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This report examines extended intra-nasal insulin treatment [INI] for an Insulin Resistant early Mild Cognitive Impairment [MCI] patient. Patient [EJ] also had medial temporal lobe [MTL] damage, poor short-term memory, significant irritability, and social and linguistic withdrawal at treatment start. Compared to baseline, nine months INI treatment increased grey matter volume, lowered beta-amyloid levels, and improved MCI and FAS scores. Patient also increased pragmatic capacities in social conversation and procedural memory. These findings align with results from prior clinical trials on INI and suggest that treatment can slow neurodegenerative disease progression in early MCI patients. [ABSTRACT FROM AUTHOR]

Abstract Objective To study the effects of selective serotonin reuptake inhibitors (SSRIs) on cognitive functions, mental improvements, and adverse effects in patients with Alzheimer’s disease (AD). Methods Registered in INPLASY (INPLASY202450004), five drugs (citalopram, s-citalopram, quetiapine, olanzapine, and sertraline) were selected as representatives. A comprehensive search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library up to May 15, 2024. Search terms were combined using Boolean operators, specifically ‘AND’ between different categories (e.g., ‘Alzheimer’s Disease’ AND ‘SSRIs’) and ‘OR’ within the same category (e.g., ‘citalopram OR s-citalopram OR quetiapine OR olanzapine OR sertraline’), to ensure a thorough retrieval of relevant studies. The selection followed rigorous inclusion and exclusion criteria for meta-analysis. Results Fourteen articles from 1118 were selected for meta-analysis. The indicators, including Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), Brief Psychiatric Rating Scale (BPRS), and Cornell Scale for Depression in Dementia (CSDD), were used to assess the effects of the drugs on AD treatment. According to the results of NPI, CSDD, BPRS, MMSE, and security assessments, the five antidepressants have significant advantages in AD treatment compared with placebo, while the MMSE of the patient treated with the antidepressants did not show notable changes compared with patients treated only with placebo. Statistical analyses were conducted using Review Manager 5.3, employing random-effects models to account for study heterogeneity and sensitivity analyses to test the robustness of our findings. Conclusion This study suggests that SSRI-related antidepressants have great potential values in AD treatment, and further research on the application of SSRI-related antidepressants in AD treatment is necessary.

BACKGROUND: Intermittent theta burst stimulation (iTBS) has demonstrated efficacy in patients with cognitive impairment. However, activation patterns and mechanisms of iTBS for post-stroke cognitive impairment (PSCI) remain insufficiently understood. OBJECTIVE: To investigate the activation patterns and potential benefits of using iTBS in patients with PSCI. METHODS: A total of forty-four patients with PSCI were enrolled and divided into an iTBS group (iTBS and cognitive training) or a control group (cognitive training alone). Outcomes were assessed based on the activation in functional near-infrared spectroscopy (fNIRS), as well as Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) and the modified Barthel Index (MBI). RESULTS: Thirty-eight patients completed the interventions and assessments. Increased cortical activation was observed in the iTBS group after the interventions, including the right superior temporal gyrus (STG), left frontopolar cortex (FPC) and left orbitofrontal cortex (OFC). Both groups showed significant improvements in LOTCA and MBI after the interventions (p < 0.05). Furthermore, the iTBS group augmented superior improvement in the total score of MBI and LOTCA compared to the control group, especially in visuomotor organization and thinking operations (p < 0.05). CONCLUSION: iTBS altered activation patterns and improved cognitive function in patients with PSCI. The activation induced by iTBS may contribute to the improvement of cognitive function. [ABSTRACT FROM AUTHOR]

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Aim: Baseline cognitive functions of patients predicted the efficacy of cognitive remediation therapy (CRT), but results are mixed. Eye movement is amore objective and advanced assessment of cognitive functions than neuropsychological testing. We aimed to investigate the applicability of eye movements in predicting cognitive improvement after patients with schizophrenia were treated with CRT. Methods: We recruited 79 patients with schizophrenia to complete 8 weeks of CRT and assessed their cognitive improvement outcomes. Eye movements were assessed by prosaccades, antisaccades, and free-viewing tasks at baseline, and neuropsychological tests in four cognitive domains were assessed before and after treatment to calculate treatment outcomes. Predictors of demographic information, clinical characteristics, and eye movement measures at baseline on cognitive improvement outcomes were analyzed using logistic regression analysis. We further compared the predictive performance between eye movement measurements and neuropsychological test regarding the effect of CRT on cognitive improvement, and explored factors that could be affect the treatment outcomes in different cognitive domains. Results: As operationally defined, 33 patients showed improved in cognition (improved group) and 46 patients did not (non-improved group) after CRT. Patients with schizophrenia being employed, lower directional error rate in antisaccade task, and lower the gap effect (i.e., the difference in saccadic latency between the gap condition and overlap condition) in prosaccade task at baseline predicted cognitive improvement in CRT. However, performance in the free-viewing task not associated with cognitive improvement in patients in CRT. Our results show that eye-movement prediction model predicted the effect of CRT on cognitive improvement in patients with schizophrenia better than neuropsychological prediction model in CRT. In addition, baseline eyemovements, cognitive reserve, antipsychotic medication dose, anticholinergic cognitive burden change, and number of training sessions were associated with improvements in four cognitive domains. Conclusion: Eye movements as a non-invasiveness, objective, and sensitive method of evaluating cognitive function, and combined saccadic measurements in pro- and anti-saccades tasks could be more beneficial than free-viewing task in predicting the effect of CRT on cognitive improvement in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

This research was motivated by the low ability of students to apply mathematical solution methods to thermodynamic functions. Thermodynamic functions are functions that consist of pressure, temperature, volume and enthalpy functions where changes in one function can occur due to changes in other functions. The aim of this research was to show the implementation of chain rules in thermodynamic function problems by relying on a process technique to improve students' cognitive awareness of thermodynamic functions. The place of this research was at the TD Pardede Institute of Science and Technology. The process of understanding chain rules is very impactful for understanding thermodynamic state functions. Differential decomposition of functions within functions is also described in the chain rule method. Thermodynamic functions which consist of pressure, temperature, volume and enthalpy functions can depend on each other so that the chain rule analysis method can be clearly used. With this method students will also be given the opportunity to connect one concept with other thermodynamic concepts. Apart from that, this method can be used anywhere. This shows a cognitive increase in terms of cognitive elements, cognitive structure and cognitive function.

AbstractButyrylcholinesterase (BuChE) and neuroinflammation have recently emerged as promising therapeutic directions for Alzheimer’s disease (AD). Herein, we synthesised 19 novel pyranone-carbamate derivatives and evaluated their activities against cholinesterases and neuroinflammation. The optimal compound 7p exhibited balanced BuChE inhibitory activity (eqBuChE IC50 = 4.68 nM; huBuChE IC50 = 9.12 nM) and anti-neuroinflammatory activity (NO inhibition = 28.82% at 10 μM, comparable to hydrocortisone). Enzyme kinetic and docking studies confirmed compound 7p was a mix-type BuChE inhibitor. Additionally, compound 7p displayed favourable drug-likeness properties in silico prediction, and exhibited high BBB permeability in the PAMPA-BBB assay. Compound 7p had good safety in vivo as verified by an acute toxicity assay (LD50 > 1000 mg/kg). Most importantly, compound 7p effectively mitigated cognitive and memory impairments in the scopolamine-induced mouse model, showing comparable effects to Rivastigmine. Therefore, we envisioned that compound 7p could serve as a promising lead compound for treating AD.

Background: Schizophrenia is a serious psychiatric disorder that significantly affects the quality of life of patients. The objective of this study is to discover a novel antipsychotic candidate with highly antagonistic activity against both serotonin and dopamine receptors, demonstrating robust efficacy in animal models of positive, negative, and cognitive symptoms of schizophrenia. Methods: In the present study, we examined the activity of antipsychotic drug (NH300094) on 5-HT2A, 5-HT2C, 5-HT1A, 5-HT1B, 5-HT7, H1, M1, Alpha1A, D2L, D2S, Alpha2A, D3 receptor functional assay in vitro. In addition, multiple animal models, including dizocilpine (MK-801) induced hyper-locomotion; APO induced climbing; Conditioned Avoidance Response (CAR); DOI-Induced Head Twitch; Forced swimming test; Scopolamine induced cognitive impairment model, were used to verify the antipsychotic activity of NH300094 in preclinical. Results: In vitro functional assays have indicated that NH300094 is a potent antagonist of 5-HT receptors and dopamine receptors, with higher relative antagonistic activity against 5-HT2A receptor (5-HT2A IC50 = 0.47 nM) than dopamine receptors (D2L IC50 = 1.04 nM; D2S IC50 = 11.71 nM; D3 IC50 = 31.55 nM). Preclinical in vivo pharmacological study results showed that NH300094 was effective in multiple models, which is more extensive than the clinic drug Risperidone. Furthermore, the safety window for extrapyramidal side effects of NH300094 is significantly wider than that of Risperidone (For NH300094, mice catalepsy model ED50/Mice MK-801 model ED50 = 104.6-fold; for Risperidone, mice catalepsy model ED50/Mice MK-801 model ED50 = 12.9-fold), which suggests a potentially better clinical safety profile for NH300094. Conclusion: NH300094 is a novel potent serotonin and dopamine receptors modulator, which has good safety profile and therapeutic potential for the treatment of schizophrenia with cognition disorders. [ABSTRACT FROM AUTHOR]

Foundational frameworks are formal theories or intervention rationales used to justify choices of and ensure congruence between variables. What are the characteristics of foundational frameworks in studies of music interventions designed to improve cognition among people with mild cognitive impairment (MCI), and are choices of music intervention and outcome measures congruent with them? This review addresses this question and allows practitioners to evaluate research-based clinical strategies and to transfer these protocols into effective practice. Experimental studies were included if they enrolled only people with MCI, focused exclusively on cognition and used music as a primary intervention. Thirteen studies met the full inclusion criteria and were selected based on consultation between the two authors. Searches were conducted between April and July 2020 and updated in August 2022. Integrative review methodology was used to extract, analyze and evaluate information pertaining to each research question, and included a quality appraisal. Results found that eight studies relied primarily on prior research to justify selection of music interventions. Twenty-five different outcome measures were used across all studies, and while music experiences appeared to be connected to the constructs represented in these measures, some connections were indirect or unclear. Finally, there was considerable variation in the depth and degree of congruence between explanatory frameworks and choices regarding music interventions and outcome measures. Findings from this review are important for the development of future theoretical models, clinical research, and evidence-based treatment protocols in this emerging area of practice. [ABSTRACT FROM AUTHOR]

This report examines extended intra-nasal insulin treatment [INI] for an Insulin Resistant early Mild Cognitive Impairment [MCI] patient. Patient [EJ] also had medial temporal lobe [MTL] damage, poor short-term memory, significant irritability, and social and linguistic withdrawal at treatment start. Compared to baseline, nine months INI treatment increased grey matter volume, lowered beta-amyloid levels, and improved MCI and FAS scores. Patient also increased pragmatic capacities in social conversation and procedural memory. These findings align with results from prior clinical trials on INI and suggest that treatment can slow neurodegenerative disease progression in early MCI patients.

Objective: Cognitive impairment is one of the core symptoms of schizophrenia, which is stable and lifelong. L-carnitine has been shown to improve cognitive function and decrease the rate of cognitive deterioration in patients with Alzheimer's disease. However, it remains unclear regarding the role of L-carnitine and its metabolites in cognitive functions in schizophrenia after treatment with olanzapine. The purpose of this study was to evaluate the relationship between changes in plasma levels of L-carnitine metabolites and cognitive improvement after olanzapine treatment. Methods: This was a prospective longitudinal study. In this study, we recruited 25 female patients with first episode schizophrenia (FES) who were drug naïve at baseline and received 4 weeks of olanzapine monotherapy. Cognitive function was assessed at baseline and 4-week follow-up using the RBANS. Plasma L-carnitine metabolite levels were determined by a metabolomics technology based on untargeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Results: We found that the immediate memory index, delayed memory index and RBANS composite score were significantly increased at the 4-week follow-up after treatment. A total of 7 differential L-carnitine metabolites were identified in FES patients after olanzapine monotherapy. In addition, we found that changes in butyrylcarnitine were positively correlated with improvements in language index and RBANS composite score. Further regression analyses confirmed the association between reduced butyrylcarnitine levels and cognitive improvement after olanzapine monotherapy in FES patients. Conclusion: Our study shows that cognitive improvement after olanzapine treatment was associated with changes in L-carnitine metabolite levels in patients with FES, suggesting a key role of L-carnitine in cognition in schizophrenia. [ABSTRACT FROM AUTHOR]

This systematic review examines the potential of digital language learning in contributing to students' cognitive gains. The study reviews existing research on the relationship between digital language learning and cognitive benefits, with a focus on enhanced problem-solving skills, memory, and multitasking ability. The research questions explored in this study are (1) does digital language learning contribute to cognitive gains in foreign language education? and (2) what are the pedagogical implications for cognitive improvement in digital foreign language education? The study employs the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to identify and analyze relevant research articles. The results of the review suggest that working with printed texts may be more effective for cognitive gains compared to electronic texts. Additionally, implementing more senses through digital language education appears to be beneficial for cognitive gains. Thus, several pedagogical implications emerge for promoting cognitive improvement in digital foreign language education. Firstly, it is crucial to implement techniques and strategies that best align with students' language needs in a digital learning environment, whether it involves pen-and-paper activities or a flipped classroom approach. Secondly, exposing students to a variety of techniques that engage multiple senses can have a positive impact on cognitive gains. Finally, providing students with feedback is essential to maintain their motivation and foster continued progress in their foreign language studies. [ABSTRACT FROM AUTHOR]

β2-Microglobulin (β2M), a component of the major histocompatibility complex class I molecule, is associated with aging-related cognitive impairment and Alzheimer’s disease. Although upregulation of β2M is considered to be highly related to ischemic stroke, the specific role and underlying mechanistic action of β2M are poorly understood. In this study, we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery. We found that β2M levels in the cerebral spinal fluid, serum, and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period. RNA interference was used to inhibit β2M expression in the acute period of cerebral stroke. Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreased β2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits, respectively. Notably, glial cell, caspase-1 (p20), and Nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation as well as production of the inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α were also effectively inhibited by β2M silencing. These findings suggest that β2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.

Purpose: Obstructive sleep apnea (OSA) can impair cognition. Continuous positive airway pressure (CPAP) is a recommended treatment for OSA but its effectiveness on cognitive improvement is uncertain, a finding which may be biased by various durations and adherence to treatment with CPAP. In a meta-analysis assessing high-quality randomized controlled trials (RCTs), we estimated whether or not CPAP benefits cognition in patients with OSA. Methods: PRISMA criteria were followed in the performance of this meta-analysis. The weighted mean difference (WMD) and 95% confidence interval (CI) of six neuropsychological scores covering eight cognitive domains were used to evaluate the benefit between CPAP and non-CPAP interventions. Subgroups of different therapeutic durations and adherence, which were divided into short-term (< 8 weeks) and long-term (≥ 12 weeks) durations, and poor (nighttime < 4 h/night) and good (nighttime ≥ 4 h/night) adherence were also analyzed. Results: Among 16 RCTs, 1529 participants with OSA were included. Comparing the CPAP group and the control group for all treatment durations and adherence, a mild improvement for digit span forward which reflected short-term memory was observed (WMD[95%CI] = 0.67[0.03,1.31], p = 0.04). Trail making test-part B, which reflected executive function was improved for participants with OSA who had good adherence to CPAP (WMD[95%CI] = − 6.24[− 12.60,0.12], p = 0.05). Patients with OSA who received short-term CPAP treatment (WMD[95%CI] = − 7.20[− 12.57, − 1.82], p = 0.009) had a significant improvement in executive function when compared with controls. There was no statistical difference for all scales between long-term (≥ 12 weeks) CPAP treatment group and control group. Conclusion: The effectiveness of CPAP on cognitive improvement in patients with OSA is limited, although good adherence to CPAP can mildly benefit executive function with short-term effectiveness. [ABSTRACT FROM AUTHOR]

Cognitive decline frequently occurs with increasing age, but mechanisms contributing to age-associated cognitive decline (ACD) are not well understood and solutions are lacking. Understanding and reversing mechanisms contributing to ACD are important because increased age is identified as the single most important risk factor for dementia. We reported earlier that ACD in older humans is associated with glutathione (GSH) deficiency, oxidative stress (OxS), mitochondrial dysfunction, glucose dysmetabolism and inflammation, and that supplementing GlyNAC (glycine and N-acetylcysteine) improved these defects. To test whether these defects occur in the brain in association with ACD, and could be improved/reversed with GlyNAC supplementation, we studied young (20-week) and old (90-week) C57BL/6J mice. Old mice received either regular or GlyNAC supplemented diets for 8 weeks, while young mice received the regular diet. Cognition and brain outcomes (GSH, OxS, mitochondrial energetics, autophagy/mitophagy, glucose transporters, inflammation, genomic damage and neurotrophic factors) were measured. Compared to young mice, the old-control mice had significant cognitive impairment and multiple brain defects. GlyNAC supplementation improved/corrected the brain defects and reversed ACD. This study finds that naturally-occurring ACD is associated with multiple abnormalities in the brain, and provides proof-of-concept that GlyNAC supplementation corrects these defects and improves cognitive function in aging. [ABSTRACT FROM AUTHOR]

Electroencephalogram (EEG)-guided adaptive neurostimulation is an innovative kind of non-invasive closed-loop brain stimulation technique that uses audio–visual stimulation on-line modulated by rhythmical EEG components of the individual. However, the opportunity to enhance its effectiveness is a challenging task and needs further investigation. The present study aims to experimentally test whether it is possible to increase the efficiency of EEG-guided adaptive neurostimulation by pre- strengthening the modulating factor (subject's EEG) through the procedure of resonance scanning, i.e., LED photostimulation with the frequency gradually increasing in the range of main EEG rhythms (4–20 Hz). Thirty-six university students in a state of exam stress were randomly assigned to two matched groups. One group was presented with the EEG-guided adaptive neurostimulation alone, whereas another matched group was presented with the combination of resonance scanning and EEG-guided adaptive neurostimulation. The changes in psychophysiological indicators after stimulation relative to the initial level were used. Although both types of stimulation led to an increase in the power of EEG rhythms, accompanied by a decrease in the number of errors in the word recognition test and a decrease in the degree of emotional maladjustment, these changes reached the level of significance only in experiments with preliminary resonance scanning. Resonance scanning increases the brain's responsiveness to subsequent EEG-guided adaptive neurostimulation, acting as a tool to enhance its efficiency. The results obtained clearly indicate that the combination of resonance scanning and EEG-guided adaptive neurostimulation is an effective way to reach the signs of cognitive improvement in stressed individuals. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), once considered a rare disease, is now the most common form of dementia in the elderly population. Current drugs (cholinesterase inhibitors and glutamate antagonists) are safe but of limited benefit to most patients, offering symptomatic relief without successful cure of the disease. Since the last several decades, there has been a great need for the development of a treatment that might cure the underlying causes of AD and thereby slow its progression in vulnerable individuals. That is why phase I, II, and III studies that act on several fronts, such as cognitive improvement, symptom reduction, and enhancing the basic biology of AD, are imperative to stop the disease. This review discusses current treatment strategies, summarizing the clinical features and pharmacological properties, along with molecular docking analyses of the existing medications. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases feature changes in cognition, and anxiety-like and autism-like behaviors, which are associated with epigenetic alterations such as DNA methylation and histone modifications. The amino acid L-serine has been shown to have beneficial effects on neurological symptoms. Here, we found that growth hormone-releasing hormone knockout (GHRH-KO) mice, a GH-deficiency mouse model characterized by extended lifespan and enhanced insulin sensitivity, showed a lower anxiety symptom and impairment of short-term object recognition memory and autism-like behaviors. Interestingly, L-serine administration exerted anxiolytic effects in mice and ameliorated the behavioral deficits in GHRH-KO. L-serine treatment upregulated histone epigenetic markers of H3K4me, H3K9ac, H3K14ac and H3K18ac in the hippocampus and H3K4me in the cerebral cortex in both GHRH-KO mice and wild type controls. L-serine-modulated epigenetic marker changes, in turn, were found to regulate mRNA expression of BDNF, grm3, foxp1, shank3, auts2 and marcksl1, which are involved in anxiety-, cognitive- and autism-like behaviors. Our study provides a novel insight into the beneficial effects of L-serine intervention on neuropsychological impairments. [ABSTRACT FROM AUTHOR]

Background and objective: We recently reported improvements of working memory across 10 years post stroke among middle-aged individuals. However, the mechanisms underlying working-memory recovery are largely unknown. This study investigated the associations between long-term improvement of working memory and resting-state functional connectivity in two frontoparietal networks: the frontoparietal network and the dorsal attention network. Methods: Working memory was repeatedly assessed by the Digit Span Backwards task in 21 persons, within 1 year after stroke onset and again 10 years post stroke onset. Brain functional connectivity was examined by resting state functional magnetic resonance imaging at the 10-year follow-up. Results: A significant improvement of working memory was found among 21 persons after stroke (median age = 64) at the 10-year follow-up compared to the within-one-year assessment. The magnitude of performance improvement on the Digit Span Backwards task was significantly positively correlated with stronger brain connectivity in the frontoparietal network (r = 0.51, p = 0.018) measured at the 10-year follow-up only. A similar association was observed in the dorsal attention network (r = 0.43, p = 0.052) but not in a visual network (r = -0.17, p = 0.46) that served as a control network. The association between functional connectivity within the above-mentioned networks and Digit Span Backwards scores at 10-year after stroke was in the same direction but did not reach significance. Conclusions: The present work relate stronger long-term performance improvement on the Digit Span Backwards task with higher integrity of frontoparietal network connectivity.

This systematic review examines the potential of digital language learning in contributing to students’ cognitive gains. The study reviews existing research on the relationship between digital language learning and cognitive benefits, with a focus on enhanced problem-solving skills, memory, and multitasking ability. The research questions explored in this study are (1) does digital language learning contribute to cognitive gains in foreign language education? and (2) what are the pedagogical implications for cognitive improvement in digital foreign language education? The study employs the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to identify and analyze relevant research articles. The results of the review suggest that working with printed texts may be more effective for cognitive gains compared to electronic texts. Additionally, implementing more senses through digital language education appears to be beneficial for cognitive gains. Thus, several pedagogical implications emerge for promoting cognitive improvement in digital foreign language education. Firstly, it is crucial to implement techniques and strategies that best align with students’ language needs in a digital learning environment, whether it involves pen-and-paper activities or a flipped classroom approach. Secondly, exposing students to a variety of techniques that engage multiple senses can have a positive impact on cognitive gains. Finally, providing students with feedback is essential to maintain their motivation and foster continued progress in their foreign language studies.

The elderly population is increasing and the implementation of stimulating training to promote active aging has become a research issue. This study aimed at investigating the effects of a cognitive-motor exergame training on cognitive functions and mood, in healthy older adults. A randomized controlled pilot study was conducted to compare a cognitive-motor exergame training with a passive control group. The training consisted of 8 sessions of 45 min each, including 10 interactive activities focused on several cognitive functions such as memory, processing speed and executive functions, all requiring motor planning and execution. A total of 57 participants were administered a battery of cognitive tests before and after the training. A mixed-effect ANOVA with group (experimental vs. control) as between factor and time (pre-and post-test) as within factor, was performed to evaluate the effect of the exergame training on cognitive abilities and mood. Results showed significant interaction effects in processing speed [STROOPC: F (1,53.4) = 9.04, p = 0.004, R2 = 0.82], inhibition [3backs’ false alarms: F (1,47.5) = 5.5, p = 0.02, R2 = 0.79], and mood [Beck Depression Inventory: F (1,55) = 4.15, p = 0.04, R2 = 0.6]. Even though post-hoc analyses did not provide statistical evidence supporting the interactions, overall data showed a trend toward better scores only for the experimental group, suggesting a potential improvement in information processing speed, working memory and mood. Exergaming may be a motivating and enjoyable approach to healthy and active aging.

Alzheimer's disease has various potential etiologies, all culminating in the accumulation of beta -amyloid derivatives and significant cognitive decline. Vascular-related pathology is one of the more frequent etiologies, especially in persons older than 65 years, as vascular risk factors are linked to both cerebrovascular disease and the development of AD. The vascular patho-mechanism includes atherosclerosis, large and small vessel arteriosclerosis, cortical and subcortical infarcts, white matter lesions, and microbleeds. These insults cause hypoperfusion, tissue ischemia, chronic inflammation, neuronal death, gliosis, cerebral atrophy, and accumulation of beta-amyloid and phosphorylated tau proteins. In preclinical studies, hyperbaric oxygen therapy has been shown to reverse brain ischemia, and thus alleviate inflammation, reverse the accumulation of beta-amyloid, induce regeneration of axonal white matter, stimulate axonal growth, promote blood-brain barrier integrity, reduce inflammatory reactions, and improve brain performance. In this perspective article we will summarize the patho-mechanisms induced by brain ischemia and their contribution to the development of AD. We will also review the potential role of interventions that aim to reverse brain ischemia, and discuss their relevance for clinical practice. [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation (rTMS) is an effective way to stimulate changes in structural and functional plasticity, which is a part of learning and memory. However, to our knowledge, rTMS-induced specific activity and neural plasticity in different brain regions that affect cognition are not fully understood; nor are its mechanisms. Therefore, we aimed to investigate rTMS-induced cognition-related neural plasticity changes and their mechanisms in different brain regions. Methods: A total of 30 healthy adult rats were randomly divided into the control group and the rTMS group (n = 15 rats per group). The rats in the control and the rTMS group received either 4 weeks of sham or highfrequency rTMS (HF-rTMS) over the prefrontal cortex (PFC). Cognitive function was detected by Morris water maze. Functional imaging was acquired by resting-state functional magnetic resonance imaging (rs-fMRI) before and after rTMS. The protein expressions of BDNF, TrkB, p-Akt, Akt, NR1, NR2A, and NR2B in the PFC, hippocampus, and primary motor cortex (M1) were detected by Western blot following rTMS. Results: After 4 weeks of rTMS, the cognitive ability of healthy rats who underwent rTMS showed a small but significant behavioral improvement in spatial episodic learning and memory performance. Compared with the prerTMS or the control group, rats in the rTMS group showed increased regional homogeneity (ReHo) in multiple brain regions in the interoceptive/default mode network (DMN) and cortico-striatal-thalamic network, specifically the bilateral PFC, bilateral hippocampus, and the left M1. Western blot analyses showed that rTMS led to a significant increase in the expressions of N-methyl- D-aspartic acid (NMDA) receptors, including NR1, NR2A, and NR2B in the PFC, hippocampus, and M1, as well as an upregulation of BDNF, TrkB, and p-Akt in these three brain regions. In addition, the expression of NR1 in these three brain regions correlated with rTMS-induced cognitive improvement. Conclusion: Overall, these data suggested that HF-rTMS can enhance cognitive performance through modulation of NMDA receptor-dependent brain plasticity. [ABSTRACT FROM AUTHOR]

Accurate early predictions of a patient's likely cognitive improvement as a result of a stroke rehabilitation programme can assist clinicians in assembling more effective therapeutic programs. In addition, sufficient levels of explainability, which can justify these predictions, are a crucial requirement, as reported by clinicians. This article presents a machine learning (ML) prediction model targeting cognitive improvement after therapy for stroke surviving patients. The prediction model relies on electronic health records from201 ischemic stroke surviving patients containing demographic information, cognitive assessments at admission from 24 different standardized neuropsychology tests (e.g., TMT, WAIS-III, Stroop, RAVLT, etc.), and therapy information collected during rehabilitation (72,002 entries collected between March 2007 and September 2019). The study population covered young-adult patients with a mean age of 49.51 years and only 4.47% above 65 years of age at the stroke event (no age filter applied). Twenty different classification algorithms (from Python's Scikit-learn library) are trained and evaluated, varying their hyper-parameters and the number of features received as input. Best-performing models reported Recall scores around 0.7 and F1 scores of 0.6, showing the model's ability to identify patients with poor cognitive improvement. The study includes a detailed feature importance report that helps interpret the model's inner decision workings and exposes the most influential factors in the cognitive improvement prediction. The study showed that certain therapy variables (e.g., the proportion of memory and orientation executed tasks) had an important influence on the final prediction of the cognitive improvement of patients at individual and population levels. This type of evidence can serve clinicians in adjusting the therapeutic settings (e.g., type and load of therapy activities) and selecting the one that maximizes cognitive improvement. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease has various potential etiologies, all culminating in the accumulation of beta -amyloid derivatives and significant cognitive decline. Vascular-related pathology is one of the more frequent etiologies, especially in persons older than 65 years, as vascular risk factors are linked to both cerebrovascular disease and the development of AD. The vascular patho-mechanism includes atherosclerosis, large and small vessel arteriosclerosis, cortical and subcortical infarcts, white matter lesions, and microbleeds. These insults cause hypoperfusion, tissue ischemia, chronic inflammation, neuronal death, gliosis, cerebral atrophy, and accumulation of beta-amyloid and phosphorylated tau proteins. In preclinical studies, hyperbaric oxygen therapy has been shown to reverse brain ischemia, and thus alleviate inflammation, reverse the accumulation of beta-amyloid, induce regeneration of axonal white matter, stimulate axonal growth, promote blood–brain barrier integrity, reduce inflammatory reactions, and improve brain performance. In this perspective article we will summarize the patho-mechanisms induced by brain ischemia and their contribution to the development of AD. We will also review the potential role of interventions that aim to reverse brain ischemia, and discuss their relevance for clinical practice.

Accurate early predictions of a patient's likely cognitive improvement as a result of a stroke rehabilitation programme can assist clinicians in assembling more effective therapeutic programs. In addition, sufficient levels of explainability, which can justify these predictions, are a crucial requirement, as reported by clinicians. This article presents a machine learning (ML) prediction model targeting cognitive improvement after therapy for stroke surviving patients. The prediction model relies on electronic health records from 201 ischemic stroke surviving patients containing demographic information, cognitive assessments at admission from 24 different standardized neuropsychology tests (e.g., TMT, WAIS-III, Stroop, RAVLT, etc.), and therapy information collected during rehabilitation (72,002 entries collected between March 2007 and September 2019). The study population covered young-adult patients with a mean age of 49.51 years and only 4.47% above 65 years of age at the stroke event (no age filter applied). Twenty different classification algorithms (from Python's Scikit-learn library) are trained and evaluated, varying their hyper-parameters and the number of features received as input. Best-performing models reported Recall scores around 0.7 and F1 scores of 0.6, showing the model's ability to identify patients with poor cognitive improvement. The study includes a detailed feature importance report that helps interpret the model's inner decision workings and exposes the most influential factors in the cognitive improvement prediction. The study showed that certain therapy variables (e.g., the proportion of memory and orientation executed tasks) had an important influence on the final prediction of the cognitive improvement of patients at individual and population levels. This type of evidence can serve clinicians in adjusting the therapeutic settings (e.g., type and load of therapy activities) and selecting the one that maximizes cognitive improvement.

Cognitive decline frequently occurs with increasing age, but mechanisms contributing to age-associated cognitive decline (ACD) are not well understood and solutions are lacking. Understanding and reversing mechanisms contributing to ACD are important because increased age is identified as the single most important risk factor for dementia. We reported earlier that ACD in older humans is associated with glutathione (GSH) deficiency, oxidative stress (OxS), mitochondrial dysfunction, glucose dysmetabolism and inflammation, and that supplementing GlyNAC (glycine and N-acetylcysteine) improved these defects. To test whether these defects occur in the brain in association with ACD, and could be improved/reversed with GlyNAC supplementation, we studied young (20-week) and old (90-week) C57BL/6J mice. Old mice received either regular or GlyNAC supplemented diets for 8 weeks, while young mice received the regular diet. Cognition and brain outcomes (GSH, OxS, mitochondrial energetics, autophagy/mitophagy, glucose transporters, inflammation, genomic damage and neurotrophic factors) were measured. Compared to young mice, the old-control mice had significant cognitive impairment and multiple brain defects. GlyNAC supplementation improved/corrected the brain defects and reversed ACD. This study finds that naturally-occurring ACD is associated with multiple abnormalities in the brain, and provides proof-of-concept that GlyNAC supplementation corrects these defects and improves cognitive function in aging.

The α7-nicotinic acetylcholine receptor (α7-nAChR) is a recognized target for the treatment of dementia associated with aging and certain developmental disorders. This study evaluates memory improvement in a rat model by the effects of polyunsaturated fatty acids EPA and DHA mediated by α7-nAChR, as well as identifying the minimum dose of EPA/DHA required to generate an effect in the improvement of cognition through α7-nAChR in rats. The modified Y-maze and object recognition behavioral tests were performed in scopolamine-induced amnesic rats, in order to study the effects of long-term supplementation (10, 15, 30, and 60 mg/kg) of the two polyunsaturated fatty acids in improving cognitive impairment. Cognitive enhancement by EPA and DHA is mediated through α7-nAChRs, as evidenced by memory recovery after treatment with a selective α7-nAChR antagonist, methyllycaconitine (MLA). Tacrine, a centrally active acetylcholinesterase inhibitor, and PNU282987, an α7-nAChR agonist, are employed as reference standards. Our data demonstrate that 15 mg/kg EPA and DHA can affect cholinergic neurotransmission positively through memory and cognition and, thus, can exert a beneficial action on learning and memory deficits. [ABSTRACT FROM AUTHOR]

Low oxygen breathing has been the subject of considerable research in recent years. The present review aims to determine the physiological and neuropsychological benefits of lowoxygen training. Specifically, we explored the ways low oxygen affects hormones, neurotransmitters and growth factors responsible for neuroplasticity, higher cognition and positive emotions. In addition, we shed light on the importance of hypoxia to expand the conscious experience. Furthermore, we investigate the role of digital technologies in assisting hypoxic training. The results showed that, when hypoxia occurs, the human body puts into action the amazing survival mission which reveals unexplored alternative plans and healing pathways. Oxygen deprivation, under certain circumstances, has beneficial effects on cognition, mood and consciousness. It was observed an increase in growth factors, which are responsible for tissue repair and regeneration. Hypoxia also was found to stimulate the hormones of pleasure, happiness, pain tolerance, socialization and relaxation. Interestingly, people under hypoxic conditions are more likely to have transcendental experiences -even to develop ‘superhuman’ abilities. Digital technologies facilitate the safe implementation of hypoxic training enabling users to take control of a powerful tool, which is none other than breathing. Metacognition in breathing can help people consciously and safely manipulate their breathing by moving themselves away from their comfort zone and exploring new pathways to rewire their brains and plumb the depths of their physical, cognitive, emotional and spiritual potential. Our findings suggest that hypoxic training could be an effective intervention strategy with important therapeutic benefits for people with learning and other disabilities (i.e adhd, memory deficits, autism, motor, impairments, depression, generalized anxiety disorder). Future educators, therapists and families should be trained to appropriate apply simple hypoxic training exercises even in the educational context. For that reason, research into the physiological and neuropsychological mechanism that is affected by hypoxic training for individuals with learning or other disabilities is necessary. [ABSTRACT FROM AUTHOR]

Electroencephalogram (EEG)-guided adaptive neurostimulation is an innovative kind of non-invasive closed-loop brain stimulation technique that uses audio–visual stimulation on-line modulated by rhythmical EEG components of the individual. However, the opportunity to enhance its effectiveness is a challenging task and needs further investigation. The present study aims to experimentally test whether it is possible to increase the efficiency of EEG-guided adaptive neurostimulation by pre- strengthening the modulating factor (subject’s EEG) through the procedure of resonance scanning, i.e., LED photostimulation with the frequency gradually increasing in the range of main EEG rhythms (4–20 Hz). Thirty-six university students in a state of exam stress were randomly assigned to two matched groups. One group was presented with the EEG-guided adaptive neurostimulation alone, whereas another matched group was presented with the combination of resonance scanning and EEG-guided adaptive neurostimulation. The changes in psychophysiological indicators after stimulation relative to the initial level were used. Although both types of stimulation led to an increase in the power of EEG rhythms, accompanied by a decrease in the number of errors in the word recognition test and a decrease in the degree of emotional maladjustment, these changes reached the level of significance only in experiments with preliminary resonance scanning. Resonance scanning increases the brain’s responsiveness to subsequent EEG-guided adaptive neurostimulation, acting as a tool to enhance its efficiency. The results obtained clearly indicate that the combination of resonance scanning and EEG-guided adaptive neurostimulation is an effective way to reach the signs of cognitive improvement in stressed individuals.

Food-derived bioactive peptides, encrypted in native protein sequence, have attracted enormous research attention due to its potential in the prevention and/or treatment of a broad range of diseases. However, administration route poses a great challenge to their development and commercial applications. Patient-friendly delivery of bioactive peptides which also enhances its efficacy urgently remain to be addressed. Here we compared the effects of oral administration (PO) to intraperitoneal injection (IP) of a walnut-derived bioactive pentapeptide PW5 (Pro-Pro-Lys-Asn-Trp) in cognitive improvement capacity in APP SWE /PS1 ΔE9 transgenic mice. Strikingly, we found that only PO administration of PW5 could effectively ameliorate cognitive impairments and reduce the β-amyloid deposits in the brain compared to the IP administration. This may be attributable to alterations in the gut microbiota communities, including alterations in microbial α- and β-diversities after PO treatment, leading to the reversal of the relative abundances of ten differential genera (e.g. Acinetobacter , Lactobacillus , Akkermansia , Allobaculum , Adlercreutzia , Coriobacteriaceae , unclassified_p_ Firmicutes , Desulfovibrionaceae , Oscillospira and Anaeroplasma) which are highly correlated with disease progression. Thus, this study has leveraged on PW5 to proof the superior efficacy of oral delivery to injection delivery in improving cognitive impairments in vivo , suggesting that oral delivery might be highly recommended as a prioritized delivery route in the development of food-derived peptides. [Display omitted] • PW5 administered orally (PO) and intraperitoneally (IP) exert different effects. • PW5-IP treatment negatively impact body weight in mice compared to PO treatment. • PW5-PO treatment is superior to IP treatment in ameliorating cognitive impairment. • Oral administration of PW5 significantly reduced the Aβ deposition in the brain. • PW5-PO treatment could restore the gut microbiota community of APP/PS1 mice. [ABSTRACT FROM AUTHOR]

Butyrylcholinesterase (BuChE) and neuroinflammation have recently emerged as promising therapeutic directions for Alzheimer's disease (AD). Herein, we synthesised 19 novel pyranone-carbamate derivatives and evaluated their activities against cholinesterases and neuroinflammation. The optimal compound 7p exhibited balanced BuChE inhibitory activity (eqBuChE IC 50 = 4.68 nM; huBuChE IC 50 = 9.12 nM) and anti-neuroinflammatory activity (NO inhibition = 28.82% at 10 μM, comparable to hydrocortisone). Enzyme kinetic and docking studies confirmed compound 7p was a mix-type BuChE inhibitor. Additionally, compound 7p displayed favourable drug-likeness properties in silico prediction, and exhibited high BBB permeability in the PAMPA-BBB assay. Compound 7p had good safety in vivo as verified by an acute toxicity assay (LD 50 > 1000 mg/kg). Most importantly, compound 7p effectively mitigated cognitive and memory impairments in the scopolamine-induced mouse model, showing comparable effects to Rivastigmine. Therefore, we envisioned that compound 7p could serve as a promising lead compound for treating AD.

Neurodegenerative diseases feature changes in cognition, and anxiety-like and autism-like behaviors, which are associated with epigenetic alterations such as DNA methylation and histone modifications. The amino acid L-serine has been shown to have beneficial effects on neurological symptoms. Here, we found that growth hormone-releasing hormone knockout (GHRH-KO) mice, a GH-deficiency mouse model characterized by extended lifespan and enhanced insulin sensitivity, showed a lower anxiety symptom and impairment of short-term object recognition memory and autism-like behaviors. Interestingly, L-serine administration exerted anxiolytic effects in mice and ameliorated the behavioral deficits in GHRH-KO. L-serine treatment upregulated histone epigenetic markers of H3K4me, H3K9ac, H3K14ac and H3K18ac in the hippocampus and H3K4me in the cerebral cortex in both GHRH-KO mice and wild type controls. L-serine-modulated epigenetic marker changes, in turn, were found to regulate mRNA expression of BDNF, grm3, foxp1, shank3, auts2 and marcksl1, which are involved in anxiety-, cognitive- and autism-like behaviors. Our study provides a novel insight into the beneficial effects of L-serine intervention on neuropsychological impairments.

Alzheimer’s disease (AD), once considered a rare disease, is now the most common form of dementia in the elderly population. Current drugs (cholinesterase inhibitors and glutamate antagonists) are safe but of limited benefit to most patients, offering symptomatic relief without successful cure of the disease. Since the last several decades, there has been a great need for the development of a treatment that might cure the underlying causes of AD and thereby slow its progression in vulnerable individuals. That is why phase I, II, and III studies that act on several fronts, such as cognitive improvement, symptom reduction, and enhancing the basic biology of AD, are imperative to stop the disease. This review discusses current treatment strategies, summarizing the clinical features and pharmacological properties, along with molecular docking analyses of the existing medications.

Aim: Baseline cognitive functions of patients predicted the efficacy of cognitive remediation therapy (CRT), but results are mixed. Eye movement is a more objective and advanced assessment of cognitive functions than neuropsychological testing. We aimed to investigate the applicability of eye movements in predicting cognitive improvement after patients with schizophrenia were treated with CRT., Methods: We recruited 79 patients with schizophrenia to complete 8 weeks of CRT and assessed their cognitive improvement outcomes. Eye movements were assessed by prosaccades, antisaccades, and free-viewing tasks at baseline, and neuropsychological tests in four cognitive domains were assessed before and after treatment to calculate treatment outcomes. Predictors of demographic information, clinical characteristics, and eye movement measures at baseline on cognitive improvement outcomes were analyzed using logistic regression analysis. We further compared the predictive performance between eye movement measurements and neuropsychological test regarding the effect of CRT on cognitive improvement, and explored factors that could be affect the treatment outcomes in different cognitive domains., Results: As operationally defined, 33 patients showed improved in cognition (improved group) and 46 patients did not (non-improved group) after CRT. Patients with schizophrenia being employed, lower directional error rate in antisaccade task, and lower the gap effect (i.e., the difference in saccadic latency between the gap condition and overlap condition) in prosaccade task at baseline predicted cognitive improvement in CRT. However, performance in the free-viewing task not associated with cognitive improvement in patients in CRT. Our results show that eye-movement prediction model predicted the effect of CRT on cognitive improvement in patients with schizophrenia better than neuropsychological prediction model in CRT. In addition, baseline eye-movements, cognitive reserve, antipsychotic medication dose, anticholinergic cognitive burden change, and number of training sessions were associated with improvements in four cognitive domains., Conclusion: Eye movements as a non-invasiveness, objective, and sensitive method of evaluating cognitive function, and combined saccadic measurements in pro- and anti-saccades tasks could be more beneficial than free-viewing task in predicting the effect of CRT on cognitive improvement in patients with schizophrenia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhu, Li, Zhou, Xu, Pu, Huang, Zhou, Lin, Tang, Yang and Shi.)

Enzyme-assisted solvent extraction (EASE) of Paeonia suffruticosa Andr. seed oil (PSO) was optimized by response surface methodology (RSM). The fatty acid composition and anti-Alzheimer's disease (AD) activity of PSO were analyzed. An enzyme mixture composed of cellulase and hemicellulase (1:1, w/w) was most effective in determining the extraction yield of PSO. The ideal extraction conditions were a pH value of 5.1, an enzymolysis time of 68 min, and a temperature of 50°. The average extraction yield of PSO was 38.2 mL/100 g, 37.4% higher than that of untreated peony seed (27.8 mL/100 g). The fatty acid composition of PSO under optimal conditions for EASE was analyzed by gas chromatography-mass spectrometry (GC-MS). The predominant unsaturated fatty acids of PSO were determined to be more than 90.00%, including n-3 a-linolenic acid (43.33%), n-6 linoleic acid (23.40%) and oleic acid (23.59%). In this experiment, the anti-AD effect of PSO was also analyzed by performing learning and memory ability tests with Drosophila. PSO retarded the decrease in climbing ability in AD Drosophila. The 1% and 5% PSO groups were significantly different from the model group (bp < 0.05). The smell short-term memory ability test revealed the number of Drosophila in barrier and barrier-free centrifuge tubes in each group. PSO feeding improved learning and memory in AD Drosophila, with the highest number entering the barrierfree centrifuge tube. The performance index (PI) measured by the Pavlov olfactory avoidance conditioning test also demonstrated the effect of PSO on the learning and memory abilities of Drosophila. The PI of the PSO group was significantly increased compared to that of the model group. HE-stained brain tissue sections of AD Drosophila showed higher neurodegenerative changes, while PSO significantly reduced neurodegenerative damage. These results indicated that PSO can significantly improve the cognitive function of AD Drosophila and may help to prevent AD. [ABSTRACT FROM AUTHOR]

Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment. The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease. Alzheimer’s disease mouse models were established by injection of beta amyloid 1−42 aggregates into dentate gyrus bilaterally. Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration. Afterwards, neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies. Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1−42-induced cognitive impairment, and these effects are similar to those shown in the mesenchymal stem cells. These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease. All procedures and experiments were approved by Institutional Animal Care and Use Committee (CICUAL) (approval No. CICUAL 2016-011) on April 25, 2016.

Psychosocial development in school age is characterized by industry / productive versus low self esteem or so-called normal and distorted development. Deviant development in school age can be overcome by several actions one of which is education about the task of normal development at school age. Appropriate media in education for school-aged children with audiovisual media. Audiovisual media displays elements of images and sounds that have several functions one of which is the cognitive function which means it makes it easier for children to understand the content delivered. Research aimed to know the difference of cognitive level before and after giving video, and to know the effect of educational video to cognitive improvement of child. Research using quasy experiment design with one group pretest-posttest design. Sampling with total sampling technique on the respondent class IV until VI which amounted to 75 respondents. Results: research analysis with statistical test showed that there is influence between educational video about stage of psychosocial development toward cognitive improvement of children with median value before 54,00 and after 56,00 giving video with ρ value that is 0,00 (ρ value

Objective: Cognitive impairment is frequently comorbid with late-life depression (LLD) and often persists despite remission of mood symptoms with antidepressant treatment. Increasing understanding of factors that predict improvement of cognitive symptoms in LLD is useful to inform treatment recommendations. Methods: We used data from 2 randomized clinical trials of geriatric depression to examine the relationships between sociodemographic factors (resilience, quality of life) and clinical factors (age of depression onset, severity of depression, apathy) with subsequent cognitive outcomes. One hundred sixty-five older adults with major depression who had completed one of 2 clinical trials were included: (1) methylphenidate plus placebo, citalopram plus placebo, and citalopram plus methylphenidate or (2) citalopram combined with Tai Chi or health education. A comprehensive neuropsychiatric battery was administered; 2 measures of cognitive improvement were examined, one defined as an increase in general cognitive performance score of at least 1 standard deviation and the other 0.5 standard deviation pre–post treatment. Results: At posttreatment, 59% of participants had remitted, but less than a third of those who remitted showed cognitive improvement (29%). Cognitive improvement was observed in 18% of nonremitters. Lower baseline depression severity, greater social functioning, and depression onset prior to 60 years of age were significantly associated with cognitive improvement. None of the other measures, including baseline apathy, resilience, and depression remission status, were significantly associated with cognitive improvement. Conclusions: Lower severity of depression, earlier onset, and greater social functioning may predict improvement in cognitive functioning with treatment for depression in LLD. [ABSTRACT FROM AUTHOR]