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Background and Objectives: Antipsychotics and cognitive enhancers are often used to treat psychosis and behavioral disturbances in individuals with dementia; however, these drugs have been linked with various adverse events including both metabolic and cerebro/cardiovascular events. Thus, this study sought to estimate the risk of major adverse cardiovascular/cerebrovascular events (MACCE) across four behavioral and psychological symptoms of dementia (BPSD) treatment models by exploring potential associations between antipsychotics (APs), cognitive-enhancing medications, dosage, and earlier MACCE onset. Methods: Patients were obtained from the Loma Linda University Medical Center database who were age ≥ 50 or older and who were diagnosed with dementia and BPSD symptoms. Treatment group and drug dosing were analyzed using Cox regression analyses to predict time until MACCE onset. Patient age at dementia diagnosis, sex, smoking status, race/ethnicity, and previous MACCE diagnoses were included as covariate variables. Results: The final study population consisted of 1162 individuals. Results indicated a significant effect of medication type on duration until MACCE, (p < 0.001), with the odds of experiencing a MACCE being 96.3% higher for individuals treated with both APs and cognitive enhancers (p < 0.001). There was also a significant effect of AP dosage on duration until MACCE (p < 0.001) and a significant effect of cognitive enhancer dosage on duration until a MACCE, (p < 0.001). The odds of experiencing a MACCE sooner were 238% higher for those on high doses of APs (p < 0.001) and 76% higher for individuals on high doses of cognitive enhancers (p < 0.010). Conclusion: The use of APs at high doses was associated with the greatest risk of an adverse medical outcome in older adults with dementia with concurrent behavioral symptoms. Use of AP medications in this population should include close monitoring for cardiovascular/cerebrovascular events. [ABSTRACT FROM AUTHOR]

Studies have found that the use of clinically approved caffeine and modafinil can alleviate cognitive impairment due to sleep deprivation (SD) to some extent. However, the neural mechanisms by which these two cognitive enhancers work to counteract the effects of SD on cognitive impairment remain unclear. A double-blind within-subjects experiment using resting-state functional magnetic resonance imaging (rs-fMRI) was designed. Participants underwent three 36-h SD trials, each of which involved taking 200 mg of caffeine, modafinil, or placebo at the 28th and 32 nd h of SD. Sixteen subregions of the thalamus were selected as the regions of interest and changes in functional connectivity (FC) between the thalamus and the other brain regions were explored after the participants took caffeine or modafinil. The subjective sleepiness of the participants increased with the duration of SD. compared with placebo, modafinil and caffeine had insignificant effects on wakefulness or sleepiness. However, in terms of neural FC, we found varying degrees of attenuation or enhancement of the FC between the thalamus and other regions. Taking caffeine during SD weakened the FC between the right rostral temporal thalamus (rTtha) subregion and the left lingual gyrus compared with placebo. Caffeine enhanced the FC between three subregions of the thalamus, namely the left sensory thalamus, the left rTtha, and the right lateral pre-frontal thalamus, and the right inferior temporal, left orbitofrontal, and right superior occipital gyris. Modafinil weakened the FC between the right posterior parietal thalamus and left middle temporal gyrus, and enhanced the FC between the left medial pre-frontal thalamus, left rTtha, and right occipital thalamus and left middle frontal gyrus. After 36 h of total SD, modafinil and caffeine administration enhanced or attenuated the time-domain correlations between various subregions of the thalamus and brain regions of the frontal and temporal lobes in healthy adults, compared with placebo. These results provide valuable evidence for further unraveling the neuropharmacological mechanisms of caffeine and modafinil, as well as important insights for exploring effective pharmacological intervention strategies against SD. • Sleep deprivation leads to weakened or enhanced functional connectivity (FC) between the thalamic subregions and other brain regions. • Compared with placebo, caffeine enhanced FC between the thalamic subregions and the inferotemporal, orbital inferior frontal, and superior occipital gyrus. • Compared with placebo, modafinil enhanced FC between the thalamic subregions and the left middle frontal gyrus. [ABSTRACT FROM AUTHOR]

Plants of the genus Tribulus have been used in folk medicine for wound healing, alleviating liver, stomach, and rheumatism pains, and as cognitive enhancers, sedatives, antiseptics, tonics, and stimulants. The present work aimed to evaluate whether Tribulus terrestris (Tt) administered for 15 days attenuated cognitive deficits and exhibited anxiolytic and antidepressant profiles in scopolamine-induced amnesia in zebrafish. Animals were randomly divided into six groups (eight animals per group): (1)–(3) Tt treatment groups (1, 3 and 6 mg/L), (4) control, (5) scopolamine (SCOP, 0.7 mg/kg), and (6) galantamine (Gal, 1 mg/L). Exposure to SCOP (100 µM) resulted in anxiety in zebrafish, as assessed by the novel tank diving test (NTT) and novel approach test (NAT). When zebrafish were given SCOP and simultaneously given Tt (1, 3, and 6 mg/L once daily for 10 days), the deficits were averted. Molecular interactions of chemical compounds from the Tt fractions with the monoamine oxidase A (MAO-A) were investigated via molecular docking experiments. Using behavioral experiments, we showed that administration of Tt induces significant anxiolytic-antidepressant-like effects in SCOP-treated zebrafish. Our result indicated that flavonoids of Tt, namely kaempferol, quercetin, luteolin, apigetrin, and epigallocatechin, could act as promising phytopharmaceuticals for improving anxiety-related disorders. [ABSTRACT FROM AUTHOR]

Agastache rugosa, a traditional Asian herbal medicine, is primarily used for digestive problems; yet, its cognitive benefits remain unexplored. This study evaluated the anti-amnesic effects of A. rugosa extract (ARE) on scopolamine (SCO)-induced memory impairment in mice. Mice received 100 or 200 mg/kg ARE orally for 5 days, followed by SCO injection. The ARE demonstrated significant antioxidant (DPPH IC50: 75.3 µg/mL) and anti-inflammatory effects (NO reduction). Furthermore, the ARE significantly improved memory performance in the passive avoidance test (escape latency: 157.2 s vs. 536.9 s), the novel object recognition test (novel object preference: 47.6% vs. 66.3%) and the Morris water maze (time spent in the target quadrant: 30.0% vs. 45.1%). The ARE reduced hippocampal acetylcholinesterase activity (1.8-fold vs. 1.1-fold) while increasing choline acetyltransferase (0.4-fold vs. 1.0-fold) and muscarinic acetylcholine receptor subtype I (0.3-fold vs. 1.6-fold) expression. The ARE improved hippocampal neurogenesis via doublecortin- (0.4-fold vs. 1.1-fold) and KI-67-positive (6.3 vs. 12.0) cells. Therefore, the ARE exerts protective effects against cognitive decline through cholinergic system modulation and antioxidant activity, supporting its potential use as a cognitive enhancer. [ABSTRACT FROM AUTHOR]

This article is about Operational art and the feature of depth. It exploits the Israeli Operational concept of takhbulah, a deceptive two-stage theory thriving on the changing nature of reality. Challenging military ideal models and rigid paradigms, it displays how conformity to emergence and courses of action outside perceived boundaries, normally choking creativity, can provide an effective cognitive depth enhancer by unlocking potential already in possession. The article is based on substantial studies in Israel, including five research trips, interviews with some 20 generals and a range of prominent others' culminating with a three-week one-on-one operational dialogue with the director of the IDF General's course. [ABSTRACT FROM AUTHOR]

The field of EEG-Neurofeedback (EEG-NF) training has showcased significant promise in treating various mental disorders, while also emerging as a cognitive enhancer across diverse applications. The core principle of EEG-NF involves consciously guiding the brain in desired directions, necessitating active engagement in neurofeedback (NF) tasks over an extended period. Music listening tasks have proven to be effective stimuli for such training, influencing emotions, mood, and brainwave patterns. This has spurred the development of musical NF systems and training protocols. Despite these advancements, there exists a gap in systematic literature that comprehensively explores and discusses the various modalities of feedback mechanisms, its benefits, and the emerging applications. Addressing this gap, our review article presents a thorough literature survey encompassing studies on musical NF conducted over the past decade. This review highlights the several benefits and applications ranging from neurorehabilitation to therapeutic interventions, stress management, diagnostics of neurological disorders, and sports performance enhancement. While acknowledged for advantages and popularity of musical NF, there is an opportunity for growth in the literature in terms of the need for systematic randomized controlled trials to compare its effectiveness with other modalities across different tasks. Addressing this gap will involve developing standardized methodologies for studying protocols and optimizing parameters, presenting an exciting prospect for advancing the field. [ABSTRACT FROM AUTHOR]

Military personnel are exposed to various stressful factors that can cause irreparable damage to the persons' mental health. Resilience is a trait that can help military personnel resist stressful factors. Today, armies seek new ways to boost resilience in soldiers. One of the proposed and under-study methods is the use of nootropics or smart drugs. This study was conducted to evaluate the effect of smart drugs on cognitive resilience. For this purpose, the literature review was conducted with the search of databases, including Google Scholar, IranMedex, Scopus, PubMed, MEDLIB, Science Direct, and Web of Science. Resilience is a multilateral framework that includes various aspects such as biologic, physiologic, and sociologic. Although some studies emphasize the efficacy of nootropics in enhancing cognitive functions through different pathways, clinical trials are still limited in this area. Despite preliminary evidence, some people suggest cognitive enhancement potential for certain compounds؛ but important questions such as safety, efficacy, and individual variability remain unanswered. More research is needed to fully understand the mechanisms of action and potential interactions of nootropics on resilience and cognitive function. Also, long-term studies are necessary to evaluate the safety and effectiveness of these compounds, especially in the military population. [ABSTRACT FROM AUTHOR]

Wastewater (WW)-based epidemiology is an approach for the objective surveillance of the consumption of (illicit) drugs in populations. The aims of this study were to monitor drugs of abuse, cognitive enhancers, and their metabolites as biomarkers in influent WW. Data obtained from different sampling points and mean daily loads were compared with previously published data. The prevalence of analytes was monitored in WW grab samples collected monthly over 22 months at two sampling points and 24 h composite WW samples collected over 2 weeks at a WW treatment plant in the same city. Quantification was performed using a previously validated and published method based on solid-phase extraction followed by liquid chromatography coupled with high-resolution tandem mass spectrometry. Grab samples allowed for frequent detection of ritalinic acid and sporadic detection of drugs of abuse. The daily mean loads calculated for 24 h WW composite samples were in accordance with data published in an international study. Furthermore, loads of amphetamine and methamphetamine increased compared with those observed in a previously published study from 2014. This study showed frequent quantification of ritalinic acid in the grab samples, while drugs of abuse were commonly quantified in the composite WW samples. Daily mean loads were in accordance with trends reported for Germany. [ABSTRACT FROM AUTHOR]

Degenerative conditions, such as neurodegenerative disorders (Alzheimer's disease (AD), Parkinson's disease (PD)) and cardiovascular diseases, are complex, multifactorial disorders whose pathophysiology has not been fully elucidated yet. As a result, the available treatment options cannot eliminate these diseases radically, but only alleviate the symptoms. Both inflammatory processes and oxidation are key factors in the development and evolution of neurodegeneration, while acetylcholinesterase inhibitors are the most used therapeutic options against AD. In this work, following the multi-targeting compound approach, we designed and synthesized a series of proline and gamma-aminobutyric acid (GABA) amides with various acidic moieties that possess an antioxidant and/or anti-inflammatory potency. Proline is the pharmacophore of nootropic drugs (e.g., piracetam) used for memory improvement, while GABA is the main inhibitory neurotransmitter in the central nervous system. The designed molecules were subjected to a preliminary screening of their bioactivity in antioxidant and anti-inflammatory assays, as well as against acetylcholinesterase. Most of the synthesized compounds could inhibit lipid peroxidation (IC50 as low as 8 μΜ) and oxidative protein glycation (inhibition of up to 48%) and reduce the 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH). In addition, all of the compounds were moderate inhibitors of lipoxygenase (LOX) (up to 46% at 100 μΜ) and could decrease carrageenan-induced paw edema in rats by up to 55%. Finally, some of the compounds were moderate acetylcholinesterase inhibitors (IC50 as low as 219 μΜ). The results confirmed the design rationale, indicating that the compounds could be further optimized as multi-targeting molecules directed against degenerative conditions. [ABSTRACT FROM AUTHOR]

Aim: Patients with dementia with Lewy bodies (DLB) are at a high risk for falls and fractures. Although cholinesterase inhibitors reportedly are effective in suppressing the progression of cognitive symptoms in DLB patients, their effects on fracture risk remain unclarified. This study aimed to evaluate the association between donepezil use and hip fracture risk in older patients with DLB. Methods: Using the Japanese insurance claim database, we collected the data of patients aged ≥65 years with DLB from April 2012 to March 2019. After propensity score matching, we compared the fracture rate over 3 years between DLB patients receiving donepezil and those not receiving antidementia drugs. Results: Altogether, 24 022 239 individuals aged ≥65 years were newly registered from April 2012 to March 2016 and had verifiable information from 6 months before to 3 years after the registration. We identified 6634 pure‐DLB patients and analyzed the data of 1182 propensity score‐matched pairs. The characteristics, including age, sex, fracture history, osteoporosis, and bone mineral density test rate, of the two groups were well balanced by propensity score matching. The incidence rate of hip fracture was significantly lower in DLB patients receiving donepezil than in those not receiving antidementia drugs (0.60 vs. 1.44/100 person‐years, P < 0.001), whereas that of vertebral fractures was the same. Conclusions: Donepezil administration in Japanese people aged ≥65 years with DLB was significantly associated with a decreased risk of hip fracture. Donepezil may provide new benefits to DLB patients. Geriatr Gerontol Int 2024; 24: 782–788. [ABSTRACT FROM AUTHOR]

Nonmedical use of psychostimulants as cognitive enhancers is increasingly common in young adults, despite studies showing mixed results and health risks, including sleep disturbance and addiction. Given the importance of sleep for complex cognitions, expected outcomes of stimulants for performance should be consider as a function of the reliance of each cognitive domain on 'offline' processes optimized during sleep. Thus, performance on attention and vigilance task may be sustained with stimulants, whereas executive functions, long-term memory, creativity and the like will show no enhancement or even worse performance. Nonmedical use of stimulants is a public health problem. More systematic investigations are needed that thoroughly account for the impact of stimulants on cognitive domains, stages of processing, and the mediating role of sleep disturbance, in the short and long term. Nonmedical use of psychostimulants for cognitive enhancement is widespread and growing in neurotypical individuals, despite mixed scientific evidence of their effectiveness. Sleep benefits cognition, yet the interaction between stimulants, sleep, and cognition in neurotypical adults has received little attention. We propose that one effect of psychostimulants, namely decreased sleep, may play an important and unconsidered role in the effect of stimulants on cognition. We discuss the role of sleep in cognition, the alerting effects of stimulants in the context of sleep loss, and the conflicting findings of stimulants for complex cognitive processes. Finally, we hypothesize that sleep may be one unconsidered factor in the mythology of stimulants as cognitive enhancers and propose a methodological approach to systematically assess this relation. [ABSTRACT FROM AUTHOR]

Identifying therapeutics to delay, and potentially reverse, age-related cognitive decline is critical in light of the increased incidence of dementia-related disorders forecasted in the growing older population1. Here we show that platelet factors transfer the benefits of young blood to the ageing brain. Systemic exposure of aged male mice to a fraction of blood plasma from young mice containing platelets decreased neuroinflammation in the hippocampus at the transcriptional and cellular level and ameliorated hippocampal-dependent cognitive impairments. Circulating levels of the platelet-derived chemokine platelet factor 4 (PF4) (also known as CXCL4) were elevated in blood plasma preparations of young mice and humans relative to older individuals. Systemic administration of exogenous PF4 attenuated age-related hippocampal neuroinflammation, elicited synaptic-plasticity-related molecular changes and improved cognition in aged mice. We implicate decreased levels of circulating pro-ageing immune factors and restoration of the ageing peripheral immune system in the beneficial effects of systemic PF4 on the aged brain. Mechanistically, we identified CXCR3 as a chemokine receptor that, in part, mediates the cellular, molecular and cognitive benefits of systemic PF4 on the aged brain. Together, our data identify platelet-derived factors as potential therapeutic targets to abate inflammation and rescue cognition in old age.

Background: Alzheimer's disease (AD) is the most common cause of dementia. Management of AD is dynamic and multidisciplinary, involving pharmacological and non-pharmacological interventions to manage patient's symptoms, prevent clinical decline and improve quality of life. This study aims to evaluate the standard of patient care provided for the management of AD. Patients and methods: This was a retrospective clinical audit of patients in Brunei Darussalam, with the International Classification of Disease and related health problems, tenth revision (ICD-10) diagnosis of AD between 2019 and 2020. Results: There was a total of 168 patients (68 males, 100 females). Their mean age was 79.5 years. Only half of the patients (n = 84) were advised on measures to take to slow down the progression of the disease, and less than half (49.1%) of eligible patients were offered cognitive stimulation therapy. 51.8% (n = 87) were referred to occupational therapists for assessment of activities of daily living. 113 patients (67.3%) were started on cognitive enhancers; of these, 92 were continued on these medications. Donepezil was the most common drug prescribed (n = 78). Only 44.2% (n = 50) of the 113 patients were maximized on their cognitive enhancer dose. 84.1% had documented follow-up evaluations on the effect of cognitive enhancers. 88 (52.4%) patients had behavioural and psychological symptoms of dementia (BPSD), of whom 64 (72.7%) received treatment, with quetiapine (n = 33, 51.6%) being the most prescribed drug. Conclusions: There are still gaps between guidelines and practice; more effort is needed to improve achieving the standards of care for the management of AD in Brunei Darussalam. [ABSTRACT FROM AUTHOR]

Cognitive decline with aging is a concern, particularly in neurodegenerative and mental diseases. Cognitive enhancers focus on cholinergic and monoaminergic systems, but Phosphodiesterases (PDEs) have gained interest in enhancing cognition by increasing intracellular accessibility of additional messengers. The present study sought to elucidate the effects of PDE-Inhibitors on perception, feasible underlying mechanisms, and their application to existing hypotheses regarding the formation of memories. The review examines literature from 2010-2023 on the effects of various PDE medications on mental processes, including studies on PDE-Is and their relation to blood flow, euphoria, and long-term potentiation. PDE inhibitors enhance brain information processing, concentration, memory, executive function and memory use, likely due to an LTP-interrelated mode of action. PDE2-Is and PDE9-Is are potential candidates for cognitive enhancement, but isoform-specific PDE-Is with minimal negative properties are needed to realize their potential fully. [ABSTRACT FROM AUTHOR]

The aim. Search for new biologically active substances with improved nootropic parameters among analogues of 4-(aminomethyl)-1-benzylpyrrolidine-2-one (Nebracetam). Materials and methods. The required reagents were purified using standard techniques. The elemental analysis was performed on a "Hewlett Packard" automatic analyzer M-180 company. 1H NMR spectra were recorded on Varian Gemini 400 MHz spectrometer in DMSO-d6 as a solvent. LC/MS spectra were recorded with a PE SCIEX API 150EX liquid chromatograph equipped. The Autodock 4.2 software package was used for molecular docking. The active centers of the peptides (PDB ID: 5CXV, 6PV7) was used as the biologycal targets. Results and discussion. Basic and alternative methods (1 and 2) of obtaining were used to synthesise target analogues of 4-(aminomethyl)-1-R-benzylpyrrolidine-2-one. As a result of synthetic studies, an optimized method with an alternative method has been proposed. The advantages include reducing the duration and number of synthesis stages and avoiding the use of sodium azide, a highly toxic and hazardous substance. Molecular docking of the synthesized compounds at well-documented acetylcholine receptor sites indicates that all tested molecules will contribute to the manifestation of nootropic activity to varying degrees through cholinergic neurotransmission mechanisms. This is evidenced by the calculated docking values in relation to the muscarinic target. According to the docking results, it was found that depending on the enantiomeric configuration, the molecules formed stable complexes with the target and had characteristic binding modes both in the orthosteric site and in the extracellular vestibule (site of positive allosteric modulation of mAChR). It indicates the prospects of modifying the "nebracetam scaffold" at the phenyl fragment with halogen substituents. Conclusions. An effective method for synthesising analogues of 4-(aminomethyl)-1-R-benzylpyrrolidin-2-ones has been developed. The molecular docking revealed potential mechanisms of nootropic action of the synthesized derivatives as potential agonists and positive allosteric modulators of the muscarinic receptor. [ABSTRACT FROM AUTHOR]

Optimum memory and cognition play essential roles in day-to-day life. Cognition involves the ability and capacity to process information, apply and utilise acquired knowledge, and modify personal preferences. Nootropics possess a diverse array of applications, incorporating enhancing cognitive function and performance, memory, attention, alertness, learning, executive functions, vigilance, creativity, and motivation. Herbal medicines have a significant impact on cognitive function and memory, serving as prominent nootropics. Commonly used nootropic herbs include Bacopa monnieri (Brahmi), Camellia sinensis (Green tea), Centella asiatica (Gotu Kola), Ginkgo biloba (Ginkgo), Melissa officinalis (Lemon Balm), Panax ginseng (Korean Ginseng), Rhodiola rosea (Rhodiola), Rosmarinus officinalis (Rosemary), Salvia officinalis (Sage), and Withania somnifera (Ashwagandha). This article briefly introduces the concept of nootropics and briefly explores the nootropic effects of regularly used herbal medicines. [ABSTRACT FROM AUTHOR]

This review focused on the concept of dementia in the Unani system of medicine and comprehensive, updated information on Majoon Vaj about the phytochemistry, nootropic, CNS activities and provide insights into potential opportunities for future research. The classical literature on Majoon Vaj for its anti-dementic properties, and therapeutic uses were gathered from nearly thirteen classical Unani books including Unani Pharmacopoeia. The information of pharmacognosy, phytochemical and pharmacological activities of Majoon Vaj and its ingredient was collected by browsing the Internet (PubMed, ScienceDirect, Wiley online library, Google Scholar, ResearchGate). The relevant primary sources were probed, analysed, and included in this review. The keywords used to browse were Majoon Vaj, Dementia, Nootropic, Acorus calamus, Piper nigram, Zingiber officinalis, Nigella sativa, Carum carvi, Plumbago zeylanica, and β-asarone. Relevant Sources were gathered up to July 2021, and the chemical structures were drawn using ACD/ChemSketch software. The species name and synonyms were checked with WFO (2021): World Flora online (http://www.worldfloraonline.org) an updated version of 'The Plant List.' Majoon Vaj contains an excess of bioactive compounds e.g., alkaloids, phenols, flavonoids, tannins, diterpenes, coumarins, carbohydrates, and fixed oils and its ingredients possess broad pharmacological properties, including cognitive-enhancing, neuroprotective, anti-inflammatory, antioxidant and antimicrobial properties. The literature of Unani medicine is quite rich in discussing the pathophysiological basis of memory disorders. It argues that memory, retention, and retrieval are regulated by a complex process involving various faculties. Majoon Vaj seems to have great potential for therapeutic applications in the treatment of dementia and thus encourage more preclinical and clinical trials in this field. [ABSTRACT FROM AUTHOR]

Objective: This analysis estimated 2013 annual healthcare costs associated with the common mental disorders of mood and anxiety disorders and psychological symptoms within a representative sample of Australian women. Methods: Data from the 15-year follow-up of women in the Geelong Osteoporosis Study were linked to 12-month Medicare Benefits Schedule and Pharmaceutical Benefits Scheme data. A Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Non-patient edition identified common mental disorders and the General Health Questionnaire 12 assessed psychological symptoms. Participants were categorised into mutually exclusive groups: (1) common mental disorder (past 12 months), (2) subthreshold (no common mental disorder and General Health Questionnaire 12 score ⩾4) or (3) no common mental disorder and General Health Questionnaire 12 score <4. Two-part and hurdle models estimated differences in service use, and adjusted generalised linear models estimated mean differences in costs between groups. Results: Compared to no common mental disorder, women with common mental disorders utilised more Medicare Benefits Schedule services (mean 26.9 vs 20.0, p < 0.001), had higher total Medicare Benefits Schedule cost ($1889 vs $1305, p < 0.01), received more Pharmaceutical Benefits Scheme prescriptions (35.8 vs 20.6, p < 0.001), had higher total Pharmaceutical Benefits Scheme cost ($1226 vs $740, p < 0.05) and had significantly higher annual out-of-pocket costs for Pharmaceutical Benefits Scheme prescriptions ($249 vs $162, p < 0.001). Compared to no common mental disorder, subthreshold women were less likely to use any Medicare Benefits Schedule service (89.6% vs 97.0%, p < 0.01), but more likely to use mental health services (11.4% vs 2.9%, p < 0.01). The subthreshold group received more Pharmaceutical Benefits Scheme prescriptions (mean 43.3 vs 20.6, p < 0.001) and incurred higher total Pharmaceutical Benefits Scheme cost ($1268 vs $740, p <.05) compared to no common mental disorder. Conclusions: Common mental disorders and subthreshold psychological symptoms place a substantial economic burden on Australian healthcare services and consumers. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced cognitive impairment (CICI) is a novel clinical condition characterized by memory, learning, and motor function deficits. Oxidative stress and inflammation are potential factors contributing to chemotherapy's adverse effects on the brain. Inhibition of soluble epoxide hydrolase (sEH) has been proven effective in neuroinflammation and reversal of memory impairment. The research aims to evaluate the memory protective effect of sEH inhibitor and dual inhibitor of sEH and COX and compare its impact with herbal extracts with known nootropic activity in an animal model of CICI. In vitro sEH, the inhibitory activity of hydroalcoholic extracts of Sizygium aromaticum, Nigella sativa, and Mesua ferrea was tested on murine and human sEH enzyme as per the protocol, and IC50 was determined. Cyclophosphamide (50 mg/kg), methotrexate (5 mg/kg), and fluorouracil (5 mg/kg) combination (CMF) were administered intraperitoneally to induce CICI. The known herbal sEH inhibitor, Lepidium meyenii and the dual inhibitor of COX and sEH (PTUPB) were tested for their protective effect in the CICI model. The herbal formulation with known nootropic activity viz Bacopa monnieri and commercial formulation (Mentat) were also used to compare the efficacy in the CICI model. Behavioral parameter such as cognitive function was assessed by Morris Water Maze besides investigating oxidative stress (GSH and LPO) and inflammatory (TNFα, IL-6, BDNF and COX-2) markers in the brain. CMF-induced CICI, which was associated with increased oxidative stress and inflammation in the brain. However, treatment with PTUPB or herbal extracts inhibiting sEH preserved spatial memory via ameliorating oxidative stress and inflammation. S. aromaticum and N. sativa inhibited COX2, but M. Ferrea did not affect COX2 activity. Lepidium meyenii was the least effective, and mentat showed superior activity over Bacopa monnieri in preserving memory. Compared to untreated animals, the mice treated with PTUPB or hydroalcoholic extracts showed a discernible improvement in cognitive function in CICI.

The article explores the connection between the use of antipsychotics, cognitive enhancers, and the risk of major adverse cardiovascular and cerebrovascular events (MACCE) in elderly patients with behavioral and psychological symptoms of dementia (BPSD). Topics discussed include the elevated cardiovascular risks associated with these medications, the importance of non-pharmacological treatment options, and the need for regular medication reviews to prevent unnecessary long-term use.

Amphetamines (Amph) are psychostimulants broadly used as physical and cognitive enhancers. However, the long-term effects of prenatal exposure to Amph have been poorly investigated. Here, we show that continuous exposure to Amph during early development induces long-lasting changes in histone methylation at the C. elegans tyrosine hydroxylase (TH) homolog cat-2 and the vesicular monoamine transporter (VMAT) homologue cat-1 genes. These Amph-induced histone modifications are correlated with enhanced expression and function of CAT-2/TH and higher levels of dopamine, but decreased expression of CAT-1/VMAT in adult animals. Moreover, while adult animals pre-exposed to Amph do not show obvious behavioral defects, when challenged with Amph they exhibit Amph hypersensitivity, which is associated with a rapid increase in cat-2/TH mRNA. Because C. elegans has helped reveal neuronal and epigenetic mechanisms that are shared among animals as diverse as roundworms and humans, and because of the evolutionary conservation of the dopaminergic response to psychostimulants, data collected in this study could help us to identify the mechanisms through which Amph induces long-lasting physiological and behavioral changes in mammals. [ABSTRACT FROM AUTHOR]

Psychotropic and somatic medications are both used in treating severe mental disorders (SMDs). Realistic estimates of the prevalence of use across medication categories are needed. We obtained this in a clinical cohort of patients with SMD and healthy controls (HCs). Prescriptions filled at Norwegian pharmacies the year before and after admittance to the Thematically Organized Psychosis (TOP) study were examined in 1406 patients with SMD (mean age 32.5 years, 48.2% women) and 920 HC (34.1 years, 46.2% women). Using data from the Norwegian Prescription Database (NorPD), the number of users in different anatomical therapeutic chemical (ATC) categories was compared using logistic regression. Population estimates were used as reference data. Use of antipsychotics (N05A), antiepileptics (N03A), antidepressants (N06A), anxiolytics (N05B), hypnotics and sedatives (N05C), anticholinergics (N04A), psychostimulants, attention deficit hyperactivity disorder and nootropic agents (N06B) and drugs for addiction disorders (N07B) was significantly more prevalent in patients with SMD than HC. Use of diabetes treatment (A10), antithrombotic drugs (B01), beta blockers (C07), lipid modifiers (C10), and thyroid and endocrine therapeutics (H03) was also more prevalent in patients with SMD, but with two exceptions somatic medication use was comparable to the general population. Among HC, there was low prevalence of use for most medication categories. Patients were using psychiatric medications, but also several types of somatic medications, more often than HC. Still, somatic medication use was mostly not higher than in the general population. The results indicate that HC had low use of most medication types. [ABSTRACT FROM AUTHOR]

With the ambition to identify novel chemical starting points that can be further optimized into small drug-like inhibitors of insulin-regulated aminopeptidase (IRAP) and serve as potential future cognitive enhancers in the clinic, we conducted an ultra-high-throughput screening campaign of a chemically diverse compound library of approximately 400,000 drug-like small molecules. Three biochemical and one biophysical assays were developed to enable large-scale screening and hit triaging. The screening funnel, designed to be compatible with high-density microplates, was established with two enzyme inhibition assays employing either fluorescent or absorbance readouts. As IRAP is a zinc-dependent enzyme, the remaining active compounds were further evaluated in the primary assay, albeit with the addition of zinc ions. Rescreening with zinc confirmed the inhibitory activity for most compounds, emphasizing a zinc-independent mechanism of action. Additionally, target engagement was confirmed using a complementary biophysical thermal shift assay where compounds causing positive/negative thermal shifts were considered genuine binders. Triaging based on biochemical activity, target engagement, and drug-likeness resulted in the selection of 50 qualified hits, of which the IC50 of 32 compounds was below 3.5 µM. Despite hydroxamic acid dominance, diverse chemotypes with biochemical activity and target engagement were discovered, including non-hydroxamic acid compounds. The most potent compound (QHL1) was resynthesized with a confirmed inhibitory IC50 of 320 nM. Amongst these compounds, 20 new compound structure classes were identified, providing many new starting points for the development of unique IRAP inhibitors. Detailed characterization and optimization of lead compounds, considering both hydroxamic acids and other diverse structures, are in progress for further exploration. [ABSTRACT FROM AUTHOR]

Functional near-infrared spectroscopy (fNIRS) relies on near-infrared (NIR) light for changes in tissue oxygenation. For decades, this technique has been used in neuroscience to measure cortical activity. However, recent research suggests that NIR light directed to neural populations can modulate their activity through "photobiomodulation" (PBM). Yet, fNIRS is being used exclusively as a measurement tool. By adopting cognitive tests sensitive to prefrontal functioning, we show that a 'classical' fNIRS device, placed in correspondence of the prefrontal cortices of healthy participants, induces faster RTs and better accuracy in some of the indexes considered. A well-matched control group, wearing the same but inactive device, did not show any improvement. Hence, our findings indicate that the 'standard' use of fNIRS devices generates PBM impacting cognition. The neuromodulatory power intrinsic in that technique has been so far completely overlooked, and future studies will need to take this into account. [ABSTRACT FROM AUTHOR]

Macromolecules are fragile when orally administered. An intestinal villi‐inspired metal–organic frameworks (MOFs)‐based smart pill with multiple advantages is developed to offer a salubrious solution for oral delivery of enzymes. In the pill, MOFs accommodate enzymes as carriers exhibit excellent in vitro and in vivo catalytic activities with good oral biosafety, displaying supreme protection from degradation or inhibition in simulated gastrointestinal tract and high tolerance in simulated gastric acid and intestinal fluid. Moreover, the bioinspired pill possesses the morphology of the small intestinal villi obtained via an in situ moulding strategy for enhancing biocatalysis, which is attributed to the increase of surface area. Collaboratively, the adhesive layer renders increased smart pill in vivo retention, which is verified in pigs, providing a clinically translational and versatile platform for long‐term oral macromolecule delivery. [ABSTRACT FROM AUTHOR]

Introduction: There is media concern over students using prescription stimulants as "cognitive enhancers" to try and improve their academic performance. However, there is limited evidence about the prevalence of this behaviour in the United Kingdom, or whether it has increased in recent years. Methods: We review survey studies on students' use of cognitive enhancers. Results: Overall reported use is low, with some inconclusive evidence that it is increasing. Use of modafinil appears to be higher than that of methylphenidate or dexamphetamine. Conclusion: There is a clear need for large‐scale research in this area, using representative sampling and survey methods that protect student anonymity. [ABSTRACT FROM AUTHOR]

Autism spectrum disorders (ASDs) comprise developmental disabilities characterized by impairments of social interaction and repetitive behavior, often associated with cognitive deficits. There is no current treatment that can ameliorate most of the ASDs symptomatology; thus, identifying novel therapies is urgently needed. Here, we used the Neuroligin 3 knockout mouse (NLG3-/y), a model that recapitulates the social deficits reported in ASDs patients, to test the effects of systemic administration of IGF-2, a polypeptide that crosses the blood-brain barrier and acts as a cognitive enhancer. We show that systemic IGF-2 treatment reverses the typical defects in social interaction and social novelty discrimination reflective of ASDs-like phenotypes. This effect was not accompanied by any change in spontaneous glutamatergic synaptic transmission in CA2 hippocampal region, a mechanism found to be crucial for social novelty discrimination. However, in both NLG3+/y and NLG3-/y mice IGF-2 increased cell excitability. Although further investigation is needed to clarify the cellular and molecular mechanisms underpinning IGF-2 effect on social behavior, our findings highlight IGF-2 as a potential pharmacological tool for the treatment of social dysfunctions associated with ASDs. [ABSTRACT FROM AUTHOR]

Introduction: University students are at a heightened risk of using cognitive enhancers and psychoactive substances, and this risk is further exacerbated by the presence of depression, which negatively impacts academic performance and increases the likelihood of substance misuse. In Iraq, the use of cognitive enhancers and psychoactive substances has grown in the past decade due to sociopolitical factors. However, depression among tobacco users remains unrecognized and overlooked, receiving inadequate attention. Objectives: This study aims to measure the levels of depression among nursing students, examine the association between smoking behavior dependence and levels of depression, as well as to find out the relationship between levels of depression and demographic characteristics. Results: The results reveal that the majority of participants (53.9%) had a moderate level of depression (M=2.36). The highest mean level was observed in all depression scale. The study also revealed a significant relationship between age group and depression at a p-value of below 0.05. Moreover, the study also revealed a significant relationship between age and depression at a p-value of below 0.05, and between ages starts smoking. Conclusions: The level of depression the smoking student was moderate. The factors include smoking type, age at which individuals started smoking, the number of cigarettes smoked per day, and the place of smoking, it can be inferred that smoking habits and behaviors contribute significantly to the likelihood of experiencing depression. [ABSTRACT FROM AUTHOR]

Objective: The use of prescription stimulants for cognitive enhancement by healthy university students, identified as the largest cohort of cognitive enhancer (CE) users, is of growing interest. The purpose of this study was to look at the understanding, perception, experience, and level of access of CEs among healthy university students in the United Arab Emirates (UAE). Methods: The study was conducted in six highly competitive university programmes. Semi-structured interviews were conducted with 18 university students to discuss their own experiences and those of their friends and peers regarding the use of prescription stimulants. In addition, semi-structured interviews were conducted with seven teaching faculty staff members (registered pharmacists and medical doctors) to explore their views on the use of CEs in their university. Results: Data were analysed thematically for the identification of themes and subthemes within the data using coding. It was found that, 'Adderall' was the most common prescribed CE drug and caffeine super strength pills were the most common non-prescribed CE drug, both reported to enhance concentration, motivation, and meet academic deadlines. Conclusions: It is expected that the findings of this study will be of interest to a wide range of services in UAE universities. This will enable them to raise awareness about the use of CEs among students. [ABSTRACT FROM AUTHOR]

Agents that positively modulate the activity of α7nAChRs are used as cognitive enhancers and for the treatment of hippocampus‐dependent functional decline. However, it is not known whether the expression and the effects of α7nAChRs apply to the entire longitudinal axis of the hippocampus equally. Given that cholinergic system‐involving hippocampal functions are not equally distributed along the hippocampus, we comparatively examined the expression and the effects of α7nAChRs on excitatory synaptic transmission between the dorsal and the ventral hippocampal slices from adult rats. We found that α7nAChRs are equally expressed in the CA1 field of the two segments of the hippocampus. However, activation of α7nAChRs by their highly selective agonist PNU 282987 induced a gradually developing increase in field excitatory postsynaptic potential only in the dorsal hippocampus. This long‐term potentiation was not reversed upon application of nonselective nicotinic receptor antagonist mecamylamine, but the induction of potentiation was prevented by prior blockade of α7nAChRs by their antagonist MG 624. In contrast to the long‐term synaptic plasticity, we found that α7nAChRs did not modulate short‐term synaptic plasticity in either the dorsal or the ventral hippocampus. These results may have implications for the role that α7nAChRs play in specifically modulating functions that depend on the normal function of the dorsal hippocampus. We propose that hippocampal functions that rely on a direct α7 nAChR‐mediated persistent enhancement of glutamatergic synaptic transmission are preferably supported by dorsal but not ventral hippocampal synapses. [ABSTRACT FROM AUTHOR]

PURPOSE: Medication nonadherence is a persistent and costly problem across health care. Measures of medication adherence are ineffective. Methods such as self-report, prescription claims data, or smart pill bottles have been used to monitor medication adherence, but these are subject to recall bias, lack real-time feedback, and are often expensive. METHODS: We proposed a method for monitoring medication adherence using a commercially available wearable device. Passively collected motion data were analyzed on the basis of the Movelet algorithm, a dictionary learning framework that builds person-specific chapters of movements from short frames of elemental activities within the movements. We adapted and extended the Movelet method to construct a within-patient prediction model that identifies medication-taking behaviors. RESULTS: Using 15 activity features recorded from wrist-worn wearable devices of 10 patients with breast cancer on endocrine therapy, we demonstrated that medication-taking behavior can be predicted in a controlled clinical environment with a median accuracy of 85%. CONCLUSION: These results in a patient-specific population are exemplar of the potential to measure real-time medication adherence using a wrist-worn commercially available wearable device. Wrist-worn tech can detect when breast cancer patients take medications based on hand motions. [ABSTRACT FROM AUTHOR]

Background: Nootropic drugs, at the beginning of their career, were used in the treatment of diseases such as attention deficit hyperactivity disorder (ADHD), Alzheimer's disease and narcolepsy. Nowadays, they are becoming more and more popular among students, where they are often called smart drugs or cognitive enhancers. Their properties that improve intellectual abilities and cognitive functions are used to, among other things, improve academic performance. Aim of the study: The purpose of this article was to summarize the current state of knowledge relating to the use of smart drugs among students. This study discusses the multidimensional issues of using this group of drugs. Material and methods: A cross-sectional search of relevant literature was performed in databases using accepted wording. Publications from 2003-2023 were included. The entire process has been supplemented with additional procedures to increase the reliability of this publication. Results: In most sources, the most common representative of smart drugs turned out to be methylphenidate. Nootropics were most often obtained by obtaining a prescription from a doctor, online trading or from friends. The factors motivating the use of substances from this group are primarily the desire to improve academic results, competitiveness and the number of obligations at the university. There are many risks associated with their use, but students are more aware of the positive effects. Conclusion: This paper presents various dimensions of the progressive spread of nootropic drugs. In addition to their undeniably positive effects, there are many risks, which are discussed in this article. Students' awareness should be formed through appropriate educational methods. [ABSTRACT FROM AUTHOR]

Amaranthus dubius is a vegetable consumed for its nutritional content in Kenya. In herbal medicine, A. dubius is utilized to relief fever, anemia and hemorrhage. Additionally, it is utilized to manage cognitive dysfunction and is considered to augment brain function, but there is no empirical evidence to support this claim. The contemporary study investigated cognitive enhancing potential of A. dubius in mice model of Alzheimer's disease (AD)-like dementia induced with ketamine. Cognitively damaged mice were treated with aqueous extract of A. dubius leaf upon which passive avoidance task (PAT) was used to assess the cognitive performance. At the end of passive avoidance test, brains of the mice were dissected to evaluate the possibility of the extract to inhibit hallmarks that propagate AD namely oxidative stress and acetylcholinesterase activity. Additionally, characterization of secondary metabolites was done using liquid chromatograph- mass spectrometry analysis. During PAT test, extract-treated mice showed significantly increased step-through latencies than AD mice, depicting ability of A. dubius to reverse ketamine-induced cognitive decline. Further, the extract remarkably lowered malondialdehyde levels to normal levels and effectively inhibited acetylcholinesterase enzyme. The study showed that A. dubius extract is endowed with phytoconstituents that possess anti-oxidant and anticholinesterase activities. Thus, this study confirmed promising therapeutic effects of 200, 300 and 400 mg/kg bw of A. dubius extract with potential to alleviate cognitive disarray observed in AD. [ABSTRACT FROM AUTHOR]

The use of so-called 'smart drugs' such as modafinil to improve cognitive performance has recently attracted considerable attention. However, their side effects have limited user enthusiasm. Open-label placebo (OLP) treatment, i.e., inert treatments that are openly disclosed to individuals as having no active pharmacological ingredient, has been shown to improve various medical symptoms and conditions, including those related to cognitive performance. OLP treatment could therefore be an exciting alternative to pharmacological cognitive enhancers. Here, we used a randomized-controlled design to investigate the effect of a 21-day OLP treatment on several sub-domains of cognitive performance in N = 78 healthy volunteers. Subjective and objective measures of cognitive performance as well as different measures of well-being were obtained before and after the treatment period. Using a combination of classic Frequentist and Bayesian analysis approaches showed no additional benefit from OLP treatment in any of the subjective or objective measures of cognitive performance. Our study thus highlights possible limitations of OLP treatment in boosting cognitive performance in healthy volunteers. These findings are discussed in the light of expectancy-value considerations that may determine OLP efficacy. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic disease at all ages including childhood and puberty. Failure to treat DM can cause retinopathy, nephropathy and neuropathy. Endocrine and metabolic changes during the pubertal period complicate management of DM. Noopept is a cognitive enhancer that exhibits antidiabetic properties. We investigated the effect of noopept on the histopathology of the cornea, retina, kidney and pancreas in pubertal diabetic rats. We allocated 60 prepubertal male rats randomly into six groups of 10: untreated control (C), DM control (DC), noopept control (NC), DM + noopept (D + N), DM + insulin (D + I) and DM + insulin + noopept (D + I + N). DM was induced by streptozotocin in the DC, D + N, D + I and D + I + N groups. Noopept was administered to the NC, D + N and D + I + N groups; insulin was administered to the D + I and D + I + N groups for 14 days. On day 18 of the experiment, animals were sacrificed and eyes, kidneys and pancreata were excised for histological investigation. Renal tubule diameter and corneal and retinal thickness were increased significantly in DC groups compared to the control group. The D + I, D + N and D + I + N groups exhibited fewer DM induced pathological changes than the DC group. The D + I + N group exhibited no significant differences in renal tubule diameter and corneal and retinal thickness compared to the DC group. Our findings suggest that noopept is protective against DM end organ complications in streptozotocin induced diabetic pubertal rats. [ABSTRACT FROM AUTHOR]

Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify "druggable" targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing.

Each patient presents a unique set of characteristics and challenges when it comes to acute cerebral ischemia resulting from craniocerebral injury. The aim of this study is to investigate the utilization of Thiocetam as part of a comprehensive treatment approach for combat-related cerebral contusion and to assess the therapeutic effects of Thiocetam in patients with mild and moderate closed combat craniocerebral trauma in comparison to standard basic therapy. Materials and methods. 79 patients with mild and moderate closed combat craniocerebral trauma were examined. Among them, 76 patients experienced craniocerebral trauma due to an explosive blast injury, which included conditions such as brain concussion, mild cerebral contusion, and cranial vault fractures. All patients were admitted to the department during the acute period of their injuries. During the study, various clinical and functional methods were employed to assess the condition of the central nervous system. These methods were used to evaluate the effects of the complex treatment administered to the patients. Results. The administration of Thiocetam to the patients did not result in an increase in excitability, nervousness, or sleep disturbances. Furthermore, the examination of autonomic reactivity following Thiocetam treatment revealed that the indicator of normal autonomic reactivity increased to 60 % in the treated group, whereas it only increased to 42 % in the control group. Additionally, the patients with initially heightened vegetative reactions experienced a decrease from 42.8 % to 17.9 % in the treated group, while the control group saw a decrease from 38.5 % to 23.1 %. In terms of clinical outcomes, a positive effect was observed in 94 % of patients in the Thiocetam-treated group within the first 5 days. In comparison, the control group showed a positive clinical effect in 76 % of cases. This improvement was evident both in the clinical field and based on indicators of autonomic reactivity in EEG data, as well as cognitive function assessed by the MMSE cognitive function test scale. Conclusions. The utilization of Thiocetam during the acute phase of mild and moderate closed combat craniocerebral trauma enhances the neuroprotective effects of basic therapy. The combined drug Thiocetam, which possesses both nootropic and neuroprotective effects, offers the advantage of reducing or even avoiding the side effects commonly associated with traditional racetam nootropics.

Background: Nootropic drugs, at the beginning of their career, were used in the treatment of diseases such as attention deficit hyperactivity disorder (ADHD), Alzheimer's disease and narcolepsy. Nowadays, they are becoming more and more popular among students, where they are often called smart drugs or cognitive enhancers. Their properties that improve intellectual abilities and cognitive functions are used to, among other things, improve academic performance. Aim of the study: The purpose of this article was to summarize the current state of knowledge relating to the use of smart drugs among students. This study discusses the multidimensional issues of using this group of drugs. Material and methods: A cross-sectional search of relevant literature was performed in databases using accepted wording. Publications from 2003-2023 were included. The entire process has been supplemented with additional procedures to increase the reliability of this publication. Results: In most sources, the most common representative of smart drugs turned out to be methylphenidate. Nootropics were most often obtained by obtaining a prescription from a doctor, online trading or from friends. The factors motivating the use of substances from this group are primarily the desire to improve academic results, competitiveness and the number of obligations at the university. There are many risks associated with their use, but students are more aware of the positive effects. Conclusion: This paper presents various dimensions of the progressive spread of nootropic drugs. In addition to their undeniably positive effects, there are many risks, which are discussed in this article. Students' awareness should be formed through appropriate educational methods.

The vast majority of research on cognitive enhancement has focused on pharmacological cognitive enhancement (PCE), with relatively little exploration of public attitudes towards non-pharmacological cognitive enhancing substances. Limited research has investigated how the lay public ethically evaluates nootropic supplements (i.e. legal and purportedly natural over-the-counter products), or how such attitudes may differ from attitudes towards other cognitive enhancers. This experimental between-subjects study used a contrastive vignette technique to explore Irish students' attitudes towards caffeine tablets, nootropic supplements and PCE. One-hundred-and-thirteen Irish university students participated in the study (46 male, 64 female), ranging from 18 to 25 years of age (M = 21.9). Quantitative analyses examined differences in mean attitudes between cognitive enhancement conditions and genders. Results suggest that the three forms of cognitive enhancement provoked similar moderate responses in relation to safety and authenticity, however, students were more concerned about implicit coercion in relation to PCE and reported heightened fairness concerns in relation to nootropic supplements. Nootropic supplements may have distinct ethical implications which are not simply equivalent to those that accompany PCE or caffeine tablets, raising questions surrounding the effects of novel cognitive enhancing products; financial barriers to legal non-pharmacological cognitive enhancement; and the permissibility of cognitive enhancement advertising. [ABSTRACT FROM AUTHOR]

Chloroquine (CQ) and hydroxychloroquine (HCQ) are classical antimalarial drugs, and recently have been used for other applications including coronavirus disease 2019 (COVID-19). Although they are considered safe, cardiomyopathy may associate CQ and HCQ applications particularly at overdoses. The goal of the present study was to evaluate the potential protective effect of the nootropic agent vinpocetine against CQ and HCQ adverse effects with a specific focus on the heart. For this purpose, a mouse model of CQ (0.5 up to 2.5 g/kg)/HCQ (1 up to 2 g/kg) toxicity was used, and the effect of vinpocetine was evaluated by survival, biochemical, as well as histopathological analyses. Survival analysis revealed that CQ and HCQ caused dose-dependent lethality, which was prevented by co-treatment with vinpocetine (100 mg/kg, oral or intraperitoneal). To gain deeper understanding, a dose of 1 g/kg CQ—which did not cause death within the first 24 h after administration—was applied with and without vinpocetine administration (100 mg/kg, intraperitoneal). The CQ vehicle group showed marked cardiotoxicity as evidenced by significant alterations of blood biomarkers including troponione-1, creatine phosphokinase (CPK), creatine kinase-myocardial band (CK-MB), ferritin, and potassium levels. This was confirmed at the tissue level by massive alteration of the heart tissue morphology and coincided with massive oxidative stress. Interestingly, co-administration of vinpocetine strongly ameliorated CQ-induced alterations and restored the antioxidant-defense system of the heart. These data suggest that vinpocetine could be used as an adjuvant therapy together with CQ/HCQ applications. [ABSTRACT FROM AUTHOR]

Cognitive enhancement (CE) covers a broad spectrum of methods, including behavioral techniques, nootropic drugs, and neuromodulation interventions. However, research on their use in children has almost exclusively been carried out in high-income countries with limited understanding of how experts working with children view their use in low- and middle- income countries (LMICs). This study examines perceptions on cognitive enhancement, their techniques, neuroethical issues about their use from an LMICs perspective. Seven Indian experts were purposively sampled for their expertise in bioethics, child development and child education. In-depth interviews were conducted using a semi-structured topic guide to examine (1) understanding of CE, (2) which approaches were viewed as cognitive enhancers, (3) attitudes toward different CE techniques and (4) neuroethical issues related to CE use within the Indian context. All interviews were audio recorded and transcribed before thematic analysis. Findings indicate Indian experts view cognitive enhancement as a holistic positive impact on overall functioning and well-being, rather than improvement in specific cognitive abilities. Exogenous agents, and neuromodulation were viewed with skepticism, whereas behavioral approaches were viewed more favorably. Neuroethical concerns included equitable access to CE, limited scientific evidence and over-reliance on technology to address societal problems. This highlights the need for more contextually relevant neuroethics research in LMICs. [ABSTRACT FROM AUTHOR]

There exists a strong correlation between the pH levels of the gastrointestinal (GI) tract and GI diseases such as inflammatory bowel disease (IBS), ulcerative colitis, and pancreatis. Existing methods for diagnosing many GI diseases predominantly rely on invasive, expensive, and time-consuming techniques such as colonoscopy and endoscopy. In this study, an autonomous ingestible smart biosensing system in a pill format with integrated pH sensors is reported. The smart sensing pills will measure the pH profile as they transit through the GI tract. The data is then downloaded from the pills after they are collected from the feces. The sensor is based on electrodeposited PANI on carbon-coated conductive threads providing high pH sensitivity. Engineering innovations allowed integration of thread-based sensors on 3D-printed pill surfaces with front-end readout electronics, memory, and microcontroller assembled on mm-size circular printed circuit boards. The entire smart sensing pill possesses an overall length of 22.1 mm and an outer diameter of 9 mm. The modular biosensing system allows integration of thread-based biosensors to monitor other biomarkers in GI tract that mitigates the complex sensor fabrication process as well as overall pill assembly. [ABSTRACT FROM AUTHOR]

Health concerns associated with the consumption of food supplements rise in parallel with the rise in the popularity and market availability of these products. In pursuit of data related to the unauthorized presence of pharmaceuticals in food supplements, the Rapid Alert System for Food and Feed (RASFF) database was searched for the 2011–2022 period. The most "popular" pharmaceuticals for the adulteration of food supplements were phosphodiesterase-5 inhibitors (235 records); anorexics and laxatives (76), including sibutramine and its active metabolite N-didesmethyl sibutramine, phenolphthalein and 2,4-dinitrophenol; stimulants, among which 1,3-dimethylamine (97), and synephrine (53) were the most numerous; nootropic drugs (24); anabolics and prohormones (16); and cannabinoid cannabidiol (14) (pending authorization as a novel food ingredient). Over 65% of notifications of interest were classified as serious risks, and over 80% of these were alert or border rejection notifications, mainly generated as a result of official control on the market. The alarming number of RASFF notifications should be considered a public health issue, demanding clear and targeted recommendation for action for the legislature and authorities. A harmonized nutrivigilance system should be considered as a tool to detect and scrutinize the adverse health effects of food supplements, along with measures to improve their safety, quality, and testing. [ABSTRACT FROM AUTHOR]

[99mTc] fonturacetam hydrazide was radiosynthesized to assess neuropsychiatric disorders by targeting the brain. The nootropic drug was labeled with technetium-99m, and factors affecting the labeling yield were studied. At optimum conditions, the radiocomplex was obtained at a high radiochemical yield (98.9%) and was stable in saline for up to 36 h and serum for more than 24 h. Labeled fonturacetam hydrazide was characterized and assessed in silico. Biodistribution studies in mice showed that the brain uptake of the complex was 8.8% injected dose per gram (% ID/g) at 5 min post-injection, surpassing the commercially available [99mTc] ECD (4.7% ID/g) and [99mTc] HMPAO (2.25% ID/g). All results suggested that the tracer is a good candidate to image the human brain for assessing neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

This document is a letter to the editor in response to an article titled "Neurotechnology and ethics guidelines for human enhancement: The case of the hippocampal cognitive prosthesis." The authors of the letter commend the original article for its analysis of the ethical implications of neurotechnologies, specifically focusing on the hippocampal cognitive prosthesis. However, they argue that there are additional considerations that should be discussed, such as the blurred line between therapy and enhancement, the societal implications of cognitive enhancement technologies, and the issues of autonomy and authenticity. The authors also emphasize the need for ongoing interdisciplinary dialogue and caution in the development of ethical guidelines without robust empirical data on the long-term effects of these technologies. [Extracted from the article]