Potential Cognitive Enhancers Research Articles

Dose-Response Effects of Short-Term Rhodiola rosea Supplementation on Cognitive Function and Readiness to Perform in Athletes: A Randomized, Crossover, Double-Blind, and Placebo-Controlled Study

Background: Rhodiola rosea (RR) is renowned for its adaptogenic qualities across diverse cultures. Contemporary research delves deeper into its potential neuroprotective capabilities and role in augmenting cognitive functions. Given the imperative nature of peak cognitive performance in athletes, the influence of RR supplementation has emerged as a focal point of scientific inquiry. This study elucidates the dose-response relationship of short-term RR consumption on cognitive prowess in resistance-trained athletes. Methods: Twenty-seven resistance-trained athletes (13 males, 14 females; 22±3 y; 170.4±10.7 cm; 75.4±21.9 kg) completed a baseline (BL) and three distinct conditions in random order: low-dose RR (LD: 200 mg/d of RR combined with 1.3 g/d of maltodextrin), high-dose RR (HD: 1.5 g/d of RR), and a placebo (PL: 1.5 g/d of maltodextrin). Each supplementation phase lasted 7d, separated by a 7-day washout period before commencing the subsequent condition. After the supplementation, participants undertook a Stroop color-word test and completed a readiness to perform using a visual analog scale. Data were analyzed using a two-way (within-within) analysis of variance (p≤0.05) with LSD's post hoc when appropriate. RESULTS: Participants were assessed using the Stroop Word-Color test at BL and following each treatment phase. In the Word section, there was a significant improvement. Post hoc analysis revealed that both RR doses surpassed BL and PL results. The scores were as follows: BL [107.8±10.6 counts (c)], PL (118.4±11.7 c), LD (122.0±15.1 c), and HD (125.2±16.2 c; p<0.001). Participants completed tasks more swiftly in the Color section after taking both RR doses than at BL. The results were: BL (79.3±12.3 c), PL (85.3±10.6 c), LD (88.0±11.1 c), and HD (91±24.8 c; p<0.031). In the Word-Color section, both RR doses led to significant cognitive enhancements, with scores being BL (94.0±18.5 c), PL (104.3±16.2 c), LD (108.9±20.6 c), and HD (113.0±18.3 c; p<0.001). When all domains were summed, a notable enhancement was observed. Subsequent post hoc analysis indicated that both RR dosages exceeded the scores of BL and PL. The respective scores were: BL (281.1±31.1 c), PL (307.9±29.7 c), LD (318.9±36.5 c), and HD (329.6±47.8 c; p<0.001). No significant alterations were noted in readiness (p>0.05). CONCLUSION: This study underscores RR as a potential cognitive enhancer for athletes. Both the low and high doses of RR yielded significant benefits in the Stroop Word-Color test, suggesting a dose-responsive relationship. However, RR did not influence the athletes' sense of readiness. While the findings are promising, further research is essential to determine RR's comprehensive effects and ideal dosing. The researchers personally financed this study, bearing all costs. Such a method guarantees the research's autonomy, free from potential influences that might come with external financial support or grants. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Potential cognitive enhancers: Discovery and development of multi‐targeting aminoalkyl chalcones

AbstractBackgroundInhibition of acetylcholinesterase (AChE) enzyme is considered as the most promising approach to improve the cognitive deficit complex disorders such as Alzheimer’s disease, dementia etc. The AChE also promote the aggregation of amyloid‐β complexes, mitochondrial dysfunction, a buildup of oxidative stress and neuronal cell death. Consequently, the development of compounds having polyfunctional potential could manage the complex neurodegenerative disorders like Alzheimer’s disease.MethodThe chalcone analogues were developed using bioisosteric replacement and SBDD strategies having improved therapeutic potential. The kinetics and interaction pattern with target protein of designed analogues were further evaluated using in silico methods. The leading compounds were synthesized and evaluated against AChE, AGEs formation with additional radical scavenging potential.ResultThe docking results revealed that synthesized chalcones properly fit into the active gorge of the target enzyme and displayed crucial interactions with the peripheral and catalytic sites of and having drug like properties. The in vitro assays of designed compounds against different targets showed IC50 values in nano to micro molar range.ConclusionThe dynamic simulations of the designed compounds will be carried out to evaluate the stability of the target‐ligand complex. Thus, the designed chalcones could be taken further to improve cognition deficit mainly in Alzheimer’s disease.

Paradigm Shift: Multiple Potential Pathways to Neurodegenerative Dementia

Neurodegenerative dementia can result from multiple underlying abnormalities, including neurotransmitter imbalances, protein aggregation, and other neurotoxic events. A major complication in identifying effective treatment targets is the frequent co-occurrence of multiple neurodegenerative processes, occurring either in parallel or sequentially. The path towards developing effective treatments for Alzheimer's disease (AD) and other dementias has been relatively slow and until recently has focused on disease symptoms. Aducanumab and lecanemab, recently approved by the FDA, are meant to target disease structures but have only modest benefit on symptom progression and remain unproven in reversing or preventing dementia. A third, donanemab, appears more promising but awaits FDA approval. Ongoing trials include potential cognition enhancers, new combinations of known drugs for synergistic effects, prodrugs with less toxicity, and increasing interest in drugs targeting neuroinflammation or microbiome. Scientific and technological advances offer the opportunity to move in new therapy directions, such as modifying microglia to prevent or suppress underlying disease. A major challenge, however, is that underlying comorbidities likely influence the effectiveness of therapies. Indeed, the full range of comorbidity, today only definitively identified postmortem, likely contributes to failed clinical trials and overmedication of older adults, since it is difficult to exclude (during life) people unlikely to respond. Our current knowledge thus signals that a paradigm shift towards individualized and multimodal treatments is necessary to effectively advance the field of dementia therapeutics.

Nootropic Herbs, Shrubs, and Trees as Potential Cognitive Enhancers.

Plant-based nootropics are a diverse group of natural drugs that can improve cognitive abilities through various physiological mechanisms, especially in cases where these functions are weakened or impaired. In many cases, the nootropics enhance erythrocyte plasticity and inhibit aggregation, which improves the blood's rheological properties and increases its flow to the brain. Many of these formulations possess antioxidant activity that protects brain tissue from neurotoxicity and improves the brain's oxygen supply. They can induce the synthesis of neuronal proteins, nucleic acids, and phospholipids for constructing and repairing neurohormonal membranes. These natural compounds can potentially be present in a great variety of herbs, shrubs, and even some trees and vines. The plant species reviewed here were selected based on the availability of verifiable experimental data and clinical trials investigating potential nootropic effects. Original research articles, relevant animal studies, meta-analyses, systematic reviews, and clinical trials were included in this review. Selected representatives of this heterogeneous group included Bacopa monnieri (L.) Wettst., Centella asiatica (L.) Urban, Eleutherococcus senticosus (Rupr. & Maxim.) Maxim., Ginkgo biloba L., Lepidium meyenii Walp., Panax ginseng C.A. Meyer, Paullinia cupana Kunth, Rhodiola rosea L., Schisandra chinensis (Turcz.) Baill., and Withania somnifera (L.) Dunal. The species are depicted and described, together with their active components and nootropic effects, and evidence of their efficacy is presented. The study provides brief descriptions of the representative species, their occurrence, history, and the chemical composition of the principle medicinal compounds, with uses, indications, experimental treatments, dosages, possible side effects, and contraindications. Most plant nootropics must be taken at optimal doses for extended periods before measurable improvement occurs, but they are generally very well tolerated. Their psychoactive properties are not produced by a single molecule but by a synergistic combination of several compounds. The available data suggest that including extracts from these plants in medicinal products to treat cognitive disorders can have substantial potential therapeutic benefits.

Leptin-based hexamers facilitate memory and prevent amyloid-driven AMPA receptor internalisation and neuronal degeneration.

Key pathological features of Alzheimer's disease (AD) include build-up of amyloid β (Aβ), which promotes synaptic abnormalities and ultimately leads to neuronal cell death. Metabolic dysfunction is known to influence the risk of developing AD. Impairments in the leptin system have been detected in AD patients, which has fuelled interest in targeting this system to treat AD. Increasing evidence supports pro-cognitive and neuroprotective actions of leptin and these beneficial effects of leptin are mirrored by a bioactive leptin fragment (leptin116-130 ). Here we extend these studies to examine the potential cognitive enhancing and neuroprotective actions of 8 six-amino acid peptides (hexamers) derived from leptin116-130 . In this study, we show that four of the hexamers (leptin116-121, 117-122, 118-123 and 120-125 ) replicate the ability of leptin to promote α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking and facilitate hippocampal synaptic plasticity. Moreover, the pro-cognitive effects of the hexamers were verified in behavioural studies, with the administration of leptin117-122 enhancing performance in episodic memory tasks. The bioactive hexamers replicated the neuroprotective actions of leptin by preventing the acute hippocampal synapto-toxic effects of Aβ, and the chronic effects of Aβ on neuronal cell viability, Aβ seeding and tau phosphorylation. These findings provide further evidence to support leptin and leptin-derived peptides as potential therapeutics for AD.

Cognitive enhancement: Effects of methylphenidate, modafinil, and caffeine on latent memory and resting state functional connectivity in healthy adults.

Stimulants like methylphenidate, modafinil, and caffeine have repeatedly shown to enhance cognitive processes such as attention and memory. However, brain‐functional mechanisms underlying such cognitive enhancing effects of stimulants are still poorly characterized. Here, we utilized behavioral and resting‐state fMRI data from a double‐blind randomized placebocontrolled study of methylphenidate, modafinil, and caffeine in 48 healthy male adults. The results show that performance in different memory tasks is enhanced, and functional connectivity (FC) specifically between the frontoparietal network (FPN) and default mode network (DMN) is modulated by the stimulants in comparison to placebo. Decreased negative connectivity between right prefrontal and medial parietal but also between medial temporal lobe and visual brain regions predicted stimulant‐induced latent memory enhancement. We discuss dopamine's role in attention and memory as well as its ability to modulate FC between large‐scale neural networks (e.g., FPN and DMN) as a potential cognitive enhancement mechanism.

Edible Bird's Nest as a Potential Cognitive Enhancer.

Cognitive enhancement is defined as the augmentation of the mind's core capabilities through the improvement of internal or external information processing systems. Recently, the focus has shifted to the potential therapeutic effects of natural products in improving cognitive function. Edible bird's nest (EBN) is a natural food substance derived from the saliva of swiftlets. Until today, EBN is regarded as a high-priced nutritious food with therapeutic effects. The effectiveness of dietary EBN supplementation to enhance brain development in mammals has been documented. Although the neuroprotection of EBN has been previously reported, however, the impact of EBN on learning and memory control and its potential as a cognitive enhancer drug remains unknown. Thus, this article aims to address the neuroprotective benefits of EBN and its potential effect as a cognitive enhancer. Notably, the current challenges and the future study direction in EBN have been demonstrated.

Pilot Study on Dose-Dependent Effects of Transcranial Photobiomodulation on Brain Electrical Oscillations: A Potential Therapeutic Target in Alzheimer’s Disease

Background: Transcranial photobiomodulation (tPBM) has recently emerged as a potential cognitive enhancement technique and clinical treatment for various neuropsychiatric and neurodegenerative disorders by delivering invisible near-infrared light to the scalp and increasing energy metabolism in the brain. Objective: We assessed whether transcranial photobiomodulation with near-infrared light modulates cerebral electrical activity through electroencephalogram (EEG) and cerebral blood flow (CBF). Methods: We conducted a single-blind, sham-controlled pilot study to test the effect of continuous (c-tPBM), pulse (p-tPBM), and sham (s-tPBM) transcranial photobiomodulation on EEG oscillations and CBF using diffuse correlation spectroscopy (DCS) in a sample of ten healthy subjects [6F/4 M; mean age 28.6±12.9 years]. c-tPBM near-infrared radiation (NIR) (830 nm; 54.8 mW/cm2; 65.8 J/cm2; 2.3 kJ) and p-tPBM (830 nm; 10 Hz; 54.8 mW/cm2; 33%; 21.7 J/cm2; 0.8 kJ) were delivered concurrently to the frontal areas by four LED clusters. EEG and DCS recordings were performed weekly before, during, and after each tPBM session. Results: c-tPBM significantly boosted gamma (t = 3.02, df = 7, p < 0.02) and beta (t = 2.91, df = 7, p < 0.03) EEG spectral powers in eyes-open recordings and gamma power (t = 3.61, df = 6, p < 0.015) in eyes-closed recordings, with a widespread increase over frontal-central scalp regions. There was no significant effect of tPBM on CBF compared to sham. Conclusion: Our data suggest a dose-dependent effect of tPBM with NIR on cerebral gamma and beta neuronal activity. Altogether, our findings support the neuromodulatory effect of transcranial NIR.

A tacrine-tetrahydroquinoline heterodimer potently inhibits acetylcholinesterase activity and enhances neurotransmission in mice

Cholinergic neurons are ubiquitous and involved in various higher brain functions including learning and memory. Patients with Alzheimer's disease exhibit significant dysfunction and loss of cholinergic neurons. Meanwhile, such cholinergic deficits can be potentially relieved pharmacologically by increasing acetylcholine. Acetylcholinesterase (AChE) inhibitors have been used to improve cholinergic transmission in the brain for two decades and have proven effective for alleviating symptoms in the early stages of Alzheimer's disease. Therefore, the search for AChE inhibitors for drug development is ongoing. The enzymatic pocket of AChE has long been the target of several drug designs over the last two decades. The peripheral and catalytic sites of AChE are simultaneously bound by several dimeric molecules, enabling more-efficient inhibition. Here, we used 6-chlorotacrine and the tetrahydroquinolone moiety of huperzine A to design and synthesize a series of heterodimers that inhibit AChE at nanomolar potency. Specifically, compound 7b inhibits AChE with an IC50 < 1 nM and spares butyrylcholinesterase. Administration of 7b to mouse brain slices restores synaptic activity impaired by pirenzepine, a muscarinic M1-selective antagonist. Moreover, oral administration of 7b to C57BL/6 mice enhances hippocampal long-term potentiation in a dose-dependent manner and is detectable in the brain tissue. All these data supported that 7b is a potential cognitive enhancer and is worth for further exploration.

Repurposing of Anti-Diabetic Agents as a New Opportunity to Alleviate Cognitive Impairment in Neurodegenerative and Neuropsychiatric Disorders.

Cognitive impairment is a shared abnormality between type 2 diabetes mellitus (T2DM) and many neurodegenerative and neuropsychiatric disorders, such as Alzheimer’s disease (AD) and schizophrenia. Emerging evidence suggests that brain insulin resistance plays a significant role in cognitive deficits, which provides the possibility of anti-diabetic agents repositioning to alleviate cognitive deficits. Both preclinical and clinical studies have evaluated the potential cognitive enhancement effects of anti-diabetic agents targeting the insulin pathway. Repurposing of anti-diabetic agents is considered to be promising for cognitive deficits prevention or control in these neurodegenerative and neuropsychiatric disorders. This article reviewed the possible relationship between brain insulin resistance and cognitive deficits. In addition, promising therapeutic interventions, especially current advances in anti-diabetic agents targeting the insulin pathway to alleviate cognitive impairment in AD and schizophrenia were also summarized.

Cognitive Enhancement: Unanswered Questions About Human Psychology and Social Behavior

Stimulant drugs, transcranial magnetic stimulation, brain-computer interfaces, and even genetic modifications are all discussed as forms of potential cognitive enhancement. Cognitive enhancement can be conceived as a benefit-seeking strategy used by healthy individuals to enhance cognitive abilities such as learning, memory, attention, or vigilance. This phenomenon is hotly debated in the public, professional, and scientific literature. Many of the statements favoring cognitive enhancement (e.g., related to greater productivity and autonomy) or opposing it (e.g., related to health-risks and social expectations) rely on claims about human welfare and human flourishing. But with real-world evidence from the social and psychological sciences often missing to support (or invalidate) these claims, the debate about cognitive enhancement is stalled. In this paper, we describe a set of crucial debated questions about psychological and social aspects of cognitive enhancement (e.g., intrinsic motivation, well-being) and explain why they are of fundamental importance to address in the cognitive enhancement debate and in future research. We propose studies targeting social and psychological outcomes associated with cognitive enhancers (e.g., stigmatization, burnout, mental well-being, work motivation). We also voice a call for scientific evidence, inclusive of but not limited to biological health outcomes, to thoroughly assess the impact of enhancement. This evidence is needed to engage in empirically informed policymaking, as well as to promote the mental and physical health of users and non-users of enhancement.

Leptin regulation of hippocampal synaptic function in health and disease.

It is widely accepted that the metabolic hormone leptin regulates food intake and body weight via activation of hypothalamic leptin receptors. However, as leptin receptors are also highly expressed in other brain regions, such as the hippocampus, alterations in leptin responsiveness also impacts on key functions of the hippocampus, like learning and memory. Within the hippocampus, high levels of leptin receptors are expressed at excitatory synapses, and in accordance with a synaptic localization, leptin potently regulates synaptic transmission at both Schaffer collateral (SC) and temporoammonic (TA) inputs to CA1 pyramidal neurons. Increasing evidence from cellular and behavioral studies examining leptin action at CA1 synapses support the notion that leptin is a potential cognitive enhancer. However, the capacity of leptin to regulate synaptic efficacy at SC-CA1 and TA-CA1 synapses declines in an age-dependent manner. Moreover, clinical evidence that supports a link between circulating leptin levels and the risk of the age-related neurodegenerative disorder, Alzheimer's disease (AD) is accumulating. Consequently, it has been proposed that the leptin system is a potential therapeutic target in AD, and that boosting the hippocampal actions of leptin may be beneficial in the treatment of AD. Here we review recent progress in our understanding of the neuronal and hippocampal synaptic functions that are regulated by leptin and how alterations in the leptin system influence age-related CNS-related disorders like AD.

Novel, non-nitrocatechol catechol-O-methyltransferase inhibitors modulate dopamine neurotransmission in the frontal cortex and improve cognitive flexibility.

Cognitive impairment is a primary feature of many neuropsychiatric disorders and there is a need for new therapeutic options. Catechol-O-methyltransferase (COMT) inhibitors modulate cortical dopaminergic function and have been proposed as potential cognitive enhancers. Unfortunately, currently available COMT inhibitors are not good candidates due to either poor blood-brain barrier penetration or severe toxicity. To address the need for safe, brain-penetrant COMT inhibitors, we tested multiple novel compounds in a set of preclinical in vivo efficacy assays in rats to determine their ability to inhibit COMT function and viability as potential clinical candidates. We measured the change in concentration of dopamine (DA) metabolites in cerebrospinal fluid (CSF) from the cisterna magna and extracellular fluid (ECF) from the frontal cortex produced by our novel compounds. Additionally, we tested the effects of our brain-penetrant COMT inhibitors in an attentional set-shifting assay (ASST). We benchmarked the performance of the novel COMT inhibitors to the effects produced by the known COMT inhibitor tolcapone. We found that multiple COMT inhibitors, exemplified by LIBD-1 and LIBD-3, significantly modulated dopaminergic function measured as decreases in homovanillic acid (HVA) and increases in 3,4-Dihydroxyphenylacetic acid (DOPAC), two DA metabolites, in CSF and the frontal cortex. Additionally, we found thatLIBD-1 significantly improved cognitive flexibility in the ASST, an effect previously reported following tolcapone administration. These results demonstrate that LIBD-1 is a novel COMT inhibitor with promising in vivo activity and the potential to serve as a new therapy for cognitive impairment.

The Mixture of Gotu Kola, Cnidium Fruit, and Goji Berry Enhances Memory Functions by Inducing Nerve-Growth-Factor-Mediated Actions Both In Vitro and In Vivo.

Nerve growth factor (NGF), a typical neurotrophin, has been characterized by the regulation of neuronal cell differentiation and survival involved in learning and memory functions. NGF has a main role in neurite extension and synapse formation by activating the cyclic adenosine monophosphate-response-element-binding protein (CREB) in the hippocampus. The purpose of this study was to determine whether a mixture of Gotu Kola, Cnidium fruit, and Goji berry (KYJ) enhances memory function by inducing NGF-mediated actions both in vitro and in vivo. The KYJ combination increased NGF concentration and neurite length in C6 glioma and N2a neuronal cells, respectively. Additionally, we discovered memory-enhancing effects of KYJ through increased NGF-mediated synapse maturation, CREB phosphorylation, and cell differentiation in the mouse hippocampus. These findings suggest that this combination may be a potential nootropic cognitive enhancer via the induction of NGF and NGF-dependent activities.

Effects of supplemental creatine and guanidinoacetic acid on spatial memory and the brain of weaned Yucatan miniature pigs.

The emergence of creatine as a potential cognitive enhancement supplement for humans prompted an investigation as to whether supplemental creatine could enhance spatial memory in young swine. We assessed memory performance and brain concentrations of creatine and its precursor guanidinoacetic acid (GAA) in 14-16-week-old male Yucatan miniature pigs supplemented for 2 weeks with either 200 mg/kg∙d creatine (+Cr; n = 7) or equimolar GAA (157 mg/kg∙d) (+GAA; n = 8) compared to controls (n = 14). Spatial memory tests had pigs explore distinct sets of objects for 5 min. Objects were spatially controlled, and we assessed exploration times of previously viewed objects relative to novel objects in familiar or novel locations. There was no effect of either supplementation on memory performance, but pigs successfully identified novel objects after 10 (p < 0.01) and 20 min (p < 0.01) retention intervals. Moreover, pigs recognized spatial transfers after 65 min (p < 0.05). Regression analyses identified associations between the ability to identify novel objects in memory tests and concentrations of creatine and GAA in cerebellum, and GAA in prefrontal cortex (p < 0.05). The concentration of creatine in brain regions was not influenced by creatine supplementation, but GAA supplementation increased GAA concentration in cerebellum (p < 0.05), and the prefrontal cortex of +GAA pigs had more creatine/g and less GAA/g compared to +Cr pigs (p < 0.05). Creatine kinase activity and maximal reaction velocity were also higher with GAA supplementation in prefrontal cortex (p < 0.05). In conclusion, there appears to be a relationship between memory performance and guanidino compounds in the cerebellum and prefrontal cortex, but the effects were unrelated to dietary supplementation. The cerebellum is identified as a target site for GAA accretion.

The effect of curcumin on cognition in Alzheimer’s disease and healthy aging: A systematic review of pre-clinical and clinical studies

Alzheimer’s disease constitutes a growing cause of cognitive impairment in aging population. Given that current treatments do not produce the desired therapeutic effects, the need for finding alternative biological and pharmacological approaches is critical. Accumulating evidence suggests inflammatory and oxidative stress responses as potential causal factors of cognitive impairments in Alzheimer’s disease and healthy aging. Curcumin has received increased interest due to its unique molecular structure that targets inflammatory and antioxidant pathways as well as (directly) amyloid aggregation; one of the major hallmarks of Alzheimer’s disease. Therefore, this review summarizes preclinical and clinical findings on curcumin as a potential cognitive enhancer in Alzheimer’s disease and normal aging. Databases used for literature searches include PubMed, EMBASE and Web of Science; in addition, clinicaltrials.gov was used to search for clinical studies. Overall, animal research has shown very promising results in potentiating cognition, both physiologically and behaviourally. However, human studies are limited and results are less consistent, complicating their interpretation. These inconsistencies may be related to differences in methodology and the included population. Taking into account measurements of important inflammatory and antioxidant biomarkers, optimal dosages of curcumin, food interactions, and duration of treatment would increase our understanding on curcumin’s promising effects on cognition. In addition, increasing curcumin’s bioavailability could benefit future research.

Language Training Leads to Global Cognitive Improvement in Older Adults: A Preliminary Study

Purpose We report a preliminary study that prospectively tests the potential cognitive enhancing effect of foreign language (FL) learning in older adults with no clear signs of cognitive decline beyond what is age typical. Because language learning engages a large brain network that overlaps with the network of cognitive aging, we hypothesized that learning a new language later in life would be beneficial. Method Older adults were randomly assigned to 3 training groups: FL, games, and music appreciation. All were trained predominately by a computer-based program for 6 months, and their cognitive abilities were tested before, immediately after, and 3 months after training. Results FL and games, but not music appreciation, improved overall cognitive abilities that were maintained at 3 months after training. Conclusion This is the 1st randomized control study providing preliminary support for the cognitive benefits of FL learning.

How perceived substance characteristics affect ethical judgement towards cognitive enhancement.

Some individuals seek to enhance their cognitive capabilities through the use of pharmacology. Such behavior entails potential health risks and raises ethical concerns. The aim of this study was to examine whether a precursor of behavior, ethical judgement towards the use of existing biological cognitive enhancers (e.g., coffee, legal and illegal drugs), is shaped by the perceived characteristics of these cognitive enhancers. Students and employees completed an online questionnaire which measured perceived characteristics of 15 substances presented as potential cognitive enhancers and a measure of ethical judgement towards these cognitive enhancers. Results of mixed model regression analyzes show that ethical judgement is more favourable when cognitive enhancers are perceived as being legal, familiar, efficient, and safe for users’ health, supporting all hypotheses. Results further show that 36% of variance (in the null model) lies at the level of cognitive enhancers and 21% at the level of participants. In conclusion, cognitive enhancers vary widely in terms of ethical judgement, which is explained by the perception of the mentioned characteristics. Implications regarding prevention and policy-making are discussed.

The Combined Extract of Black Sticky Rice and Dill Improves Poststroke Cognitive Impairment in Metabolic Syndrome Condition.

Despite the increase in cognitive deficit following stroke in metabolic syndrome (MetS) condition, the therapeutic strategy is still limited. Since oxidative stress and neuroinflammation play the crucial roles on the pathophysiology of aforementioned conditions, the cognitive enhancing effect of the combined extract of Oryza sativa and Anethum graveolens was considered based on their antioxidant, anti-inflammation, and neuroprotective effects together with the synergistic effect concept. Male Wistar rats weighing 180-220 g were induced metabolic syndrome-like condition by using a high-carbohydrate high-fat diet (HCHF diet). Then, reperfusion injury following cerebral ischemia was induced by the occlusion of right middle cerebral artery and treated with the combined extract of O. sativa and A. graveolens (OA extract) at doses of 0.5, 5, and 50 mg/kg BW once daily for 21 days. Spatial memory was assessed every 7 days throughout the experimental period. At the end of the study, neuron and glial fibrillary acidic protein- (GFAP-) positive cell densities, the oxidative stress status, AChE, and the expression of proinflammatory cytokines (TNF-α, IL-6) in the hippocampus were determined. The results showed that OA extract at all doses used in this study significantly improved memory together with the reductions of MDA, TNF-α, IL-6, AChE, and density of GFAP-positive cell but increased neuron density in the hippocampus. Taken together, OA is the potential cognitive enhancer in memory impairment following stroke in MetS condition. The possible underlying mechanism may occur partly via the reductions of oxidative stress status, GFAP-positive cell density, and neuroinflammatory cytokines such as TNF-α and IL-6 together with the suppression of AChE activity in the hippocampus. This study suggests that OA is the potential functional ingredient to improve the cognitive enhancer. However, further clinical research is required.

On the Design of Broad-Based Neuropsychological Test Batteries to Assess the Cognitive Abilities of Individuals with Down Syndrome in the Context of Clinical Trials.

Down syndrome (DS) is the most common genetically-defined cause of intellectual disability. Neurodevelopmental deficits displayed by individuals with DS are generally global, however, disproportionate deficits in cognitive processes that depend heavily on the hippocampus and prefrontal cortex are also well documented. Additionally, DS is associated with relative strengths in visual processing and visuospatial short-term memory, and weaknesses in the verbal domain. Although reports of pharmacological rescuing of learning and memory deficits in mouse models of DS abound in the literature, proving the principle that cognitive ability of persons with DS can be boosted through pharmacological means is still an elusive goal. The design of customized batteries of neuropsychological efficacy outcome measures is essential for the successful implementation of clinical trials of potential cognitive enhancing strategies. Here, we review the neurocognitive phenotype of individuals with DS and major broad-based test batteries designed to quantify specific cognitive domains in these individuals, including the one used in a pilot trial of the drug memantine. The main goal is to illustrate the essential considerations in planning trials to enhance cognitive functions in individuals with DS, which should also have implications for the design of similar studies in individuals with other forms of intellectual disability.