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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]

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]

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]

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]

Cognitive decline is commonly seen both in normal aging and in neurodegenerative and neuropsychiatric diseases. Various experimental animal models represent a valuable tool to study brain cognitive processes and their deficits. Equally important is the search for novel drugs to treat cognitive deficits and improve cognitions. Complementing rodent and clinical findings, studies utilizing zebrafish (Danio rerio) are rapidly gaining popularity in translational cognitive research and neuroactive drug screening. Here, we discuss the value of zebrafish models and assays for screening nootropic (cognitive enhancer) drugs and the discovery of novel nootropics. We also discuss the existing challenges, and outline future directions of research in this field. • Rising prevalence of cognitive deficits necessitates novel promnestic therapies be developed. • Animal models are a valuable tool to discover novel nootropic drugs. • Zebrafish are increasingly utilized to study cognitive processes and their deficits. • Zebrafish models markedly facilitate screening and discovery of nootropic drugs. [ABSTRACT FROM AUTHOR]

[Display omitted] • The encapsulation of piracetam in nonionic micellar system to calculate partition coefficient and binding constant. • Tween 80 and Triton X – 100 are utilized to enhance the solubility and bioavailability of piracetam. • The encapsulation of piracetam in tween 80 micelles is more prominent and more spontaneous. • Mixed micellization is more favorable and effective than single surfactant micellization. Nonionic surfactants have drawn tremendous attention for micellar solubilization, sustained release of the drug, encapsulation of pharmaceutically active ingredients, and permeabilization due to their distinct physicochemical characteristics. Concise solubility investigations are required for the appropriate selection of nonionic surfactant that is to be used for a formulation. In the present research, a cluster of micelles was developed that relies on trapping and stabilizing piracetam by balancing the hydrophilic and hydrophobic forces of nonionic surfactants. Tween 80 and Triton-X 100 and a mixture of these surfactants were used to clarify the drug-surfactant interaction in an aqueous and micellar medium. The interaction was investigated in premicellar, micellar, and post-micellar regions by using UV/Visible spectroscopy. Spectroscopic parameters were calculated to determine the degree of solubilization in terms of the partition coefficient (K x), binding constant (K b), and their respective energies in terms of Gibbs free energy of partition (ΔG p) and Gibbs free energy of binding (ΔG b) for piracetam. The solubilization of piracetam is enhanced by mixing an adequate amount of both nonionic surfactants. The obtained results demonstrated that solubilization is spontaneous and entropically favorable and the cluster of micelles in both single and mixed micellar mediums are stable due to the presence of a much more hydrophobic and hydrophilic culture which provides a synergistic link between the two surfactants. [ABSTRACT FROM AUTHOR]