive data on lifestyle and health from the follow‐up questionnaires. The association between cannabis use and age‐related cognitive decline was investigated in linear regression models.ResultsMen with a history of cannabis use had less cognitive decline from early adulthood to late midlife compared to men without a history of cannabis use. Among cannabis users, neither age of initiation of cannabis use nor frequent use was significantly associated with a greater age‐related cognitive decline.Discussion and ConclusionsIn a sample of more than 5000 men followed for a mean of 44 years, we found no significant harmful effects of cannabis use on age‐related cognitive decline.

Cerebral blood flow and arterial transit time responses to exercise training in older adults

Brain vascular health worsens with age, as is made evident by resting grey matter cerebral blood flow (CBFGM) reductions and lengthening arterial transit time (ATTGM). Exercise training can improve aspects of brain health in older adults, yet its effects on CBFGM and ATTGM remain unclear. This randomised controlled trial assessed responses of CBFGM and ATTGM to a 26 week exercise intervention in 65 healthy older adults (control: n = 33, exercise: n = 32, aged 60–81 years), including whether changes in CBFGM or ATTGM were associated with cognitive function changes. Multiple-delay pseudo-continuous arterial spin labelling data were used to estimate resting global and regional CBFGM and ATTGM. Results showed no between-group differences in CBFGM or ATTGM following the intervention. However, exercise participants with the greatest cardiorespiratory gains (n = 17; ∆V̇O2peak >2 mL/kg/min) experienced global CBFGM reductions (-4.0 [-7.3, -0.8] mL/100 g/min). Cognitive functions did not change in either group and changes were not associated with changes in CBFGM or ATTGM. Our findings indicate that exercise training in older adults may induce global CBFGM reductions when high cardiorespiratory fitness gains are induced, but this does not appear to affect cognitive functions.

A neural implementation of cognitive reserve: Insights from a longitudinal fMRI study of set-switching in aging

Aging is often accompanied by changes in brain structure and executive functions, particularly in tasks involving cognitive flexibility, such as task-switching. However, substantial individual differences in the degree of cognitive impairment indicate that some individuals can cope with brain changes more effectively than others, suggesting higher cognitive reserve (CR). This study identified a neural basis for CR by examining the longitudinal relationship between task-related brain activation, structural brain changes, and changes in cognitive performance during an executive task-switching paradigm including single and dual conditions. Fifty-two older individuals were assessed at baseline and followed up after five years. Structural brain changes related to task-switching performance were analyzed using elastic net regression. Task-related functional brain activation was measured using ordinal trends canonical variate analysis (OrT CVA), capturing patterns of activation increasing from single to dual conditions. A differential task-related expression score (dOrT) was calculated as the difference in pattern expression scores between single and dual conditions at baseline. A linear regression model tested whether dOrT moderated the impact of brain changes on changes in switch cost over five years. Results showed a significant interaction between changes in brain structure and dOrT activation on switch cost change, indicating a moderation effect of task-related activation. Higher dOrT buffered the impact of brain structural decline on switch costs, enabling older adults to better cope with age-related brain structural changes and preserve cognitive flexibility. These findings suggest that these task-related activation patterns represent a neural basis for CR.

Identification of new instances of white matter hyperintensities in patients following TAVI (from the CAPITA study)

Abstract A third of patients diagnosed with symptomatic severe aortic valve stenosis and scheduled for transcatheter aortic valve implantation (TAVI) exhibit some level of cognitive impairment. The prospective CAPITA study aimed to systematically evaluate the impact of TAVI on cerebral and cognitive outcomes in patients undergoing the procedure. In this report, we focus on the identification of new incidence of white matter hyperintensities (WMH) and the correlation with changes in cognitive functioning. The CAPITA (CArdiac OutPut, Cerebral Blood Flow and Cognition In Patients With Severe Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Implantation) study is a prospective study of cerebral and cognitive outcomes following TAVI. Patients underwent magnetic resonance imaging (MRI) and extensive neuropsychological testing at baseline and three month follow-up. New cerebral infarcts were defined according to NeuroARC criteria. We examined the incidence of new WMH in terms of volume (Δ mL) and number on FLAIR MRI, and explored the correlation between new WMH and cognitive functioning. A total of 148 patients were included who underwent TAVI between August 2020 and October 2022. Mean age was 80.5±5.7 years, of whom 43% female with a median STS-PROM of 2.0% (IQR 1.4%-2.9%). Median baseline WMH comprised 127 (IQR 32-216) lesions, with a total volume of 13.1 (IQR 7.0-24.6) mL. At 3 months follow-up, the number of lesions increased to 164 (IQR 121-301) lesions, with a total volume of 13.3 (IQR 5.8-21.5) mL. Median WMH volume increase was 0.1 (IQR 0.0-0.3) ml (p=0.02). A total of 9 patients (9.5%) had an increase of 1 mL of WMH or more. At follow-up, 12% of patients exhibited cognitive decline of &amp;gt;0.5SD. These patient tended to have a greater increase in white matter hyperintensity volume (1.26±2.96 ml), compared to the 53% of patients with stable cognition (0.29±0.45 ml) and the 36% of patients with improved cognition (0.31±0.91 ml), (p=0.06). WMH lesions did not exhibit distribution patterns across various locations within the groups characterized by declined, stable, or improved cognition (Figure 1). WMH volumes were higher in patients who experienced postprocedural delirium than in patients without delirium (27.1±14.0 vs 15.0±12.5 mL, p&amp;lt;0.001). In this study, patients with severe symptomatic aortic valve stenosis undergoing TAVI, there was an overall increase of white matter hyperintensity volume between baseline and 3-month follow-up. Up to 12% of patients had cognitive decline, which was associated with new white matter hyperintensities on MRI.

Multidomain cognitive improvement in patients with severe aortic valve stenosis undergoing transcatheter aortic valve implantation

Abstract Background Cognitive impairment is prevalent in one third of patients with symptomatic severe aortic valve stenosis scheduled for transcatheter aortic valve implantation (TAVI). How TAVI affects cognitive functioning in these patients remains unknown. Purpose The CAPITA study (CArdiac outPut, cerebral blood flow and cognition In patients with severe aortic valve stenosis undergoing Transcatheter Aortic valve implantation) assessed the effects of TAVI on cerebral lesions and cognitive functioning. Methods CAPITA is a prospective study of cerebral and cognitive outcomes in 148 patients undergoing TAVI. One day before and three months after TAVI, patients underwent a standardized multidomain neuropsychological assessment, and simultaneous brain magnetic resonance imaging. The primary outcome was change in global cognitive functioning as measured with z-scores. Also, we assessed the cognitive subdomains of attention/psychomotor speed, memory, language, and executive functioning. Z-scores for each cognitive domain were constructed as: (test score - mean baseline score) / standard deviation. Global cognitive function was calculated as the mean from the four domain scores. Results Mean age was 80.5±5.7 years, 43% was female and median STS-PROM (Society for Thoracic Surgeons Predicted Risk for 30-day Mortality) was 2.0% (IQR 1.4%-2.9%). MoCA scores improved from 23.3±3.7 to 24.4±3.3, (p&amp;lt;0.001) and MMSE scores from 26.4±2.6 to 26.9±2.4 (p=0.01). There was an overall increase in global cognitive z-scores (0.02±0.52 to 0.15±0.48, p&amp;lt;0.001). Cognitive domains of memory (0.03±0.77 to 0.18±0.80, p=0.003) and language (-0.07±1.07 to 0.20±0.80, p=0.02) significantly improved, whereas executive function (0.01±0.70 to 0.06±0.76, p=0.42) and attention (0.10±0.69 to 0.17±0.69, p=0.06) did not significantly change. Quality of life on the visual analogue scale improved from 66.4±15.9 to 72.9±12.8, (p&amp;lt;0.001). Patients in the lowest tertile of baseline cognitive functioning (i.e., those with worst baseline cognitive functioning), had the largest increase in cognitive functioning, compared with patients in the intermediate or highest tertile of baseline cognitive functioning (0.30±0.55 vs 0.09±0.27 vs 0.01±0.16, p=0.002). Patients with &amp;gt;0.5 SD decline in cognitive functioning (12%), had a higher volume of new white matter hyperintensities on follow-up MRI than patients with stable or improved cognitive functioning (1.26±2.96, vs 0.29±0.45 vs 0.31±0.91 mL, p=0.06). Conclusions In 148 patients who underwent TAVI, there was an overall improvement in cognitive functioning at three months follow-up. This improvement was consistent through different cognitive domains and most prominent in patient with lowest baseline cognitive functioning.Change in cognitive functionin

Amplifying School Mental Health Literacy Through Neuroscience Education

Children and adolescents face a wide variety of developmental changes and environmental challenges, and it is estimated that at least one in five children aged 3–17 will experience behavioral or mental health issues. This period of life coincides with major changes in brain structure and function that have profound long-term consequences for learning, decision-making (including risk taking), and emotional processing. For example, continued development of the prefrontal cortex in adolescence is a sensitive period during which individuals are particularly susceptible to risky behaviors, environmental stressors, and substance use. While recent advances in mental health literacy programs have paved the way for increased awareness of the benefits of mental health curricula in schools, these efforts could be greatly bolstered with support in basic neuroscience education in developmentally appropriate and area-specific content. Here, we provide a discussion on the basic structural and functional changes occurring in the brain throughout childhood, how this contributes to changes in cognitive function, and the risk factors posed by early life adversity, stress, and drug use. Finally, we provide a perspective on the benefits of integrating findings from the field of neuroscience and suggestions for tools to better equip students, teachers, administrators, and school mental health staff to provide new directions for addressing the mental health crises faced by millions of children and youth each year.

Varoglutamstat: Inhibiting Glutaminyl Cyclase as a Novel Target of Therapy in Early Alzheimer's Disease.

Varoglutamstat is a first-in-class, small molecule being investigated as a treatment for early Alzheimer's disease (AD). It is an inhibitor of glutaminyl cyclase (QC), the enzyme that post-translationally modifies amyloid-β (Aβ) peptides into a toxic form of pyroglutamate Aβ (pGlu-Aβ) and iso-QC which post-translationally modifies cytokine monocyte chemoattractant protein-1 (CCL2) into neuroinflammatory pGlu-CCL2. Early phase clinical trials identified dose margins for safety and tolerability of varoglutamstat and biomarker data supporting its potential for clinical efficacy in early AD. Present the scientific rationale of varoglutamstat in the treatment of early AD and the methodology of the VIVA-MIND (NCT03919162) trial, which uses a seamless phase 2A-2B design. Our review also includes other pharmacologic approaches to pGlu-Aβ. Phase 2A of the VIVA-MIND trial will determine the highest dose of varoglutamstat that is safe and well tolerated with sufficient plasma exposure and a calculated target occupancy. Continuous safety evaluation using a pre-defined safety stopping boundary will help determine the highest tolerated dose that will carry forward into phase 2B. An interim futility analysis of cognitive function and electroencephalogram changes will be conducted to inform the decision of whether to proceed with phase 2B. Phase 2B will assess the efficacy and longer-term safety of the optimal selected phase 2A dose through 72 weeks of treatment. Varoglutamstat provides a unique dual mechanism of action addressing multiple pathogenic contributors to the disease cascade. VIVA-MIND provides a novel and efficient trial design to establish its optimal dosing, safety, tolerability, and efficacy in early AD.

Effects of repetitive transcranial magnetic stimulation on cognitive function and hormone levels in early stroke patients with low thyroid hormone levels.

This study aimed to observe the effects of repetitive transcranial magnetic stimulation (rTMS) on cognitive function and thyroid hormone levels in early older stroke patients with low thyroid hormone levels, and to investigate the correlation between the changes in thyroid hormone levels and the improvements in cognitive function after stroke. Forty older stroke patients who met the inclusion criteria were recruited and randomized into a magnetic-stimulation group (rTMS group) and a sham-stimulation group (Sham group). The rTMS group received low-frequency true stimulation and the Sham group received low-frequency sham stimulation. Patients' cognitive scores, activity of daily living(ADL) scores, and their levels of triiodothyronine (T3), free triiodothyronine (FT3), thyroxin (T4), free thyroxine (FT4), and thyroid stimulating hormone (TSH) were assessed before the intervention, after the 4-week intervention, and after an additional 4 weeks of follow-up; Repeated measurement analysis of variance was used to compare the changes of each index in the two groups at different times and the correlations between patiens' cognitive function scores and their changing hormone levels were subsequently investigated. Thirty-one patients were included in this study: 16 patients in rTMS group and 15 patients in the Sham group. Repeated-measures ANOVA showed that patients' T3,FT3 and TSH levels tended to increase at 4-week intervention and at the follow up (p < 0.05), and that the rTMS group had a better effect on improving T3 than the Sham group (Fgroup = 5.319, p = 0.028); The cognitive scale at different time points in both groups showed an upward trend (p < 0.05), and the MoCA, DSF, DSB scores in the rTMS group were statistically higher than those in the Sham group at the end of the 4-week intervention and at the follow-up (p < 0.05); The changes in the levels of T3 before and after 4-week intervention were positively correlated with the changes in the MoCA scores (r = 0.638, p < 0.05). And the difference in T3 level change was positively correlated with the difference in delayed recall, attention and naming score change (r = 0.562, p < 0.05; r = 0.562, p < 0.05; r = 0.531, p < 0.05); and the difference in FT3 level change was positively correlated with the visuospatial and executive function (r = 0.514, p < 0.05). Repetitive transcranial magnetic stimulation improved cognitive function and elevated T3 levels in older patients with post-stroke cognitive dysfunction who had low thyroid hormone levels. Within the normal range, increases in T3 levels are positively correlated with changes in cognitive function.

Efficacy of high-frequency rTMS in the treatment of gait disorder and cognition in patients with Parkinson's disease based on wearable devices and eye-movement assessments.

Postural instability and gait disorder and cognitive dysfunction are common symptoms of Parkinson's disease (PD). Scale assessment is frequently used in the clinic to evaluate PD, but this technique is limited by its lack of sensitivity to changes in disease progression and its difficulty in capturing subtle movements and changes in cognitive function. It is currently believed that high-frequency repetitive transcranial magnetic stimulation (rTMS) can improve motor and cognitive dysfunction in patients with PD, though it remains controversial. Therefore, it is imperative to monitor and dynamically identify changes in postural instability and gait disorder, as well as those in cognitive dysfunction, in PD to develop targeted interventions. In this study, we observed the effect of high-frequency rTMS on gait disorders and cognitive functions in patients with PD by comparing data from wearable devices and eye-tracking devices before and after treatment. A total of 159 patients with PD were included in this study. A GYENNO MATRIX wearable gait analyzer was used to monitor the objective gait data (including the timed up-and-go, narrow-track, and turning tests), the Eyeknow eye-tracking evaluation system was used to monitor the patient's eye movement cognition data (including the smooth pursuit, pro-saccade, and anti-saccade tests), and gait and cognitive function-related scales, including the Tinetti Balance Scale, Tinetti Gait Scale, Berg Balance Scale, Mini-Mental State Examination, and Montreal Cognitive Assessment (MoCA), were evaluated at the same time before and after high-frequency rTMS treatment. The mean step length, mean stride velocity, stride length, and mean step frequency of patients with PD in the timed up-and-go test all increased compared with those before rTMS treatment, whereas the mean stride time and double support decreased. In the narrow-track test, the mean stride velocity increased and the mean stride time decreased. In the turning test, the turning left duration, turning right duration, mean duration, mean number of steps, and average step duration decreased, while the mean angular velocity increased after rTMS treatment. Compared with those before rTMS treatment, the latency period of patients with PD in overlapping saccades decreased, the completion time of overlapping saccades decreased, and the average saccade speed increased. In the anti-saccade test, the completion time decreased and the average saccade speed increased after rTMS treatment. Compared with those before rTMS treatment, the Tinetti Balance Scale, Tinetti Gait Scale, Berg Balance Scale, Mini-Mental State Examination, and MoCA scores increased, and the MoCA sub-items improved in terms of visual-spatial and executive function, language, abstraction, delayed recall, and orientation after rTMS treatment. High-frequency rTMS may be an effective therapy for improving gait disorders and cognitive functions in patients with PD.

Handgrip Strength and Cognitive Recovery in Older Stroke Survivors: A Prospective Study

Background and Objectives: Handgrip strength (HGS) is an important indicator of overall physical capability and is linked to various health outcomes in older adults. Despite extensive research on the relationship between HGS and cognitive decline, longitudinal studies on poststroke cognitive changes in relation to HGS are scarce. This study aimed to observe whether HGS at discharge from acute stroke rehabilitation affects cognitive function 6–12 months after stroke onset and to compare cognitive outcomes between patients with normal and low HGS at discharge. Materials and Methods: This prospective cohort study was conducted in the Department of Rehabilitation Medicine at a tertiary care hospital. In agreement with the Asian Working Group for Sarcopenia 2019 criteria, low muscle strength was defined as an HGS of less than 28 kg for men and less than 18 kg for women, and participants were categorized into normal and low HGS groups. Neuropsychological evaluations were conducted before discharge (approximately one month after stroke onset) and between 6 and 12 months after stroke onset. Results: The low HGS group was older and had lower Montreal Cognitive Assessment scores. However, after adjusting for covariates, the linear mixed model analysis showed no significant differences between the groups in global cognition or specific cognitive domains, except for psychomotor speed during the subacute phase. Notable improvements in language ability were observed in both groups over time, while significant improvements in executive function were observed exclusively in the low HGS group. Conclusions: This longitudinal study is the first to explore the relationship between HGS and changes in cognitive function in older adults with stroke, providing insights into physical strength and cognitive recovery during stroke rehabilitation.

Predicting cognitive function changes from oral health status: a longitudinal cohort study

Recent studies indicate a potential link between oral health and cognitive function; however, long-term associations remain unclear. This study aimed to identify oral health factors that predict changes in cognitive function among older adults over time. The study included 583 independent older adults (201 male, 382 female) with a mean age of 72.7 years. Cognitive function was assessed using Mini-Mental State Examination (MMSE) at baseline and follow-up over two years, with relative change in MMSE (rMMSE) calculated. Baseline oral health variables included number of remaining teeth, masticatory performance, occlusal force, oral diadochokinesis and tongue pressure. Physical performance and confounding factors were also considered. The relationship between rMMSE and the variables was analyzed using Pearson’s correlation, Mann-Whitney U test, and multiple linear regression analysis. Cognitive function declined in 196 subjects, with rMMSE significantly correlated with oral diadochokinesis. Regression analysis revealed significant associations between cognitive changes and oral diadochokinesis (p = 0.020) and knee extension strength as a physical performance (p = 0.047). Our findings suggest that cognitive decline may be indicated by declines in both physical and oral motor performance. Incorporating oral diadochokinesis testing into health screenings could aid early detection of cognitive decline, improving outcomes and reducing healthcare burdens.

Value of narcotrend anesthesia depth monitoring in predicting POCD in gastrointestinal tumor anesthesia block patients

BackgroundThe purpose of this research was to evaluate the efficacy of Narcotrend (NT) monitoring on cognitive dysfunction in patients undergoing anesthesia blockade for gastrointestinal tumors and its effect on cerebral oxygen metabolism and inflammatory response.MethodsPatients preparing to undergo resection of gastrointestinal tumor resection were included and randomly divided into a control group (depth of anesthesia assessed by physician experience) and a research group (depth of anesthesia monitored by NT). HR and MAP were monitored at the preoperatively (T0), 12 h postoperative (T1), 24 h postoperative (T2), and 48 h postoperative (T3) stages. MMSE score was recorded to assess changes in cognitive function. Intracerebral oxygenation indicators (CjvO2, CERO2, and rSO2) were assessed by a blood gas analyzer. ELISA assay was conducted to explore the serum inflammatory indexes (CRP, IL-1β, and TNF-α) and neurological function indicators (NSE and MBP).ResultsMAP was higher in the research group than in the control group at T1 and T2 (P < 0.05). MMSE scores at T1, T2, and T3 stages were higher in the research group than in the control (P < 0.05). The incidence of POCD was also lower in the research group compared with the control (P < 0.05). CjvO2, CERO2, and rSO2 were significantly higher (P < 0.05) and were positively correlated with the MMSE scores. Postoperative serum inflammatory indexes were significantly elevated in both groups, but more significantly in the control group (P < 0.05). Both neurological function indicators were usually reduced after surgery, but the reduction was more significant in the research group (P < 0.05).ConclusionNT monitoring of anesthetic depth has a less physical impact on patients with gastrointestinal tumor anesthetic block, reduces the degree of postoperative POCD, and has significant clinical value.

Safety, tolerability, and efficacy outcomes of the Investigation of Levetiracetam in Alzheimer's disease (ILiAD)study: a pilot, double-blind placebo-controlled crossover trial.

To assess whether the antiseizure medication levetiracetam may improve cognition in individuals with Alzheimer's disease who have not previously experienced a seizure. We performed a randomized, double-blind, placebo-controlled crossover pilot study in individuals with mild-to-moderate Alzheimer's disease. Electroencephalography was performed at baseline and those with active epileptiform discharges were excluded. Eligible participants were randomized to placebo for 12 weeks or an active arm of oral levetiracetam (4 weeks up-titration to levetiracetam 500 mg twice daily, 4 weeks maintained on this dose followed by 4 weeks down-titration to nil). Participants then crossed over to the other arm. The primary outcome was change in cognitive function assessed by the Oxford Memory Task, a task sensitive to hippocampal memory binding. Secondary outcomes included tolerability, other neuropsychological scales, and general questionnaires. Recruitment numbers were severely limited owing to restrictions from the COVID-19 pandemic at the time of the study. Eight participants completed both arms of the study (mean age 68.4 years [SD = 9.2]; 5 females [62.5%]). No participants withdrew from the study and there was no significant difference between reported side effects in the active levetiracetam or placebo arm. Measures of mood and quality of life were also not significantly different between the two arms based on participant or carer reports. In limited data analysis, there was no statistically significant difference between participants in the active levetiracetam and placebo arm on the memory task. This pilot study demonstrates that levetiracetam was well tolerated in individuals with Alzheimer's disease who do not have a history of seizures and has no detrimental effect on mood or quality of life. Larger studies are needed to assess whether levetiracetam may have a positive effect on cognitive function in subsets of individuals with Alzheimer's disease. Abnormal electrical activity within the brain, such as is seen in seizures, might contribute to memory problems in people with dementia. We completed a clinical trial to see if an antiseizure medication, levetiracetam, could help with memory difficulties in people with Alzheimer's disease (the most common cause of dementia). In this pilot study, we could not prove whether levetiracetam helped memory function. We did show that the drug is safe and well tolerated in people with dementia who have not had a seizure. This work, therefore, offers a platform for future research exploring antiseizure medications in people with dementia.