Approaches to Measuring the Effects of Wake-Promoting Drugs: A Focus on Cognitive Function

PubMed Central

Edgar, Christopher J.; Pace-Schott, Edward F.; Wesnes, Keith A.

2009-01-01

Objectives In clinical drug development, wakefulness and wake-promotion maybe assessed by a large number of scales and questionnaires. Objective assessment of wakefulness is most commonly made using sleep latency/maintenance of wakefulness tests, polysomnography and/or behavioral measures. The purpose of the present review is to highlight the degree of overlap in the assessment of wakefulness and cognition, with consideration of assessment techniques and the underlying neurobiology of both concepts. Design Reviews of four key areas were conducted: commonly used techniques in the assessment of wakefulness; neurobiology of sleep/wake and cognition; targets of wake promoting and/or cognition enhancing drugs; and ongoing clinical trials investigating wake promoting effects. Results There is clear overlap between the assessment of wakefulness and cognition. There are common techniques which may be used to assess both concepts; aspects of the neurobiology of both concepts may be closely related; and wake promoting drugs may have nootropic properties (and vice-versa). Clinical trials of wake promoting drugs often, though not routinely, assess aspects of cognition. Conclusions Routine and broad assessment of cognition in the development of wake promoting drugs may reveal important nootropic effects, which are not secondary to alertness/wakefulness, whilst existing cognitive enhancers may have under explored or unknown wake promoting properties. PMID:19565524

Aniracetam does not alter cognitive and affective behavior in adult C57BL/6J mice.

PubMed

Elston, Thomas W; Pandian, Ashvini; Smith, Gregory D; Holley, Andrew J; Gao, Nanjing; Lugo, Joaquin N

2014-01-01

There is a growing community of individuals who self-administer the nootropic aniracetam for its purported cognitive enhancing effects. Aniracetam is believed to be therapeutically useful for enhancing cognition, alleviating anxiety, and treating various neurodegenerative conditions. Physiologically, aniracetam enhances both glutamatergic neurotransmission and long-term potentiation. Previous studies of aniracetam have demonstrated the cognition-restoring effects of acute administration in different models of disease. No previous studies have explored the effects of aniracetam in healthy subjects. We investigated whether daily 50 mg/kg oral administration improves cognitive performance in naïve C57BL/6J mice in a variety of aspects of cognitive behavior. We measured spatial learning in the Morris water maze test; associative learning in the fear conditioning test; motor learning in the accelerating rotarod test; and odor discrimination. We also measured locomotion in the open field test, anxiety through the elevated plus maze test and by measuring time in the center of the open field test. We measured repetitive behavior through the marble burying test. We detected no significant differences between the naive, placebo, and experimental groups across all measures. Despite several studies demonstrating efficacy in impaired subjects, our findings suggest that aniracetam does not alter behavior in normal healthy mice. This study is timely in light of the growing community of healthy humans self-administering nootropic drugs.

Aniracetam Does Not Alter Cognitive and Affective Behavior in Adult C57BL/6J Mice

PubMed Central

Elston, Thomas W.; Pandian, Ashvini; Smith, Gregory D.; Holley, Andrew J.; Gao, Nanjing; Lugo, Joaquin N.

2014-01-01

There is a growing community of individuals who self-administer the nootropic aniracetam for its purported cognitive enhancing effects. Aniracetam is believed to be therapeutically useful for enhancing cognition, alleviating anxiety, and treating various neurodegenerative conditions. Physiologically, aniracetam enhances both glutamatergic neurotransmission and long-term potentiation. Previous studies of aniracetam have demonstrated the cognition-restoring effects of acute administration in different models of disease. No previous studies have explored the effects of aniracetam in healthy subjects. We investigated whether daily 50 mg/kg oral administration improves cognitive performance in naïve C57BL/6J mice in a variety of aspects of cognitive behavior. We measured spatial learning in the Morris water maze test; associative learning in the fear conditioning test; motor learning in the accelerating rotarod test; and odor discrimination. We also measured locomotion in the open field test, anxiety through the elevated plus maze test and by measuring time in the center of the open field test. We measured repetitive behavior through the marble burying test. We detected no significant differences between the naive, placebo, and experimental groups across all measures. Despite several studies demonstrating efficacy in impaired subjects, our findings suggest that aniracetam does not alter behavior in normal healthy mice. This study is timely in light of the growing community of healthy humans self-administering nootropic drugs. PMID:25099639

Design, synthesis and nootropic activity of new analogues of sunifiram and sapunifiram, two potent cognition-enhancers.

PubMed

Martini, Elisabetta; Salvicchi, Alberto; Ghelardini, Carla; Manetti, Dina; Dei, Silvia; Guandalini, Luca; Martelli, Cecilia; Melchiorre, Michele; Cellai, Cristina; Scapecchi, Serena; Teodori, Elisabetta; Romanelli, Maria Novella

2009-11-01

A series of amides and sulfonamides, structurally related to DM235 (sunifiram) and MN19 (sapunifiram), derived by ring expansion or contraction, or by inversion of the exocyclic amide function, have been synthesized and tested for cognition-enhancing activity in the mouse passive-avoidance test. Some of the compounds display good antiamnesic and procognitive activity, with higher potency than piracetam, and with a potency similar to the parent compounds.

Substituted piperazines as nootropic agents: 2- or 3-phenyl derivatives structurally related to the cognition-enhancer DM235.

PubMed

Guandalini, Luca; Martino, Maria Vittoria; Di Cesare Mannelli, Lorenzo; Bartolucci, Gianluca; Melani, Fabrizio; Malik, Ruchi; Dei, Silvia; Floriddia, Elisa; Manetti, Dina; Orlandi, Francesca; Teodori, Elisabetta; Ghelardini, Carla; Romanelli, Maria Novella

2015-04-15

A series of 2-phenyl- or 3-phenyl piperazines, structurally related to DM235 and DM232, two potent nootropic agents, have been prepared and tested in the mouse passive-avoidance test, to assess their ability to revert scopolamine-induced amnesia. Although the newly synthesized molecules were less potent than the parent compounds, some useful information has been obtained from structure-activity relationships. A small but significant enantioselectivity has been found for the most potent compound 5a. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influence of ring size on the cognition-enhancing activity of DM235 and MN19, two potent nootropic drugs.

PubMed

Guandalini, L; Martini, E; Di Cesare Mannelli, L; Dei, S; Manetti, D; Scapecchi, S; Teodori, E; Ghelardini, C; Romanelli, M N

2012-03-01

A series of analogs of DM235 and MN19, characterized by rings with different size, have been prepared and evaluated for their nootropic activity in the mouse passive-avoidance test. It was found that the optimal ring size for the analogs of DM235, showing endocyclic both amidic groups, is 6 or 7 atoms. For the compounds structurally related to MN19, carrying an exocyclic amide group, the piperidine ring is the moiety which gives the most interesting compounds. Copyright © 2012 Elsevier Ltd. All rights reserved.

The cognitive-enhancing effects of Bacopa monnieri: a systematic review of randomized, controlled human clinical trials.

PubMed

Pase, Matthew P; Kean, James; Sarris, Jerome; Neale, Chris; Scholey, Andrew B; Stough, Con

2012-07-01

Traditional knowledge suggests that Bacopa monnieri enhances cognitive performance. Such traditional beliefs have now been scientifically tested through a handful of randomized, controlled human clinical trials. The current systematic review aimed to examine the scientific evidence as to whether Bacopa can enhance cognitive performance in humans. A systematic review of randomized controlled trials is presented. Multiple databases were systematically searched by multiple authors. Relevant trials were objectively assessed for methodological quality. The subjects studied were adult humans without dementia or significant cognitive impairment. B. monnieri, including Bacopa extracts, were administered over long-term supplementation periods. Any validated cognitive test, whether a primary or secondary outcome. Six (6) studies met the final inclusion criteria and were included in review. Trials were all conducted over 12 weeks. Across trials, three different Bacopa extracts were used at dosages of 300-450 mg extract per day. All reviewed trials examined the effects of Bacopa on memory, while other cognitive domains were less well studied. There were no cognitive tests in the areas of auditory perceptual abilities or idea production and only a paucity of research in the domains of reasoning, number facility, and language behavior. Across studies, Bacopa improved performance on 9 of 17 tests in the domain of memory free recall. There was little evidence of enhancement in any other cognitive domains. There is some evidence to suggest that Bacopa improves memory free recall with evidence for enhancement in other cognitive abilities currently lacking perhaps due to inconsistent measures employed by studies across these cognitive domains. Research into the nootropic effects of Bacopa is in its infancy, with research still yet to investigate the effects of Bacopa across all human cognitive abilities. Similarly, future research should examine the nootropic effects of Bacopa at varied dosages and across different extracts.

Piperazines as nootropic agents: New derivatives of the potent cognition-enhancer DM235 carrying hydrophilic substituents.

PubMed

Martino, Maria Vittoria; Guandalini, Luca; Di Cesare Mannelli, Lorenzo; Menicatti, Marta; Bartolucci, Gianluca; Dei, Silvia; Manetti, Dina; Teodori, Elisabetta; Ghelardini, Carla; Romanelli, Maria Novella

2017-03-15

The piperazine ring of the potent nootropic drug DM235 has been decorated with H-bond donor and acceptor groups (CH 2 OH, CH 2 OMe, CH 2 OCOMe, COOEt); the aim was to insert new functional groups, suitable for further chemical manipulation. The influence of these modifications on nootropic activity was assessed by means of the mouse passive avoidance test; some of the newly synthesized molecules (alcohol 7b, acetate 8b and ester 10d) showed interesting in vivo potency. This makes it possible to use these functional groups for adding other residues, in order to increase molecular diversity, or for anchoring a biotin group, to obtain compounds useful to capture the biological target. Moreover, the new compounds will improve our knowledge of structure activity relationships of this family of drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hypericum perforatum as a cognitive enhancer in rodents: A meta-analysis

PubMed Central

Ben-Eliezer, Daniel; Yechiam, Eldad

2016-01-01

Considered an antidepressant and anti-anxiety agent, Hypericum perforatum affects multiple neurotransmitters in a non-competitive synergistic manner, and may have nootropic potential. We quantitatively reviewed the pre-clinical literature to examine if there is a cognitive-enhancing effect of H. perforatum in healthy rodents. Additionally, within these studies, we compared the effects observed in intact rodents versus those whose performance has been impaired, mostly through stress manipulations. The meta-analysis incorporated studies that examined the effect of H. perforatum versus placebo on memory indices of task performance. All analyses were based on weighting different studies according to their inverse variance. Thirteen independent studies (published 2000–2014) involving 20 experimental comparisons met our inclusion criteria. The results showed a large positive effect of H. perforatum on cognitive performance for intact, healthy rodents (d = 1.11), though a larger effect emerged for stress-impaired rodents (d = 3.10 for restraint stress). The positive effect on intact rodents was observed in tasks assessing reference memory as well as working memory, and was not moderated by the type of memory or motivation (appetitive versus aversive). Thus, while primarily considered as a medication for depression, H. perforatum shows considerable nootropic potential in rodents. PMID:27762349

Cognitive enhancers (nootropics). Part 2: drugs interacting with enzymes. Update 2014.

PubMed

Froestl, Wolfgang; Muhs, Andreas; Pfeifer, Andrea

2014-01-01

Scientists working in the field of Alzheimer's disease and, in particular, cognitive enhancers are very productive. The review on Drugs interacting with Enzymes was accepted in August 2012. However, this field is very dynamic. New potential targets for the treatment of Alzheimer's disease were identified. This update describes drugs interacting with 60 enzymes versus 43 enzymes in the first paper. Some compounds progressed in their development, while many others were discontinued. The present review covers the evolution of research in this field through April 2014.

[The original nootropic and neuroprotective drug noopept potentiates the anticonvulsant activity of valproate in mice].

PubMed

Kravchenko, E V; Ponteleeva, I V; Trofimov, S S; Lapa, V I; Ostrovskaia, R U; Voronina, T A

2009-01-01

The influence of the original dipeptide drug noopept, known to possess nootrope, neuroprotector, and anxiolytic properties, on the anticonvulsant activity of the antiepileptic drug valproate has been studied on the model of corazole-induced convulsions in mice. Neither a single administration of noopept (0.5 mg/kg, i.p.) nor its repeated introduction in 10 or 35 days enhanced the convulsant effect of corazole, which is evidence that noopept alone does not possess anticonvulsant properties. Prolonged (five weeks) preliminary administration of noopept enhanced the anticonvulsant activity of valproate. This result justifies the joint chronic administration of noopept in combination with valproate in order to potentiate the anticonvulsant effect of the latter drug. In addition, the administration of noopept favorably influences the cognitive functions and suppresses the development of neurodegenerative processes.

A randomized, double-blind, placebo controlled, parallel group, efficacy study of alpha BRAIN® administered orally.

PubMed

Solomon, Todd M; Leech, Jarrett; deBros, Guy B; Murphy, Cynthia A; Budson, Andrew E; Vassey, Elizabeth A; Solomon, Paul R

2016-03-01

Alpha BRAIN® is a nootropic supplement that purports to enhance cognitive functioning in healthy adults. The goal of this study was to investigate the efficacy of this self-described cognitive enhancing nootropic on cognitive functioning in a group of healthy adults by utilizing a randomized, double blind, placebo-controlled design. A total of 63-treatment naïve individuals between 18 and 35 years of age completed the randomized, double-blind, placebo controlled trial. All participants completed a 2-week placebo run in before receiving active product, Alpha BRAIN® or new placebo, for 6 weeks. Participants undertook a battery of neuropsychological tests at randomization and at study completion. Primary outcome measures included a battery of neuropsychological tests and measures of sleep. Compared with placebo, Alpha BRAIN® significantly improved on tasks of delayed verbal recall and executive functioning. Results also indicated significant time-by-group interaction in delayed verbal recall for the Alpha BRAIN® group. The use of Alpha BRAIN® for 6 weeks significantly improved recent verbal memory when compared with controls, in a group of healthy adults. While the outcome of the study is encouraging, this is the first randomized controlled trial of Alpha BRAIN®, and the results merit further study. Copyright © 2016 John Wiley & Sons, Ltd.

An acute, double-blind, placebo-controlled cross-over study of 320 mg and 640 mg doses of Bacopa monnieri (CDRI 08) on multitasking stress reactivity and mood.

PubMed

Benson, Sarah; Downey, Luke A; Stough, Con; Wetherell, Mark; Zangara, Andrea; Scholey, Andrew

2014-04-01

Little research exists in humans concerning the anxiolytic, antidepressant, sedative, and adaptogenic actions the traditional Ayurvedic medicine Bacopa monnieri (BM) possesses in addition to its documented cognitive-enhancing effects. Preclinical work has identified a number of acute anxiolytic, nootropic, and adaptogenic effects of BM that may also co-occur in humans. The current double-blind, placebo-controlled cross-over study assessed the acute effects of a specific extract of BM (KeenMind® - CDRI 08) in normal healthy participants during completion of a multitasking framework (MTF). Seventeen healthy volunteers completed the MTF, at baseline, then 1 h and 2 h after consuming a placebo, 320 mg BM and 640 mg of BM. Treatments were separated by a 7-day washout with order determined by Latin Square. Outcome measures included cognitive outcomes from the MTF, with mood and salivary cortisol measured before and after each completion of the MTF. Change from baseline scores indicated positive cognitive effects, notably at both 1 h post and 2 h post BM consumption on the Letter Search and Stroop tasks, suggesting an earlier nootropic effect of BM than previously investigated. There were also some positive mood effects and reduction in cortisol levels, pointing to a physiological mechanism for stress reduction associated with BM consumption. It was concluded that acute BM supplementation produced some adaptogenic and nootropic effects that need to be replicated in a larger sample and in isolation from stressful cognitive tests in order to quantify the magnitude of these effects. The study was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12612000834853). Copyright © 2013 John Wiley & Sons, Ltd.

Neuropharmacological Review of the Nootropic Herb Bacopa monnieri

PubMed Central

Borowski, Thomas

2013-01-01

Abstract This review synthesizes behavioral research with neuromolecular mechanisms putatively involved with the low-toxicity cognitive enhancing action of Bacopa monnieri (BM), a medicinal Ayurvedic herb. BM is traditionally used for various ailments, but is best known as a neural tonic and memory enhancer. Numerous animal and in vitro studies have been conducted, with many evidencing potential medicinal properties. Several randomized, double-blind, placebo-controlled trials have substantiated BM's nootropic utility in humans. There is also evidence for potential attenuation of dementia, Parkinson's disease, and epilepsy. Current evidence suggests BM acts via the following mechanisms—anti-oxidant neuroprotection (via redox and enzyme induction), acetylcholinesterase inhibition and/or choline acetyltransferase activation, β-amyloid reduction, increased cerebral blood flow, and neurotransmitter modulation (acetylcholine [ACh], 5-hydroxytryptamine [5-HT], dopamine [DA]). BM appears to exhibit low toxicity in model organisms and humans; however, long-term studies of toxicity in humans have yet to be conducted. This review will integrate molecular neuroscience with behavioral research. PMID:23772955

Neuropharmacological review of the nootropic herb Bacopa monnieri.

PubMed

Aguiar, Sebastian; Borowski, Thomas

2013-08-01

This review synthesizes behavioral research with neuromolecular mechanisms putatively involved with the low-toxicity cognitive enhancing action of Bacopa monnieri (BM), a medicinal Ayurvedic herb. BM is traditionally used for various ailments, but is best known as a neural tonic and memory enhancer. Numerous animal and in vitro studies have been conducted, with many evidencing potential medicinal properties. Several randomized, double-blind, placebo-controlled trials have substantiated BM's nootropic utility in humans. There is also evidence for potential attenuation of dementia, Parkinson's disease, and epilepsy. Current evidence suggests BM acts via the following mechanisms-anti-oxidant neuroprotection (via redox and enzyme induction), acetylcholinesterase inhibition and/or choline acetyltransferase activation, β-amyloid reduction, increased cerebral blood flow, and neurotransmitter modulation (acetylcholine [ACh], 5-hydroxytryptamine [5-HT], dopamine [DA]). BM appears to exhibit low toxicity in model organisms and humans; however, long-term studies of toxicity in humans have yet to be conducted. This review will integrate molecular neuroscience with behavioral research.

Nootropic agents stimulate neurogenesis. Brain Cells, Inc.: WO2007104035.

PubMed

Taupin, Philippe

2009-05-01

The application is in the field of adult neurogenesis, neural stem cells and cellular therapy. It aims to characterize the activity of nootropic agents on adult neurogenesis in vitro. Nootropic agents are substances improving cognitive and mental abilities. AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) and nootropic agents were assessed for the potential to differentiate human neural progenitor and stem cells into neuronal cells in vitro. They were also tested for their behavioural activity on the novel object recognition task. AMPA, piracetam, FK-960 and SGS-111 induce and stimulate neuronal differentiation of human-derived neural progenitor and stem cells. SGS-111 increases the number of visits to the novel object. The neurogenic activity of piracetam and SGS-111 is mediated through AMPA receptor. The neurogenic activity of SGS-111 may contribute and play a role in its nootropic activity. These results suggest that nootropic agents may elicit some of their effects through their neurogenic activity. The application claims the use of nootropic agents for their neurogenic activity and for the treatment of neurological diseases, disorders and injuries, by stimulating or increasing the generation of neuronal cells in the adult brain.

In Vitro Effects of Cognitives and Nootropics on Mitochondrial Respiration and Monoamine Oxidase Activity.

PubMed

Singh, Namrata; Hroudová, Jana; Fišar, Zdeněk

2017-10-01

Impairment of mitochondrial metabolism, particularly the electron transport chain (ETC), as well as increased oxidative stress might play a significant role in pathogenesis of Alzheimer's disease (AD). Some effects of drugs used for symptomatic AD treatment may be related to their direct action on mitochondrial function. In vitro effects of pharmacologically different cognitives (galantamine, donepezil, rivastigmine, 7-MEOTA, memantine) and nootropic drugs (latrepirdine, piracetam) were investigated on selected mitochondrial parameters: activities of ETC complexes I, II + III, and IV, citrate synthase, monoamine oxidase (MAO), oxygen consumption rate, and hydrogen peroxide production of pig brain mitochondria. Complex I activity was decreased by galantamine, donepezil, and memantine; complex II + III activity was increased by galantamine. None of the tested drugs caused significant changes in the rate of mitochondrial oxygen consumption, even at high concentrations. Except galantamine, all tested drugs were selective MAO-A inhibitors. Latrepirdine, donepezil, and 7-MEOTA were found to be the most potent MAO-A inhibitors. Succinate-induced mitochondrial hydrogen peroxide production was not significantly affected by the drugs tested. The direct effect of cognitives and nootropics used in the treatment of AD on mitochondrial respiration is relatively small. The safest drugs in terms of disturbing mitochondrial function appear to be piracetam and rivastigmine. The MAO-A inhibition by cognitives and nootropics may also participate in mitochondrial neuroprotection. The results support the future research aimed at measuring the effects of currently used drugs or newly synthesized drugs on mitochondrial functioning in order to understand their mechanism of action.

[Comparative study of the long-term behavioral effects of noopept and piracetam in adult male rats and female rats in postnatal period].

PubMed

Voronina, T A; Guzevatykh, L S; Trofimov, S S

2005-01-01

Adult male and female rats were treated with the peptide nootrope drug noopept (daily dose, 0.1 mg/kg) and piracetam (200 mg/kg). In the period from 8th to 20th day, both drugs (cognitive enhancers) suppressed the horizontal and vertical activity and the anxiety in test animals as compared to the control group treated with 0.9 % aqueous NaCl solution. Early postnatal injections of the nootropes influenced neither the morphology development nor the behavior of adult female rats in the plus maze, extrapolational escape, passive avoidance, and pain sensitivity threshold tests. Animals in the "intact" group (having received neither drugs not physiological solution, that is, developing in a poor sensor environment), showed less pronounced habituation in the open field test as compared to the control and drug treated groups.

Improved Mitochondrial Function in Brain Aging and Alzheimer Disease – the New Mechanism of Action of the Old Metabolic Enhancer Piracetam

PubMed Central

Leuner, Kristina; Kurz, Christopher; Guidetti, Giorgio; Orgogozo, Jean-Marc; Müller, Walter E.

2010-01-01

Piracetam, the prototype of the so-called nootropic drugs’ is used since many years in different countries to treat cognitive impairment in aging and dementia. Findings that piracetam enhances fluidity of brain mitochondrial membranes led to the hypothesis that piracetam might improve mitochondrial function, e.g., might enhance ATP synthesis. This assumption has recently been supported by a number of observations showing enhanced mitochondrial membrane potential, enhanced ATP production, and reduced sensitivity for apoptosis in a variety of cell and animal models for aging and Alzheimer disease. As a specific consequence, substantial evidence for elevated neuronal plasticity as a specific effect of piracetam has emerged. Taken together, this new findings can explain many of the therapeutic effects of piracetam on cognition in aging and dementia as well as different situations of brain dysfunctions. PMID:20877425

Nootropic activity of Crataeva nurvala Buch-Ham against scopolamine induced cognitive impairment

PubMed Central

Bhattacharjee, Atanu; Shashidhara, Shastry Chakrakodi; Saha, Santanu

2015-01-01

Loss of cognition is one of the age related mental problems and a characteristic symptom of neurodegenerative disorders like Alzheimer’s. Crataeva nurvala Buch-Ham, a well explored traditional Indian medicinal plant of Westernghats, is routinely used as folkloric medicine to treat various ailments in particular urolithiasis and neurological disorders associated with cognitive dysfunction. The objective of the study was to evaluate the nootropic activity of Crataeva nurvala Buch-Ham stem bark in different learning and memory paradigm viz. Elevated plus maze and Y-maze against scopolamine induced cognitive impairment. Moreover, to elucidate possible mechanism, we studied the influence of Crataeva nurvala ethanolic extract on central cholinergic activity via estimating the whole brain acetyl cholinesterase enzyme. Ethanolic extracts of Crataeva nurvala (100, 200 and 400 mg/kg body weight) were administered to adult Wistar rats for successive seven days and the acquisition, retention and retrieval of spatial recognition memory was determined against scopolamine (1 mg/kg, i.p.) induced amnesia through exteroceptive behavioral models viz. Elevated plus maze and Y-maze models. Further, whole brain acetyl cholinesterase enzyme was estimated through Ellman’s method. Pretreatment with Crataeva nurvala ethanolic extract significantly improved spatial learning and memory against scopolamine induced amnesia. Moreover, Crataeva nurvala extract decreased rat brain acetyl cholinesterase activity in a dose dependent manner and comparable to the standard drug Piracetam. The results indicate that ethanolic extract of Crataeva nurvala might be a useful as nootropic agent to delay the onset and reduce the severity of symptoms associated with dementia and Alzheimer’s disease. The underlying mechanism of action of its nootropic potentiality might be attributed to its anticholinesterase property. PMID:27065767

The Combination of Antidepressant Duloxetine with Piracetam in Mice does not Produce Enhancement of Nootropic Activity.

PubMed

Kale, Pravin Popatrao; Addepalli, Veeranjaneyulu; Sarkar, Amrita; Patel, Sonam; Savai, Jay

2014-09-01

There is a strong association between depression and memory impairment. The present study aims to assess the nootropic activity of duloxetine and piracetam combination. Male Swiss Albino mice were divided randomly into 4 groups. Treatment of normal saline (10 ml/kg), duloxetine (10 mg/kg), piracetam (100 mg/kg), and duloxetine (5 mg/kg) plus piracetam (50 mg/kg) were given through intra-peritoneal route to group I-IV, respectively. Transfer latency in elevated plus maze (EPM) and time spent in target quadrant in Morris water maze (MWM) were recorded. Estimation of brain monoamines in hippocampus, cerebral cortex, and whole brain were done using HPLC with fluorescence detector. Piracetam treated group showed significant decrease in transfer latency in EPM and increase in time spent in target quadrant recorded in MWM. Combination treated group failed to produce statistically significant nootropic effect in both EPM and MWM. Combination treated group failed to increase brain monoamine levels when compared against duloxetine and piracetam treated groups, separately. But there was exception of significant increase in norepinephrine levels in hippocampi when compared against duloxetine treated group. Results indicate no cognitive benefits with piracetam plus duloxetine combination. These findings can be further probed with the aim of understanding the interaction between duloxetine and piracetam as a future endeavor.

[Clinical and electroencephalographic characteristic of noopept in patients with mild cognitive impairment of posttraumatic and vascular origin].

PubMed

Bochkarev, V K; Teleshova, E S; Siuniakov, S A; Davydova, D V; Neznamov, G G

2008-01-01

An effect of a new nootropic drug noopept on the dynamics of main EEG rhythms and narrow-band spectral EEG characteristics in patients with cerebral asthenic and cognitive disturbances caused by traumas or vascular brain diseases has been studied. Noopept caused the EEG changes characteristic of the action of nootropics: the increase of alpha- and beta-rhythms power and reduction of delta-rhythms power. The reaction of alpha-rhythm was provided mostly by the dynamics of its low and medium frequencies (6,7-10,2 Hz), the changes of beta-rhythm were augmented in frontal and attenuated in occipital areas. The analysis of frequency and spatial structure of EEG changes reveals that noopept exerts a nonspecific activation and anxyolytic effect. The differences in EEG changes depending on the brain pathology were found. The EEG indices of nootropic effect of the drug were most obvious in cerebral vascular diseases. The EEG changes in posttraumatic brain lesion were less typical.

The Brain Tourniquet: Physiological Isolation of Brain Regions Damaged by Traumatic Head Injury

DTIC Science & Technology

2008-06-19

brain slices were treated after injury with either a nootropic agent ( aniracetam , cyclothiazide, IDRA 21, or 1-BCP) or the antiepileptic drug...tourniquet approach. Four well-known nootropic agents were evaluated: aniracetam , a pyrrolidione analog that slows non-NMDA (AMPA/kainate) receptor...to improve cognition in rats [Stdubli et al., 1994], and has more potent effects than aniracetam in rat brain slices [Arai et al., 1994]. In

Efficacy of acetylcholinesterase inhibitors versus nootropics in Alzheimer's disease: a retrospective, longitudinal study.

PubMed

Tsolaki, M; Pantazi, T; Kazis, A

2001-01-01

The aim of this study was to investigate the efficacy of nootropics (piracetam, aniracetam, nimodopine and dihydroergicristine) versus acetylcholinesterase inhibitors (AChE-Is) (tacrine and donepezil) in the treatment of Alzheimer's disease. This is a retrospective study of 510 patients with Alzheimer's disease. To determine clinical efficacy of treatment, we used the mean change over time in scores for the following tests: the Mini-Mental State Examination (MMSE); the Cambridge Cognitive Examination for the Elderly; and the Functional Rating Scale for Symptoms of Dementia. In all patients and in patients with severe Alzheimer's disease (baseline MMSE < 11), no significant differences were seen in the neuropsychological test scores between the two treatment groups. In patients with moderate dementia (baseline MMSE between 11 and 20), however, there was a significantly greater deterioration, as shown on the CAMCOG scale, after 12 months' treatment for patients receiving AChE-Is compared with those receiving nootropics (-4.38 for AChE-Is group versus 1.48 for nootropics group). For patients with mild dementia (baseline MMSE score between 21 and 26), there was a significantly greater deterioration on the MMSE scale for each time-point in the nootropics group compared with the AChE-Is group. In conclusion, we did not find any strong evidence that a difference in efficacy exists between AChE-Is and nootropics in the treatment of Alzheimer's disease.

[The influence of piracetam on behavior and brain receptors in C57BL/6 and BALB/c mice: nootropic and anxiolytic effects].

PubMed

Kovalev, G I; Kondrakhin, E A; Salimov, R M; Neznamov, G G

2013-01-01

The influence of acute and long-term piracetam administration on the dynamics of rapid (non-specific, anxiolytic) and slow (specific, nootropic) behavioral drug effects, as well as on their interrelation with NMDA- and BDZ-receptors was studied in inbred mice strains differing in cognitive and emotional status--C57BL/6 and BALB/c. The BALB/c strain contained 17% less [3H]-flunitrazepam binding sites in frontal cortex and 22% less [3H]-MK801 binding sites in hippocampus as compared to those in C57BL/6 mice. Based on these data, BALB/c strain was used as a model of psychopathology, combining increased anxiety and cognitive deficit. Under the action of single, 7-fold, and 14-fold piracetam i.p. injections (200 mg/kg body weight, daily), a fast increase in NMDA-receptor density and slow escalation of the specific nootropic effect was observed in BALB/c mice. Non-specific anxiolytic effects in these mice increased for the first 1 - 7 days without any changes in BDZ-binding and then decreased to initial values accompanied by decrement of brain receptor concentration. Thus, in BALB/c mice, a slowly manifested specific nootropic action of piracetam develops, following an increase in NMDA receptor density, whereas the non-specific anxiolytic effect precedes the fast-paced changes in BDZ-binding site density.

Nootropic and anxiolytic activity of saponins of Albizzia lebbeck leaves.

PubMed

Une, H D; Sarveiya, V P; Pal, S C; Kasture, V S; Kasture, S B

2001-01-01

The effect of saponin containing, n-butanolic fraction (BF), extracted from dried leaves of Albizzia lebbeck, was studied on cognitive behavior and anxiety in albino mice. The elevated plus maze was used for assessment of both nootropic and anxiolytic activity. The nootropic activity was evaluated by recording the effect of BF (0, 10, 25, and 50 mg/kg) on the transfer latency, whereas anxiolytic activity was assessed by studying its effect on the duration of occupancy in the closed arm. Results showed significant improvement in the retention ability of the normal and amnesic mice as compared to their respective controls. Animals treated with BF (25 mg/kg) spent more time in the open arm in a dose-dependent manner. The BF was without any significant effect on motor coordination. However, it significantly inhibited passivity and hypothermia induced by baclofen (10 mg/kg), a GABA(B) agonist. The data emanated in the present study suggests involvement of gamma-aminobutyric acid (GABA) in the nootropic and anxiolytic activity of saponins obtained from A. lebbeck.

Smart Drugs and Synthetic Androgens for Cognitive and Physical Enhancement: Revolving Doors of Cosmetic Neurology

PubMed Central

Frati, Paola; Kyriakou, Chrystalla; Del Rio, Alessandro; Marinelli, Enrico; Vergallo, Gianluca Montanari; Zaami, Simona; Busardò, Francesco P.

2015-01-01

Cognitive enhancement can be defined as the use of drugs and/or other means with the aim to improve the cognitive functions of healthy subjects in particular memory, attention, creativity and intelligence in the absence of any medical indication. Currently, it represents one of the most debated topics in the neuroscience community. Human beings always wanted to use substances to improve their cognitive functions, from the use of hallucinogens in ancient civilizations in an attempt to allow them to better communicate with their gods, to the widespread use of caffeine under various forms (energy drinks, tablets, etc.), to the more recent development of drugs such as stimulants and glutamate activators. In the last ten years, increasing attention has been given to the use of cognitive enhancers, but up to now there is still only a limited amount of information concerning the use, effect and functioning of cognitive enhancement in daily life on healthy subjects. The first aim of this paper was to review current trends in the misuse of smart drugs (also known as Nootropics) presently available on the market focusing in detail on methylphenidate, trying to evaluate the potential risk in healthy individuals, especially teenagers and young adults. Moreover, the authors have explored the issue of cognitive enhancement compared to the use of Anabolic Androgenic Steroids (AAS) in sports. Finally, a brief overview of the ethical considerations surrounding human enhancement has been examined. PMID:26074739

Smart drugs and synthetic androgens for cognitive and physical enhancement: revolving doors of cosmetic neurology.

PubMed

Frati, Paola; Kyriakou, Chrystalla; Del Rio, Alessandro; Marinelli, Enrico; Vergallo, Gianluca Montanari; Zaami, Simona; Busardò, Francesco P

2015-01-01

Cognitive enhancement can be defined as the use of drugs and/or other means with the aim to improve the cognitive functions of healthy subjects in particular memory, attention, creativity and intelligence in the absence of any medical indication. Currently, it represents one of the most debated topics in the neuroscience community. Human beings always wanted to use substances to improve their cognitive functions, from the use of hallucinogens in ancient civilizations in an attempt to allow them to better communicate with their gods, to the widespread use of caffeine under various forms (energy drinks, tablets, etc.), to the more recent development of drugs such as stimulants and glutamate activators. In the last ten years, increasing attention has been given to the use of cognitive enhancers, but up to now there is still only a limited amount of information concerning the use, effect and functioning of cognitive enhancement in daily life on healthy subjects. The first aim of this paper was to review current trends in the misuse of smart drugs (also known as Nootropics) presently available on the market focusing in detail on methylphenidate, trying to evaluate the potential risk in healthy individuals, especially teenagers and young adults. Moreover, the authors have explored the issue of cognitive enhancement compared to the use of Anabolic Androgenic Steroids (AAS) in sports. Finally, a brief overview of the ethical considerations surrounding human enhancement has been examined.

Anti-stress and nootropic activity of drugs affecting the renin-angiotensin system in rats based on indirect biochemical evidence.

PubMed

Anil Kumar, K V; Nagwar, Shrasti; Thyloor, Rama; Satyanarayana, Sreemantula

2015-12-01

Various stress hormones are responsible for bringing out stress-related changes and are implicated in learning and memory processes. The extensive clinical experience of angiotensin receptor blockers (ARBs) and direct renin inhibitor as antihypertensive agents provides anecdotal evidence of improvements in cognition. The neurochemical basis underlying the anti-stress and nootropic effects are unclear. This study was aimed to determine the effects of aliskiren, valsartan and their combination on the neuromediators of the central nervous system (CNS) and periphery as well as on cognitive function. Groups of rats were subjected to a forced swim stress for one hour after daily treatment with aliskiren, valsartan and their combination. The 24 h urinary excretion of vanillylmandellic acid (VMA), 5-hydroxyindoleacetic acid (5-HIAA), 6-β-hydroxycortisol (6-β-OH) cortisol and homovanillic acid (HVA) was determined in all groups under normal and stressed conditions. Nootropic activity was studied using cook's pole climbing apparatus and acetylcholinesterase (AChE) inhibitory activity by Ellman's method. Administration of aliskiren (10 mg/kg), valsartan (20 mg/kg) and their combination at a dose of 5 and 10 mg/kg respectively reduced the urinary metabolite levels. Further, all drugs showed significant improvement in scopolamine-impaired performance and produced inhibition of the AChE enzyme. The present study provides scientific support for the anti-stress and nootropic activities of aliskiren, valsartan and their combination. © The Author(s) 2014.

Nootropic dipeptide noopept enhances inhibitory synaptic transmission in the hippocampus.

PubMed

Povarov, I S; Kondratenko, R V; Derevyagin, V I; Ostrovskaya, R U; Skrebitskii, V G

2015-01-01

Application of nootropic agent Noopept on hippocampal slices from Wistar rats enhanced the inhibitory component of total current induced by stimulation of Shaffer collaterals in CA1 pyramidal neurons, but did not affect the excitatory component. A direct correlation between the increase in the amplitude of inhibitory current and agent concentration was found. The substance did not affect the release of inhibitory transmitters from terminals in the pyramidal neurons, which indicated changes in GABAergic interneurons.

[Nootropics and antioxidants in the complex therapy of symptomatic posttraumatic epilepsy].

PubMed

Savenkov, A A; Badalian, O L; Avakian, G N

2013-01-01

To study the possibility of application of nootropics and antioxidants in the complex antiepileptic therapy, we examined 75 patients with symptomatic focal posttraumatic epilepsy. A statistically significant reduction in the number of epileptic seizures, improvement of cognitive function and quality of life of the patients as well as a decrease in the severity of depression and epileptic changes in the EEG were identified. The potentiation of antiepileptic activity of basic drugs, normalization of brain's electrical activity and reduction in EEG epileptiform activity, in particular coherent indicators of slow-wave activity, were noted after treatment with the antioxidant mexidol. A trend towards the improvement of neuropsychological performance and quality of life was observed. There was a lack of seizure aggravation typical of many nootropic drugs. Thus, phenotropil and mexidol can be recommended for complex treatment of symptomatic posttraumatic epilepsy.

Cognition enhancers between treating and doping the mind.

PubMed

Lanni, Cristina; Lenzken, Silvia C; Pascale, Alessia; Del Vecchio, Igor; Racchi, Marco; Pistoia, Francesca; Govoni, Stefano

2008-03-01

Memory, attention and creativity represent three different cognitive domains, which are interconnected and contribute the "mental performance" of an individual. Modern neuroscience has investigated some of the neuronal circuits and of the neurotransmitters and molecular events underlying the above-mentioned cognitive functions. Within this renewed reference context, some of the properties of the components of the remedies to increase mental performance have been studied and validated in experimental models and, to date, these substances are named "smart drugs", "memory enhancing drugs" or "nootropic drugs" (from the Greek root noos for mind and tropein for toward). Recently pharmaceutical industries are increasingly focusing on the research for potential substances in this field: several "smart drugs" are in clinical trials and could be on the market in few years. Furthermore, a quick survey from Internet highlights the presence of a great variety of both approved and non-approved drugs, with some of them addressing to only medical and others to performance-oriented use, opening room to some reflections or speculations from scientific and ethical points of view. In order to point out the effect of nootropic drugs on cognition of healthy people, we reviewed the literature on drug enhancement of various cognitive functions, including memory, attention and creativity. As their simplest, memory is regarded as the ability to remember events or learned material, attention is the cognitive process of selectively concentrating on one aspect while ignoring distracters and creativity could be described as the ability to create products or ideas which are original and which possess a social usefulness. Reports from literature reveal that some medications currently available to patients with memory disorders may also increase performances in healthy people and that drugs designed for psychiatric disorders can also be used to enhance certain mental functions. However, the long-term effects of these drugs are unknown, but their apparent effectiveness allows room to their use and misuse. At variance with these literature data showing scientific, even if poor, evidence of the effect of smart drugs in the field of memory and attention, only indirect information on creativity can be obtained by studies of the effects of diseases and drugs on the artistic productivity of classic painters and famous authors, offering a link to understand the neuronal basis of this cognitive function and a cue to understand how drugs (used to correct the illness) may affect the function. On the basis of these cues, in this review we will discuss some critical aspects of the different cerebral circuits and molecular events regulating memory, attention and creativity in order to outline the neurobiological bases of the effects of "smart drugs" on cognitive functions, and to evaluate their putative pharmaceutical development.

Examining the nootropic effects of a special extract of Bacopa monniera on human cognitive functioning: 90 day double-blind placebo-controlled randomized trial.

PubMed

Stough, Con; Downey, Luke A; Lloyd, Jenny; Silber, Beata; Redman, Stephanie; Hutchison, Chris; Wesnes, Keith; Nathan, Pradeep J

2008-12-01

While Ayurvedic medicine has touted the cognitive enhancing effects of Bacopa monniera for centuries, there is a need for double-blind placebo-controlled investigations. One hundred and seven healthy participants were recruited for this double-blind placebo-controlled independent group design investigation. Sixty-two participants completed the study with 80% treatment compliance. Neuropsychological testing using the Cognitive Drug Research cognitive assessment system was conducted at baseline and after 90 days of treatment with a special extract of Bacopa monniera (2 x 150 mg KeenMind) or placebo. The Bacopa monniera product significantly improved performance on the 'Working Memory' factor, more specifically spatial working memory accuracy. The number of false-positives recorded in the Rapid visual information processing task was also reduced for the Bacopa monniera group following the treatment period. The current study provides support for the two other published studies reporting cognitive enhancing effects in healthy humans after a 90 day administration of the Bacopa monniera extract. Further studies are required to ascertain the effective dosage range, the time required to attain therapeutic levels and the effects over a longer term of administration. (c) 2008 John Wiley & Sons, Ltd.

Pharmacological and neurophysiological aspects of space/motion sickness

NASA Technical Reports Server (NTRS)

Lucot, James B.; Crampton, George H.

1991-01-01

A motorized motion testing device modeled after a Ferris wheel was constructed to perform motion sickness tests on cats. Details of the testing are presented, and some of the topics covered include the following: xylazine-induced emesis; analysis of the constituents of the cerebrospinal fluid (CSF) during motion sickness; evaluation of serotonin-1A (5-HT sub 1A) agonists; other 5HT receptors; antimuscarinic mechanisms; and antihistaminergic mechanisms. The ability of the following drugs to reduce motion sickness in the cats was examined: amphetamines, adenosinergic drugs, opioid antagonists, peptides, cannabinoids, cognitive enhancers (nootropics), dextromethorphan/sigma ligands, scopolamine, and diphenhydramine.

Evaluation of anticonvulsant and nootropic effect of ondansetron in mice.

PubMed

Jain, S; Agarwal, N B; Mediratta, P K; Sharma, K K

2012-09-01

The role of serotonin receptors have been implicated in various types of experimentally induced seizures. Ondansetron is a highly selective 5-hydroxytryptamine 3 (5-HT(3)) receptor antagonist used as antiemetic agent for chemotherapy-, and radiotherapy-induced nausea and vomiting. The present study was carried out to examine the effect of ondansetron on electroshock, pentylenetetrazole (PTZ)-induced seizures and cognitive functions in mice. Ondansetron was administered intraperitoneally (i.p.) at doses of 0.5, 1.0 and 2.0 mg/kg (single dose) to observe its effect on the increasing current electroshock seizure (ICES) test and PTZ-induced seizure test. In addition, a chronic study (21 days) was also performed to assess the effects of ondansetron on electroshock-induced convulsions and cognitive functions. The effect on cognition was assessed by elevated plus maze and passive avoidance paradigms. Phenytoin (25 mg/kg, i.p.) was used as a standard anticonvulsant drug and piracetam (200 mg/kg) was administered as a standard nootropic drug. The results were compared with an acute study, wherein it was found that the administration of ondansetron (1.0 and 2.0 mg/kg) significantly raised the seizure-threshold current as compared to control group in the ICES test. Similar results were observed after chronic administration of ondansetron. In PTZ test, ondansetron in all the three tested doses failed to show protective effect against PTZ-induced seizure test. Administration of ondansetron for 21 days significantly decreased the transfer latency (TL) and prolonged the step-down latency (SDL). The results of present study suggest the anticonvulsant and memory-enhancing effect of ondansetron in mice.

Nootropic, anxiolytic and CNS-depressant studies on different plant sources of shankhpushpi.

PubMed

Malik, Jai; Karan, Maninder; Vasisht, Karan

2011-12-01

Shankhpushpi, a well-known drug in Ayurveda, is extensively used for different central nervous system (CNS) effects especially memory enhancement. Different plants are used under the name shankhpushpi in different regions of India, leading to an uncertainty regarding its true source. Plants commonly used under the name shankhpushpi are: Convolvulus pluricaulis Chois., Evolvulus alsinoides Linn., both from Convolvulaceae, and Clitoria ternatea Linn. (Leguminosae). To find out the true source of shankhpushpi by evaluating and comparing memory-enhancing activity of the three above mentioned plants. Anxiolytic, antidepressant and CNS-depressant activities of these three plants were also compared and evaluated. The nootropic activity of the aqueous methanol extract of each plant was tested using elevated plus-maze (EPM) and step-down models. Anxiolytic, antidepressant and CNS-depressant studies were evaluated using EPM, Porsolt?s swim despair and actophotometer models, respectively. C. pluricaulis extract (CPE) at a dose of 100 mg/kg, p.o. showed maximum nootropic and anxiolytic activity (p < 0.001). E. alsinoides extract (EAE) and C. ternatea extract (CTE) showed maximum memory-enhancing and anxiolytic activity (p < 0.001) at 200 and 100?mg/kg, respectively. Amongst the three plants, EAE and CTE showed significant (p < 0.05), while CPE did not exhibit any antidepressant activity. All the three plants showed CNS-depressant action at higher dose levels. The above results showed all the three plants possess nootropic, anxiolytic and CNS-depressant activity. The results of memory-enhancing activity suggest C. pluricaulis to be used as true source of shankhpushpi.

[Plant metabolites as nootropics and cognitives].

PubMed

Cervenka, F; Jahodár, L

2006-09-01

Nowadays several millions of people suffer from Alzheimer's disease and other types of dementia. Etiology of these diseases is not known very well. There occur different levels of neurotransmitters, the level of acetylcholine in the brain is decreased and pathological changes affect the brain tissue. Organic and toxic damage of the brain, free radicals, and other changes participate in the development of these diseases. Drugs as nootropics, cognitives, and neuroprotectives are commonly used to treat these diseases. Some of these drugs have often side and undesirable effects. In recent years some natural substances (galanthamine, huperzine A, vinpocetine), and standardized plant extracts (Ginkgo biloba L., Centella asiatica L.) Urban, Bacopa monniera L., Evolvulus alsinoides L.) are often used. These plant preparations produce fewer undesirable effects and the same effectiveness as the classic therapy, or these preparations are used as a supplement to the classic therapy.

[Role of functional state of neuronal mitochondria of cerebral cortex in mechanisms of nootropic activity of neuroprotectors in rats with alloxan hyperglycemia].

PubMed

Zhiliuk, V I; Mamchur, V I; Pavlov, S V

2015-01-01

The influence of citicoline, phenylpiracetam, pentoxifylline and N-phenylacetyl-L-prolylglycine on cognitive processes and functional state of mitochondria in the neocortex of alloxan-diabetic rats has been studied. The drug effects on cognitive processes were assessed using passive avoidance tests in the dark-light camera. Latent period and the number of animals with amnesia skill on 6th and 20th days of drug administration were recorded. Functional status of mitochondria was assessed by mitochondrial pore opening and mitochondrial transmembrane potential (Y) on 20th day. It has been established that course administration of phenylpiracetam, citicoline and to a lesser extent N-phenylacetyl-L-prolylglycine, but not pentoxifylline, improves the processes of learning and storing conditional skill. At the same time, the nootropic activity of studied drugs was comparable to their effect on the functional state of mitochondria in neocortical neurons in rats with chronic hyperglycemia. According to mitoprotective activity (prevention of opening of mitochondrial cyclosporin-A-sensitive pores and restoration of mitochondrial transmembrane potential), the maximum potential was observed for citicoline and phenylpiracetam, and the minimum--for pentoxifylline. The results point out the importance of mitoprotective properties in nootropic effects of studied drugs.

Piracetam and other structurally related nootropics.

PubMed

Gouliaev, A H; Senning, A

1994-05-01

Nearly three decades have now passed since the discovery of the piracetam-like nootropics, compounds which exhibit cognition-enhancing properties, but for which no commonly accepted mechanism of action has been established. This review covers clinical, pharmacokinetic, biochemical and behavioural results presented in the literature from 1965 through 1992 (407 references) of piracetam, oxiracetam, pramiracetam, etiracetam, nefiracetam, aniracetam and rolziracetam and their structural analogues. The piracetam-like nootropics are capable of achieving reversal of amnesia induced by, e.g., scopolamine, electroconvulsive shock and hypoxia. Protection against barbiturate intoxication is observed and some benefit in clinical studies with patients suffering from mild to moderate degrees of dementia has been demonstrated. No affinity for the alpha 1-, alpha 2-, beta-, muscarinic, 5-hydroxytryptamine-, dopamine, adenosine-A1-, mu-opiate, gamma-aminobutyric acid (GABA) (except for nefiracetam (GABAA)), benzodiazepine and glutamate receptors has been found. The racetams possess a very low toxicity and lack serious side effects. Increased turnover of different neurotransmitters has been observed as well as other biochemical findings, e.g., inhibition of enzymes such as prolylendopeptidase. So far, no generally accepted mechanism of action has, however, emerged. We believe that the effect of the racetams is due to a potentiation of already present neurotransmission and that much evidence points in the direction of a modulated ion flux by, e.g., potentiated calcium influx through non-L-type voltage-dependent calcium channels, potentiated sodium influx through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor gated channels or voltage-dependent channels or decreases in potassium efflux. Effects on carrier mediated ion transport are also possible.

The nootropic properties of ginseng saponin Rb1 are linked to effects on anxiety.

PubMed

Churchill, James D; Gerson, Jennifer L; Hinton, Kendra A; Mifek, Jennifer L; Walter, Michael J; Winslow, Cynthia L; Deyo, Richard A

2002-01-01

Previous studies have shown that crude ginseng extracts enhance performance on shock-motivated tasks. Whether such performance enhancements are due to memory-enhancing (nootropic) properties of ginseng, or to other non-specific effects such as an influence on anxiety has not been determined. In the present study, we evaluated both the nootropic and anxiolytic effects of the ginseng saponin Rb1. In the first experiment, 80 five-day-old male chicks received intraperitoneal injections of 0, 0.25, 2.5 or 5.0 mg/kg Rb1. Performance on a visual discrimination task was evaluated 15 minutes, 24 and 72 hours later. Acquisition of a visual discrimination task was unaffected by drug treatment, but the number of errors was significantly reduced in the 0.25 mg/kg group during retention trials completed 24 and 72 hours after injection. Animals receiving higher dosages showed trends towards enhancement initially, but demonstrated impaired performance when tested 72 hours later. Rb1 had no effect on response rates or body weight. In the second experiment, 64 five-day-old male chicks received similar injections of Rb1 (0, 0.25, 2.5 or 5.0 mg/kg) and separation distress was evaluated 15 minutes, 24 and 72 hours later. Rb1 produced a change in separation distress that depended on the dose and environmental condition under which distress was recorded. These data suggest that Rb1 can improve memory for a visual discrimination task and that the nootropic effect may be related to changes in anxiety.

Brahmi rasayana Improves Learning and Memory in Mice

PubMed Central

Joshi, Hanumanthachar; Parle, Milind

2006-01-01

Cure of cognitive disorders such as amnesia, attention deficit and Alzheimer's disease is still a nightmare in the field of medicine. Nootropic agents such as piracetam, aniracetam and choline esterase inhibitors like Donepezil® are being used to improve memory, mood and behavior, but the resulting side effects associated with these agents have made their use limited. The present study was undertaken to assess the potential of Brahmi rasayana (BR) as a memory enhancer. BR (100 and 200 mg kg−1 p.o.) was administered for eight successive days to both young and aged mice. Elevated plus maze and passive-avoidance paradigm were employed to evaluate learning and memory parameters. Scopolamine (0.4 mg kg−1 i.p.) was used to induce amnesia in mice. The effect of BR on whole brain AChE activity was also assessed. Piracetam (200 mg kg−1 i.p.) was used as a standard nootropic agent. BR significantly improved learning and memory in young mice and reversed the amnesia induced by both scopolamine (0.4 mg kg−1 i.p.) and natural aging. BR significantly decreased whole brain acetyl cholinesterase activity. BR might prove to be a useful memory restorative agent in the treatment of dementia seen in elderly. PMID:16550227

Probable Nootropicinduced Psychiatric Adverse Effects: A Series of Four Cases

PubMed Central

Ajaltouni, Jean

2015-01-01

The misuse of nootropics—any substance that may alter, improve, or augment cognitive performance, mainly through the stimulation or inhibition of certain neurotransmitters—may potentially be dangerous and deleterious to the human brain, and certain individuals with a history of mental or substance use disorders might be particularly vulnerable to their adverse effects. We describe four cases of probable nootropic-induced psychiatric adverse effects to illustrate this theory. To the best of our knowledge this has not been previously reported in the formal medical literature. We briefly describe the most common classes of nootropics, including their postulated or proven methods of actions, their desired effects, and their adverse side effects, and provide a brief discussion of the cases. Our objective is to raise awareness among physicians in general and psychiatrists and addiction specialists in particular of the potentially dangerous phenomenon of unsupervised nootropic use among young adults who may be especially vulnerable to nootropics’ negative effects. PMID:27222762

Evaluation of nootropic potential of Ocimum sanctum Linn. in mice.

PubMed

Joshi, Hanumanthachar; Parle, Milind

2006-02-01

Dementia is one of the age related mental problems and a characteristic symptom of various neurodegenerative disorders including Alzheimer's disease. Certain drugs like diazepam, barbiturates and alcohol disrupt learning and memory in animals and man. However, a new class of drugs known as nootropic agents is now used in situations where there is organic disorder in learning abilities. The present work was undertaken to assess the potential of O. sanctum extract as a nootropic and anti-amnesic agent in mice. Aqueous extract of dried whole plant of O. sanctum ameliorated the amnesic effect of scopolamine (0.4 mg/kg), diazepam (1 mg/kg) and aging induced memory deficits in mice. Elevated plus maze and passive avoidance paradigm served as the exteroceptive behavioral models. O. sanctum extract decreased transfer latency and increased step down latency, when compared to control (piracetam treated), scopolamine and aged groups of mice significantly. O. sanctum preparations could of beneficial in the treatment of cognitive disorders such as dementia and Alzheimer's disease.

Nootropic α7 nicotinic receptor allosteric modulator derived from GABAA receptor modulators

PubMed Central

Ng, Herman J.; Whittemore, Edward R.; Tran, Minhtam B.; Hogenkamp, Derk J.; Broide, Ron S.; Johnstone, Timothy B.; Zheng, Lijun; Stevens, Karen E.; Gee, Kelvin W.

2007-01-01

Activation of brain α7 nicotinic acetylcholine receptors (α7 nAChRs) has broad therapeutic potential in CNS diseases related to cognitive dysfunction, including Alzheimer's disease and schizophrenia. In contrast to direct agonist activation, positive allosteric modulation of α7 nAChRs would deliver the clinically validated benefits of allosterism to these indications. We have generated a selective α7 nAChR-positive allosteric modulator (PAM) from a library of GABAA receptor PAMs. Compound 6 (N-(4-chlorophenyl)-α-[[(4-chloro-phenyl)amino]methylene]-3-methyl-5-isoxazoleacet-amide) evokes robust positive modulation of agonist-induced currents at α7 nAChRs, while preserving the rapid native characteristics of desensitization, and has little to no efficacy at other ligand-gated ion channels. In rodent models, it corrects sensory-gating deficits and improves working memory, effects consistent with cognitive enhancement. Compound 6 represents a chemotype for allosteric activation of α7 nAChRs, with therapeutic potential in CNS diseases with cognitive dysfunction. PMID:17470817

Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets.

PubMed

Lam, Max; Trampush, Joey W; Yu, Jin; Knowles, Emma; Davies, Gail; Liewald, David C; Starr, John M; Djurovic, Srdjan; Melle, Ingrid; Sundet, Kjetil; Christoforou, Andrea; Reinvang, Ivar; DeRosse, Pamela; Lundervold, Astri J; Steen, Vidar M; Espeseth, Thomas; Räikkönen, Katri; Widen, Elisabeth; Palotie, Aarno; Eriksson, Johan G; Giegling, Ina; Konte, Bettina; Roussos, Panos; Giakoumaki, Stella; Burdick, Katherine E; Payton, Antony; Ollier, William; Chiba-Falek, Ornit; Attix, Deborah K; Need, Anna C; Cirulli, Elizabeth T; Voineskos, Aristotle N; Stefanis, Nikos C; Avramopoulos, Dimitrios; Hatzimanolis, Alex; Arking, Dan E; Smyrnis, Nikolaos; Bilder, Robert M; Freimer, Nelson A; Cannon, Tyrone D; London, Edythe; Poldrack, Russell A; Sabb, Fred W; Congdon, Eliza; Conley, Emily Drabant; Scult, Matthew A; Dickinson, Dwight; Straub, Richard E; Donohoe, Gary; Morris, Derek; Corvin, Aiden; Gill, Michael; Hariri, Ahmad R; Weinberger, Daniel R; Pendleton, Neil; Bitsios, Panos; Rujescu, Dan; Lahti, Jari; Le Hellard, Stephanie; Keller, Matthew C; Andreassen, Ole A; Deary, Ian J; Glahn, David C; Malhotra, Anil K; Lencz, Todd

2017-11-28

Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability ("g"), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum). Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Nefiracetam facilitates hippocampal neurotransmission by a mechanism independent of the piracetam and aniracetam action.

PubMed

Nomura, T; Nishizaki, T

2000-07-07

Nefiracetam, a nootropic (cognition-enhancing) agent, facilitated neurotransmission in the dentate gyrus of rat hippocampal slices in a dose-dependent manner at concentrations ranged from 1 nM to 1 microM, being evident at 60-min washing-out of the drug. The facilitatory action was blocked by the nicotinic acetylcholine (ACh) receptor antagonists, alpha-bungarotoxin and mecamylamine. A similar facilitation was induced by the other nootropic agents, piracetam and aniracetam, but the facilitation was not inhibited by nicotinic ACh receptor antagonists and it did not occlude the potentiation induced by nefiracetam. In the Xenopus oocyte expression systems, nefiracetam potentiated currents through a variety of neuronal nicotinic ACh receptors (alpha 3beta 2, alpha 3beta 4, alpha 4 beta 2, alpha 4 beta 4, and alpha 7) to a different extent. In contrast, neither piracetam nor aniracetam had any potentiating action on alpha 7 receptor currents. While aniracetam delayed the decay time of currents through the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, GluR1, -2, -3, expressed in oocytes, nefiracetam or piracetam had no effect on the currents. Nefiracetam, thus, appears to facilitate hippocampal neurotransmission by functionally targeting nicotinic ACh receptors, independently of the action of piracetam and aniracetam.

[The original novel nootropic and neuroprotective agent noopept].

PubMed

Ostrovskaia, R U; Gudasheva, T A; Voronina, T A; Seredenin, S B

2002-01-01

The paper describes pharmacological properties of the new nootropic drug noopept created using an original approach based on the imitation of a nonpeptide nootrope structure by means of the short-peptide design. In particular, the structure of pyracetam was designed using dipeptide nootropes. Experimental investigations of noopept (N-phenylacetyl-L-polyglycine ethyl ester) showed that the new drug exceeds pyracetam both with respect to the effective dose level (1000 times lower for noopept than for pyracetam) and in the spectrum of mnemotropic activity. In contrast to pyracetam facilitating only the early stages of the memory process, noopept positively influences the memory consolidation and retrieval steps as well. The new drug produces an additional selective anxiolytic action. The pronounced neuroprotective effect of noopept was demonstrated both in vivo (in cases of various forms of brain ischemia) and in vitro (on various neuronal models). The drug action is based on the antioxidant effect, the antiinflammatory action, and the ability to inhibit the neurotoxicity of excess calcium and glutamate, and to improve the blood rheology. It was established for the first time that the activity of noopept is retained both upon parenteral introduction and upon peroral administration, which is a principal advantage of this proline-containing dipeptide over other, more complex peptides. This property provided a basis for the development of a medicinal form of noopept for peroral usage. At present, noopept tablets (noopept 5 and 10 mg) are under clinical assessment as a means of treating cognitive deficiency of cerebrovascular and post-traumatic origin.

Enhancement of nootropic effect of duloxetine and bupropion by caffeine in mice.

PubMed

Kale, Pravin Popatrao; Addepalli, Veeranjaneyulu

2015-01-01

The existing evidence suggests an association between depression and memory impairment. The objective of present study was to assess the effect of low dose caffeine with duloxetine and bupropion on memory. Mice were divided randomly into seven groups. Intra-peritoneal treatment of normal saline (10 ml/kg), caffeine (10 mg/kg), duloxetine (10 mg/kg), bupropion alone (10 mg/kg), caffeine + duloxetine (5 mg/kg, each), caffeine + bupropion (5 mg/kg, each), and bupropion + duloxetine (5 mg/kg, each) were given to groups I-VII, respectively. Elevated plus maze was used to evaluate transfer latency (TL) and Morris water maze was used to estimate the time spent in target quadrant. Caffeine with duloxetine treated group was better than other combination treated groups in terms of a significant decrease in TL and increase in the time spent in target quadrant recorded. Combining lower dose of caffeine with duloxetine may enhance cognitive benefits than respective monotherapies.

Evaluation of antibacterial, antioxidant and nootropic activities of Tiliacora racemosa Colebr. leaves: In vitro and in vivo approach.

PubMed

T, Vivek Kumar; M, Vishalakshi; M, Gangaraju; Das, Parijat; Roy, Pratiti; Banerjee, Anindita; Dutta Gupta, Sayan

2017-02-01

The antibacterial and antioxidant potential of Tiliacora racemosa leaf extracts in various solvents (methanolic, hexane, chloroform and ethyl acetate) was determined. Additionally, the presence of bisbenzylisoquinoline alkaloids in the plant prompted us to evaluate the nootropic activity of the methanolic extract in mice. Further, we seek to verify the nootropic effect by examining the anticholinesterase inhibition potential of the methanolic extract. The leaf extracts in various solvents were evaluated for their antibacterial and antioxidant activity by agar diffusion technique and α, α-diphenyl-β-picrylhydrazyl (DPPH) free radical scavenging method, respectively. The ex vivo acetylcholine esterase inhibitory activity of the methanolic extract was carried out by Ellman's method in male Wistar rats. The nootropic capacity of the methanolic extract was examined in Swiss albino mice by utilizing the diazepam induced acute amnesic model. The chloroform/n-hexane and ethyl acetate fraction showed promising antioxidant and antibacterial (Gram positive and Gram negative bacteria) property, respectively. The methanolic extract was able to diminish the amnesic effect induced by diazepam (1mg/kg i.p.) in mice. The extract also showed significant acetyl cholinesterase inhibition in rats. The findings prove that the memory enhancing capability is due to increased acetyl choline level at the nerve endings. The strong antioxidant nature and potential nootropic activity shown by the extract suggests its future usage in the treatment of neurodegenerative disorders such as dementia and Alzheimer. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Comparative study of the neuroprotective and nootropic activities of the carboxylate and amide forms of the HLDF-6 peptide in animal models of Alzheimer's disease.

PubMed

Bogachouk, Anna P; Storozheva, Zinaida I; Solovjeva, Olga A; Sherstnev, Vyacheslav V; Zolotarev, Yury A; Azev, Vyacheslav N; Rodionov, Igor L; Surina, Elena A; Lipkin, Valery M

2016-01-01

A comparative study of the neuroprotective and nootropic activities of two pharmaceutical substances, the HLDF-6 peptide (HLDF-6-OH) and its amide form (HLDF-6-NH2), was conducted. The study was performed in male rats using two models of a neurodegenerative disorder. Cognitive deficit in rats was induced by injection of the beta-amyloid fragment 25-35 (βA 25-35) into the giant-cell nucleus basalis of Meynert or by coinjection of βA 25-35 and ibotenic acid into the hippocampus. To evaluate cognitive functions in animals, three tests were used: the novel object recognition test, the conditioned passive avoidance task and the Morris maze. Comparative analysis of the data demonstrated that the neuroprotective activity of HLDF-6-NH2, evaluated by improvement of cognitive functions in animals, surpassed that of the native HLDF-6-OH peptide. The greater cognitive/ behavioral effects can be attributed to improved kinetic properties of the amide form of the peptide, such as the character of biodegradation and the half-life time. The effects of HLDF-6-NH2 are comparable to, or exceed, those of the reference compounds. Importantly, HLDF-6-NH2 exerts its effects at much lower doses than the reference compounds. © The Author(s) 2015.

GVS-111 prevents oxidative damage and apoptosis in normal and Down's syndrome human cortical neurons.

PubMed

Pelsman, Alejandra; Hoyo-Vadillo, Carlos; Gudasheva, Tatiana A; Seredenin, Sergei B; Ostrovskaya, Rita U; Busciglio, Jorge

2003-05-01

The neuroprotective activity of a novel N-acylprolyl-containing dipeptide analog of the nootropic 2-oxo-1-pyrrolidine acetamide (Piracetam) designated as GVS-111 (DVD-111/Noopept) was tested in two in vitro models of neuronal degeneration mediated by oxidative stress: normal human cortical neurons treated with H(2)O(2), and Down's syndrome (DS) cortical neurons. Incubation of normal cortical neurons with 50 microM H(2)O(2) for 1h resulted in morphological and structural changes consistent with neuronal apoptosis and in the degeneration of more than 60% of the neurons present in the culture. GVS-111 significantly increased neuronal survival after H(2)O(2)-treatment displaying a dose-dependent neuroprotective activity from 10nM to 100 microM, and an IC(50) value of 1.21+/-0.07 microM. GVS-111 inhibited the accumulation of intracellular free radicals and lipid peroxidation damage in neurons treated with H(2)O(2) or FeSO(4), suggesting an antioxidant mechanism of action. GVS-111 exhibited significantly higher neuroprotection compared to the standard cognition enhancer Piracetam, or to the antioxidants Vitamin E, propyl gallate and N-tert-butyl-2-sulpho-phenylnitrone (s-PBN). In DS cortical cultures, chronic treatment with GVS-111 significantly reduced the appearance of degenerative changes and enhanced neuronal survival. The results suggest that the neuroprotective effect of GVS-111 against oxidative damage and its potential nootropic activity may present a valuable therapeutic combination for the treatment of mental retardation and chronic neurodegenerative disorders.

The effect of Bacopa monnieri on gene expression levels in SH-SY5Y human neuroblastoma cells.

PubMed

Leung, How-Wing; Foo, Gabriel; Banumurthy, Gokulakrishna; Chai, Xiaoran; Ghosh, Sujoy; Mitra-Ganguli, Tora; VanDongen, Antonius M J

2017-01-01

Bacopa monnieri is a plant used as a nootropic in Ayurveda, a 5000-year-old system of traditional Indian medicine. Although both animal and clinical studies supported its role as a memory enhancer, the molecular and cellular mechanism underlying Bacopa's nootropic action are not understood. In this study, we used deep sequencing (RNA-Seq) to identify the transcriptome changes upon Bacopa treatment on SH-SY5Y human neuroblastoma cells. We identified several genes whose expression levels were regulated by Bacopa. Biostatistical analysis of the RNA-Seq data identified biological pathways and molecular functions that were regulated by Bacopa, including regulation of mRNA translation and transmembrane transport, responses to oxidative stress and protein misfolding. Pathway analysis using the Ingenuity platform suggested that Bacopa may protect against brain damage and improve brain development. These newly identified molecular and cellular determinants may contribute to the nootropic action of Bacopa and open up a new direction of investigation into its mechanism of action.

The effect of Bacopa monnieri on gene expression levels in SH-SY5Y human neuroblastoma cells

PubMed Central

Foo, Gabriel; Banumurthy, Gokulakrishna; Chai, Xiaoran; Ghosh, Sujoy

2017-01-01

Bacopa monnieri is a plant used as a nootropic in Ayurveda, a 5000-year-old system of traditional Indian medicine. Although both animal and clinical studies supported its role as a memory enhancer, the molecular and cellular mechanism underlying Bacopa’s nootropic action are not understood. In this study, we used deep sequencing (RNA-Seq) to identify the transcriptome changes upon Bacopa treatment on SH-SY5Y human neuroblastoma cells. We identified several genes whose expression levels were regulated by Bacopa. Biostatistical analysis of the RNA-Seq data identified biological pathways and molecular functions that were regulated by Bacopa, including regulation of mRNA translation and transmembrane transport, responses to oxidative stress and protein misfolding. Pathway analysis using the Ingenuity platform suggested that Bacopa may protect against brain damage and improve brain development. These newly identified molecular and cellular determinants may contribute to the nootropic action of Bacopa and open up a new direction of investigation into its mechanism of action. PMID:28832626

Evaluation of nootropic and neuroprotective effects of low dose aspirin in rats.

PubMed

Ghosh, Arijit; Dhumal, V R; Tilak, A V; Das, Nina; Singh, Amarinder; Bondekar, Abhijit A

2011-01-01

To evaluate the nootropic and neuroprotective effects of aspirin in Sprague Dawley rats. Retention of conditioned avoidance response (CAR) and central 5-HT-mediated behavior (lithium-induced head twitches) were assessed using repeated electroconvulsive shock (ECS) in rats. Rats were divided into eight groups: control (pretreated with distilled water), scopolamine (0.5 mg/kg i.p.), ECS (150 V, 50 Hz sinusoidal with intensity of 210 mA for 0.5 s) pretreated, aspirin (6.75 mg/kg orally) pretreated, combined scopolamine and aspirin pretreated, ondansetron (0.36 mg/kg orally) pretreated, combined ECS and ondansetron pretreated and combined ECS and aspirin pretreated groups. Data was analyzed by the chi-square test and ANOVA. Findings show that administration of single ECS daily for consecutive 8 days results in enhancement of 5-HT-mediated behavior (lithium-induced head twitches) and in disruption of the retention of CAR. Aspirin and ondansetron administration significantly increased the retention of conditioned avoidance response compared to control. Ondansetron and aspirin significantly prevented ECS-induced attenuation of the retention of conditioned avoidance response also. On the other hand, ondansetron and aspirin significantly retarded the ECS-induced enhancement of 5-HT-mediated behavior. Inhibition of the serotonergic transmission by aspirin is responsible for its nootropic and neuroprotective actions.

Evaluation of nootropic and neuroprotective effects of low dose aspirin in rats

PubMed Central

Ghosh, Arijit; Dhumal, V. R.; Tilak, A. V.; Das, Nina; Singh, Amarinder; Bondekar, Abhijit A.

2011-01-01

Objective: To evaluate the nootropic and neuroprotective effects of aspirin in Sprague Dawley rats. Materials and Methods: Retention of conditioned avoidance response (CAR) and central 5-HT-mediated behavior (lithium-induced head twitches) were assessed using repeated electroconvulsive shock (ECS) in rats. Rats were divided into eight groups: control (pretreated with distilled water), scopolamine (0.5 mg/kg i.p.), ECS (150 V, 50 Hz sinusoidal with intensity of 210 mA for 0.5 s) pretreated, aspirin (6.75 mg/kg orally) pretreated, combined scopolamine and aspirin pretreated, ondansetron (0.36 mg/kg orally) pretreated, combined ECS and ondansetron pretreated and combined ECS and aspirin pretreated groups. Data was analyzed by the chi-square test and ANOVA. Results: Findings show that administration of single ECS daily for consecutive 8 days results in enhancement of 5-HT-mediated behavior (lithium-induced head twitches) and in disruption of the retention of CAR. Aspirin and ondansetron administration significantly increased the retention of conditioned avoidance response compared to control. Ondansetron and aspirin significantly prevented ECS-induced attenuation of the retention of conditioned avoidance response also. On the other hand, ondansetron and aspirin significantly retarded the ECS-induced enhancement of 5-HT-mediated behavior. Conclusion: Inhibition of the serotonergic transmission by aspirin is responsible for its nootropic and neuroprotective actions. PMID:21701638

Immunostimulant, cerebroprotective & nootropic activities of Andrographis paniculata leaves extract in normal & type 2 diabetic rats.

PubMed

Radhika, P; Annapurna, A; Rao, S Nageswara

2012-05-01

A large number of plants have been recognized to be effective in the treatment of diabetes mellitus. Persistent hyperglycaemia is associated with decreased function of immune system and cerebral ischaemia mainly due to increased oxidative stress and inflammatory response. Andrographis paniculata is a medicinal plant widely used in folk medicine for various purposes. In this study the effect of chronic administration (7 days) of methanolic extract of A. paniculata leaves was studied in rats with experimentally induced diabetes, nootropic and immunostimulant activities were evaluated. The effect of acute administration of methanolic extract of A. paniculata leaves was also studied for cerebroprotective activity. Type 2 diabetes was induced in rats by streptozotocin (STZ) (65 mg/kg) + nicotinamide (150 mg/kg). Various biochemical parameters were estimated using standard methods. A significant (P<0.05) increase in cognitive function was observed in both normal and type 2 diabetic rats. Nootropic activity in terms of per cent reduction in latency period was more in type 2 diabetic rats. A significant increase in blood lymphocyte count, splenic lymphocyte count and peritoneal macrophage count was observed in both normal and type 2 diabetic rats. Immunostimulant activity was observed more in type 2 diabetic rats. The per cent decrease in cerebral infarction was more in type 2 diabetic rats when compared to normal rats. The per cent increase in superoxide dismutase (SOD) levels was more in type 2 diabetic rats. The antioxidant activity of the methanolic extract of A. paniculata leaves was evident by decreased tissue malondialdehyde (MDA) levels and increased SOD levels. These properties may be responsible for the observed cerebroprotective activity. The methanolic leaf extract of A. paniculata showed significant immunostimulant, cerebroprotective and nootropic activities in normal and type 2 diabetic rats.

Immunostimulant, cerebroprotective & nootropic activities of Andrographis paniculata leaves extract in normal & type 2 diabetic rats

PubMed Central

Radhika, P.; Annapurna, A.; Rao, S. Nageswara

2012-01-01

Background & objectives: A large number of plants have been recognized to be effective in the treatment of diabetes mellitus. Persistent hyperglycaemia is associated with decreased function of immune system and cerebral ischaemia mainly due to increased oxidative stress and inflammatory response. Andrographis paniculata is a medicinal plant widely used in folk medicine for various purposes. In this study the effect of chronic administration (7 days) of methanolic extract of A. paniculata leaves was studied in rats with experimentally induced diabetes, nootropic and immunostimulant activities were evaluated. The effect of acute administration of methanolic extract of A. paniculata leaves was also studied for cerebroprotective activity. Methods: Type 2 diabetes was induced in rats by streptozotocin (STZ) (65 mg/kg) + nicotinamide (150 mg/kg). Various biochemical parameters were estimated using standard methods. Results: A significant (P<0.05) increase in cognitive function was observed in both normal and type 2 diabetic rats. Nootropic activity in terms of per cent reduction in latency period was more in type 2 diabetic rats. A significant increase in blood lymphocyte count, splenic lymphocyte count and peritoneal macrophage count was observed in both normal and type 2 diabetic rats. Immunostimulant activity was observed more in type 2 diabetic rats. The per cent decrease in cerebral infarction was more in type 2 diabetic rats when compared to normal rats. The per cent increase in superoxide dismutase (SOD) levels was more in type 2 diabetic rats. Interpretation & conclusions: The antioxidant activity of the methanolic extract of A. paniculata leaves was evident by decreased tissue malondialdehyde (MDA) levels and increased SOD levels. These properties may be responsible for the observed cerebroprotective activity. The methanolic leaf extract of A. paniculata showed significant immunostimulant, cerebroprotective and nootropic activities in normal and type 2 diabetic rats. PMID:22771592

Enhancement of nootropic effect of duloxetine and bupropion by caffeine in mice

PubMed Central

Kale, Pravin Popatrao; Addepalli, Veeranjaneyulu

2015-01-01

Objective: The existing evidence suggests an association between depression and memory impairment. The objective of present study was to assess the effect of low dose caffeine with duloxetine and bupropion on memory. Materials and Methods: Mice were divided randomly into seven groups. Intra-peritoneal treatment of normal saline (10 ml/kg), caffeine (10 mg/kg), duloxetine (10 mg/kg), bupropion alone (10 mg/kg), caffeine + duloxetine (5 mg/kg, each), caffeine + bupropion (5 mg/kg, each), and bupropion + duloxetine (5 mg/kg, each) were given to groups I-VII, respectively. Elevated plus maze was used to evaluate transfer latency (TL) and Morris water maze was used to estimate the time spent in target quadrant. Results: Caffeine with duloxetine treated group was better than other combination treated groups in terms of a significant decrease in TL and increase in the time spent in target quadrant recorded. Conclusion: Combining lower dose of caffeine with duloxetine may enhance cognitive benefits than respective monotherapies. PMID:25878382

Novel nootropic drug sunifiram enhances hippocampal synaptic efficacy via glycine-binding site of N-methyl-D-aspartate receptor.

PubMed

Moriguchi, Shigeki; Tanaka, Tomoya; Narahashi, Toshio; Fukunaga, Kohji

2013-10-01

Sunifiram is a novel pyrrolidone nootropic drug structurally related to piracetam, which was developed for neurodegenerative disorder like Alzheimer's disease. Sunifiram is known to enhance cognitive function in some behavioral experiments such as Morris water maze task. To address question whether sunifiram affects N-methyl-D-aspartate receptor (NMDAR)-dependent synaptic function in the hippocampal CA1 region, we assessed the effects of sunifiram on NMDAR-dependent long-term potentiation (LTP) by electrophysiology and on phosphorylation of synaptic proteins by immunoblotting analysis. In mouse hippocampal slices, sunifiram at 10-100 nM significantly enhanced LTP in a bell-shaped dose-response relationship which peaked at 10 nM. The enhancement of LTP by sunifiram treatment was inhibited by 7-chloro-kynurenic acid (7-ClKN), an antagonist for glycine-binding site of NMDAR, but not by ifenprodil, an inhibitor for polyamine site of NMDAR. The enhancement of LTP by sunifilam was associated with an increase in phosphorylation of α-amino-3-hydroxy-5-methylisozazole-4-propionate receptor (AMPAR) through activation of calcium/calmodulin-dependent protein kinase II (CaMKII) and an increase in phosphorylation of NMDAR through activation of protein kinase Cα (PKCα). Sunifiram treatments at 1-1000 nM increased the slope of field excitatory postsynaptic potentials (fEPSPs) in a dose-dependent manner. The enhancement was associated with an increase in phosphorylation of AMPAR receptor through activation of CaMKII. Interestingly, under the basal condition, sunifiram treatments increased PKCα (Ser-657) and Src family (Tyr-416) activities with the same bell-shaped dose-response curve as that of LTP peaking at 10 nM. The increase in phosphorylation of PKCα (Ser-657) and Src (Tyr-416) induced by sunifiram was inhibited by 7-ClKN treatment. The LTP enhancement by sunifiram was significantly inhibited by PP2, a Src family inhibitor. Finally, when pretreated with a high concentration of glycine (300 μM), sunifiram treatments failed to potentiate LTP in the CA1 region. Taken together, sunifiram stimulates the glycine-binding site of NMDAR with concomitant PKCα activation through Src kinase. Enhancement of PKCα activity triggers to potentiate hippocampal LTP through CaMKII activation. Copyright © 2013 Wiley Periodicals, Inc.

[Noopept in the treatment of mild cognitive impairment in patients with stroke].

PubMed

Amelin, A V; Iliukhina, A Iu; Shmonin, A A

2011-01-01

Noopept is a neuroprotector and nootropics. Literature data revealed the treatment effect of noopept on mild cognitive impairment in patients with discirculatory encephalopathy. The present open prospective study included 60 patients with stroke treated with noopept during 12 months. Cognitive functions were assessed before and after treatment using neuropsychological tests. An analysis of MMSE scores and lateral and categorical associations revealed the significant improvement of cognitive functions after 2 months in patients of the main group compared to the controls. The global assessment of efficacy revealed the mild improvement in the main group while no changes were found in the control group. The results have demonstrated that noopept, used in dose 20 mg daily during 2 months, improves cognitive functions in stroke patients and has a high level of safety.

Nootropic and hypophagic effects following long term intake of almonds (Prunus amygdalus) in rats.

PubMed

Haider, S; Batool, Z; Haleem, D J

2012-01-01

Over a period of time researchers have become more interested in finding out the potential of various foods to maintain the general health and to treat diseases. Almonds are a very good source of many nutrients which may help to sharpen the memory and to reduce cardiovascular risk factors. The present study was conducted to evaluate the nootropic effects of almonds. Effect of oral intake of almond was also monitored on food intake and plasma cholesterol levels. Rats were given almond paste orally with the help of feeding tube for 28 days. Memory function in rats was assessed by Elevated Plus Maze (EPM) and Radial Arm Maze (RAM). Brain tryptophan, 5-HT and 5-HIAA were estimated at the end of the treatment by HPLC-EC method. A significant improvement in learning and memory of almond treated rats compared to controls was observed. Almond treated rats also exhibited a significant decrease in food intake and plasma cholesterol levels while the change in growth rate (in terms of percentage) remained comparable between the two groups. Analysis of brain tryptophan (TRP) monoamines exhibited enhanced TRP levels and serotonergic turnover in rat brain following oral intake of almonds. The findings show that almonds possess significant hypophagic and nootropic effects. Results are discussed in context of enhanced 5-HT metabolism following almond administration.

[Effects of nootropic drugs on hippocampal and cortical BDNF levels in mice with different exploratory behavior efficacy].

PubMed

Firstova, Iu Iu; Dolotov, O V; Kondrakhin, e A; Dubynina, E V; Grivennikov, I A; Kovalev, G I

2009-01-01

The influence of subchronic administration of nootropic drugs (piracetam, phenotropil, meclophenoxate, pantocalcine, semax, nooglutil) on the brain-derived neurotrophic factor (BDNF) content in hippocampal and cortical tissues in mice with different exploratory behavior--high efficacy (HE) against low efficacy (LE)--in cross-maze test has been studied. The initial BDNF concentration in hippocamp (but not in cortex) of control HE mice was higher than that in LE mice (LE, 0.091 +/- 0.005 pg/microg; HE, 0.177 +/- 0.005 pg/microg; p < 0.0005). After drug administration, changes in the BDNF level were only observed in the hippocamp of LE mice, where it reached (pg/microg) 0.115 +/- 0.004 (for piracetam); 0.119 +/- 0.006 (for phenotropil); 0.123 +/- 0.007 (for semax); and 0.122 +/- 0.009 (for meclophenoxate). In the LE mice cortex, the BDNF content increased only after piracetam and semax injections (to 0.083 +/- 0.003 and 0.093 +/- 0.008, respectively, vs. 0.071 +/- 0.003 pg/microg in the control group; p < 0.0005). No changes were observed in the cortex of HE mice. Thus, the obtained results demonstrate that clinically used drugs piracetam, phenotropil, meclophenoxate, and semax realize their nootrope effects, at least partially, via increase in hippocampal BDNF level, which is achieved only under conditions of cognitive deficiency.

[Electrophysiological correlates of efficacy of nootropic drugs in the treatment of consequences of traumatic brain injury in adolescents].

PubMed

Iznak, E V; Iznak, A F; Pankratova, E A; Zavadenko, N N; Guzilova, L S; Guzilova, Iu I

2010-01-01

To assess objectively a dynamics of brain functional state, EEG spectral power and peak latency of the P300 component of cognitive auditory evoked potentials have been analyzed in adolescents during the course of nootropic therapy of residual asthenic consequences of traumatic brain injury (ICD-10 F07.2). The study included 76 adolescents, aged 12-18 years, who have undergone severe closed head trauma with brain commotion 1/2--5 years ago. Patients have been divided into 3 groups treated during one month with cerebrolysin, piracetam or magne-B6, respectively. After the end of the nootropic therapy, 77% of patients treated with cerebrolysin as well as 50% of patients treated with piracetam and magne-B6 have demonstrated the positive dynamics of their brain functional state that manifested itself in the appearance of occipital EEG alpha rhythm or in the increase of its spectral power; in the normalization of alpha rhythm frequency; in the decrease in the spectral power of slow wave (theta and delta) EEG activity, in the amount (up to the disappearance) of paroxysmal EEG activity, in the EEG response to hyperventilation and in the shortening of the P300 peak latency. Such positive changes of neurophysiological parameters have been associated with the improvement of clinical conditions of patients and correlated significantly with the dynamics of psychometric scores of attention and memory.

PASS assisted prediction and pharmacological evaluation of novel nicotinic analogs for nootropic activity in mice.

PubMed

Khurana, Navneet; Ishar, Mohan Pal Singh; Gajbhiye, Asmita; Goel, Rajesh Kumar

2011-07-15

The aim of present study is to predict the probable nootropic activity of novel nicotine analogues with the help of computer program, PASS (prediction of activity spectra for substances) and evaluate the same. Two compounds from differently substituted pyridines were selected for synthesis and evaluation of nootropic activity based on their high probable activity (Pa) value predicted by PASS computer program. Evaluation of nootropic activity of compounds after acute and chronic treatment was done with transfer latency (TL) and step down latency (SDL) methods which showed significant nootropic activity. The effect on scopolamine induced amnesia was also observed along with their acetylcholine esterase inhibitory activity which also showed positive results which strengthened their efficacy as nootropic agents through involvement of cholinergic system. This nootropic effect was similar to the effect of nicotine and donepezil used as standard drugs. Muscle coordination and locomotor activity along with their addiction liability, safety and tolerability studies were also evaluated. These studies showed that these compounds are well tolerable and safe over a wide range of doses tested along with the absence of withdrawal effect which is present in nicotine due to its addiction liability. The study showed that these compounds are true nicotine analogs with desirable efficacy and safety profile for their use as effective nootropic agents. Copyright © 2011 Elsevier B.V. All rights reserved.

An acute, double-blind, placebo-controlled crossover study of 320 mg and 640 mg doses of a special extract of Bacopa monnieri (CDRI 08) on sustained cognitive performance.

PubMed

Downey, Luke A; Kean, James; Nemeh, Fiona; Lau, Angela; Poll, Alex; Gregory, Rebecca; Murray, Margaret; Rourke, Johanna; Patak, Brigit; Pase, Matthew P; Zangara, Andrea; Lomas, Justine; Scholey, Andrew; Stough, Con

2013-09-01

Standardized extracts of the traditional Ayurvedic medicine Bacopa monnieri (BM) (Brahmi) have been recently shown to have cognitive enhancing effects in chronic administration studies. Pre-clinical work has also identified a number of acute anxiolytic, nootropic, and cardiovascular effects of BM. There has, however, been little research on the acute effects of BM on cognitive function. The current study aimed to assess the acute effects of a specific extract of BM (KeenMind®-CDRI 08) in a double-blind, placebo-controlled study in normal healthy participants who completed a cognitively demanding series of tests. Twenty-four healthy volunteers completed six repetitions of the Cognitive Demand Battery (CDB) after consuming a placebo, 320 mg BM or 640 mg of BM in a cross-over design and provided cardiovascular and mood assessments before and after treatment. Change from baseline scores indicated that the 320 mg dose of BM improved performance at the first, second, and fourth repetition post-dosing on the CDB, and the treatments had no effect upon cardiovascular activity or in attenuating task-induced ratings of stress and fatigue. It was concluded that assessment of an earlier pharmacological window and use of less memory-specific cognitive tests together with more temporally sensitive measures of brain activity may improve our understanding of the acute neurocognitive properties of BM. Copyright © 2012 John Wiley & Sons, Ltd.

Effects of Ganglioside on Working Memory and the Default Mode Network in Individuals with Subjective Cognitive Impairment: A Randomized Controlled Trial.

PubMed

Jeon, Yujin; Kim, Binna; Kim, Jieun E; Kim, Bori R; Ban, Soonhyun; Jeong, Jee Hyang; Kwon, Oran; Rhie, Sandy Jeong; Ahn, Chang-Won; Kim, Jong-Hoon; Jung, Sung Ug; Park, Soo-Hyun; Lyoo, In Kyoon; Yoon, Sujung

2016-01-01

This randomized, double-blind, placebo-controlled trial examined whether the administration of ganglioside, an active ingredient of deer bone extract, can improve working memory performance by increasing gray matter volume and functional connectivity in the default mode network (DMN) in individuals with subjective cognitive impairment. Seventy-five individuals with subjective cognitive impairment were chosen to receive either ganglioside (330[Formula: see text][Formula: see text]g/day or 660[Formula: see text][Formula: see text]g/day) or a placebo for 8 weeks. Changes in working memory performance with treatment of either ganglioside or placebo were assessed as cognitive outcome measures. Using voxel-based morphometry and functional connectivity analyses, changes in gray matter volume and functional connectivity in the DMN were also assessed as brain outcome measures. Improvement in working memory performance was greater in the ganglioside group than in the placebo group. The ganglioside group, relative to the placebo group, showed greater increases in gray matter volume and functional connectivity in the DMN. A significant relationship between increased functional connectivity of the precuneus and improved working memory performance was observed in the ganglioside group. The current findings suggest that ganglioside has cognitive-enhancing effects in individuals with subjective cognitive impairment. Ganglioside-induced increases in gray matter volume and functional connectivity in the DMN may partly be responsible for the potential nootropic effects of ganglioside. The clinical trial was registered with ClinicalTrials.gov (identifier: NCT02379481).

Nootropic, neuroprotective and neurotrophic effects of phloretin in scopolamine induced amnesia in mice.

PubMed

Ghumatkar, Priya J; Patil, Sachin P; Jain, Pankaj D; Tambe, Rufi M; Sathaye, Sadhana

2015-08-01

Phloretin (PHL), a dihydrochalcone flavonoid usually present in the roots and leaves of apple tree. In vitro study on GT1-7 immortalized hypothalamic neurons exposed to amyloid beta (25-35), demonstrated that PHL significantly influenced membrane fluidity and potential. PHL also significantly decreased excitotoxicity by restoring the calcium homeostasis in the same. Thus, PHL proves to be a promising therapeutic moiety which should be further screened in the treatment of Alzheimer's disease. The objective of the present study was to evaluate the nootropic, neuroprotective and neurotrophic roles of PHL in the subacute scopolamine induced amnesia in mice. In this study, mice were pretreated with PHL 2.5mg/kg, 5mg/kg, 10mg/kg and Donepezil (DON) 1mg/kg intraperitoneally (i.p) for 14days. The last 7days of treatment regimen included daily injection of SCP 1.5mg/kg to induce cognitive deficits. Mice were subjected to behavioral analysis. Biochemical estimation of the brain homogenates for acetylcholinesterase and oxidative stress biomarkers were conducted. Furthermore, immunohistochemical analysis for the brain derived neurotrophic factor (BDNF) was carried out particularly in the hippocampus. PHL was found to significantly improve the performance of mice in Morris water maze test (P<0.001) and significantly decreased the acetylcholinesterase activity (P<0.001) at all doses compared to SCP treated mice. Also, PHL significantly elevated the activity of antioxidant enzymes viz. superoxide dismutase, catalase, reduced glutathione levels (P<0.001) and decreased malonaldehyde levels (P<0.001) in comparison with the SCP group. Immunohistochemistry revealed that PHL treatment dose dependently improved BDNF levels in the hippocampus which were found to be significantly depleted (P<0.001) in the SCP group. Additionally, PHL (10mg/kg) significantly enhanced the spatial memory formation (P<0.05) and neurotrophicity (P<0.001) compared to DON (1mg/kg). The aforementioned research findings suggested that PHL has nootropic, neuroprotective and neurotrophic activities in SCP induced memory impaired mice and hence, is a promising therapeutic moiety in the treatment of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

The fluorescence and resonance Rayleigh scattering spectra study on the interactions of palladium (II)-Nootropic chelate with Congo red and their analytical applications

NASA Astrophysics Data System (ADS)

Chen, Fang; Peng, Jingdong; Liu, Shaopu; Peng, Huanjun; Pan, Ziyu; Bu, Lingli; Xiao, Huan; Zhang, Ruiwen

2017-04-01

A highly sensitive detection approach of resonance Rayleigh scattering spectra (RRS) is firstly applied to analyzing nootropic drugs including piracetam (PIR) and oxiracetam (OXI). In HCl-NaAc buffer solution (pH = 3.0), the OXI chelated with palladium (II) to form the chelate cation [Pd2·OXI]2 +, and then reacted with Congo red (CGR) by virtue of electrostatic attraction and hydrophobic force to form binary complex [Pd2·OXI]. CGR2, which could result in the great enhancement of RRS. The resonance Rayleigh scattering signal was recorded at λex = λem = 375 nm. This mixture complex not only has higher RRS, but also makes contribution to significant increase of fluorescence, and the same phenomena also were discovered in PIR. The enhanced RRS intensity is in proportion to the PIR and OXI concentration in the range of 0.03-3.0 μg mL- 1, and the detection limit (DL) of RRS method for PIR and OXI is 2.3 ng mL- 1 and 9.7 ng mL- 1. In addition, the DL of fluorescence method for PIR and OXI is 8.4 μg mL- 1 and 19.5 μg mL- 1. Obviously, the RRS is the highly sensitive method, and the recoveries of the two kinds of nootropic drugs were range from 100.4% to 101.8.0% with RSD (n = 5) from 1.1% to 3.1% by RRS method. This paper not only investigated the optimum conditions for detecting nootropics with using RRS method, but also focused on the reasons for enhancing RRS intensity and the reaction mechanism, which in order to firm and contract the resultant. Finally, The RRS method has been applied to detect nootropic drugs in human urine samples with satisfactory results. Fig. S2. The effect of ionic strength: Pd (II)-CGR system (curve a); Pd (II)-OXI-CGR system (curve b); Pd (II)-PIR- CGR system (curve c). Pd (II): 2.0 × 10- 4 mol L- 1; CGR: 1.0 × 10- 5 mol L- 1; OXI: 1.5 μg mL- 1; PIR: 2 μg mL- 1; NaCl: 1 mol L- 1. Fig. S3. The effect of time: Pd (II)-OXI-CGR system (curve a); Pd (II)-PIR-CGR system (curve b). Pd (II): 2.0 × 10- 4 mol L- 1; CGR: 1.0 × 10- 5 mol L- 1; OXI: 1.5 μg mL- 1. Fig. S4 Absorption spectra for Pd (II)-Nootropic-CGR system. Measured using a water blank: (1) OXI; (2) GIR; (3) OXI-CGR; (4) Pd (II); (5) Pd(II)-OXI; (6) PIR-OXI-CGR, OXI: 1.0 μg mL- 1; Pd (II) concentration: 3.0 × 10- 4 mol L- 1; CGR concentration: 1.0 × 10- 5 mol L- 1; HCl-NaAc: pH 3.0.

Adaptogenic and nootropic activities of aqueous extract of Vitis vinifera (grape seed): an experimental study in rat model

PubMed Central

Sreemantula, Satyanarayana; Nammi, Srinivas; Kolanukonda, Rajabhanu; Koppula, Sushruta; Boini, Krishna M

2005-01-01

Background The aerial parts of Vitis vinifera (common grape or European grape) have been widely used in Ayurveda to treat a variety of common and stress related disorders. In the present investigation, the seed extract of V. vinifera was evaluated for antistress activity in normal and stress induced rats. Furthermore, the extract was studied for nootropic activity in rats and in-vitro antioxidant potential to correlate its antistress activity. Methods For the evaluation of antistress activity, groups of rats (n = 6) were subjected to forced swim stress one hour after daily treatment of V. vinifera extract. Urinary vanillylmandelic acid (VMA) and ascorbic acid were selected as non-invasive biomarkers to assess the antistress activity. The 24 h urinary excretion of vanillylmandelic acid (VMA) and ascorbic acid were determined by spectrophotometric methods in all groups under normal and stressed conditions. The nootropic activity of the extract as determined from acquisition, retention and retrieval in rats was studied by conditioned avoidance response using Cook's pole climbing apparatus. The in vitro antioxidant activity was determined based on the ability of V. vinifera to scavenge hydroxyl radicals. Results Daily administration of V. vinifera at doses of 100, 200 and 300 mg/kg body weight one hour prior to induction of stress inhibited the stress induced urinary biochemical changes in a dose dependent manner. However, no change in the urinary excretion of VMA and ascorbic acid was observed in normal animals at all the doses studied. The cognition, as determined by the acquisition, retention and recovery in rats was observed to be dose dependent. The extract also produced significant inhibition of hydroxyl radicals in comparison to ascorbic acid in a dose dependent manner. Conclusion The present study provides scientific support for the antistress (adaptogenic), antioxidant and nootropic activities of V. vinifera seed extract and substantiate the traditional claims for the usage of grape fruits and seeds in stress induced disorders. PMID:15656916

The nootropic and neuroprotective proline-containing dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimer's disease model.

PubMed

Ostrovskaya, Rita U; Gruden, Marina A; Bobkova, Natalya A; Sewell, Robert D E; Gudasheva, Tatyana A; Samokhin, Alexander N; Seredinin, Sergey B; Noppe, Wim; Sherstnev, Vladimir V; Morozova-Roche, Ludmilla A

2007-08-01

The effects of the novel proline-containing nootropic and neuroprotective dipeptide, noopept (GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) were investigated in NMRI mice following olfactory bulbectomy. We have shown previously that these animals developed Alzheimer's disease (AD)-like behaviour, morphology and biochemistry including impairment of spatial memory, regional neuronal degeneration and elevated Abeta peptide brain levels. In the current investigation, spatial memory was assessed using the Morris water maze and serum antibodies to in vitro morphologically characterized amyloid structures of both Abeta((25-35)) peptide and equine lysozyme, as well as to neurotrophic glial factor S100b, were analyzed by enzyme-linked immunosorbent assay (ELISA). Noopept (administered at a dose of 0.01 mg/kg for a period of 21 days and during a further 5 days training) restored spatial memory and increased serum antibody levels to oligomers of Abeta((25-35)) peptide but not to equine lysozyme amyloid or S100b protein in bulbectomized animals. The positive immunotropic effect of noopept to Abeta((25-35)) peptide prefibrillar aggregates was more marked in sham-operated compared to the bulbectomized subjects which were characterized by an overall suppression of immunoreactivity. Enhancement of the immune response to Abeta((25-35)) peptide prefibrils caused by noopept may attenuate the neurotoxic consequences of amyloid fibrillization and also be associated with an improvement in spatial memory in bulbectomized mice. These actions of noopept, combined with its previously reported neuroprotective and cholinomimetic properties, suggests that this dipeptide may well be useful for improving cognitive deficits induced by neurodegenerative diseases.

Pharmacological validation of in-silico guided novel nootropic potential of Achyranthes aspera L.

PubMed

Gawande, Dinesh Yugraj; Goel, Rajesh Kumar

2015-12-04

Achyranthes aspera (A. aspera) has been used as a brain tonic in folk medicine. Although, ethnic use of medicinal plant has been basis for drug discovery from medicinal plants, but the available in-silico tools can be useful to find novel pharmacological uses of medicinal plants beyond their ethnic use. To validate in-silico prediction for novel nootropic effect of A. aspera by employing battery of tests in mice. Phytoconstituents of A. aspera reported in Dictionary of Natural Product were subjected to in-silico prediction using PASS and Pharmaexpert. The nootropic activity predicted for A. aspera was assessed using radial arm maze, passive shock avoidance and novel object recognition tests in mice. After behavioral evaluation animals were decapitated and their brains were collected and stored for estimation of glutamate levels and acetylcholinesterase activity. In-silico activity spectrum for majority of A. aspera phytoconstituents exhibited excellent prediction score for nootropic activity of this plant. A. aspera extract treatment significantly improved the learning and memory as evident by decreased working memory errors, reference memory errors and latency time in radial arm maze, step through latency in passive shock avoidance and increased recognition index in novel object recognition were observed, moreover significantly enhanced glutamate levels and reduced acetylcholinesterase activity in hippocampus and cortex were observed as compared to the saline treated group. In-silico and in-vivo results suggest that A. aspera plant may improve the learning and memory by modulating the brain glutamatergic and cholinergic neurotransmission. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Noopept stimulates the expression of NGF and BDNF in rat hippocampus.

PubMed

Ostrovskaya, R U; Gudasheva, T A; Zaplina, A P; Vahitova, Ju V; Salimgareeva, M H; Jamidanov, R S; Seredenin, S B

2008-09-01

We studied the effect of original dipeptide preparation Noopept (N-phenylacetyl-L-prolylglycine ethyl ester, GVS-111) with nootropic and neuroprotective properties on the expression of mRNA for neurotropic factors NGF and BDNF in rat hippocampus. Expression of NGF and BDNF mRNA in the cerebral cortex and hippocampus was studied by Northern blot analysis. Taking into account the fact that pharmacological activity of Noopept is realized after both acute and chronic treatment, we studied the effect of single and long-term treatment (28 days) with this drug. Expression of the studied neurotropic factors in the cerebral cortex was below the control after single administration of Noopept, while chronic administration caused a slight increase in BDNF expression. In the hippocampus, expression of mRNA for both neurotrophins increased after acute administration of Noopept. Chronic treatment with Noopept was not followed by the development of tolerance, but even potentiated the neurotrophic effect. These changes probably play a role in neuronal restoration. We showed that the nootropic drug increases expression of neurotrophic factors in the hippocampus. Our results are consistent with the hypothesis that neurotrophin synthesis in the hippocampus determines cognitive function, particularly in consolidation and delayed memory retrieval. Published data show that neurotrophic factor deficiency in the hippocampus is observed not only in advanced Alzheimer's disease, but also at the stage of mild cognitive impairment (pre-disease state). In light of this our findings suggest that Noopept holds much promise to prevent the development of Alzheimer's disease in patients with mild cognitive impairment. Moreover, therapeutic effectiveness of Noopept should be evaluated at the initial stage of Alzheimer's disease.

Pharmaceutical cognitive doping in students: A chimeric way to get-a-head?

PubMed

Carton, Louise; Cabé, Nicolas; Ménard, Olivier; Deheul, Sylvie; Caous, Anne-Sylvie; Devos, David; Cottencin, Olivier; Bordet, Régis

2018-03-06

For students, the pressing demands for memorization, top-level performance, and peer competition create an environment favorable for pharmaceutical cognitive doping behavior. We aimed to describe recent practices and the benefit/risk ratio of such behavior and to discuss the issues at stake. The prevalence of pharmaceutical cognitive doping among students has been reported from 1.3% to 33% across studies, with variations depending on country and definition of pharmaceutical cognitive doping. The therapeutic classes most frequently cited as being diverted for doping purposes are psychostimulants and nootropics (methylphenidate, modafinil, piracetam), corticosteroids, sedative drugs and beta-blockers. Some illegal substances such as cannabis, amphetamines and cocaine are also consumed in order to boost mental function. Finally, over-the-counter products, such as caffeine-based tablets or energy drinks, or alcohol, are also widely used by students whose motivations involve enhanced performance, concentration, memory, and staying awake during the revision and exam period. However, the expected (often fantasized) effectiveness of these products does not correspond to the reality of a modest controversial impact on cognitive performance. There appears to be an emerging profile of the student more inclined to doping behavior. Cognitive doping thus raises the question of its regulation, opening a debate opposing, on one hand, individual freedom and supposed collective benefits and, on the other hand, health consequences, educational (in)equality, and the risk of tarnished academic success. Strengthening school and university medicine, through prevention campaigns and the identification of subjects at risk, is essential to limit the extent, risk, and damages associated with such practices. Copyright © 2018. Published by Elsevier Masson SAS.

[Comparative efficiency of nootropic drugs in complex treatment of patients with remote consequences of closed craniocereberal trauma].

PubMed

Hliebova, O S; Tkachenko, O V

2008-01-01

Main data of the research were data obtained after a complex treatment of 120 persons with late consequences of closed craniocereberal trauma (CCRCT). The treatment included administration of one of nootropic agents (noophen, aminolon or entropil), magnesium sulfate, group B vitamins. All patients have passed a complex examination: specially developed questionnaire, anamnesis gathering, neurologic status, neuropsychological status with the use of multiple-aspect scales and questionnaires, examination of fundus of eye, rheoencephalography, echoencephalography, brain MRT. Results of a complex examination proved positive effect of the use of nootropic agents, in particular noophen, entropil and aminolon in complex treatment of late consequences of closed craniocereberal trauma. For optimisation of the use of nootropic agents in the treatment of late consequences of closed craniocereberal trauma it is recommended to consider features of influence of nootropic agents on certain clinical aspects of the disease.

Phytochemical analysis, antioxidant, antistress, and nootropic activities of aqueous and methanolic seed extracts of ladies finger (Abelmoschus esculentus L.) in mice.

PubMed

Doreddula, Sathish Kumar; Bonam, Srinivasa Reddy; Gaddam, Durga Prasad; Desu, Brahma Srinivasa Rao; Ramarao, Nadendla; Pandy, Vijayapandi

2014-01-01

Abelmoschus esculentus L. (ladies finger, okra) is a well-known tropical vegetable, widely planted from Africa to Asia and from South Europe to America. In the present study, we investigated the in vitro antioxidant capacity and in vivo protective effect of the aqueous and methanolic seed extracts of Abelmoschus esculentus against scopolamine-induced cognitive impairment using passive avoidance task and acute restraining stress-induced behavioural and biochemical changes using elevated plus maze (EPM) and forced swimming test (FST) in mice. Our results demonstrated that the pretreatment of mice with aqueous and methanolic seed extracts of Abelmoschus esculentus (200 mg/kg, p.o.) for seven days significantly (P < 0.01) attenuated scopolamine-induced cognitive impairment in the passive avoidance test. In addition, these extracts significantly reduced the blood glucose, corticosterone, cholesterol, and triglyceride levels elevated by acute restraint stress and also significantly increased the time spent in open arm in EPM and decreased the immobility time in FST. It has also been revealed that these extracts showed a significant antioxidant activity and no signs of toxicity or death up to a dose of 2000 mg/kg, p.o. These results suggest that the seed extracts of Abelmoschus esculentus L. possess antioxidant, antistress, and nootropic activities which promisingly support the medicinal values of ladies finger as a vegetable.

Phytochemical Analysis, Antioxidant, Antistress, and Nootropic Activities of Aqueous and Methanolic Seed Extracts of Ladies Finger (Abelmoschus esculentus L.) in Mice

PubMed Central

Doreddula, Sathish Kumar; Bonam, Srinivasa Reddy; Gaddam, Durga Prasad; Desu, Brahma Srinivasa Rao; Ramarao, Nadendla; Pandy, Vijayapandi

2014-01-01

Abelmoschus esculentus L. (ladies finger, okra) is a well-known tropical vegetable, widely planted from Africa to Asia and from South Europe to America. In the present study, we investigated the in vitro antioxidant capacity and in vivo protective effect of the aqueous and methanolic seed extracts of Abelmoschus esculentus against scopolamine-induced cognitive impairment using passive avoidance task and acute restraining stress-induced behavioural and biochemical changes using elevated plus maze (EPM) and forced swimming test (FST) in mice. Our results demonstrated that the pretreatment of mice with aqueous and methanolic seed extracts of Abelmoschus esculentus (200 mg/kg, p.o.) for seven days significantly (P < 0.01) attenuated scopolamine-induced cognitive impairment in the passive avoidance test. In addition, these extracts significantly reduced the blood glucose, corticosterone, cholesterol, and triglyceride levels elevated by acute restraint stress and also significantly increased the time spent in open arm in EPM and decreased the immobility time in FST. It has also been revealed that these extracts showed a significant antioxidant activity and no signs of toxicity or death up to a dose of 2000 mg/kg, p.o. These results suggest that the seed extracts of Abelmoschus esculentus L. possess antioxidant, antistress, and nootropic activities which promisingly support the medicinal values of ladies finger as a vegetable. PMID:25401145

Cannabis-induced impairment of learning and memory: effect of different nootropic drugs.

PubMed

Abdel-Salam, Omar M E; Salem, Neveen A; El-Sayed El-Shamarka, Marwa; Al-Said Ahmed, Noha; Seid Hussein, Jihan; El-Khyat, Zakaria A

2013-01-01

Cannabis sativa preparations are the most commonly used illicit drugs worldwide. The present study aimed to investigate the effect of Cannabis sativa extract in the working memory version of the Morris water maze (MWM; Morris, 1984[43]) test and determine the effect of standard memory enhancing drugs. Cannabis sativa was given at doses of 5, 10 or 20 mg/kg (expressed as Δ(9)-tetrahydrocannabinol) alone or co-administered with donepezil (1 mg/kg), piracetam (150 mg/ kg), vinpocetine (1.5 mg/kg) or ginkgo biloba (25 mg/kg) once daily subcutaneously (s.c.) for one month. Mice were examined three times weekly for their ability to locate a submerged platform. Mice were euthanized 30 days after starting cannabis injection when biochemical assays were carried out. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, glucose and brain monoamines were determined. Cannabis resulted in a significant increase in the time taken to locate the platform and enhanced the memory impairment produced by scopolamine. This effect of cannabis decreased by memory enhancing drugs with piracetam resulting in the most-shorter latency compared with the cannabis. Biochemically, cannabis altered the oxidative status of the brain with decreased MDA, increased GSH, but decreased nitric oxide and glucose. In cannabis-treated rats, the level of GSH in brain was increased after vinpocetine and donepezil and was markedly elevated after Ginkgo biloba. Piracetam restored the decrease in glucose and nitric oxide by cannabis. Cannabis caused dose-dependent increases of brain serotonin, noradrenaline and dopamine. After cannabis treatment, noradrenaline is restored to its normal value by donepezil, vinpocetine or Ginkgo biloba, but increased by piracetam. The level of dopamine was significantly reduced by piracetam, vinpocetine or Ginkgo biloba. These data indicate that cannabis administration is associated with impaired memory performance which is likely to involve decreased brain glucose availability as well as alterations in brain monoamine neurotransmitter levels. Piracetam is more effective in ameliorating the cognitive impairments than other nootropics by alleviating the alterations in glucose, nitric oxide and dopamine in brain.

Cannabis-induced impairment of learning and memory: effect of different nootropic drugs

PubMed Central

Abdel-Salam, Omar M.E.; Salem, Neveen A.; El-Sayed El-Shamarka, Marwa; Al-Said Ahmed, Noha; Seid Hussein, Jihan; El-Khyat, Zakaria A.

2013-01-01

Cannabis sativa preparations are the most commonly used illicit drugs worldwide. The present study aimed to investigate the effect of Cannabis sativa extract in the working memory version of the Morris water maze (MWM; Morris, 1984[43]) test and determine the effect of standard memory enhancing drugs. Cannabis sativa was given at doses of 5, 10 or 20 mg/kg (expressed as Δ9-tetrahydrocannabinol) alone or co-administered with donepezil (1 mg/kg), piracetam (150 mg/ kg), vinpocetine (1.5 mg/kg) or ginkgo biloba (25 mg/kg) once daily subcutaneously (s.c.) for one month. Mice were examined three times weekly for their ability to locate a submerged platform. Mice were euthanized 30 days after starting cannabis injection when biochemical assays were carried out. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, glucose and brain monoamines were determined. Cannabis resulted in a significant increase in the time taken to locate the platform and enhanced the memory impairment produced by scopolamine. This effect of cannabis decreased by memory enhancing drugs with piracetam resulting in the most-shorter latency compared with the cannabis. Biochemically, cannabis altered the oxidative status of the brain with decreased MDA, increased GSH, but decreased nitric oxide and glucose. In cannabis-treated rats, the level of GSH in brain was increased after vinpocetine and donepezil and was markedly elevated after Ginkgo biloba. Piracetam restored the decrease in glucose and nitric oxide by cannabis. Cannabis caused dose-dependent increases of brain serotonin, noradrenaline and dopamine. After cannabis treatment, noradrenaline is restored to its normal value by donepezil, vinpocetine or Ginkgo biloba, but increased by piracetam. The level of dopamine was significantly reduced by piracetam, vinpocetine or Ginkgo biloba. These data indicate that cannabis administration is associated with impaired memory performance which is likely to involve decreased brain glucose availability as well as alterations in brain monoamine neurotransmitter levels. Piracetam is more effective in ameliorating the cognitive impairments than other nootropics by alleviating the alterations in glucose, nitric oxide and dopamine in brain. PMID:26417227

Clinical efficacy of aniracetam, either as monotherapy or combined with cholinesterase inhibitors, in patients with cognitive impairment: a comparative open study.

PubMed

Koliaki, Chrysi C; Messini, Chaido; Tsolaki, Magda

2012-04-01

Dementia constitutes an increasingly prevalent cognitive disorder with serious socioeconomic implications. In the present study, we aimed to evaluate the efficacy of aniracetam, either as monotherapy or combined with cholinesterase inhibitors (ChEIs), in terms of several neuropsychological parameters, in a considerable number of patients with dementia. In our prospective, open-label study, we enrolled a total of 276 patients (mean age 71 ± 8 years, 95 males) with cognitive disorders. Our study population comprised four groups: no treatment group (n = 75), aniracetam monotherapy group (n = 58), ChEIs monotherapy group (n = 68), and group of combined treatment (n = 68). Patients were examined with validated neuropsychological tests at baseline, 3, 6, and 12 months of treatment. In patients treated with aniracetam, all studied parameters were adequately maintained at 6 and 12 months, while emotional state was significantly improved at 3 months. In patients treated with ChEIs, we observed a significant cognitive deterioration at 12 months. The comparison between aniracetam and ChEIs in patients with relatively mild dementia (15 ≤ MMSE ≤ 25) revealed a significantly better cognitive performance with aniracetam at 6 months and improved functionality at 3 months. Comparing aniracetam monotherapy with combined treatment in the same population, aniracetam performed better in the cognitive scale at 6 months, and displayed a notable tendency for enhanced mood at 12 months and improved functionality at 6 months. Our findings indicate that aniracetam (a nootropic compound with glutamatergic activity and neuroprotective potential) is a promising option for patients with cognitive deficit of mild severity. It preserved all neuropsychological parameters for at least 12 months, and seemed to exert a favorable effect on emotional stability of demented patients. © 2011 Blackwell Publishing Ltd.

Pharmaco-electroencephalographic and clinical effects of the cholinergic substance--acetyl-L-carnitine--in patients with organic brain syndrome.

PubMed

Herrmann, W M; Dietrich, B; Hiersemenzel, R

1990-01-01

In two double-blind, placebo-controlled clinical studies of the nootropic compound acetyl-L-carnitine on the electroencephalogram (EEG) and impaired brain functions of elderly outpatients with mild to moderate cognitive decline of the organic brain syndrome, statistically significant effects could be detected after eight weeks (on the EEG), and after 12 weeks of treatment (on the physician's clinical global impression and the patient-rated level of activities of daily living). Side-effects of acetyl-L-carnitine were generally minor and overall rare. Longer treatment periods and further specifications with regard to the aetiopathology and degree of cognitive impairment are recommended for further clinical studies of this promising compound.

Aniracetam. An overview of its pharmacodynamic and pharmacokinetic properties, and a review of its therapeutic potential in senile cognitive disorders.

PubMed

Lee, C R; Benfield, P

1994-03-01

Aniracetam is a member of the nootropic class of drugs, which have possible cognition enhancing effects. It appears to positively modulate metabotropic glutamate receptors and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-sensitive glutamate receptors, and may facilitate cholinergic transmission, effects which are possibly related to its mechanism of action. Results from trials in elderly patients with mild to moderate cognitive impairment due to senile dementia of the Alzheimer type suggest that aniracetam may be of benefit, with further trials required to confirm its efficacy profile and to define more precisely those patients most likely to respond to treatment. Aniracetam 1500 mg/day was significantly more effective than placebo in all tests at 4 and 6 months, and in a further 6-month trial was more effective than piracetam 2400 mg/day in 8 of 18 tests. Preliminary evidence in the treatment of patients with cognitive impairment of cerebrovascular origin suggests aniracetam may also be of benefit in this condition. Whilst incidence rates of adverse effects are not yet available, data from trials suggest aniracetam is well tolerated. In particular, aniracetam does not appear to cause increases in liver enzyme levels. The evaluation of drugs for patients with senile cognitive disorders is a difficult area and therapeutic options are currently limited. Preliminary evidence of the potential benefits and good tolerability profile of aniracetam support continued evaluation of its use in patients with mild to moderate senile dementia of the Alzheimer type.

The Effects of Anti-Dementia and Nootropic Treatments on the Mortality of Patients with Dementia: A Population-Based Cohort Study in Taiwan.

PubMed

Wu, Chen-Yi; Hu, Hsiao-Yun; Chow, Lok-Hi; Chou, Yiing-Jenq; Huang, Nicole; Wang, Pei-Ning; Li, Chung-Pin

2015-01-01

Few studies have examined the contribution of treatment on the mortality of dementia based on a population-based study. To investigate the effects of anti-dementia and nootropic treatments on the mortality of dementia using a population-based cohort study. 12,193 incident dementia patients were found from 2000 to 2010. Their data were compared with 12,193 age- and sex-matched non-dementia controls that were randomly selected from the same database. Dementia was classified into vascular (VaD) and degenerative dementia. Mortality incidence and hazard ratios (HRs) were calculated. The median survival time was 3.39 years (95% confidence interval [CI]: 2.88-3.79) for VaD without medication, 6.62 years (95% CI: 6.24-7.21) for VaD with nootropics, 3.01 years (95% CI: 2.85-3.21) for degenerative dementia without medication, 8.11 years (95% CI: 6.30-8.55) for degenerative dementia with anti-dementia medication, 6.00 years (95% CI: 5.73-6.17) for degenerative dementia with nootropics, and 9.03 years (95% CI: 8.02-9.87) for degenerative dementia with both anti-dementia and nootropic medications. Compared to the non-dementia group, the HRs among individuals with degenerative dementia were 2.69 (95% CI: 2.55-2.83) without medication, 1.46 (95% CI: 1.39-1.54) with nootropics, 1.05 (95% CI: 0.82-1.34) with anti-dementia medication, and 0.92 (95% CI: 0.80-1.05) with both nootropic and anti-dementia medications. VaD with nootropics had a lower mortality (HR: 1.25, 95% CI: 1.15-1.37) than VaD without medication (HR: 2.46, 95% CI: 2.22-2.72). Pharmacological treatments have beneficial effects for patients with dementia in prolonging their survival.

The Effects of Anti-Dementia and Nootropic Treatments on the Mortality of Patients with Dementia: A Population-Based Cohort Study in Taiwan

PubMed Central

Wu, Chen-Yi; Hu, Hsiao-Yun; Chow, Lok-Hi; Chou, Yiing-Jenq; Huang, Nicole; Wang, Pei-Ning; Li, Chung-Pin

2015-01-01

Background Few studies have examined the contribution of treatment on the mortality of dementia based on a population-based study. Objective To investigate the effects of anti-dementia and nootropic treatments on the mortality of dementia using a population-based cohort study. Methods 12,193 incident dementia patients were found from 2000 to 2010. Their data were compared with 12,193 age- and sex-matched non-dementia controls that were randomly selected from the same database. Dementia was classified into vascular (VaD) and degenerative dementia. Mortality incidence and hazard ratios (HRs) were calculated. Results The median survival time was 3.39 years (95% confidence interval [CI]: 2.88–3.79) for VaD without medication, 6.62 years (95% CI: 6.24–7.21) for VaD with nootropics, 3.01 years (95% CI: 2.85–3.21) for degenerative dementia without medication, 8.11 years (95% CI: 6.30–8.55) for degenerative dementia with anti-dementia medication, 6.00 years (95% CI: 5.73–6.17) for degenerative dementia with nootropics, and 9.03 years (95% CI: 8.02–9.87) for degenerative dementia with both anti-dementia and nootropic medications. Compared to the non-dementia group, the HRs among individuals with degenerative dementia were 2.69 (95% CI: 2.55–2.83) without medication, 1.46 (95% CI: 1.39–1.54) with nootropics, 1.05 (95% CI: 0.82–1.34) with anti-dementia medication, and 0.92 (95% CI: 0.80–1.05) with both nootropic and anti-dementia medications. VaD with nootropics had a lower mortality (HR: 1.25, 95% CI: 1.15–1.37) than VaD without medication (HR: 2.46, 95% CI: 2.22–2.72). Conclusion Pharmacological treatments have beneficial effects for patients with dementia in prolonging their survival. PMID:26098910

"Asparagus Racemosus" Enhances Memory and Protects against Amnesia in Rodent Models

ERIC Educational Resources Information Center

Ojha, Rakesh; Sahu, Alakh N.; Muruganandam, A. V.; Singh, Gireesh Kumar; Krishnamurthy, Sairam

2010-01-01

"Asparagus Racemosus" (AR) is an Ayurvedic rasayana possessing multiple neuropharmacological activities. The adpatogenic and antidepressant activity of AR is well documented. The present study was undertaken to assess nootropic and anti-amnesic activities of MAR in rats. The Morris water maze (MWM) and elevated plus maze (EPM) models were employed…

Delayed nootropic effects of arginine vasopressin after early postnatal chronic administration to albino rat pups.

PubMed

Kim, P A; Voskresenskaya, O G; Kamensky, A A

2009-06-01

Intranasal administration of arginine vasopressin (10 microg/kg) to albino rat pups had a strong nootropic effect during training with positive and negative reinforcement. This effect was different in animals of various age groups: training with positive reinforcement was improved in "adolescent" rats and pubertal animals, while during training with negative reinforcement, the nootropic effect of the peptide was more prolonged and persisted also in adult animals.

[Pharmaceutical cognitive doping in students: a chimeric way to get-a-head?

PubMed

Carton, Louise; Cabé, Nicolas; Ménard, Olivier; Deheul, Sylvie; Caous, Anne-Sylvie; Devos, David; Cottencin, Olivier; Bordet, Régis

2017-11-22

For students, the pressing demands for memorization, top-level performance, and peer competition create an environment favorable for pharmaceutical cognitive doping behavior. We aimed to describe recent practices and the benefit / risk ratio of such behavior and to discuss the issues at stake. The prevalence of pharmaceutical cognitive doping among students has been reported from 1.3% to 33% across studies, with variations depending on country and definition of pharmaceutical cognitive doping. The therapeutic classes most frequently cited as being diverted for doping purposes are psychostimulants and nootropics (methylphenidate, modafinil, piracetam), corticosteroids, sedative drugs and beta-blockers. Some illegal substances such as cannabis, amphetamines and cocaine are also consumed in order to boost mental function. Finally, over-the-counter products, such as caffeine-based tablets or energy drinks, or alcohol, are also widely used by students whose motivations involve enhanced performance, concentration, memory, and staying awake during the revision and exam period. However, the expected (often fantasized) effectiveness of these products does not correspond to the reality of a modest controversial impact on cognitive performance. There appears to be an emerging profile of the student more inclined to doping behavior. Cognitive doping thus raises the question of its regulation, opening a debate opposing, on one hand, individual freedom and supposed collective benefits and, on the other hand, health consequences, educational (in)equality, and the risk of tarnished academic success. Strengthening school and university medicine, through prevention campaigns and the identification of subjects at risk, is essential to limit the extent, risk, and damages associated with such practices. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

The major metabolite of dipeptide piracetam analogue GVS-111 in rat brain and its similarity to endogenous neuropeptide cyclo-L-prolylglycine.

PubMed

Gudasheva, T A; Boyko, S S; Ostrovskaya, R U; Voronina, T A; Akparov, V K; Trofimov, S S; Rozantsev, G G; Skoldinov, A P; Zherdev, V P; Seredenin, S B

1997-01-01

The metabolism of a new piracetam analogue, the dipeptide cognitive enhancer N-phenylacetyl-L-prolylglycine ethyl ester (GVS-111) was studied in vivo. GVS-111 itself was not found in rat brain 1 h after 5 mg/kg i.p. administration up to limit of detection (LOD) under high performance liquid chromatography (HPLC) conditions. Three substances corresponding to the three possible GVS-111 metabolites, namely phenylacetic acid, prolylglycine and cyclo-prolylglycine, were found in experimental rat brain samples as well as in controls using HPLC, gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) methods. Only cyclo-prolylglycine concentration increased (2.5-fold) 1 h after GVS-111 administration. Cyclo-prolylglycine formation from GVS-111 in the presence of plasma and brain enzymes was shown in vitro. These data could be considered as evidence that GVS-111 is prodrug which converts in the body to cyclo-prolylglycine, and which is identical to the endogenous cyclopeptide that produces the nootropic activity.

Nootropic activity of Celastrus paniculatus seed.

PubMed

Bhanumathy, M; Harish, M S; Shivaprasad, H N; Sushma, G

2010-03-01

The effect of Celastrus paniculatus Willd. (Celastraceae) seed aqueous extract on learning and memory was studied using elevated plus maze and passive avoidance test (sodium nitrite induced amnesia rodent model). The aqueous seed extract was administered orally in two different doses to rats (350 and 1050 mg/kg) and to mice (500 and 1500 mg/kg). The results were compared to piracetam (100 mg/kg, p.o.) used as a standard drug. Chemical hypoxia was induced by subcutaneous administration of sodium nitrite (35 mg/kg), immediately after acquisition training. In elevated plus maze and sodium nitrite-induced amnesia model, Celastrus paniculatus extract has showed statistically significant improvement in memory process when compared to control. The estimation of acetylcholinesterase enzyme in rat brain supports the plus maze and passive avoidance test by reducing acetylcholinesterase activity which helps in memory performance. The study reveals that the aqueous extract of Celastrus paniculatus seed has dose-dependent cholinergic activity, thereby improving memory performance. The mechanism by which Celastrus paniculatus enhances cognition may be due to increased acetylcholine level in rat brain.

Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport

PubMed Central

Naftalin, Richard J; Cunningham, Philip; Afzal-Ahmed, Iram

2004-01-01

Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide galanin in human erythrocytes in vitro. The potencies of nootropic drugs in opposing scopolamine-induced memory loss correlate with their potencies in antagonising pentobarbital inhibition of erythrocyte glucose transport in vitro (P<0.01). Less potent nootropics, D-levetiracetam and D-pyroglutamate, have higher antagonist Ki's against pentobarbital inhibition of glucose transport than more potent L-stereoisomers (P<0.001). Piracetam and TRH have no direct effects on net glucose transport, but competitively antagonise hypnotic drug inhibition of glucose transport. Other nootropics, like aniracetam and levetiracetam, while antagonising pentobarbital action, also inhibit glucose transport. Analeptics like bemigride and methamphetamine are more potent inhibitors of glucose transport than antagonists of hypnotic action on glucose transport. There are similarities between amino-acid sequences in human glucose transport protein isoform 1 (GLUT1) and the benzodiazepine-binding domains of GABAA (gamma amino butyric acid) receptor subunits. Mapped on a 3D template of GLUT1, these homologies suggest that the site of diazepam and piracetam interaction is a pocket outside the central hydrophilic pore region. Nootropic pyrrolidone antagonism of hypnotic drug inhibition of glucose transport in vitro may be an analogue of TRH antagonism of galanin-induced narcosis. PMID:15148255

Nootropic activity of tuber extract of Pueraria tuberosa (Roxb).

PubMed

Rao, N Venkata; Pujar, Basavaraj; Nimbal, S K; Shantakumar, S M; Satyanarayana, S

2008-08-01

Nootropic effect of alcoholic (ALE; 50, 75, 100 mg/kg) and aqueous (AQE; 100, 200, 400 mg/kg) extracts of P. tuberosa was evaluated by using Elevated Plus Maze (EPM), scopolamine-induced amnesia (SIA), diazepam-induced amnesia (DIA), clonidine-induced (NA-mediated) hypothermia (CIH), lithium-induced (5-HT mediated) head twitches (LIH) and haloperidol-induced (DA- mediated) catalepsy (HIC) models. Piracetam was used as the standard drug. A significant increase in inflexion ratio (IR) was recorded in EPM, SIA and DIA models. A significant reversal effect was observed on rectal temperature in CIH model, reduction of head twitches in LIH models. However no significant reduction in catalepsy scores in HIC models were observed with test extracts and standard piracetam. The results indicate that nootropic activity observed with ALE and AQE of tuber extracts of P. tuberosa could be through improved learning and memory either by augmenting the noradrenaline (NA) transmission or by interfering with 5-hydroxytryptamine (5-HT) release. Further, the extracts neither facilitated nor blocked release of the dopamine (DA). Thus ALE and AQE elicited significant nootropic effect in mice and rats by interacting with cholinergic, GABAnergic, adrenergic and serotonergic systems. Phytoconstituents like flavonoids have been reported for their nootropic effect and these are present in both ALE and AQE extracts of tubers of P. tuberosa (Roxb) and these active principles may be responsible for nootropic activity.

Moringa oleifera mitigates memory impairment and neurodegeneration in animal model of age-related dementia.

PubMed

Sutalangka, Chatchada; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-mee, Wipawee

2013-01-01

To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180-220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s) are still required.

Effect of piracetam on the cognitive performance of patients undergoing coronary bypass surgery: A meta-analysis

PubMed Central

FANG, YU; QIU, ZHANDONG; HU, WENTAO; YANG, JIA; YI, XIYAN; HUANG, LIANGJIANG; ZHANG, SUMING

2014-01-01

Cognitive impairments are observed in numerous patients following coronary bypass surgery, and piracetam are nootropic compounds that modulate cerebral functions by directly enhancing cognitive processes. The present meta-analysis was conducted to evaluate the protective effect of piracetam on the cognitive performance of patients undergoing coronary bypass surgery. The relevant studies were identified by searching Medline, EMBASE, PubMed and the Cochrane Library up to June 2013 and the pertinent bibliographies from the retrieved studies were reviewed. Data were selected from the studies according to predefined criteria. The meta-analysis included two randomized control trials involving 184 patients and including the Syndrom-Kurz test (SKT). Findings of the meta-analysis showed that following treatment the change from baseline observed in five SKT subtest scores, conducted with piracetam patients, indicated a significant advantage over those patients that were in the placebo group. The subtests included immediate pictured object recall, weighted mean difference (WMD)=0.91, 95% confidence interval (CI) 0.51–1.31, P<0.00001; delayed pictured object recall, WMD=0.74, 95% CI 0.19–1.28, P=0.008; delayed picture recognition, WMD=0.82, 95% CI 0.31–1.31, P=0.001; immediate word recall, WMD=0.87, 95% CI 0.47–1.28, P<0.0001; and letter interference, WMD=3.46, 95% CI −5.69 to −1.23, P=0.002. These results indicated that piracetam may have been effective in improving the short-term cognitive performance of patients undergoing coronary bypass surgery. High quality, well-controlled and longer randomized trials are required to corroborate this result. PMID:24396419

Methyl jasmonate mediates upregulation of bacoside A production in shoot cultures of Bacopa monnieri.

PubMed

Sharma, Poojadevi; Yadav, Sheetal; Srivastava, Anshu; Shrivastava, Neeta

2013-07-01

Methyl jasmonate (MJ) enhances the production of a range of secondary metabolites including triterpenoid saponins in a variety of plant species. Here, it enhanced production of bacoside A, a valuable triterpenoid saponin having nootropic therapeutic activity in in vitro shoot cultures of Bacopa monnieri, the only known source of bacoside A. The highest yield was with 50 μM MJ giving 4.4 mg bacoside A/g dry wt; an 1.8-fold increase (compared to control) after 1 week.

[Nootropic and analgesic effects of Semax following different routes of administration].

PubMed

Manchenko, D M; Glazova, N Iu; Levitskaia, N G; Andreeva, L A; Kamenskiĭ, A A; Miasoedov, N F

2010-10-01

Heptapeptide Semax (MEHFPGP) is the fragment of ACTH(4-10) analogue with prolonged neurotropic activity. The aim of the present work was to study the Semax effects on learning capability and pain sensitivity in white rats following intraperitoneal and intranasal administration in different doses. Semax nootropic effects were studied in the test of acquisition of passive avoidance task. Pain sensitivity was estimated in Randall-Selitto paw-withdrawal test. It was shown that Semax exerts nootropic and analgesic activities following intraperitoneal administration. Analysis of dependence of these effects on dose resulted in different dose-response curves. Following intranasal administration, Semax was more potent in learning improvement compared to intraperitoneal administration. The peptide failed to affect the animal pain sensitivity following intranasal administration as opposed to intraperitoneal administration. The data obtained suggest different mechanisms and brain structures involved in realization of the nootropic and analgesic effects of Semax.

Design, synthesis, and preliminary pharmacological evaluation of 1, 4-diazabicyclo[4.3.0]nonan-9-ones as a new class of highly potent nootropic agents.

PubMed

Manetti, D; Ghelardini, C; Bartolini, A; Bellucci, C; Dei, S; Galeotti, N; Gualtieri, F; Romanelli, M N; Scapecchi, S; Teodori, E

2000-05-18

Several 4-substituted 1,4-diazabicyclo[4.3.0]nonan-9-ones have been synthesized and tested in vivo on mouse passive avoidance test, to evaluate their nootropic activity. The results show that they represent a new class of nootropic drugs with a pharmacological profile very similar to that of piracetam, showing much higher potency with respect to the reference. Among the compounds studied, 7 (DM 232) shows outstanding potency, being active at the dose of 0. 001 mg kg(-1) sc.

Moringa oleifera Mitigates Memory Impairment and Neurodegeneration in Animal Model of Age-Related Dementia

PubMed Central

Sutalangka, Chatchada; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-mee, Wipawee

2013-01-01

To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180–220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s) are still required. PMID:24454988

Neurological Effects of Honey: Current and Future Prospects

PubMed Central

Mijanur Rahman, Mohammad; Gan, Siew Hua; Khalil, Md. Ibrahim

2014-01-01

Honey is the only insect-derived natural product with therapeutic, traditional, spiritual, nutritional, cosmetic, and industrial value. In addition to having excellent nutritional value, honey is a good source of physiologically active natural compounds, such as polyphenols. Unfortunately, there are very few current research projects investigating the nootropic and neuropharmacological effects of honey, and these are still in their early stages. Raw honey possesses nootropic effects, such as memory-enhancing effects, as well as neuropharmacological activities, such as anxiolytic, antinociceptive, anticonvulsant, and antidepressant activities. Research suggests that the polyphenol constituents of honey can quench biological reactive oxygen species and counter oxidative stress while restoring the cellular antioxidant defense system. Honey polyphenols are also directly involved in apoptotic activities while attenuating microglia-induced neuroinflammation. Honey polyphenols are useful in improving memory deficits and can act at the molecular level. Therefore, the ultimate biochemical impact of honey on specific neurodegenerative diseases, apoptosis, necrosis, neuroinflammation, synaptic plasticity, and behavior-modulating neural circuitry should be evaluated with appropriate mechanistic approaches using biochemical and molecular tools. PMID:24876885

Neuroprotective effect of novel cognitive enhancer noopept on AD-related cellular model involves the attenuation of apoptosis and tau hyperphosphorylation.

PubMed

Ostrovskaya, Rita U; Vakhitova, Yulia V; Kuzmina, Uliyana Sh; Salimgareeva, Milyausha Kh; Zainullina, Liana F; Gudasheva, Tatiana A; Vakhitov, Vener A; Seredenin, Sergey B

2014-08-06

Noopept (N-phenyl-acetyl-L-prolylglycine ethyl ester) was constructed as a dipeptide analog of the standard cognition enhancer, piracetam. Our previous experiments have demonstrated the cognition restoring effect of noopept in several animal models of Alzheimer disease (AD). Noopept was also shown to prevent ionic disbalance, excitotoxicity, free radicals and pro-inflammatory cytokines accumulation, and neurotrophine deficit typical for different kinds of brain damages, including AD. In this study, we investigated the neuroprotective action of noopept on cellular model of AD, Aβ 25-35-induced toxicity in PC12 cells and revealed the underlying mechanisms. The neuroprotective effect of noopept (added to the medium at 10 μM concentration, 72 hours before Аβ 25-35) was studied on Аβ 25-35-induced injury (5 μM for 24 h) in PC12 cells. The ability of drug to protect the impairments of cell viability, calcium homeostasis, ROS level, mitochondrial function, tau phosphorylation and neurite outgrowth caused by Аβ 25-35 were evaluated. Following the exposure of PC12 cells to Аβ 25-35 an increase of the level of ROS, intracellular calcium, and tau phosphorylation at Ser396 were observed; these changes were accompanied by a decrease in cell viability and an increase of apoptosis. Noopept treatment before the amyloid-beta exposure improved PC12 cells viability, reduced the number of early and late apoptotic cells, the levels of intracellular reactive oxygen species and calcium and enhanced the mitochondrial membrane potential. In addition, pretreatment of PC12 cell with noopept significantly attenuated tau hyperphosphorylation at Ser396 and ameliorated the alterations of neurite outgrowth evoked by Аβ25-35. Taken together, these data provide evidence that novel cognitive enhancer noopept protects PC12 cell against deleterious actions of Aβ through inhibiting the oxidative damage and calcium overload as well as suppressing the mitochondrial apoptotic pathway. Moreover, neuroprotective properties of noopept likely include its ability to decrease tau phosphorylation and to restore the altered morphology of PC12 cells. Therefore, this nootropic dipeptide is able to positively affect not only common pathogenic pathways but also disease-specific mechanisms underlying Aβ-related pathology.

Neuroprotective effect of novel cognitive enhancer noopept on AD-related cellular model involves the attenuation of apoptosis and tau hyperphosphorylation

PubMed Central

2014-01-01

Background Noopept (N-phenyl-acetyl-L-prolylglycine ethyl ester) was constructed as a dipeptide analog of the standard cognition enhancer, piracetam. Our previous experiments have demonstrated the cognition restoring effect of noopept in several animal models of Alzheimer disease (AD). Noopept was also shown to prevent ionic disbalance, excitotoxicity, free radicals and pro-inflammatory cytokines accumulation, and neurotrophine deficit typical for different kinds of brain damages, including AD. In this study, we investigated the neuroprotective action of noopept on cellular model of AD, Aβ25–35-induced toxicity in PC12 cells and revealed the underlying mechanisms. Results The neuroprotective effect of noopept (added to the medium at 10 μM concentration, 72 hours before Аβ25–35) was studied on Аβ25–35-induced injury (5 μM for 24 h) in PC12 cells. The ability of drug to protect the impairments of cell viability, calcium homeostasis, ROS level, mitochondrial function, tau phosphorylation and neurite outgrowth caused by Аβ25–35 were evaluated. Following the exposure of PC12 cells to Аβ25–35 an increase of the level of ROS, intracellular calcium, and tau phosphorylation at Ser396 were observed; these changes were accompanied by a decrease in cell viability and an increase of apoptosis. Noopept treatment before the amyloid-beta exposure improved PC12 cells viability, reduced the number of early and late apoptotic cells, the levels of intracellular reactive oxygen species and calcium and enhanced the mitochondrial membrane potential. In addition, pretreatment of PC12 cell with noopept significantly attenuated tau hyperphosphorylation at Ser396 and ameliorated the alterations of neurite outgrowth evoked by Аβ25–35. Conclusions Taken together, these data provide evidence that novel cognitive enhancer noopept protects PC12 cell against deleterious actions of Aβ through inhibiting the oxidative damage and calcium overload as well as suppressing the mitochondrial apoptotic pathway. Moreover, neuroprotective properties of noopept likely include its ability to decrease tau phosphorylation and to restore the altered morphology of PC12 cells. Therefore, this nootropic dipeptide is able to positively affect not only common pathogenic pathways but also disease-specific mechanisms underlying Aβ-related pathology. PMID:25096780

Dipeptide preparation Noopept prevents scopolamine-induced deficit of spatial memory in BALB/c mice.

PubMed

Belnik, A P; Ostrovskaya, R U; Poletaeva, I I

2007-04-01

The effect of original nootropic preparation Noopept on learning and long-term memory was studied with BALB/c mice. Scopolamine (1 mg/kg) impaired long-term memory trace, while Noopept (0.5 mg/kg) had no significant effect. Noopept completely prevented the development of cognitive disorders induced by scopolamine (blockade of muscarinic cholinergic receptors). Our results confirmed the presence of choline-positive effect in dipeptide piracetam analogue Noopept on retrieval of learned skill of finding a submerged platform (spatial memory). We conclude that the effectiveness of this drug should be evaluated in patients with Alzheimer's disease.

The Nootropic Concept and Dyslexia.

ERIC Educational Resources Information Center

Wilsher, Colin R.

1986-01-01

Studies with Nootropic psychoactive drugs (such as Piracetam) suggest that Piracetam lacks significant side effects; promotes memory and learning; and improves the reading ability of dyslexics, possibly by directly affecting the left-brain hemisphere. Results are contrasted with studies showing the lack of effectiveness of intensive teaching.…

Synthesis and nootropic activity of some 2,3-dihydro-1H-isoindol-1-one derivatives structurally related with piracetam.

PubMed

Reyes, Adelfo; Huerta, Leticia; Alfaro, Marisol; Navarrete, Andrés

2010-11-01

Three 2,3-dihydro-1H-isoindol-1-ones structurally related with piracetam (=2-oxopyrrolidine-1-acetamide) have been synthesized and tested for their nootropic effects in the passive avoidance test in mice. Compounds (RS)-2, (R,R)-3, and (R,S)-3 were obtained in good yields in only two steps starting from methyl DL-phthaloylalanine. Compound (RS)-2 exhibited nootropic activity at lower doses than piracetam, used as reference drug, but it showed lower efficacy. Whereas diastereoisomers (R,R)-3 and (R,S)-3 were as potent as piracetam to revert amnesia induced by scopolamine, (R,S)-3 showed lower efficacy than (R,R)-3. Only (R,R)-3 showed myorelaxant effect at doses of 10 and 30 mg/kg; other compounds did not exhibit any anticonvulsant, sedative, myorelaxant, or impaired motor-coordination effect in mice. These synthesized 2,3-dihydro-1H-isoindol-1-one derivatives constitute a new kind of nootropic compounds.

Bacopa monnieri (L.) exerts anti-inflammatory effects on cells of the innate immune system in vitro.

PubMed

Williams, Roderick; Münch, Gerald; Gyengesi, Erika; Bennett, Louise

2014-03-01

Bacopa monnieri (L., BM) is a traditional Ayurvedic medicinal herb recognised for its efficacy in relieving acute pain and inflammation, as related to selective inhibition of cyclo-oxygenase-2 (COX-2) enzyme and consequent reduction in COX-2-mediated prostanoid mediators. BM is also associated with cognitive enhancing (nootropic) activity including improving memory free recall, observed after prolonged intake (>3 months). It is likely that the time frame required to exert an effect in the brain reflects regulation by BM of chronic inflammation and oxidative stress associated with aging and chronic diseases, and other polypharmacological effects. We report down-regulation by BM of NO and TNF-α in stimulated RAW 246.7 macrophages and of IFN-γ in stimulated human blood cells. Furthermore, in human blood cells, IL-10 was slightly elevated indicating polarisation towards a regulatory T cell phenotype. These results provide further supportive evidence to justify the clinical evaluation of BM for managing diseases involving chronic systemic and brain inflammation driven by the innate immune system.

Nootropic activity of extracts from wild and cultivated Alfredia cernua.

PubMed

Mustafin, R N; Shilova, I V; Suslov, N I; Kuvacheva, N V; Amelchenko, V P

2011-01-01

Antihypoxic and nootropic activities of extracts from aerial parts of wild and cultivated Alfredia cernua (L.) Cass. were studied on the models of pressure chamber hypoxia, open field test, and passive avoidance conditioning. The extracts of Alfredia cernua promoted retention of the orientation reflex and passive avoidance conditioned response and normalized orientation and exploratory activities disordered as a result of hypoxic injury. The efficiency of the extracts was superior to that of piracetam by the effect on retention of passive avoidance response throughout the greater part of the experiment. Nootropic activity of cultivated Alfredia cernua was not inferior to that of the wild plant.

[The effect of the new nootropic dipeptide GVS-111 in different functional disorders of the escape reaction].

PubMed

Inozemtsev, A N; Trofimov, S S; Borlikova, G G; Firova, F A; Pragina, L L; Gudasheva, T A; Ostrovskaia, R U; Tushmalova, N A; Voronina, T A

1998-01-01

The authors studied the effect of a new nootropic agent with anxiolytic properties GVS-111 (ethyl ether N-phenylacetyl-L-prolylglycine) on formation of the avoidance reaction (AR) in rats and its functional disorders which were induced by two methods. In one case the stereotype of the relations between the stimulus, reaction and its consequence which developed during the experiment were urgently disturbed: the change of the animal to the other half of the chamber in response to a conditioned stimulus did not lead to its cutting off and prevention of the electropain stimulation for three successive combinations (AR error). In another case the spatial stereotype of the experiment was altered by changing the place of the opening through which the animal avoided the stimulus (spatial remodeling). Intraperitoneal injection of GVS-111 (0.1 mg/kg/day) improved the learning, but the effect differed from experiment to experiment. Along with this, the dipeptide prevented AR disturbance during the error and quickened restoration of the habit in spatial remodeling. It was shown earlier that AR disorders during an error are prevented by anxiolytics and nootropic agents but during spatial remodeling only by nootropic agents. It may be assumed that the positive effect of GSV-111 on AR in functional disorders is due to its nootropic effect.

Traditional Chinese Nootropic Medicine Radix Polygalae and Its Active Constituent Onjisaponin B Reduce β-Amyloid Production and Improve Cognitive Impairments

PubMed Central

Li, Xiaohang; Cui, Jin; Yu, Yang; Li, Wei; Hou, Yujun; Wang, Xin; Qin, Dapeng; Zhao, Cun; Yao, Xinsheng; Zhao, Jian; Pei, Gang

2016-01-01

Decline of cognitive function is the hallmark of Alzheimer’s disease (AD), regardless of the pathological mechanism. Traditional Chinese medicine has been used to combat cognitive impairments and has been shown to improve learning and memory. Radix Polygalae (RAPO) is a typical and widely used herbal medicine. In this study, we aimed to follow the β-amyloid (Aβ) reduction activity to identify active constituent(s) of RAPO. We found that Onjisaponin B of RAPO functioned as RAPO to suppress Aβ production without direct inhibition of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and γ-secretase activities. Our mechanistic study showed that Onjisaponin B promoted the degradation of amyloid precursor protein (APP). Further, oral administration of Onjisaponin B ameliorated Aβ pathology and behavioral defects in APP/PS1 mice. Taken together, our results indicate that Onjisaponin B is effective against AD, providing a new therapeutic agent for further drug discovery. PMID:26954017

Traditional Chinese Nootropic Medicine Radix Polygalae and Its Active Constituent Onjisaponin B Reduce β-Amyloid Production and Improve Cognitive Impairments.

PubMed

Li, Xiaohang; Cui, Jin; Yu, Yang; Li, Wei; Hou, Yujun; Wang, Xin; Qin, Dapeng; Zhao, Cun; Yao, Xinsheng; Zhao, Jian; Pei, Gang

2016-01-01

Decline of cognitive function is the hallmark of Alzheimer's disease (AD), regardless of the pathological mechanism. Traditional Chinese medicine has been used to combat cognitive impairments and has been shown to improve learning and memory. Radix Polygalae (RAPO) is a typical and widely used herbal medicine. In this study, we aimed to follow the β-amyloid (Aβ) reduction activity to identify active constituent(s) of RAPO. We found that Onjisaponin B of RAPO functioned as RAPO to suppress Aβ production without direct inhibition of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and γ-secretase activities. Our mechanistic study showed that Onjisaponin B promoted the degradation of amyloid precursor protein (APP). Further, oral administration of Onjisaponin B ameliorated Aβ pathology and behavioral defects in APP/PS1 mice. Taken together, our results indicate that Onjisaponin B is effective against AD, providing a new therapeutic agent for further drug discovery.

Antidepressant, psychostimulant, and nootropic effects of major and trace element composition.

PubMed

Afanasieva, O G; Suslov, N I; Shilova, I V

2013-06-01

The antidepressant, psychostimulant, and nootropic effects of a composition of major and trace elements including KCl, RbNO3, magnesium sulfate, and zinc sulfate were studied on the models of behavioural despair (Porsolt test) and conditioned passive avoidance test. The preparation was found to shorten the immobilization time in the Porsolt test and promote retention of the conditioned passive avoidance. The most pronounced psychostimulant effect of the substance was observed at a dose of 4.68 mg/kg and the most pronounced antidepressant effect was found at a dose of 18.72 mg/kg. Maximum nootropic activity of the preparation was found at a dose of 93.6 mg/kg.

Nootropic Effects of Filipendula Vulgaris Moench Water Extract Fractions.

PubMed

Shilova, I V; Suslov, N I; Amelchenko, V P

2015-07-01

Nootropic activity of water extract fractions from aerial parts of Filipendula vulgaris Moench was demonstrated on the models of hermetic volume hypoxia, conditioned passive avoidance response, open field test, and forced swimming with a load. The fractions stimulated hypoxic resistance, normalized orientation and exploratory behavior, improved conditioned response reproduction during testing after hypoxic injury, and increased exercise tolerance. Fractionation of the extract led to dissociation of the effect components, which suggests that individual constituents have specific characteristics. Ethylacetate fraction exhibited most pronounced nootropic activity and was superior to plant extract by some characteristics. The detected effects seemed to be caused by modulation of the hippocampus activity the under the effects of phenol and triterpene compounds.

Swedish Defence Research Abstracts 82/83-2 (Froe Foersvars Forsknings Referat 82/83-2).

DTIC Science & Technology

1983-08-01

alarm (78) Carbon dioxide retention inside motorcycle helmets (79) Vibration and decompression gas bubbles (80) No effects of nootropic drugs on memory... nootropic drugs on memory and psychomotor performance during reduced air pressure (in English) S. Levander and others Report I from the Roche Clinical Unit

[Effect of the novel dipeptide nootropic agent noopept and its metabolite cyclo-L-prolylglycine on the transcallosal evoked potential in the rat brain].

PubMed

Molodavkin, G M; Borlikova, G G; Voronina, T A; Gudasheva, T A; Ostrovskaia, R U; Tushmalova, N A; Seredenin, S B

2002-01-01

The effect of new nootropic dipeptides--noopept (N-phenylacetyl-L-prolylglycine, GVS-111) and its metabolite (cyclo-L-prolylglycine)--and a standard nootrope piracetam on the transcallosal evoked potential (TEP) in rat brain was studied. In the dose range from 150 to 300 mg/kg, piracetam increased the TEP amplitude, which exhibited a maximum after 1.5-2 h and then gradually decreased. Both noopept and cyclo-L-prolylglycine also increased the TEP amplitude, which attained a plateau and retained this level over the entire observation time (above 3.5 h). All the nootropes studied increased both components of the evoked potential. Piracetam and cyclo-L-prolylglycine led to an approximately equal increase in both waves, while noopept induced a somewhat greater increase in the negative TEP wave amplitude. It is suggested that the positive effect of noopept and cyclo-L-prolylglycine upon the interhemispheric signal transfer (indicated by the improved transcallosal response) can be considered as a potential neurophysiological basis for a positive drug influence on the behavioral level.

Pharmacokinetics of new nootropic acylprolyldipeptide and its penetration across the blood-brain barrier after oral administration.

PubMed

Boiko, S S; Ostrovskaya, R U; Zherdev, V P; Korotkov, S A; Gudasheva, T A; Voronina, T A; Seredenin, S B

2000-04-01

Pharmacokinetics of GVS-111, a new acylprolyldipeptide with nootropic properties and its penetration across the blood-brain barrier were studied in rats using HPLC. It was found that the dipeptide is absorbed in the gastrointestinal tract, enters the circulation, and penetrates through the blood-brain barrier in an unmodified state.

Cyclopropyl glycine and proline-containing preparation noopept evoke two types of membrane potential responses in synaptoneurosomes.

PubMed

Lutsenko, V K; Vukolova, M N; Gudasheva, T A

2003-06-01

Proline, cyclo(Pro-Gly), and acyl-prolyl-containing dipeptide GVS-111 decreased synaptoneurosome membrane potential in a Ca2+-free medium. The efficiency of these preparations decreased in the following order: GVS>cyclo(Pro-Gly)>proline. Depolarization responses induced by endogenous nootropic agent cyclo(Pro-Gly) was dose-dependent and saturable; the threshold concentration of cyclo(Pro-Gly) was 10(-9) M. In a Ca2+-containing medium GVS and cyclo(Pro-Gly) induced both hyperpolarizing and depolarizing membrane responses of synaptoneurosomes. Possible mechanisms underlying changes in the membrane potential of synaptoneurosomes induced by nootropic agents are discussed. It was interesting whether modulation of electrogenesis can improve memory and potentiate the neuroprotective effect of the test nootropic agents.

Preparation of silica nanoparticles loaded with nootropics and their in vivo permeation through blood-brain barrier.

PubMed

Jampilek, Josef; Zaruba, Kamil; Oravec, Michal; Kunes, Martin; Babula, Petr; Ulbrich, Pavel; Brezaniova, Ingrid; Opatrilova, Radka; Triska, Jan; Suchy, Pavel

2015-01-01

The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of an in vivo model of rat brain perfusion. The size and morphology of the nanoparticles were characterized by transmission electron microscopy. The content of the drug substances in silica-based nanocarriers was analysed by elemental analysis and UV spectrometry. Microscopic analysis of visualized silica nanocarriers in the perfused brain tissue was performed. The concentration of the drug substances in the tissue was determined by means of UHPLC-DAD/HRMS LTQ Orbitrap XL. It was found that the drug substances in silica-based nanocarriers permeated through the blood brain barrier to the brain tissue, whereas bulk materials were not detected in the brain.

Preparation of Silica Nanoparticles Loaded with Nootropics and Their In Vivo Permeation through Blood-Brain Barrier

PubMed Central

Zaruba, Kamil; Kunes, Martin; Ulbrich, Pavel; Brezaniova, Ingrid; Triska, Jan; Suchy, Pavel

2015-01-01

The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of an in vivo model of rat brain perfusion. The size and morphology of the nanoparticles were characterized by transmission electron microscopy. The content of the drug substances in silica-based nanocarriers was analysed by elemental analysis and UV spectrometry. Microscopic analysis of visualized silica nanocarriers in the perfused brain tissue was performed. The concentration of the drug substances in the tissue was determined by means of UHPLC-DAD/HRMS LTQ Orbitrap XL. It was found that the drug substances in silica-based nanocarriers permeated through the blood brain barrier to the brain tissue, whereas bulk materials were not detected in the brain. PMID:26075264

Molecular simplification of 1,4-diazabicyclo[4.3.0]nonan-9-ones gives piperazine derivatives that maintain high nootropic activity.

PubMed

Manetti, D; Ghelardini, C; Bartolini, A; Dei, S; Galeotti, N; Gualtieri, F; Romanelli, M N; Teodori, E

2000-11-16

Several 4-substituted 1-acylpiperazines, obtained by molecular simplification of 4-substituted 1,4-diazabicyclo[4.3.0]nonan-9-ones, have been synthesized and tested in vivo on the mouse passive avoidance test, to evaluate their nootropic activity. The results show that, apparently, an N-acylpiperazine group can mimic the 2-pyrrolidinone ring of 1,4-diazabicyclo[4.3.0]nonan-9-one, as the compounds of the new series maintain high nootropic activity. Moreover molecular simplification produces more clear-cut structure-activity relationships with respect to the parent series. The mechanism of action also appears to be similar in the two series. In fact, although the molecular mechanism remains to be elucidated, the most potent compound of each class (DM232 and 13, DM235) is able to increase acetylcholine release in rat brain. Piperazine derivatives represent a new class of nootropic drugs with an in vivo pharmacological profile very similar to that of piracetam, showing much higher potency with respect to the reference compound. Among the compounds studied, 13 (DM235) shows outstanding potency, being active at a dose of 0.001 mg kg(-1) sc.

Ginkgo Biloba Extract and Long-Term Cognitive Decline: A 20-Year Follow-Up Population-Based Study

PubMed Central

Amieva, Hélène; Meillon, Céline; Helmer, Catherine; Barberger-Gateau, Pascale; Dartigues, Jean François

2013-01-01

Background Numerous studies have looked at the potential benefits of various nootropic drugs such as Ginkgo biloba extract (EGb761®; Tanakan®) and piracetam (Nootropyl®) on age-related cognitive decline often leading to inconclusive results due to small sample sizes or insufficient follow-up duration. The present study assesses the association between intake of EGb761® and cognitive function of elderly adults over a 20-year period. Methods and Findings The data were gathered from the prospective community-based cohort study ‘Paquid’. Within the study sample of 3612 non-demented participants aged 65 and over at baseline, three groups were compared: 589 subjects reporting use of EGb761® at at least one of the ten assessment visits, 149 subjects reporting use of piracetam at one of the assessment visits and 2874 subjects not reporting use of either EGb761® or piracetam. Decline on MMSE, verbal fluency and visual memory over the 20-year follow-up was analysed with a multivariate mixed linear effects model. A significant difference in MMSE decline over the 20-year follow-up was observed in the EGb761® and piracetam treatment groups compared to the ‘neither treatment’ group. These effects were in opposite directions: the EGb761® group declined less rapidly than the ‘neither treatment’ group, whereas the piracetam group declined more rapidly (β = −0.6). Regarding verbal fluency and visual memory, no difference was observed between the EGb761® group and the ‘neither treatment’ group (respectively, β = 0.21 and β = −0.03), whereas the piracetam group declined more rapidly (respectively, β = −1.40 and β = −0.44). When comparing the EGb761® and piracetam groups directly, a different decline was observed for the three tests (respectively β = −1.07, β = −1.61 and β = −0.41). Conclusion Cognitive decline in a non-demented elderly population was lower in subjects who reported using EGb761® than in those who did not. This effect may be a specific medication effect of EGb761®, since it was not observed for another nootropic medication, piracetam. PMID:23326356

[Behavioral and electrophysiological analysis of the choline-positive effect of nootropic dipeptide acylproline (GVS-111)].

PubMed

Ostrovskaia, R U; Mirzoev, T Kh; Firova, F A; Trofimof, S S; Gudasheva, T A; Grechenko, T N; Gutyrchik, E F; Barkova, E B

2001-01-01

The behavioral experiments using a passive avoidance learning model showed that the new cognition-enhancing acyl-prolyn containing dipeptide GVS-111 promotes recovery of the test performance in animals with a long-term memory deficit caused by the M-cholinolytic scopolamine (1 mg/kg/day scopolamine for 20 days, followed by 0.5 mg/kg/day GVS-111 for 10 days). At the same time, GVS-111 increased the duration of tremor induced by the M-cholinomimetic arecoline. The results of electrophysicological experiments showed that GVS-111 in a concentration range from 10(-11) to 10(-9) M increased amplitude of the neural response to acetylcholine (Ach) microappications in 75% of the isolated neurons of Helix Pomatum and produced a predominantly facilitating effect upon the endoneuronal pacemaker activity. The effect of GVS-111 upon the Ach response in a part of neurons was attenuated or even blocked by scopolamine, and in the other neurons--by the N-cholinolytic d-tubocurarine. This fact indicates that both muscarinic and nicotinic receptors are involved in the mechanism of the cholino-sensitizing action of GVS-111 upon the neuronal activity.

[Effects of nootropic agents on visual functions and lacrimal antioxidative activity in patients with primary open-angle glaucoma].

PubMed

Davydova, N G; Kuznetsova, T P; Borisova, S A; Abdulkadyrova, M Zh

2006-01-01

The paper presents the results of an investigation of the effect of the nootropic agents pantogam and nooclerine on visual functions in patients with primary open-angle glaucoma. These agents have been found to have a beneficial effect on the functional activity of the retina and optic nerve, light sensitivity, hemo- and hydrodynamics of the eye.

Nootropic and antiamnestic effects of tenoten (pediatric formulation) in immature rat pups.

PubMed

Voronina, T A; Molodavkin, G M; Borodavkina, M V; Kheyfets, I A; Dugina, Yu L; Sergeeva, S A

2009-09-01

The antiamnestic effects of tenoten (pediatric formulation) was demonstrated on the model of scopolamine-induced amnesia of passive avoidance reflex and the nootropic effect of this preparation was demonstrated on the model of incomplete conditioning and in rat pups with experimental attention deficit syndrome. The efficiency of the preparation was comparable to that of piracetam and phenibut and even surpassed it by some parameters.

Nootropic nefiracetam inhibits proconvulsant action of peripheral-type benzodiazepines in epileptic mutant EL mice.

PubMed

Nakamoto, Yurie; Shiotani, Tadashi; Watabe, Shigeo; Nabeshima, Toshitaka; Yoshii, Mitsunobu

2004-10-01

Piracetam and structurally related nootropics are known to potentiate the anticonvulsant effects of antiepileptic drugs. It remains to be seen, however, whether these nootropics inhibit proconvulsant actions of many toxic agents including Ro 5-4864, a specific agonist for peripheral-type benzodiazepine receptors (PBR). The present study was designed to address this issue using EL mice, an animal model of epilepsy. In behavioral pharmacological experiments, EL mice were highly susceptible to convulsions induced by Ro 5-4864 (i.p.) in comparison with nonepileptic DDY mice. Nefiracetam administered orally to EL mice inhibited spontaneous seizures. In DDY mice, convulsions induced by Ro 5-4864 were prevented by nefiracetam when administered by i.v. injection. Aniracetam (i.v.) was partially effective, but piracetam and oxiracetam were ineffective as anticonvulsants. Binding assay for brain tissues revealed a higher density of mitochondrial PBR in EL mice compared with DDY mice. Binding of the PBR ligands Ro 5-4864 to either EL or DDY mouse brain was inhibited by micromolar concentrations of these nootropic agents in the sequence of nefiracetam > aniracetam > oxiracetam, piracetam. This rank order is identical to potency as anticonvulsants. These data suggest that nefiracetam may prevent toxic effects of PBR agonists through interacting with PBR.

Effect of donepezil in patients with Alzheimer's disease previously untreated or treated with memantine or nootropic agents in Germany: an observational study.

PubMed

Klinger, Tatjana; Ibach, Bernd; Schoenknecht, Peter; Kamleiter, Martin; Silver, Gabrielle; Schroeder, Johannes; Mielke, Ruediger

2005-05-01

This open-label, prospective, observational, Post-Marketing Surveillance (PMS) study assessed the efficacy and safety of donepezil in patients who had been switched from therapies currently used in Germany to treat Alzheimer's disease (AD), such as memantine and nootropics, due to insufficient efficacy or poor tolerability. A treatment-naive population was included as a comparator. Patients with AD were treated with donepezil and observed for a period of approximately 3 months. A cognitive assessment was made using the Mini-Mental State Examination (MMSE). Quality of life (QoL) was assessed by the investigators who answered the question 'How did therapy with donepezil influence the QoL of the patient and/or his family over the observation period?' and was graded using three ratings: improved/unchanged/worsened. Adverse events (AEs) were also monitored. A total of 913 patients entered the study (mean +/- SD MMSE score 18.03 +/- 5.34). Efficacy assessments were analyzed for three groups: an overall group of patients who had received any form of prior AD drug therapy (N+ group; n = 709); a subgroup of patients from the N+ group who had received prior memantine therapy only (M+ group; n = 111) and patients who were drug treatment naive (N- group; n = 204). In the evaluable population donepezil improved MMSE scores by 2.21 +/- 3.47 points on average, with similar improvements observed in all three groups. QoL was judged to be improved in at least 70% of patients, again with similar results obtained for all three groups. Donepezil was well tolerated, with 85 of 913 (9.3%) patients reporting AEs. The most common AEs were those typically seen with cholinergic therapies (i.e., diarrhoea, vomiting and nausea). In this observational PMS study, donepezil was shown to be efficacious and well tolerated in patients who were being insufficiently treated with memantine or nootropic therapy. The magnitude of response was similar to that observed in patients who were previously treatment naive, suggesting prior medication does not effect donepezil's efficacy.

[Platelet hyperreactivity and antiaggregatory properties of nootropic drugs under conditions of alloxan-induced diabetes in rats].

PubMed

Zhiliuk, V I; Levykh, A É; Mamchur, V I

2012-01-01

The effects of nootropic drugs (noopept, pentoxifylline, piracetam, pramiracetam, Ginkgo biloba extract, entrop, cerebrocurin and citicoline) on platelet aggregation in rats with experimental diabetes have been studied. It is established that all these drugs exhibit an inhibitory action of various degrees against platelet hyperreactivity under conditions of chronic hyperglycemia. The maximum universality of the antiaggregatory action is characteristic of pramiracetam, entrop and Ginkgo biloba extract.

Nootropic nanocomplex with enhanced blood-brain barrier permeability for treatment of traumatic brain injury-associated neurodegeneration.

PubMed

Park, Jeongmin; Choi, Eunshil; Shin, Seulgi; Lim, Sungsu; Kim, Dohee; Baek, Suji; Lee, Kang Pa; Lee, Jae Jun; Lee, Byeong Han; Kim, Bokyung; Jeong, Keunsoo; Baik, Ja-Hyun; Kim, Yun Kyung; Kim, Sehoon

2018-06-15

Traumatic brain injury (TBI) is an intracranial injury which can induce immediate neuroinflammation and long-term neurological deficits. Methylene blue (MB) as a nootropic has a great potential to treat neurodegeneration after TBI because of its anti-inflmmatory and neuroprotective functions. However, its limited accumulation to the brain across the blood-brain barrier (BBB) remains a major hurdle to be overcome. In this paper, we present a polymer surfactant-encapsulated nanocomplex of MB as a delivery system with high BBB permeability for efficacious treatment of TBI-induced neurodegeneration. MB was formulated via electrostatically/hydrophobically directed assembly with fatty acid and Pluronic surfactant (F-127 or F-68) to construct nanocomplexes of two different colloidal sizes (<10 nm and ~108 nm in hydrodynamic diameter for NanoMB-127 and NanoMB-68, respectively). Compared to uncomplexed free MB, formulation into the ultrasmall nanocomplex (NanoMB-127) significantly enhanced the uptake of MB by blood-brain vascular endothelial bEnd3 cells in vitro, and indeed improved its BBB penetration upon systemic administration to normal mice in vivo. However, large-size NanoMB-68 showed negligible BBB crossing despite the efficient bEnd3 cell internalization in vitro, probably due to the unfavorable pharmacokinetic profile associated with its large particle size. By virtue of the efficient BBB penetration and cellular uptake, ultrasmall NanoMB-127 was shown to distinctively reduce the expression level of an inflammatory cytokine with no notable toxicity in vitro and also considerably prevent the neurodegeneration after TBI in mice at much lower doses than free MB. Overall, the Pluronic-supported nanocomplexation method allows efficient brain delivery of MB, offering a novel way of enhancing the efficacy of neurotherapeutics to treat brain diseases. Copyright © 2018. Published by Elsevier B.V.

The effects of huperzine A and IDRA 21 on visual recognition memory in young macaques

PubMed Central

Malkova, Ludise; Kozikowski, Alan P.; Gale, Karen

2011-01-01

Nootropic agents or cognitive enhancers are purported to improve mental functions such as cognition, memory, or attention. The aim of our study was to determine the effects of two possible cognitive enhancers, huperzine A and IDRA 21, in normal young adult monkeys performing a visual memory task of varying degrees of difficulty. Huperzine A is a reversible acetylcholinesterase (AChE) inhibitor, its administration results in regionally specific increases in acetylcholine levels in the brain. In human clinical trials, Huperzine A resulted in cognitive improvement in patients with mild to moderate form of Alzheimer's disease (AD) showing its potential as a palliative agent in the treatment of AD. IDRA 21 is a positive allosteric modulator of glutamate AMPA receptors. It increases excitatory synaptic strength by attenuating rapid desensitization of AMPA receptors and may thus have beneficial therapeutic effects to ameliorate memory deficits in patients with cognitive impairments, including AD. The present study evaluated the effects of the two drugs in normal, intact, young adult monkeys to determine whether they can result in cognitive enhancement in a system that is presumably functioning optimally. Six young pigtail macaques (Macaca nemestrina) were trained on delayed non-matching-to-sample task, a measure of visual recognition memory, up to criterion of 90% correct responses on each of the four delays (10s, 30s, 60s, and 90s). They were then tested on two versions of the task: Task 1 included the four delays intermixed within a session and the monkeys performed it with the accuracy of 90%. Task 2 included, in each of 24 trials, a list of six objects presented in succession. Two objects from the list were then presented for choice paired with novel objects and following two of the four delays intermixed within a session. This task with a higher mnemonic demand yielded an average performance of 64% correct. Oral administration of huperzine A did not significantly affect the monkeys' performance on either task. However, a significant negative correlation was found between the baseline performance on each delay and the change in performance under huperzine A, suggesting that under conditions in which the subjects were performing poorly (55 – 69%), the drug resulted in improved performance, whereas no improvement was obtained when the baseline was close to 90%. In fact, when the subjects were performing very well, huperzine A tended to reduce the performance accuracy, indicating that in a system that functions optimally, the increased availability of acetylcholine does not improve performance or memory, especially when the animals are close to the maximum performance. In contrast, oral administration of IDRA 21 significantly improved performance on Task 2, especially on the longest delay. This finding supports the potential use of this drug in treatment of cognitive and memory disorders. PMID:21185313

Senile dementia of the Alzheimer type treated with aniracetam: a new nootropic agent.

PubMed

Sourander, L B; Portin, R; Mölsä, P; Lahdes, A; Rinne, U K

1987-01-01

Forty-four patients with senile dementia of the Alzheimer type were randomly allocated into double-blind treatment with either aniracetam (RO 13-5057) 1 g or placebo daily for 3 months. Neurological examinations were made before and after treatment and psychometric tests were performed before and after 1 month's and after 3 month's treatment. Treatment was interrupted due to occurrence of confusion in four cases in the aniracetam group and in one case in the placebo group. During treatment, an improvement was seen in several cognitive tests, especially those associated with memory, but this improvement occurred in the placebo as well as in the aniracetam-treated group. In clinical evaluation no difference was seen in efficacy between the two treatment groups.

[Effect of the novel nootropic and neuroprotective dipeptide noopept on the streptozotocin-induced model of sporadic Alzheimer disease in rats].

PubMed

Ostrovskaia, R U; Tsaplina, A P; Vakhitova, Iu V; Salimgareeva, M Kh; Iamidanov, R S

2010-01-01

Streptozotocin-intracerebroventricularly treated rats are proposed as an experimental model of sporadic Alzheimer disease (AD). Diabetogenic toxin streptozotocin (STZ) administered in both cerebral ventricles in a dose of 3 mg/kg decreases the expression of NGF and BDNF mainly in the hippocampus and increases the content of malonic dialdehyde (MDA)--a product of lipid peroxidation--in the brain tissues. These metabolic changes are accompanied by a pronounced cognitive deficiency, which is manifested by long-term memory deterioration in the passive avoidance test. These manifestations of pathology are not accompanied by hyperglycemia in the case of intraventricular STZ administration, in contrast to the systemic (in particular, intraperitoneal) route of introduction that causes a pronounced increase in the blood glucose level. These results are consistent with the existing notions that (i) STZ administered intraventricularly provokes a complex of changes imitating the sporadic AD and (ii) this disease can be considered as a manifestation of type-III diabetes. The new original cognition enhancing and neuroprotective dipeptide noopept decreases the aforementioned metabolic changes and the accompanying long-term deterioration of the memory. Previously, this systemically active dipeptide was shown to be capable of increasing expression of NGF and BDNF in the hippocampus, stimulating the antibody production to beta-amyloid, inhibiting the lipid peroxidation, activating the endogenous antioxidant systems, and decreasing the rate of glutamate release (cholinopositive effect). Taken together, these data indicate that noopept can be considered as a multipotent substance acting upon several important pathogenic chainsof the sporadic AD.

Protective effect of a phenolic extract containing indoline amides from Portulaca oleracea against cognitive impairment in senescent mice induced by large dose of D-galactose /NaNO2.

PubMed

Wang, Peipei; Sun, Hongxiang; Liu, Dianyu; Jiao, Zezhao; Yue, Su; He, Xiuquan; Xia, Wen; Ji, Jianbo; Xiang, Lan

2017-05-05

Portulaca oleracea L. is a potherb and also a widely used traditional Chinese medicine. In accordance with its nickname "longevity vegetable", pharmacological study demonstrated that this plant possessed antioxidant, anti-aging, and cognition-improvement function. Active principles pertaining to these functions of P. oleracea need to be elucidated. The present study evaluated the effect of a phenolic extract (PAAs) from P. oleracea which contained specific antioxidant indoline amides on cognitive impairment in senescent mice. PAAs was prepared through AB-8 macroporous resin column chromatography. Total phenol content was determined using colorimetric method, and contents of indoline amides were determined using HPLC-UV method. Senescent Kunming mice with cognitive dysfunction were established by intraperitoneal injection of D-galactose (D-gal, 1250mg/kg/day) and NaNO 2 (90mg/kg/day) for 8 weeks, L-PAAs (360mg/kg/day), H-PAAs (720mg/kg/day), and nootropic drug piracetam (PA, 400mg/kg/day) as the positive control were orally administered. Spatial learning and memory abilities were evaluated by Morris water maze experiment. Activities of AChE, SOD, CAT, and levels of GSH and MDA in the brain or plasma were measured. Hippocampal morphology was observed by HE staining. Chronic treatment of large dose of D-gal/NaNO 2 significantly reduced lifespan, elevated AChE activity, decreased CAT activity, compensatorily up-regulated SOD activity and GSH level, increased MDA level, induced neuronal damage in hippocampal CA1, CA3 and CA4 regions, and impaired cognitive function. Similar to PA, PAAs prolonged the lifespan and improved spatial memory ability. Moreover, PAAs improved learning ability. H-PAAs significantly reversed compensatory increase in SOD activity to the normal level, elevated serum CAT activity, and reduced MDA levels in brain and plasma, more potent than L-PAAs. Besides these, PAAs evidently inhibited hippocampal neuronal damage. However, it had no effect on brain AChE activity. PAAs as the bioactive principles of P. oleracea attenuated oxidative stress, improved survival rate, and enhanced cognitive function in D-gal/NaNO 2 -induced senile mice, similar to piracetam. This phenolic extract provides a promising candidate for prevention of aging and aging-related cognitive dysfunction in clinic. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Varsity Medical Ethics Debate 2015: should nootropic drugs be available under prescription on the NHS?

PubMed

Thorley, Emma; Kang, Isaac; D'Costa, Stephanie; Vlazaki, Myrto; Ayeko, Olaoluwa; Arbe-Barnes, Edward H; Swerner, Casey B

2016-09-13

The 2015 Varsity Medical Ethics debate convened upon the motion: "This house believes nootropic drugs should be available under prescription". This annual debate between students from the Universities of Oxford and Cambridge, now in its seventh year, provided the starting point for arguments on the subject. The present article brings together and extends many of the arguments put forward during the debate. We explore the current usage of nootropic drugs, their safety and whether it would be beneficial to individuals and society as a whole for them to be available under prescription. The Varsity Medical Debate was first held in 2008 with the aim of allowing students to engage in discussion about ethics and policy within healthcare. The event is held annually and it is hoped that this will allow future leaders to voice a perspective on the arguments behind topics that will feature heavily in future healthcare and science policy. This year the Oxford University Medical Society at the Oxford Union hosted the debate.

Selective suppression of the slow-inactivating potassium currents by nootropics in molluscan neurons.

PubMed

Bukanova, Julia V; Solntseva, Elena I; Skrebitsky, Vladimir G

2002-09-01

The role of the voltage-gated K+ channels in the effect of some nootropics was investigated. Earlier, the multiple effect of high concentrations of two nootropics, piracetam and its peptide analogue GVS-111 [Seredenin et al. (1995), US Patent No. 5,439,930], on Ca2+ and K+ currents of molluscan neurons was shown [Solntseva et al. (1997), General Pharmacology 29, 85-89]. In the present work, we describe the selective effect of low concentrations of these nootropics as well as vinpocetine on certain types of K+ current. The experiments were performed on isolated neurons of the land snail Helix pomatia using a two-microelectrode voltage-clamp method. The inward voltage-gated Ca2+ current (ICa) and three subtypes of the outward voltage-gated K+ current were recorded: Ca2+-dependent K+ current (IK(Ca)), delayed rectifying current (IKD), and fast-inactivating K+ current (IA). It has been found that I Ca was not changed in the presence of 30 microM vinpocetine, 100 microM piracetam or 10 nM GVS-111, while slow-inactivating, TEA-sensitive IK(Ca) and IKD were inhibited (IK(Ca) more strongly than IKD). In contrast, the fast-inactivating, 4-AP-sensitive K+ current (IA) was not diminished by low concentrations of piracetam and GVS-111, while vinpocetine even augmented it. A possible role of slow-inactivating subtypes of the K+ channels in the development of different forms of dementia is discussed.

Nootropic potential of Ashwagandha leaves: Beyond traditional root extracts.

PubMed

Wadhwa, Renu; Konar, Arpita; Kaul, Sunil C

2016-05-01

Rapidly increasing aging population and environmental stressors are the two main global concerns of the modern society. These have brought in light rapidly increasing incidence of a variety of pathological conditions including brain tumors, neurodegenerative & neuropsychiatric disorders, and new challenges for their treatment. The overlapping symptoms, complex etiology and lack of full understanding of the brain structure and function to-date further complicate these tasks. On the other hand, several herbal reagents with a long history of their use have been asserted to possess neurodifferentiation, neuroregenerative and neuroprotective potentials, and hence been recommended as supplement to enhance and maintain brain health and function. Although they have been claimed to function by holistic approach resulting in maintaining body homeostasis and brain health, there are not enough laboratory studies in support to these and mechanism(s) of such beneficial activities remain largely undefined. One such herb is Ashwagandha, also called "Queen of Ayurveda" for its popular use in Indian traditional home medicine because of its extensive benefits including anticancer, anti-stress and remedial potential for aging and neurodegenerative pathologies. However, active principles and underlying mechanism(s) of action remain largely unknown. Here we provide a review on the effects of Ashwagandha extracts and active principles, and underlying molecular mechanism(s) for brain pathologies. We highlight our findings on the nootropic potential of Ashwagandha leaves. The effects of Ashwagandha leaf extracts are multidimensional ranging from differentiation of neuroblastoma and glioma cells, reversal of Alzheimer and Parkinson's pathologies, protection against environmental neurotoxins and enhancement of memory. Copyright © 2015 Elsevier Ltd. All rights reserved.

In vitro evaluation of Bacopa monniera extract and individual constituents on human recombinant monoamine oxidase enzymes.

PubMed

Singh, Rajbir; Ramakrishna, Rachumallu; Bhateria, Manisha; Bhatta, Rabi Sankar

2014-09-01

Bacopa monniera is a traditional Ayurvedic medicinal plant that has been used worldwide for its nootropic action. Chemically standardized extract of B. monniera is now available as over the counter herbal remedy to enhance memory in children and adults. Considering the nootropic action of B. monniera, we evaluated the effect of clinically available B. monniera extract and six of B. monniera constituents (bacoside A3, bacopaside I, bacopaside II, bacosaponin C, bacosine, and bacoside A mixture) on recombinant human monoamine oxidase (MAO) enzymes. The effect of B. monniera extract and individual constituents on human recombinant MAO-A and MAO-B enzymes was evaluated using MAO-Glo(TM) assay kit (Promega Corporation, USA), following the instruction manual. IC50 and mode of inhibition were measured for MAO enzymes. Bacopaside I and bacoside A mixture inhibited the MAO-A and MAO-B enzymes. Bacopaside I exhibited mixed mode of inhibition with IC50 and Ki values of 17.08 ± 1.64 and 42.5 ± 3.53 µg/mL, respectively, for MAO-A enzyme. Bacopaside I is the major constituent of B. monniera, which inhibited the MAO-A enzyme selectively. Copyright © 2014 John Wiley & Sons, Ltd.

[Effect of nootropic agents on impulse activity of cerebral cortex neurons].

PubMed

Iasnetsov, V V; Pravdivtsev, V A; Krylova, I N; Kozlov, S B; Provornova, N A; Ivanov, Iu V; Iasnetsov, V V

2001-01-01

The effect of nootropes (semax, mexidol, and GVS-111) on the activity of individual neurons in various cerebral cortex regions was studied by microelectrode and microionophoresis techniques in cats immobilized by myorelaxants. It was established that the inhibiting effect of mexidol upon neurons in more than half of cases is prevented or significantly decreased by the GABA antagonists bicuculline and picrotoxin. The inhibiting effect of semax and GVS-111 upon neurons in more than half of cases is related to stimulation of the M-choline and NMDA receptors, respectively.

[The pharmacokinetics of the dipeptide analog of piracetam with nootropic activity GVS-111 and of its basic metabolites].

PubMed

Boĭko, S S; Zherdev, V P; Dvorianinov, A A; Gudasheva, T A; Ostrovskaia, R U; Voronina, T A; Rozantsev, G G; Seredenin, S B

1997-01-01

The pharmacokinetics of a new nootropic dipeptide analog of piracetam-N-phenylacetyl-L-prolylglycine (GWS-111) and its main metabolites were studied in rats by means of high performance liquid chromatography and gas-liquid chromatography. The compound under study showed a greater resistance to an enzymatic effect than natural neuropeptides. In addition to an unchanged compound three of its metabolites were found in the blood plasma of the rats. One of them, cyclo-Pro-Gly was an active metabolite of GWS-111.

Comment on 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' by Lam et al.

PubMed

Hill, W David

2018-04-01

Intelligence and educational attainment are strongly genetically correlated. This relationship can be exploited by Multi-Trait Analysis of GWAS (MTAG) to add power to Genome-wide Association Studies (GWAS) of intelligence. MTAG allows the user to meta-analyze GWASs of different phenotypes, based on their genetic correlations, to identify association's specific to the trait of choice. An MTAG analysis using GWAS data sets on intelligence and education was conducted by Lam et al. (2017). Lam et al. (2017) reported 70 loci that they described as 'trait specific' to intelligence. This article examines whether the analysis conducted by Lam et al. (2017) has resulted in genetic information about a phenotype that is more similar to education than intelligence.

Aniracetam (Ro 13-5057) in the treatment of senile dementia of Alzheimer type (SDAT): results of a placebo controlled multicentre clinical study.

PubMed

Senin, U; Abate, G; Fieschi, C; Gori, G; Guala, A; Marini, G; Villardita, C; Parnetti, L

1991-12-01

One hundred and nine elderly patients suffering from mild to moderate cognitive impairment fulfilling NINCDS-ADRDA criteria for probable dementia of the Alzheimer type were treated for 6 months with a new nootropic drug, aniracetam (Ro 13-5057) in a double-blind randomized study versus placebo. The two treatment groups were comparable at baseline for demographic and behaviourial parameters and symptomatology. Patients underwent clinical, behaviourial and psychometric evaluation every other month. The aniracetam group differed significantly from the placebo group by the end of the study and also showed a statistically significant improvement versus baseline in the psychobehavioural parameters, while in the placebo group a steady deterioration was observed. Tolerability to aniracetam was excellent.

Neurocognitive Effect of Nootropic Drug Brahmi (Bacopa monnieri) in Alzheimer's Disease

PubMed Central

Chaudhari, Kaustubh S.; Tiwari, Nishant R.; Tiwari, Rakesh R.; Sharma, Rohan S.

2017-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease of the elderly. The rapid increase in its incidence has necessitated development of newer drugs. Ayurvedic herbal medications are increasingly researched due to their biosafety profile and usefulness in cognitive impairment. In this article, we critically reviewed one such Medhya Rasayana (nootropic drug) Brahmi-derived from extract of Bacopa monnieri (EBm). Studies have shown that EBm promotes free radical scavenger mechanisms and protects cells in prefrontal cortex, hippocampus, and striatum against cytotoxicity and DNA damage implicated in AD. It also reduces lipoxygenase activity reducing lipid peroxidation, increases glutathione peroxidase and chelates iron. Administration of EBm was seen to protect the cholinergic neurons and reduce anticholinesterase activity comparable to donepezil, rivastigmine, and galantamine. It also reduces hippocampal β-amyloid deposition and stress-induced hippocampal damage. The neuroprotective effect of EBm is also due to nitric oxide-mediated cerebral vasodilation. EBm improved the total memory score and maximum improvement was seen in logical memory and paired associate learning in humans and reversed phenytoin-induced memory impairment in experimental model. EBm has not shown any serious clinical, neurological, hematological complications, or vital organs damage in experimental studies. Rats showed marked reduction in fertility; however, libido was unaffected. There is no experimental evidence of genotoxicity or teratogenesis by use of EBm. Mild nausea and gastrointestinal upset are seen in humans. Brahmi promises to be a novel agent in AD; however, further human trials are recommended to verify the efficacy and rule out any side effects as evidenced by the experimental models. PMID:28588366

[Studying specific effects of nootropic drugs on glutamate receptors in the rat brain].

PubMed

Firstova, Iu Iu; Vasil'eva, E V; Kovalev, G I

2011-01-01

The influence of nootropic drugs of different groups (piracetam, phenotropil, nooglutil, noopept, semax, meclofenoxate, pantocalcine, and dimebon) on the binding of the corresponding ligands to AMPA, NMDA, and mGlu receptors of rat brain has been studied by the method of radio-ligand binding in vitro. It is established that nooglutil exhibits pharmacologically significant competition with a selective agonist of AMPA receptors ([G-3H]Ro 48-8587) for the receptor binding sites (with IC50 = 6.4 +/- 0.2 microM), while the competition of noopept for these receptor binding sites was lower by an order of magnitude (IC50 = 80 +/- 5.6 microM). The heptapeptide drug semax was moderately competitive with [G-3H]LY 354740 for mGlu receptor sites (IC50 = 33 +/- 2.4 microM). Dimebon moderately influenced the specific binding of the ligand of NMDA receptor channel ([G-3H]MK-801) at IC50 = 59 +/- 3.6 microM. Nootropic drugs of the pyrrolidone group (piracetam, phenotropil) as well as meclofenoxate, pantocalcine (pantogam) in a broad rage of concentrations (10(-4)-10(-10) M) did not affect the binding of the corresponding ligands to glutamate receptors (IC50 100 pM). Thus, the direct neurochemical investigation was used for the first time to qualitatively characterize the specific binding sites for nooglutil and (to a lower extent) noopept on AMPA receptors, for semax on metabotropic glutamate receptors, and for dimebon on the channel region of NMDA receptors. The results are indicative of a selective action of some nootropes on the glutamate family.

[The role of non-NMDA glutamate receptors in the EEG effects of chronic administration of noopept GVS-111 in awake rats].

PubMed

Kovalev, G I; Vorob'ev, V V

2002-01-01

Participation of the non-NMDA glutamate receptor subtype in the formation of the EEG frequency spectrum was studied in wakeful rats upon a long-term (10 x 0.2 mg/kg, s.c.) administration of the nootropic dipeptide GVS-111 (noopept or N-phenylacetyl-L-prolyglycine ethylate). The EEGs were measured with electrodes implanted into somatosensor cortex regions, hippocampus, and a cannula in the lateral ventricle. The acute reactions (characteristic of nootropes) in the alpha and beta ranges of EEG exhibited inversion after the 6th injection of noopept and almost completely vanished after the 9th injection. Preliminary introduction of the non-NMDA antagonist GDEE (glutamic acid diethyl ester) in a dose of 1 mumole into the lateral ventricle restored the EEG pattern observed upon the 6th dose of GVS-111. The role of glutamate receptors in the course of a prolonged administration of nootropes, as well as the possible mechanisms accounting for a difference in the action of GVS-111 and piracetam are discussed.

X-ray and 1H-NMR spectroscopic studies of the structures and conformations of the new nootropic agents RU-35929, RU-47010 and RU-35965

NASA Astrophysics Data System (ADS)

Amato, Maria E.; Bandoli, Giuliano; Casellato, Umberto; Pappalardo, Giuseppe C.; Toja, Emilio

1990-10-01

The crystal and molecular structures of the nootropics (±)1-benzenesulphonyl-2-oxo-5-ethoxypyrrolidine ( 1), (±)1-(3-pyridinylsulphonyl)-2-oxo-5-ethoxypyrrolidine ( 2) and (±)1-benzenesulphonyl-2-oxo-5-isopropyloxypyrrolidine ( 3) have been determined by X-ray analysis. The solution conformation of 1, 2 and 3 has been investigated by 1H NMR spectroscopy. In the solid state, the main feature consists of the similar structural parameters and conformations, with the exception of the conformation adopted by the 5-ethoxy moiety which changes on passing from 1 to 2. The solid state overall enveloped conformation of the 2-pyrrolidinone ring for the three nootropics is found to be retained in solution on the basis of NMR evidence. Comparison between calculated and experimental coupling constant values shows that one of the two possible puckered opposite conformational isomers (half-chair shapes) occurs in solution. The relative pharmacological potencies of 1, 2 and 3 cannot therefore be interpreted in terms of the different conformation features presently detectable by available experimental methods.

Genotype-dependent characteristics of behavior in mice in cognitive tests. The effects of Noopept.

PubMed

Bel'nik, A P; Ostrovskaya, R U; Poletaeva, I I

2009-01-01

Male C57BL/6J, BALB/c, and DBA/2J mice showed differences in their abilities to perform two cognitive tests. C57BL/6J mice had good learning ability and memory trace retention (at 10 days) in a simplified Morris maze, while BALB/c mice had low levels of memory trace retention and DBA/2J mice had low learning ability in this test. I.p. administration of the nootropic agent Noopept (GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) at a dose of 0.5 mg/kg 15 min before the start of the test induced significant improvements in long-term memory in this test in BALB/c mice but no further improvement in C57BL/6J mice, and had no effect in DBA/2J mice. On testing the ability to extrapolate the direction of movement of a stimulus, administration of Noopept increased the proportion of correct responses in C57BL/6J and BALB/c mice, but had no effect in DBA/2J mice.

[Genotype-dependent mice behavior in cognitive tasks. Effect of noopept].

PubMed

Bel'nik, A P; Ostrovskaia, R U; Poletaeva, I I

2007-01-01

The interstrain differences in performance of C57BL/6J, BALB/c and DBA/2J male mice in two cognitive tasks were found. Mice C57BL/6J showed good learning ability and preservation of memory traces tested 10 days after performance in a simplified version of Morris water maze. Mice BALB/c learned the task but, virtually, no long-term memory traces were revealed, whereas DBA/2J demonstrated poor learning. The effect of nootropic drug Noopept (GVS-111, N-phenil-acetyl-L-prolylglycin ethyl ether) was shown to be genotype-dependent. Its administration (0.5 mg/kg i.p., 15 min before learning) improved the long-term memory in Morris test in BALB/c mice but failed to produce any improvement in C57BL/6J. The ability of mice for extrapolation of the direction of stimulus movement differently changed after Noopept injections: the proportion of correct task solutions increased in C57BL/6J and BALB/c mice, whereas the performance of DBA/2J did not change.

Novel nootropic dipeptide Noopept increases inhibitory synaptic transmission in CA1 pyramidal cells.

PubMed

Kondratenko, Rodion V; Derevyagin, Vladimir I; Skrebitsky, Vladimir G

2010-05-31

Effects of newly synthesized nootropic and anxiolytic dipeptide Noopept on inhibitory synaptic transmission in hippocampal CA1 pyramidal cells were investigated using patch-clamp technique in whole-cell configuration. Bath application of Noopept (1 microM) significantly increased the frequency of spike-dependant spontaneous IPSCs whereas spike-independent mIPSCs remained unchanged. It was suggested that Noopept mediates its effect due to the activation of inhibitory interneurons terminating on CA1 pyramidal cells. Results of current clamp recording of inhibitory interneurons residing in stratum radiatum confirmed this suggestion. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Early postnatal effects of noopept and piracetam on declarative and procedural memory of adult male and female rats.

PubMed

Trofimov, S S; Voronina, T A; Guzevatykh, L S

2005-06-01

We studied the effect of a new nootropic dipeptide Noopept and reference nootropic preparation piracetam injected subcutaneously on days 8-20 of life on learning of alternative feeding response in a 6-arm-maze in male and female rats. Early postnatal administration of Noopept disturbed the dynamics of learning by parameters of declarative and procedural memory. Piracetam impaired learning by parameters of procedural, but not declarative memory (only in males). Both preparations decreased the ratio of successfully learned males (but not females). The observed effects were not associated with changes in locomotor activity.

Synthesis and biological evaluation of 3,7-diazabicyclo[4.3.0]nonan-8-ones as potential nootropic and analgesic drugs.

PubMed

Martini, Elisabetta; Di Cesare Mannelli, Lorenzo; Bartolucci, Gianluca; Bertucci, Carlo; Dei, Silvia; Ghelardini, Carla; Guandalini, Luca; Manetti, Dina; Scapecchi, Serena; Teodori, Elisabetta; Romanelli, Maria Novella

2011-04-14

A series of cis and trans 3,7-diazabicyclo[4.3.0]nonan-8-ones has been synthesized and tested for their ability to revert scopolamine-induced amnesia in the mouse passive-avoidance test. The racemates of the most potent compounds 4 and 7 were separated and tested, but no enantioselectivity was found for the nootropic activity. Compounds 4 and 7 and their enantiomers displayed interesting antihyperalgesic activity in two models of neuropathic pain (streptozotocin-induced and oxalilplatin-induced neuropathy) in comparison with pregabalin.

Study of the protective effects of nootropic agents against neuronal damage induced by amyloid-beta (fragment 25-35) in cultured hippocampal neurons.

PubMed

Sendrowski, Krzysztof; Sobaniec, Wojciech; Stasiak-Barmuta, Anna; Sobaniec, Piotr; Popko, Janusz

2015-04-01

Alzheimer's disease (AD) is a common neurodegenerative disorder, in which progressive neuron loss, mainly in the hippocampus, is observed. The critical events in the pathogenesis of AD are associated with accumulation of β-amyloid (Aβ) peptides in the brain. Deposits of Aβ initiate a neurotoxic "cascade" leading to apoptotic death of neurons. Aim of this study was to assess a putative neuroprotective effects of two nootropic drugs: piracetam (PIR) and levetiracetam (LEV) on Aβ-injured hippocampal neurons in culture. Primary cultures of rat's hippocampal neurons at 7 day in vitro were exposed to Aβ(25-35) in the presence or absence of nootropics in varied concentrations. Flow cytometry with Annexin V/PI staining was used for counting and establishing neurons as viable, necrotic or apoptotic. Additionally, release of lactate dehydrogenase (LDH) to the culture medium, as a marker of cell death, was evaluated. Aβ(25-35) caused concentration-dependent death of about one third number of hippocampal neurons, mainly through an apoptotic pathway. In drugs-containing cultures, number of neurons injured with 20 μM Aβ(25-35) was about one-third lesser for PIR and almost two-fold lesser for LEV. When 40 μM Aβ(25-35) was used, only LEV exerted beneficial neuroprotective action, while PIR was ineffective. Our results suggest the protective potential of both studied nootropics against Aβ-induced death of cultured hippocampal neurons with more powerful neuroprotective effects of LEV. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Aniracetam, 1-BCP and cyclothiazide differentially modulate the function of NMDA and AMPA receptors mediating enhancement of noradrenaline release in rat hippocampal slices.

PubMed

Pittaluga, A; Bonfanti, A; Arvigo, D; Raiteri, M

1999-04-01

Aniracetam, 1-(1,3-benzodioxol-5-yl-carbonyl)piperidine (1-BCP) and cyclothiazide, three compounds considered to enhance cognition through modulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors, were evaluated in the 'kynurenate test', a biochemical assay in which some nootropics have been shown to prevent the antagonism by kynurenic acid of the N-methyl-D-aspartate (NMDA)-evoked [3H]noradrenaline ([3H]NA) release from rat hippocampal slices. Aniracetam attenuated the kynurenate (100 microM) antagonism of the [3H]NA release elicited by 100 microM NMDA with high potency (EC50< or =0.1 microM). Cyclothiazide and 1-BCP were about 10 and 100 times less potent than aniracetam, respectively. The effect of aniracetam persisted in the presence of the AMPA receptor antagonist 6-nitro-7-sulphamoyl-benzo[f]quinoxaline-2,3-dione (NBQX) added at 5 microM, a concentration that did not affect NMDA receptors; in contrast, NBQX reduced the effect of 1-BCP and abolished that of cyclothiazide. The AMPA-evoked release of [3H]NA from hippocampal slices or synaptosomes was enhanced by cyclothiazide, less potently by 1-BCP and weakly by aniracetam. High concentrations of kynurenate (1 mM) antagonized the AMPA-evoked [3H]NA release in slices; this antagonism was attenuated by 1 microM cyclothiazide and reversed to an enhancement of AMPA-evoked [3H]NA release by 10 microM of the drug, but was insensitive to 1-BCP or aniracetam. It is concluded that aniracetam exerts a dual effect on glutamatergic transmission: modulation of NMDA receptor function at nanomolar concentrations, and modulation of AMPA receptors at high micromolar concentrations. As to cyclothiazide and 1-BCP, our data concur with the idea that both compounds largely act through AMPA receptors, although an NMDA component may be involved in the effect of 1-BCP.

Efficiency of noopept in streptozotocin-induced diabetes in rats.

PubMed

Ostrovskaya, R U; Ozerova, I V; Gudascheva, T A; Kapitsa, I G; Ivanova, E A; Voronina, T A; Seredenin, S B

2013-01-01

We studied the effects of new nootropic and neuroprotective drug Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) in various dosage regimens on the dynamics of glycemia, body weight, and pain sensitivity in rats receiving diabetogenic toxin streptozotocin. In experimental diabetic rats, Noopept alleviated glycemia and weight loss and normalized enhanced pain sensitivity. The normalizing effect of Noopept was most pronounced when it was administered as a preventive agent prior to injection of the toxin. Both preventive and therapeutic administration of Noopept (delayed injections included) significantly weakened the examined metabolic effects of diabetogenic toxin. Possible mechanisms of the antidiabetic action of Noopept are analyzed.

Proline-containing dipeptide GVS-111 retains nootropic activity after oral administration.

PubMed

Ostrovskaya, R U; Mirsoev, T K; Romanova, G A; Gudasheva, T A; Kravchenko, E V; Trofimov, C C; Voronina, T A; Seredenin, S B

2001-10-01

Experiments on rats trained passive avoidance task showed that N-phenyl-acetyl-L-prolyl-glycyl ethyl ester, peptide analog of piracetam (GVS-111, Noopept) after oral administration retained antiamnesic activity previously observed after its parenteral administration. Effective doses were 0.5-10 mg/kg. Experiments on a specially-developed model of active avoidance (massive one-session learning schedule) showed that GVS-111 stimulated one-session learning after single administration, while after repeated administration it increased the number of successful learners among those animals who failed after initial training. In this respect, GVS-111 principally differs from its main metabolite cycloprolylglycine and standard nootropic piracetam.

Aniracetam reversed learning and memory deficits following prenatal ethanol exposure by modulating functions of synaptic AMPA receptors.

PubMed

Vaglenova, Julia; Pandiella, Noemi; Wijayawardhane, Nayana; Vaithianathan, Tiru; Birru, Sandjay; Breese, Charles; Suppiramaniam, Vishnu; Randal, Clark

2008-04-01

Specific pharmacological treatments are currently not available to address problems resulting from fetal ethanol exposure, described as Fetal Alcohol Syndrome or Fetal Alcohol Spectrum Disorders (FASD). The present study evaluated the therapeutic effects of aniracetam against cognitive deficits in a well-characterized and sensitive FASD Sprague-Dawley rat model. Ethanol, administered orally at a moderate dose (4 g/kg/24 h; 38% v/v) during the entire course of pregnancy, caused severe cognitive deficits in offspring. Furthermore, both progeny genders were affected by a spectrum of behavioral abnormalities, such as a delay in the development of the righting reflex, poor novelty seeking behavior, and high anxiety levels in female rats. Cognitive disabilities, monitored in adult rats by a two-way active avoidance task, correlated well with a significant reduction of AMPA (alpha-amino-3 hydro-5 methyl-isoxazole propionic acid) receptor-mediated miniature excitatory postsynaptic responses (mEPSCs) in the hippocampus. Administration of aniracetam for 10 days (post-natal days (PND) 18-27), at a dose of 50 mg/kg reversed cognitive deficits in both rat genders, indicated by a significant increase in the number of avoidances and the number of 'good learners'. After the termination of the nootropic treatment, a significant increase in both amplitude and frequency of AMPA receptor-mediated mEPSCs in hippocampal CA-1 pyramidal cells was observed. Significant anxiolytic effects on PND 40 also preceded acquisition improvements in the avoidance task. This study provides evidence for the therapeutic potential of aniracetam in reversing cognitive deficits associated with FASD through positive post-natal modulation of AMPA receptors.

[The antiamnestic effect of nootropic substances in rats].

PubMed

Iasnetsov, Vik V; Krylova, I N

2013-01-01

It has been established in experiments in rats that some nootropic substances (oxyracetam, aniracetam, nooglutil, mexidol, new 3-hydroxypyridine derivative SK-170, piracetam and noopept) produce marked antiamnestic effect on various models of amnesia (induced by microwave irradiation, acute hypoxia, and motion sickness). At the same time, meclophenoxate exhibited antiamnestic effect in the first and second models of amnesia, while 9-aminoacridine derivative HTOS-404 was only effective in the model of amnesia caused by microwave irradiation. The antiamnestic effect of nooglutil and SK-170 was caused to a significant degree by activation of non-NMDA receptors of excitatory amino acids (generally AMPA receptors), while the effect of mexidol was related to GABA(A) receptors.

Molecular determinants for drug-receptor interactions. Part 2. An ab initio molecular orbital and dipole moment study of the novel nootropic agent piracetam (2-oxopyrrolidin-1-ylacetamide)

NASA Astrophysics Data System (ADS)

Lumbroso, H.; Liégeois, C.; Pappalardo, G. C.; Grassi, A.

From the ab initio molecular energies of the possible conformers and from a classical dipole moment analysis of 2-oxopyrrolidin-l-ylacetamide (μ = 4.02 D in dioxan at 30.0°C), the preferred conformation in solution of this novel nootropic agent has been determined. The exocyclic N-CH 2 bond is rotated in one sense by 90° and the exocyclic CH 2-C bond rotated in the same sense by 120° from the "planar" ( OO)- cis conformation. The structures of the two enantiomers in solution differ from that of the crystalline molecule.

Phenibut (β-Phenyl-γ-aminobutyric Acid) Dependence and Management of Withdrawal: Emerging Nootropics of Abuse.

PubMed

Ahuja, Tania; Mgbako, Ofole; Katzman, Caroline; Grossman, Allison

2018-01-01

This case report describes the development of withdrawal from phenibut, a gamma-aminobutyric acid-receptor type B agonist. Although phenibut is not an FDA-approved medication, it is available through online retailers as a nootropic supplement. There are reports of dependence in patients that misuse phenibut. We report a case in which a patient experienced withdrawal symptoms from phenibut and was successfully treated with a baclofen taper. This case report highlights the development of phenibut use disorder with coingestion of alcohol and potential management for phenibut withdrawal. We believe clinicians must be aware of how phenibut dependence may present and how to manage the withdrawal syndrome.

Noopept efficiency in experimental Alzheimer disease (cognitive deficiency caused by beta-amyloid25-35 injection into Meynert basal nuclei of rats).

PubMed

Ostrovskaya, R U; Belnik, A P; Storozheva, Z I

2008-07-01

Experiments on adult Wistar rats showed that injection of beta-amyloid25-35 (2 microg) into Meynert basal nuclei caused long-term memory deficiency which was detected 24 days after this injection by the memory trace retrieval in conditioned passive avoidance reflex (CPAR). The effects of noopept, an original nootropic and neuroprotective dipeptide, on the severity of this cognitive deficiency were studied. Preventive (for 7 days before the injury) intraperitoneal injections of noopept in a dose of 0.5 mg/kg completely prevented mnestic disorders under conditions of this model. Noopept exhibited a significant normalizing effect, if the treatment was started 15 days after the injury, when neurodegenerative changes in the basal nuclei, cortex, and hippocampus were still acutely pronounced. The mechanisms of this effect of the drug are studied, including, in addition to the choline-positive effect, its multicomponent neuroprotective effect and stimulation of production of antibodies to beta-amyloid25-35. Noopept efficiency in many models of Alzheimer disease, its high bioavailability and low toxicity suggest this dipeptide for further studies as a potential agent for the treatment of this condition (initial and moderate phases).

A novel CaV2.2 channel inhibition by piracetam in peripheral and central neurons.

PubMed

Bravo-Martínez, Jorge; Arenas, Isabel; Vivas, Oscar; Rebolledo-Antúnez, Santiago; Vázquez-García, Mario; Larrazolo, Arturo; García, David E

2012-10-01

No mechanistic actions for piracetam have been documented to support its nootropic effects. Voltage-gated calcium channels have been proposed as a promising pharmacological target of nootropic drugs. In this study, we investigated the effect of piracetam on Ca(V)2.2 channels in peripheral neurons, using patch-clamp recordings from cultured superior cervical ganglion neurons. In addition, we tested if Ca(V)2.2 channel inhibition could be related with the effects of piracetam on central neurons. We found that piracetam inhibited native Ca(V)2.2 channels in superior cervical ganglion neurons in a dose-dependent manner, with an IC(50) of 3.4 μmol/L and a Hill coefficient of 1.1. GDPβS dialysis did not prevent piracetam-induced inhibition of Ca(V)2.2 channels and G-protein-coupled receptor activation by noradrenaline did not occlude the piracetam effect. Piracetam altered the biophysical characteristics of Ca(V)2.2 channel such as facilitation ratio. In hippocampal slices, piracetam and ω-conotoxin GVIA diminished the frequency of excitatory postsynaptic potentials and action potentials. Our results provide evidence of piracetam's actions on Ca(V)2.2 channels in peripheral neurons, which might explain some of its nootropic effects in central neurons.

Neurite outgrowth of murine cerebellar granule cells can be enhanced by aniracetam with or without alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA).

PubMed

Fushiki, S; Matsumoto, K; Nagata, A

1995-10-27

To assess the neurotrophic effects of a nootropic drug, aniracetam, we studied neurite extension of mouse cerebellar granule cells in culture with low or with high K+ under different combinations of drugs and then immunohistochemically stained the cells with an antibody against L1, a neural cell adhesion molecule on cerebellar granule cells. Quantitative analyses using parameters of the total neurite length, maximal neurite length and number of branches disclosed that aniracetam, in the presence of high K+ and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), significantly enhanced neurite extension of cultured granule neurons. Aniracetam alone also stimulated neurite extension of cerebellar granule cells at a longer period of culture with low K+ showing a bell-shaped dose response curve with maximal effects at 10 microM. Aniracetam may influence remodeling of the neural network after injury.

Classification and evaluation of the pharmacodynamics of psychotropic drugs by single-lead pharmaco-EEG, EEG mapping and tomography (LORETA).

PubMed

Saletu, B; Anderer, P; Saletu-Zyhlarz, G M; Arnold, O; Pascual-Marqui, R D

2002-01-01

Utilizing computer-assisted quantitative analyses of human scalp-recorded electroencephalogram (EEG) in combination with certain statistical procedures (quantitative pharmaco-EEG) and mapping techniques (pharmaco-EEG mapping), it is possible to classify psychotropic substances and objectively evaluate their bioavailability at the target organ: the human brain. Specifically, one may determine at an early stage of drug development whether a drug is effective on the central nervous system (CNS) compared with placebo, what its clinical efficacy will be like, at which dosage it acts, when it acts and the equipotent dosages of different galenic formulations. Pharmaco-EEG profiles and maps of neuroleptics, antidepressants, tranquilizers, hypnotics, psychostimulants and nootropics/cognition-enhancing drugs will be described in this paper. Methodological problems, as well as the relationships between acute and chronic drug effects, alterations in normal subjects and patients, CNS effects, therapeutic efficacy and pharmacokinetic and pharmacodynamic data will be discussed. In recent times, imaging of drug effects on the regional brain electrical activity of healthy subjects by means of EEG tomography such as low-resolution electromagnetic tomography (LORETA) has been used for identifying brain areas predominantly involved in psychopharmacological action. This will be demonstrated for the representative drugs of the four main psychopharmacological classes, such as 3 mg haloperidol for neuroleptics, 20 mg citalopram for antidepressants, 2 mg lorazepam for tranquilizers and 20 mg methylphenidate for psychostimulants. LORETA demonstrates that these psychopharmacological classes affect brain structures differently.

Nootropic activity of Albizzia lebbeck in mice.

PubMed

Chintawar, S D; Somani, R S; Kasture, Veena S; Kasture, S B

2002-08-01

The effect of saponin containing n-butanolic fraction (BF) extracted from dried leaves of Albizzia lebbeck on learning and memory was studied in albino mice using passive shock avoidance paradigm and the elevated plus maze. Significant improvement was observed in the retention ability of the normal and amnesic mice as compared to their respective controls. We have also studied the effects of BF on the behavior influenced by serotonin (5-HT), noradrenaline and dopamine. The brain levels of serotonin, gamma-aminobutyric acid (GABA) and dopamine were also estimated to correlate the behavior with neurotransmitter levels. The brain concentrations of GABA and dopamine were decreased, whereas the 5-HT level was increased. The data indicate the involvement of monoamine neurotransmitters in the nootropic action of BF of A. lebbeck.

Piracetam attenuates binge eating disorder related symptoms in rats.

PubMed

Hussain, Yusuf; Krishnamurthy, Sairam

2018-06-01

Binge eating disorder (BED) is a stress-related disorder characterized by acute episodes of excessive food intake. Piracetam, a nootropic agent has been reported to show several other neuropharmacological properties. The present study, evaluated the pharmacological effect of piracetam (200 mg/kg i.p.) on BED in female rats, induced by free access to palatable cookies for 2 h on alternate days. BED was confirmed by an increase in binge eating behavior and weight gain. BED leads to anxiety, cognitive and memory deficits, as evaluated by EPM (Elevated plus maze), OFT (open field test), and Y-maze tests. Increased levels of plasma corticosterone (CORT), glutamate in nucleus accumbens (NAC), hypothalamus (HYP) and prefrontal cortex (PFC) indicate stress and excitotoxicity. Moreover, it was observed that the levels of dopamine were higher in NAC and PFC, and less in HYP which may be responsible for motivational behavior for palatable feeding and cognitive deficits. More surprisingly, feeding behaviour regulating hormones namelyleptin was increased and ghrelin level was decreased in BED. Further, level of acetylcholine which regulates cognitive behaviour was compromised in BED. Piracetam significantly decreased binge eating behavior and associated body weight and regulated the levels of concerned neurotransmitters in respective regions. However, piracetam did not alter normal feeding behavior in the fast-refed model. Further, piracetam showed brain region-specific decrease in vascular endothelial growth factor expression. Piracetam showed anxiolytic activity and also alleviated cognitive deficit observed in BED. Hence, preclinical evidence indicates the potential use of piracetam for the treatment of BED. Copyright © 2018 Elsevier Inc. All rights reserved.

[Antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives and their nootropic action in alloxan diabetes].

PubMed

Volchegorskiĭ, I A; Rassokhina, L M; Miroshnichenko, I Iu

2011-01-01

Relationship between the antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives (emoxipine, reamberin and mexidol) and their effect on conditional learning, glycemia, and lipidemia was studied in rats with alloxan-induced diabetes. In parallel, the analogous relationship was investigated for alpha-lipoic acid that is regarded as a "gold standard" in treatment of diabetic neuropathy. It was established that single administration of emoxipine and mexidol in mice in doses equivalent to therapeutic-range doses in humans produces antihypoxic effect manifested by increased resistance to acute hypoxic hypoxia in test animals. Alpha-lipoic acid is inferior to emoxipin and mexidol in the degree of antihypoxic action. Reamberin does not exhibit this effect. The introduction of emoxipin, reamberin, mexidol, and alpha-lipoic acid in rats with alloxan diabetes during 7 or 14 days in doses equivalent to therapeutic-range doses in humans corrects conditional learning disorders in direct relationship with the antihypoxic activity of these drugs. The development of the nootropic effect of emoxipin, mexidol, and alpha-lipoic acid is related to a decrease in hyperglycemia and hyperlipidemia in rats with alloxan diabetes. The nootropic action of reamberin is accompanied by a transient hypoglycemizing effect and aggravation of dyslipidemic disorders. The antihypoxic activity of investigated drugs determines the direction and expression of their lipidemic effect, but is not correlated with the hypoglycemizing action these drugs on test animals with alloxan diabetes.

Piracetam inhibits ethanol (EtOH)-induced memory deficit by mediating multiple pathways.

PubMed

Yang, Yifan; Feng, Jian; Xu, Fangyuan; Wang, Jianglin

2017-12-01

Excessive ethanol (EtOH) intake, especially to prenatal exposure, can significantly affect cognitive function and cause permanent learning and memory injures in children. As a result, how to protect children from EtOH neurotoxicity has gained increasing attention in recent years. Piracetam (Pir) is a nootropic drug derived from c-aminobutyric acid and can manage cognition impairments in multiple neurological disorders. Studies have shown that Pir can exert therapeutic effects on EtOH-induced memory impairments, but the underlying mechanism is still unknown. In this study, we found that Pir inhibited ethanol-induced memory deficit by mediating multiple pathways. Treatment with EtOH could cause cognitive deficit in juvenile rats, and triggered the alteration of synaptic plasticity. Administration with Pir significantly increased long-term potentiation and protected hippocampus neurons from EtOH neurotoxicity. Pir intervention ameliorated EtOH-induced cell apoptosis and inhibited the activation of Caspase-3 in vitro, suggesting that Pir protected neurons by anti-apoptotic effects. Pir could decrease the expression of LC3-II and Beclin-1 induced by EtOH, and increase the phosphorylation of mTOR and reduce the phosphorylation of Akt, which suggested that the protective effect of Pir was involved in regulation of autophagic process and mTOR/Akt pathways. In conclusion, we speculate that Pir reduces EtOH-induced neuronal damage by regulation of apoptotic action and autophagic action, and our research offers preclinical evidence for the application of Pir in ethanol toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel nootropic drug sunifiram improves cognitive deficits via CaM kinase II and protein kinase C activation in olfactory bulbectomized mice.

PubMed

Moriguchi, Shigeki; Tanaka, Tomoya; Tagashira, Hideaki; Narahashi, Toshio; Fukunaga, Kohji

2013-04-01

Alzheimer's disease (AD) shows degeneration of the cholinergic system in the medial septum, thereby eliciting down-regulation of the olfactory function in patients. We have previously reported that olfactory bulbectomized (OBX) mice show hippocampus-dependent memory impairment as assessed by memory-related behavioral tasks and hippocampal long-term potentiation (LTP). In the present study, we focused whether novel pyrrolidone nootropic drug sunifiram improves both memory impairment and depression observed in OBX mice. OBX mice were administered once a day for 7-12 days with sunifiram (0.01-1.0mg/kg p.o.) from 10 days after operation with or without gavestinel (10mg/kg i.p.), which is glycine-binding site inhibitor of N-methyl-d-aspartate receptor (NMDAR). The spatial reference memory assessed by Y-maze and short-term memory assessed by novel object recognition task were significantly improved by sunifiram treatment in OBX mice. Sunifiram also restored hippocampal LTP injured in OBX mice without treatment with gavestinel. By contrast, sunifiram treatment did not ameliorate the depressive behaviors assessed by tail suspension task in OBX mice. Notably, sunifiram treatment restored CaMKIIα (Thr-286) autophosphorylation and GluR1 (Ser-831) phosphorylation in the hippocampal CA1 region from OBX mice to the levels of control mice. Likewise, sunifiram treatment improved PKCα (Ser-657) autophosphorylation and NR1 (Ser-896) phosphorylation to the control levels. Stimulation of CaMKII and PKC autophosphorylation by sunifiram was significantly inhibited by pre-treatment with gavestinel. However, sunifiram treatment did not affect the phosphorylation of CaMKIV (Thr-196) and ERK. Taken together, sunifiram ameliorates OBX-induced deficits of memory-related behaviors and impaired LTP in the hippocampal CA1 region via stimulation of glycine-binding site of NMDAR. Copyright © 2013 Elsevier B.V. All rights reserved.

Beta-hydroxy-beta-methylbutyrate (HMB) ameliorates age-related deficits in water maze performance, especially in male rats.

PubMed

Kougias, Daniel G; Hankosky, Emily R; Gulley, Joshua M; Juraska, Janice M

2017-03-01

Beta-hydroxy-beta-methylbutyrate (HMB) is commonly supplemented to maintain muscle in elderly and clinical populations and has potential as a nootropic. Previously, we have shown that in both male and female rats, long-term HMB supplementation prevents age-related dendritic shrinkage within the medial prefrontal cortex (mPFC) and improves cognitive flexibility and working memory performance that are both age- and sex-specific. In this study, we further explore the cognitive effects by assessing visuospatial learning and memory with the Morris water maze. Female rats were ovariectomized at 11months of age to model human menopause. At 12months of age, male and female rats received relatively short- or long-term (1- or 7-month) dietary HMB (450mg/kg/dose) supplementation twice a day prior to testing. Spatial reference learning and memory was assessed across four days in the water maze with four trials daily and a probe trial on the last day. Consistent with previous work, there were age-related deficits in water maze performance in both sexes. However, these deficits were ameliorated in HMB-treated males during training and in both sexes during probe trial performance. Thus, HMB supplementation prevented the age-related decrement in water maze performance, especially in male rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Analgesic activity of piracetam: effect on cytokine production and oxidative stress.

PubMed

Navarro, Suelen A; Serafim, Karla G G; Mizokami, Sandra S; Hohmann, Miriam S N; Casagrande, Rubia; Verri, Waldiceu A

2013-04-01

Piracetam is a prototype of nootropic drugs used to improve cognitive impairment. However, recent studies suggest that piracetam can have analgesic and anti-inflammatory effects. Inflammatory pain is the result of a process that depends on neutrophil migration, cytokines and prostanoids release and oxidative stress. We analyze whether piracetam has anti-nociceptive effects and its mechanisms. Per oral pretreatment with piracetam reduced in a dose-dependent manner the overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone, formalin and complete Freund's adjuvant. Piracetam also diminished carrageenin-induced mechanical and thermal hyperalgesia, myeloperoxidase activity, and TNF-α-induced mechanical hyperalgesia. Piracetam presented analgesic effects as post-treatment and local paw treatment. The analgesic mechanisms of piracetam were related to inhibition of carrageenin- and TNF-α-induced production of IL-1β as well as prevention of carrageenin-induced decrease of reduced glutathione, ferric reducing ability and free radical scavenging ability in the paw. These results demonstrate that piracetam presents analgesic activity upon a variety of inflammatory stimuli by a mechanism dependent on inhibition of cytokine production and oxidative stress. Considering its safety and clinical use for cognitive function, it is possible that piracetam represents a novel perspective of analgesic. Copyright © 2013 Elsevier Inc. All rights reserved.

Postnatal aniracetam treatment improves prenatal ethanol induced attenuation of AMPA receptor-mediated synaptic transmission.

PubMed

Wijayawardhane, Nayana; Shonesy, Brian C; Vaglenova, Julia; Vaithianathan, Thirumalini; Carpenter, Mark; Breese, Charles R; Dityatev, Alexander; Suppiramaniam, Vishnu

2007-06-01

Aniracetam is a nootropic compound and an allosteric modulator of AMPA receptors (AMPARs) which mediate synaptic mechanisms of learning and memory. Here we analyzed impairments in AMPAR-mediated synaptic transmission caused by moderate prenatal ethanol exposure and investigated the effects of postnatal aniracetam treatment on these abnormalities. Pregnant Sprague-Dawley rats were gavaged with ethanol or isocaloric sucrose throughout pregnancy, and subsequently the offspring were treated with aniracetam on postnatal days (PND) 18 to 27. Hippocampal slices prepared from these pups on PND 28 to 34 were used for the whole-cell patch-clamp recordings of AMPAR-mediated spontaneous and miniature excitatory postsynaptic currents in CA1 pyramidal cells. Our results indicate that moderate ethanol exposure during pregnancy results in impaired hippocampal AMPAR-mediated neurotransmission, and critically timed aniracetam treatment can abrogate this deficiency. These results highlight the possibility that aniracetam treatment can restore synaptic transmission and ameliorate cognitive deficits associated with the fetal alcohol syndrome.

[Design of the novel dipeptide neuropsychotropic drug preparations].

PubMed

Gudasheva, T A; Skoldinov, A P

2003-01-01

The paper considers a new strategy in the field of neuropsychotropic dipeptide drug design, the main points being as follows: (i) determination of the structural elements of dipeptides, such as fragments of amino acid side radicals and peptide bonds, in nonpeptide drugs; (ii) design of peptide analogs topologically close to the drug; (iii) synthesis and activity testing of these analogs; (iv) determination of the corresponding endogenous neuropeptide among the known neuropeptides or identification of the new neuropeptides in the brain of experimental animals. Using this approach, new pyroglutamyl- and prolyl-containing dipeptides were obtained based on the structure of the well-known classical nootropic drug piracetam. The new drugs exhibit nootropic activity in doses 100-10,000 times lower than those of piracetam. The structure of most active pyroglutamyl dipeptide pGlu-Asn-NH2 coincides with that of the N-end fragment of the endogenous memory peptide AVP(4-9). Noopept (N-phenylacetylprolylglycine ethyl ester), patented in Russia and USA as a new nootropic drug, is currently under stage 2 of successful clinical trials. The main metabolite of noopept, cyclo-Pro-Gly, is identical to the endogenous dipeptide designed in this work and is most close analog of piracetam with respect to pharmacological activity. The universal character of the proposed strategy is demonstrated by the design of active dipeptide analogs of an atypical neuroleptic drug sulpiride. As a result, a potential dipeptide neuroleptic dilept was obtained, which has been patented in Russia and now passes broad preclinical trials.

Prosopis cineraria: a potential nootropic agent.

PubMed

Bithu, Bhawani Singh; Reddy, N Ranga; Prasad, Satyendra K; Sairam, Krishnamurthy; Hemalatha, S

2012-10-01

Prosopis cineraria (L.) Druce (Leguminosae), a plant of the Thar Desert of India and Pakistan is used traditionally by local people for the treatment of memory disorders and to arrest wandering of the mind. The study includes scientific validation of P. cineraria for nootropic activity. To elucidate the possible mechanism, the anticholinesterase activity was also investigated in different parts of the brain. Methanol extract of P. cineraria stem bark (200, 400 and 600 mg/kg body weight p.o.) was administered once in a day for 7 days to rats and these rats were then subjected to Morris water-maze (MWM) test for spatial reference memory (SRM) and spatial working memory (SWM) versions of memory testing. The inhibitory effect of the extract on acetylcholinesterase (AChE) in discrete rat brain regions (prefrontal cortex [PFC], hippocampus [HIP] and amygdala [AMY]) was also investigated using acetyl thiocholine iodide and dithiobisnitrobenzoic acid reagent. The oral administrations of methanol extract of P. cineraria in all doses tested, significantly (p < 0.05) improved both spatial reference and working memories in the MWM test in terms of decrease in escape latency during SRM and increase in time spent in the target quadrant during SWM probe trial. A ceiling effect was observed at 400 mg/kg. Pre-treatment for 7 days significantly inhibited the activity of AChE in the HIP, PFC and AMY. The extract exerted significant nootropic activity in the MWM test which may be attributed to the inhibition of brain AChE.

Effect of piracetam, a nootropic agent, on rat brain monoamines and prostaglandins.

PubMed

Bhattacharya, S K; Upadhyay, S N; Jaiswal, A K; Bhattacharya, S

1989-03-01

Piracetam is the prototype of a new class of psychotropic drugs, the nootropic agents, which are claimed to selectively improve the higher telencephalic integrative activities. The effect of piracetam on rat brain monoamines and prostaglandins (PGs) was assessed so as to garner information on its mode of action. Two doses of the drug were used, a lower dose (20 mg/kg ip) and a higher dose (100 mg/kg, ip), the latter being known to exert a facilitatory effect on learning and memory. Piracetam produced a dose-related effect on rat brain serotonin (5HT) and noradrenaline (NA), with the lower dose inducing a decrease in 5HT levels and an increase in NA concentrations. The higher dose of piracetam produced the opposite effect. Dopamine (DA) levels were not significantly affected. The lower dose of the drug attenuated 5HT turnover and augmented that of NA, whereas the higher dose of piracetam produced the reverse effects, in clorgyline treated rats. The lower dose of piracetam produced a slight and statistically insignificant increase in rat brain PGE2 and PGF2 alpha. However, the higher dose of the drug produced marked increase in the levels of both the PGs. The observed biochemical effects may provide a basis for the nootropic effect of piracetam. However, they may also be due to the GA-BA-mimetic action of the drug, particularly those observed with the lower dose of piracetam.

Аnticonvulsant effects of citicoline and diazepam at their combined application on model of the acute generalized convulsions induced by pentylenetetrazole in Wistar rats.

PubMed

Kuznetsova, L V; Karpova, M N; Zinkovski, K A; Klishina, N Yu

2016-01-01

Studying of efficiency of the combined application of the citicoline possessing nootropic and anticonvulsive action and antiepileptic drug of diazepam on the acute generalized convulsions (AGC) caused by a convulsant pentylentetrazole (PTZ). Experiments are executed on the male Wistar rats (n = 68) weighing 160-190 g on the AGС model caused by of PTZ in a dose of 80 mg/kg, intraperitoneally (i.p.). For studying of efficiency of the combined use of drugs determined the minimum anticonvulsive action of a citicoline (Tserakson, «Nicomed Ferrer Internacional, S.A.») and diazepam (Relanium, Warsaw pharmaceutical plant of Polf AO, Warsaw, Poland). For this citicoline were administered i.p. in doses 500 and 300 mg/kg 1 hour before the PTZ and diazepam - in doses of 0,5 and 0,25 mg/kg 30 min before administration of PTZ. Control animals were injected with saline to the same extent and under the same experimental conditions. It is shown that the combined administration of a citicoline and diazepam in minimum active doses (300 and 0.25 mg/kg respectively), increases anticonvulsive properties of both drugs. The combined administration of citicoline with diazepam in minimally active doses enhances anticonvulsant properties of both drugs, thereby reducing the risk of development of side effects. In addition, the research may serve as experimental justification for the use of drugs in case of convulsions for the purpose beneficial effect on cognitive function and delays of progressing of neurodegenerative processes.

Aniracetam reduces glutamate receptor desensitization and slows the decay of fast excitatory synaptic currents in the hippocampus.

PubMed Central

Isaacson, J S; Nicoll, R A

1991-01-01

Aniracetam is a nootropic drug that has been shown to selectively enhance quisqualate receptor-mediated responses in Xenopus oocytes injected with brain mRNA and in hippocampal pyramidal cells [Ito, I., Tanabe, S., Kohda, A. & Sugiyama, H. (1990) J. Physiol. (London) 424, 533-544]. We have used patch clamp recording techniques in hippocampal slices to elucidate the mechanism for this selective action. We find that aniracetam enhances glutamate-evoked currents in whole-cell recordings and, in outside-out patches, strongly reduces glutamate receptor desensitization. In addition, aniracetam selectively prolongs the time course and increases the peak amplitude of fast synaptic currents. These findings indicate that aniracetam slows the kinetics of fast synaptic transmission and are consistent with the proposal [Trussell, L. O. & Fischbach, G. D. (1989) Neuron 3, 209-218; Tang, C.-M., Dichter, M. & Morad, M. (1989) Science 243, 1474-1477] that receptor desensitization governs the strength of fast excitatory synaptic transmission in the brain. PMID:1660156

Aniracetam reduces glutamate receptor desensitization and slows the decay of fast excitatory synaptic currents in the hippocampus.

PubMed

Isaacson, J S; Nicoll, R A

1991-12-01

Aniracetam is a nootropic drug that has been shown to selectively enhance quisqualate receptor-mediated responses in Xenopus oocytes injected with brain mRNA and in hippocampal pyramidal cells [Ito, I., Tanabe, S., Kohda, A. & Sugiyama, H. (1990) J. Physiol. (London) 424, 533-544]. We have used patch clamp recording techniques in hippocampal slices to elucidate the mechanism for this selective action. We find that aniracetam enhances glutamate-evoked currents in whole-cell recordings and, in outside-out patches, strongly reduces glutamate receptor desensitization. In addition, aniracetam selectively prolongs the time course and increases the peak amplitude of fast synaptic currents. These findings indicate that aniracetam slows the kinetics of fast synaptic transmission and are consistent with the proposal [Trussell, L. O. & Fischbach, G. D. (1989) Neuron 3, 209-218; Tang, C.-M., Dichter, M. & Morad, M. (1989) Science 243, 1474-1477] that receptor desensitization governs the strength of fast excitatory synaptic transmission in the brain.

[Effects of noopept and cortexin on the behavior of matured rats treated with corticoliberin or 70-kDa heat shock proteins in early ontogeny].

PubMed

Shabanov, P D; Lebedev, A A; Stetsenko, V P; Lavrov, N V; Sablina, G V; Gudasheva, T A; Ostrovaskaia, R U

2007-01-01

Young Wistar rats aged 4 days were injected intraperitoneally with corticotropin releasing hormone (CRH), which is an agent activating the stress system, or 70-kDa heat shock proteins (HSP-70)--intracellular shaperons, possessing antistress properties. In grown adult rats aged 90-100 days, the effects of nootropic drugs noopept and cortexin (1 mg/kg, i.p.) were assessed. The activation of stress or antistress systems with CRH or HSP-70 significantly altered the drug action. The effects were different in males and females and depended on animal gender. The spectrum of pharmacological activity of noopept and cortexin changed: noopept demonstrated preferable psychoactivating and antiaggressive effects, whereas cortexin showed mild anxiolytic and antidepressant activity. It is suggested that the behavioral effects of nootropes depend on the conditions of the stress system formation in early ontogeny.

Comparison of Nootropic and Neuroprotective Features of Aryl-Substituted Analogs of Gamma-Aminobutyric Acid.

PubMed

Tyurenkov, I N; Borodkina, L E; Bagmetova, V V; Berestovitskaya, V M; Vasil'eva, O S

2016-02-01

GABA analogs containing phenyl (phenibut) or para-chlorophenyl (baclofen) substituents demonstrated nootropic activity in a dose of 20 mg/kg: they improved passive avoidance conditioning, decelerated its natural extinction, and exerted antiamnestic effect on the models of amnesia provoked by scopolamine or electroshock. Tolyl-containing GABA analog (tolibut, 20 mg/kg) exhibited antiamnestic activity only on the model of electroshock-induced amnesia. Baclofen and, to a lesser extent, tolibut alleviated seizures provoked by electroshock, i.e. both agents exerted anticonvulsant effect. All examined GABA aryl derivatives demonstrated neuroprotective properties on the maximum electroshock model: they shortened the duration of coma and shortened the period of spontaneous motor activity recovery. In addition, these agents decreased the severity of passive avoidance amnesia and behavioral deficit in the open field test in rats exposed to electroshock. The greatest neuroprotective properties were exhibited by phenyl-containing GABA analog phenibut.

[Effect of centrophenoxine, piracetam and aniracetam on the monoamine oxidase activity in different brain structures of rats].

PubMed

Stancheva, S L; Alova, L G

1988-01-01

In vitro studies of effects of some nootropic drugs (centrophenoxine, piracetam and aniracetam) on monoamine oxidase (MAO) activity in the rat striatum and hypothalamus, using tyramine, serotonin and beta-phenylethylamine as substrates, were carried out. At all concentrations used (5.10(-5)-1.10(-3) M) centrophenoxine inhibited total MAO, MAO A and MAO B in both brain structures. Piracetam activated striatal and hypothalamic total MAO, hypothalamic MAO A and MAO B but exerted a pronounced inhibitory effect on MAO A and MAO B activity in the striatum. Aniracetam inhibited total MAO and MAO A in both brain structures but activated striatal and hypothalamic MAO B. The different effects of centrophenoxine, piracetam and aniracetam on MAO activity in the brain structures support the view for the independent mode of action of nootropic drugs in spite of their similar molecular and metabolic activity.

Nootropic activity of lipid-based extract of Bacopa monniera Linn. compared with traditional preparation and extracts.

PubMed

Lohidasan, Sathiyanarayanan; Paradkar, Anant R; Mahadik, Kakasaheb R

2009-11-01

The aim was to design an alternative solvent-free extraction method using the hydrophilic lipid Gelucire (polyethylene glycol glycerides) for herbal extraction and to confirm the efficacy of extraction using biological screening. Bacopa monniera Linn. (BM) was selected for the study. Conventional methanolic extract (MEBM), Ayurvedic ghrita (AGBM) and lipid extracts (LEBM) were prepared and standardised by high-performance thin-layer chromatography (HPTLC). Nootropic activity in rats was evaluated using the two-trial Y-maze test and the anterograde amnesia induced by scopolamine (1 mg/kg i.p.) determined by the conditioned avoidance response. The extracts were administered daily at doses of 100, 200 and 400 mg/kg orally. At the end of the conditioned avoidance response test, brain monoamine levels were estimated by HPLC. The LEBM, MEBM and AGBM contained 3.56%, 4.10% and 0.005% bacoside A, respectively. Significantly greater spatial recognition was observed with LEBM (P < 0.001 at 400 and 200 mg/kg) and MEBM (P < 0.001 at 400 mg/kg, P < 0.01 at 200 mg/kg) than AGBM. The conditioned avoidance response was significantly higher in the groups treated with high doses of LEBM and MEBM than AGBM. There were significant decreases in brain noradrenaline (P < 0.001) and 5-hydroxytryptamine (P < 0.01) levels and an increase in dopamine levels (P < 0.05) in the LEBM-treated groups compared with the stress control group. The proposed LEBM is solvent free, does not have the shortcomings associated with conventional extraction, and had comparable nootropic activity to the MEBM.

Chromatographic behaviour predicts the ability of potential nootropics to permeate the blood-brain barrier.

PubMed

Farsa, Oldřich

2013-01-01

The log BB parameter is the logarithm of the ratio of a compound's equilibrium concentrations in the brain tissue versus the blood plasma. This parameter is a useful descriptor in assessing the ability of a compound to permeate the blood-brain barrier. The aim of this study was to develop a Hansch-type linear regression QSAR model that correlates the parameter log BB and the retention time of drugs and other organic compounds on a reversed-phase HPLC containing an embedded amide moiety. The retention time was expressed by the capacity factor log k'. The second aim was to estimate the brain's absorption of 2-(azacycloalkyl)acetamidophenoxyacetic acids, which are analogues of piracetam, nefiracetam, and meclofenoxate. Notably, these acids may be novel nootropics. Two simple regression models that relate log BB and log k' were developed from an assay performed using a reversed-phase HPLC that contained an embedded amide moiety. Both the quadratic and linear models yielded statistical parameters comparable to previously published models of log BB dependence on various structural characteristics. The models predict that four members of the substituted phenoxyacetic acid series have a strong chance of permeating the barrier and being absorbed in the brain. The results of this study show that a reversed-phase HPLC system containing an embedded amide moiety is a functional in vitro surrogate of the blood-brain barrier. These results suggest that racetam-type nootropic drugs containing a carboxylic moiety could be more poorly absorbed than analogues devoid of the carboxyl group, especially if the compounds penetrate the barrier by a simple diffusion mechanism.

A Systematic Review of Intervention Studies Examining Nutritional and Herbal Therapies for Mild Cognitive Impairment and Dementia Using Neuroimaging Methods: Study Characteristics and Intervention Efficacy

PubMed Central

MacMillan, Freya; Camfield, David A.; Seto, Sai W.

2017-01-01

Neuroimaging facilitates the assessment of complementary medicines (CMs) by providing a noninvasive insight into their mechanisms of action in the human brain. This is important for identifying the potential treatment options for target disease cohorts with complex pathophysiologies. The aim of this systematic review was to evaluate study characteristics, intervention efficacy, and the structural and functional neuroimaging methods used in research assessing nutritional and herbal medicines for mild cognitive impairment (MCI) and dementia. Six databases were searched for articles reporting on CMs, dementia, and neuroimaging methods. Data were extracted from 21/2,742 eligible full text articles and risk of bias was assessed. Nine studies examined people with Alzheimer's disease, 7 MCI, 4 vascular dementia, and 1 all-cause dementia. Ten studies tested herbal medicines, 8 vitamins and supplements, and 3 nootropics. Ten studies used electroencephalography (EEG), 5 structural magnetic resonance imaging (MRI), 2 functional MRI (fMRI), 3 cerebral blood flow (CBF), 1 single photon emission tomography (SPECT), and 1 positron emission tomography (PET). Four studies had a low risk of bias, with the majority consistently demonstrating inadequate reporting on randomisation, allocation concealment, blinding, and power calculations. A narrative synthesis approach was assumed due to heterogeneity in study methods, interventions, target cohorts, and quality. Eleven key recommendations are suggested to advance future work in this area. PMID:28303161

Effects of nootropics on the EEG in conscious rats and their modification by glutamatergic inhibitors.

PubMed

Vorobyov, Vasily; Kaptsov, Vladimir; Kovalev, Georgy; Sengpiel, Frank

2011-05-30

To study the effects of acute and repeated injections of nootropics and to learn how glutamate receptors might be involved in their mediation, the frequency spectra of cortical and hippocampal electroencephalogram (EEG) were analyzed in non-narcotized rats subcutaneously injected repeatedly with Piracetam (400mg/kg) or its analogue, Noopept (0.2mg/kg), after intracerebroventricular infusions of saline (5 μl) or the antagonists of NMDA and quisqualate/AMPA receptors: CPP (0.1 nmol) and GDEE (1 μmol), respectively. Piracetam increased alpha/beta1 EEG activity in the left frontal cortex, and alpha activity in both the right cortex and hippocampus, with a 10-min latency and 40-min duration. Noopept increased alpha/beta1 activity, with 30-min latency and 40-min duration in all brain areas. CPP pretreatment eliminated Piracetam EEG effects; reduced Noopept effects in the cortex and completely suppressed them in the hippocampus. After four injections of Piracetam, EEG effects were very small in the cortex, and completely lacking in the hippocampus, while GDEE pretreatment partially recovered them. The effect of Noopept in the alpha/beta1 ranges was replaced by increased beta2 activity after the eighth injection, while no effects were observed after the ninth one. GDEE pretreatment restored the effect of Noopept in the beta2 frequency range. These results demonstrate similarities in EEG effects and their mediatory mechanisms for Piracetam and its much more effective analogue, Noopept. Activation of NMDA receptors is involved in the effects of a single injection of the nootropics, whereas activation of quisqualate/AMPA receptors is associated with the decrease in their efficacy after repeated use. Copyright © 2011 Elsevier Inc. All rights reserved.

Chromatographic Behaviour Predicts the Ability of Potential Nootropics to Permeate the Blood-Brain Barrier

PubMed Central

Farsa, Oldřich

2013-01-01

The log BB parameter is the logarithm of the ratio of a compound’s equilibrium concentrations in the brain tissue versus the blood plasma. This parameter is a useful descriptor in assessing the ability of a compound to permeate the blood-brain barrier. The aim of this study was to develop a Hansch-type linear regression QSAR model that correlates the parameter log BB and the retention time of drugs and other organic compounds on a reversed-phase HPLC containing an embedded amide moiety. The retention time was expressed by the capacity factor log k′. The second aim was to estimate the brain’s absorption of 2-(azacycloalkyl)acetamidophenoxyacetic acids, which are analogues of piracetam, nefiracetam, and meclofenoxate. Notably, these acids may be novel nootropics. Two simple regression models that relate log BB and log k′ were developed from an assay performed using a reversed-phase HPLC that contained an embedded amide moiety. Both the quadratic and linear models yielded statistical parameters comparable to previously published models of log BB dependence on various structural characteristics. The models predict that four members of the substituted phenoxyacetic acid series have a strong chance of permeating the barrier and being absorbed in the brain. The results of this study show that a reversed-phase HPLC system containing an embedded amide moiety is a functional in vitro surrogate of the blood-brain barrier. These results suggest that racetam-type nootropic drugs containing a carboxylic moiety could be more poorly absorbed than analogues devoid of the carboxyl group, especially if the compounds penetrate the barrier by a simple diffusion mechanism. PMID:23641330

EEG topography and tomography (LORETA) in the classification and evaluation of the pharmacodynamics of psychotropic drugs.

PubMed

Saletu, Bernd; Anderer, Peter; Saletu-Zyhlarz, Gerda M

2006-04-01

By multi-lead computer-assisted quantitative analyses of human scalp-recorded electroencephalogram (QEEG) in combination with certain statistical procedures (quantitative pharmaco-EEG) and mapping techniques (pharmaco-EEG mapping or topography), it is possible to classify psychotropic substances and objectively evaluate their bioavailability at the target organ, the human brain. Specifically, one may determine at an early stage of drug development whether a drug is effective on the central nervous system (CNS) compared with placebo, what its clinical efficacy will be like, at which dosage it acts, when it acts and the equipotent dosages of different galenic formulations. Pharmaco-EEG maps of neuroleptics, antidepressants, tranquilizers, hypnotics, psychostimulants and nootropics/cognition-enhancing drugs will be described. Methodological problems, as well as the relationships between acute and chronic drug effects, alterations in normal subjects and patients, CNS effects and therapeutic efficacy will be discussed. Imaging of drug effects on the regional brain electrical activity of healthy subjects by means of EEG tomography such as low-resolution electromagnetic tomography (LORETA) has been used for identifying brain areas predominantly involved in psychopharmacological action. This will be shown for the representative drugs of the four main psychopharmacological classes, such as 3 mg haloperidol for neuroleptics, 20 mg citalopram for antidepressants, 2 mg lorazepam for tranquilizers and 20 mg methylphenidate for psychostimulants. LORETA demonstrates that these psychopharmacological classes affect brain structures differently. By considering these differences between psychotropic drugs and placebo in normal subjects, as well as between mental disorder patients and normal controls, it may be possible to choose the optimum drug for a specific patient according to a key-lock principle, since the drug should normalize the deviant brain function. Thus, pharmaco-EEG topography and tomography are valuable methods in human neuropsychopharmacology, clinical psychiatry and neurology.

[Study of acetylsalicylic acid role in the potentiation of antiamnesic and neuroprotective properties of piracetam in rats with alloxan diabetes].

PubMed

Zhiliuk, V I; Levykh, A E; Mamchur, V I

2013-01-01

It has been established that prolonged alloxan-induced hyperglycemia in rats potentiates amnesic properties of scopolamine hydrobromide. It was characterized by shortening of the latent period by 44% (p<0,01) and by 47,7% (p<0,05) after 24 hours and on the 20th day of conditioned passive avoidance test. This effect was accompanied by increase in oxidative modification of proteins and nitric oxide synthesis in the cerebral cortex. Along with this, a significant enhancement of ADP- and collagen-induced platelet aggregation was observed. These processes may play the leading role in the development of cognitive deficit in diabetes. Meanwhile, co-administration of piracetam with acetylsalicylic acid was accompanied by an expressed antiamnetic potential - the reduction of early markers of proteins degradation (aldehydephenylhydrazones, APH) by 21,7% (p<0,05) and late markers of proteins degradation (ketonephenylhydrazones, KPH) by 23,8% (p<0,001) was noted. This combination was 15,7% (p<0,05) more active than piracetam according to the effect upon KPH. NO2-/NO3- level was also decreased by 30,3% (p<0,05) in comparison with alloxan-diabetic rats. The significant anti-platelet effect was observed: degree of collagen-induced platelet aggregation was reduced by 56,8% (p<0,01), ADP (5 μmol/l)-induced - by 31,7% (p<0,01), ADP (20 μmol/l)-induced - by 47,3% (p<0,01) as compared to the hyperglycemic rats. Such an increase in nootropic activity of piracetam may be assumed to be directly related to the ability of acetylsalicylic acid to improve microcirculation in the ischemic areas of the brain in diabetes and probably to its neuroprotective potential.

[The dynamics of behavioral and neuroreceptor effects after acute and long-term noopept administration in C57BL/6 and BALB/c mice].

PubMed

Kovalev, G I; Kondrakhin, E A; Salimov, R M; Neznamov, G G

2014-01-01

The effect of acute, 7-fold and 14-fold noopept (1 mg/kg/day) administration on the dynamics of anxiolitic and nootropic behavioral effects in cross-maze, as well as their correlations with NMDA- and BDZ-receptor density was studied in inbred mice strains, differing in exploratory and emotional status--C57BL/6 and BALB/c. The dipeptide failed to affect the anxiety and exploration activity in C57BL/6 mice at each of 3 steps of experimental session. In this strain the B(max) values of [3H]-MK-801 and [3H]-Flunitrazepam binding changed only after single administration. In respect to BALB/c mice noopept induced both the anxiolitic and nootropic effects reaching their maximum on 7th day. In BALB/c strain the dynamics of hippocampal NMDA-receptor binding corresponds to the dynamics of exploratory efficacy whereas the dynamics of BDZ-receptors in prefrontal cortex was reciprocally to dynamics of anxiety level.

[Dipeptide nootropic agent GVS-111 prevents accumulation of the lipid peroxidation products during immobilization].

PubMed

Lysenko, A V; Uskova, N I; Ostrovskaia, R U; Gudasheva, T A; Voronina, T A

1997-01-01

Immobilization of rats in a narrow plastic chamber for 24 h caused a sharp increase in the level of diene conjugates and the content of schiff bases in the synaptosomes of the brain cortex as well as accumulation of extraerythrocytic hemoglobin in blood serum. The dipeptide nootropic agent GVS-111 (ethyl ether of phenylacetylprolylglycine), when administered 15 and particularly 60 min before immobilization reduced the accumulation of these products of lipid peroxidation in the brain and blood. GVS-111 demonstrated these signs of its antioxidant effect after a single i.p. injection in doses of 0.12 and 0.5 mg/kg. Pyracetam produced a similar effect on the listed parameters in injection in a dose of 300 mg/kg for three successive days. The protective effect of the new pyracetam dipeptide analog GVS-111 in relation to activation of free-radical processes induced by immobilization is additional proof of the antistress action of this dipeptide.

Cognitive aspects of congenital learned helplessness and its reversal by the monoamine oxidase (MAO)-B inhibitor deprenyl

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schulz, D.; Schulz, D.; Mirrione, M.

2009-11-29

Cognitive processes are assumed to change with learned helplessness, an animal model of depression, but little is known about such deficits. Here we investigated the role of cognitive and related functions in selectively bred helpless (cLH, n = 10), non-helpless (cNLH, n = 12) and wild type (WT, n = 8) Sprague Dawley rats. The animals were exposed to an open field for 10 min on each of two test days. On the third day, an object exploration paradigm was carried out. The animals were later tested for helplessness. Both cLH and cNLH rats were more active than WTs onmore » the first day in the open field. Over trials, cNLH and WT rats lowered their activity less than cLH rats. This resistance-to-habituation co-varied with a resistance to develop helplessness. In cLH rats, higher 'anxiety' or less time spent in the center of the open field co-varied with severe helplessness. In WTs, a greater reactivity to novel objects and to a spatially relocated object predicted lower levels of helplessness. In cLH rats (n = 4-5 per group), chronic treatment with a high dose of the monoamineoxidase (MAO)-Binhibitordeprenyl (10 mg/kg; i.p.), an anti-Parkinson, nootropic and antidepressant drug, attenuated helplessness. Remarkably, helplessness reversal required the experience of repeated test trials, reminiscent of a learning process. Chronic deprenyl (10 mg/kg; i.p.) did not alter locomotion/exploration or 'anxiety' in the open field. In conclusion, helplessness may be related to altered mechanisms of reinforcement learning and working memory, and to abnormalities in MAO-A and/or MAO-B functioning.« less

Cognitive aspects of congenital learned helplessness and its reversal by the monoamine oxidase (MAO)-B inhibitor deprenyl.

PubMed

Schulz, Daniela; Mirrione, Martine M; Henn, Fritz A

2010-02-01

Cognitive processes are assumed to change with learned helplessness, an animal model of depression, but little is known about such deficits. Here we investigated the role of cognitive and related functions in selectively bred helpless (cLH, n=10), non-helpless (cNLH, n=12) and wild type (WT, n=8) Sprague Dawley rats. The animals were exposed to an open field for 10min on each of two test days. On the third day, an object exploration paradigm was carried out. The animals were later tested for helplessness. Both cLH and cNLH rats were more active than WTs on the first day in the open field. Over trials, cNLH and WT rats lowered their activity less than cLH rats. This resistance-to-habituation co-varied with a resistance to develop helplessness. In cLH rats, higher 'anxiety' or less time spent in the center of the open field co-varied with severe helplessness. In WTs, a greater reactivity to novel objects and to a spatially relocated object predicted lower levels of helplessness. In cLH rats (n=4-5 per group), chronic treatment with a high dose of the monoamine oxidase (MAO)-B inhibitor deprenyl (10mg/kg; i.p.), an anti-Parkinson, nootropic and antidepressant drug, attenuated helplessness. Remarkably, helplessness reversal required the experience of repeated test trials, reminiscent of a learning process. Chronic deprenyl (10mg/kg; i.p.) did not alter locomotion/exploration or 'anxiety' in the open field. In conclusion, helplessness may be related to altered mechanisms of reinforcement learning and working memory, and to abnormalities in MAO-A and/or MAO-B functioning. Copyright 2009 Elsevier Inc. All rights reserved.

[Multicomponent antithrombotic effect of the neuroprotective prolyl dipeptide GVS-111 and its major metabolite cyclo-L-prolylglycine].

PubMed

Ostrovskaia, R U; Liapina, L A; Pastorova, V E; Mirzoev, T Kh; Gudasheva, T A; Seredenin, S B; Ashmarin, I P

2002-01-01

The experiments in vivo showed that the new nootropic prolyl-containing GVS-111 produces an antithrombotic effect, influencing various stages of the blood coagulation process. GVS-111 exhibits anticoagulant and fibrinolytic properties and enhances fibrin destabilization by reducing the XIIIa factor activity. These effects are manifested upon both intraperitoneal (1 mg/kg) and peroral (10 mg/kg) administration of GVS-111 (in both cases, a single daily treatment over a period of 10 days). The same effects (anticoagulant, fibrinolytic, antifibrin-stabilizing) were observed in in vitro experiments with both GVS-111 (10(-3)-10(-6) M) and its main metabolite cyclo-L-prolylglycine (up to 10(-10) M). In addition, the latter metabolite exhibited an antiaggregant effect. The antithrombotic activity of GVS-111, together with previously established neuroprotector properties, low toxicity, and the absence of complications, makes this compound a promising antistroke drug.

Role of vinpocetine in cerebrovascular diseases.

PubMed

Patyar, Sazal; Prakash, Ajay; Modi, Manish; Medhi, Bikash

2011-01-01

A cerebrovascular accident, or stroke, is defined as the abrupt onset of a neurological deficit, which can be due to ischemia. Cerebral ischemia is caused by a reduction in blood flow that thereby decreases cerebral metabolism. Chronic cerebral hypoperfusion leads to irreversible brain damage and plays an important role in the development of certain types of dementia. Vinpocetine, chemically known as ethyl apovincaminate, is a vinca alkaloid that exhibits cerebral blood-flow enhancing and neuroprotective effects. Non-clinical and clinical studies have suggested multiple mechanisms responsible for the beneficial neuroprotective effects of vinpocetine. As no significant side effects related to vinpocetine treatment have been reported, it is considered to be safe for long-term use. This vasoactive alkaloid is widely marketed as a supplement for vasodilation and as a nootropic for the improvement of memory. The present review focuses on studies investigating the role of vinpocetine in cerebrovascular diseases.

Cognitive Enhancement and Education

ERIC Educational Resources Information Center

Buchanan, Allen

2011-01-01

Cognitive enhancement--augmenting normal cognitive capacities--is not new. Literacy, numeracy, computers, and the practices of science are all cognitive enhancements. Science is now making new cognitive enhancements possible. Biomedical cognitive enhancements (BCEs) include the administration of drugs, implants of genetically engineered or…

[Melatonin as a universal stabilizing factor of mental activity].

PubMed

Arushanian, Ē B

2011-01-01

Pineal hormone melatonin stabilizes mental activity of man and animals due to its somnogenic, anxiolytic, antidepressant and nootropic properties. Melatonin effects are based on the synchronization of biological rhythms via the influence on the cerebral structures which control biological rhythms and emotions and normalize endocrine and immune state.

From 'Hard' Neuro-Tools to 'Soft' Neuro-Toys? Refocussing the Neuro-Enhancement Debate.

PubMed

Brenninkmeijer, Jonna; Zwart, Hub

2017-01-01

Since the 1990's, the debate concerning the ethical, legal and societal aspects of 'neuro-enhancement' has evolved into a massive discourse, both in the public realm and in the academic arena. This ethical debate, however, tends to repeat the same sets of arguments over and over again. Normative disagreements between transhumanists and bioconservatives on invasive or radical brain stimulators, and uncertainties regarding the use and effectivity of nootropic pharmaceuticals dominate the field. Building on the results of an extensive European project on responsible research and innovation in neuro-enhancement (NERRI), we observe and encourage that the debate is now entering a new and, as we will argue, more realistic and societally relevant stage. This new stage concerns those technologies that enter the market as ostensibly harmless contrivances that consumers may use for self-care or entertainment. We use the examples and arguments of participants in NERRI debates to describe three case studies of such purportedly innocent 'toys'. Based upon this empirical material, we argue that these 'soft' enhancement gadgets are situated somewhere in the boundary zone between the internal and the external, between the intimate and the intrusive, between the familiar and the unfamiliar, between the friendly and the scary and, in Foucauldian terms, between technologies of the self and technologies of control. Therefore, we describe their physiognomy with the help of a term borrowed from Jacques Lacan, namely as "extimate" technologies.

Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.

PubMed

Verma, Dinesh Kumar; Joshi, Neeraj; Raju, Kunumuri Sivarama; Wahajuddin, Muhammad; Singh, Rama Kant; Singh, Sarika

2015-01-01

Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells in region specific manner. The study is also revealing the rationale for its clinical use in cognitive impairment and other neurological diseases.

Effect of Noopept on Dynamics of Intracellular Calcium in Neurons of Cultured Rat Hippocampal Slices.

PubMed

Kolbaev, S N; Aleksandrova, O P; Sharonova, I N; Skrebitsky, V G

2018-01-01

A neuroprotective and nootropic drug Noopept increased the frequency of spontaneous calcium transients in neurons of CA1 radial layer in cultured rat hippocampal slices. In contrast, the drug exerted no significant effect on intracellular calcium concentration and its dynamics in neurons of hippocampal CA1 pyramidal layer.

[A method for reproducing amnesia in mice by the complex extremal exposure].

PubMed

Iasnetsov, V V; Provornova, N A

2003-01-01

It is suggested to reproduce a retrograde amnesia in mice by means of a complex extremal action: emaciating swim in cold water with simultaneous wheel rotation. It was found that nootropes such as pyracetam, mexidol, semax, nooglutil, acephen, and noopept fully or completely prevent from the amnesia development.

Neuroprotective and nootropic drug noopept rescues α-synuclein amyloid cytotoxicity.

PubMed

Jia, Xueen; Gharibyan, Anna L; Öhman, Anders; Liu, Yonggang; Olofsson, Anders; Morozova-Roche, Ludmilla A

2011-12-16

Parkinson's disease is a common neurodegenerative disorder characterized by α-synuclein (α-Syn)-containing Lewy body formation and selective loss of dopaminergic neurons in the substantia nigra. We have demonstrated the modulating effect of noopept, a novel proline-containing dipeptide drug with nootropic and neuroprotective properties, on α-Syn oligomerization and fibrillation by using thioflavin T fluorescence, far-UV CD, and atomic force microscopy techniques. Noopept does not bind to a sterically specific site in the α-Syn molecule as revealed by heteronuclear two-dimensional NMR analysis, but due to hydrophobic interactions with toxic amyloid oligomers, it prompts their rapid sequestration into larger fibrillar amyloid aggregates. Consequently, this process rescues the cytotoxic effect of amyloid oligomers on neuroblastoma SH-SY5Y cells as demonstrated by using cell viability assays and fluorescent staining of apoptotic and necrotic cells and by assessing the level of intracellular oxidative stress. The mitigating effect of noopept against amyloid oligomeric cytotoxicity may offer additional benefits to the already well-established therapeutic functions of this new pharmaceutical. Copyright © 2011 Elsevier Ltd. All rights reserved.

S-52, a novel nootropic compound, protects against β-amyloid induced neuronal injury by attenuating mitochondrial dysfunction.

PubMed

Gao, Xin; Zheng, Chun Yan; Qin, Guo Wei; Tang, Xi Can; Zhang, Hai Yan

2012-10-01

Accumulating evidence suggests that β-amyloid (Aβ)-induced oxidative DNA damage and mitochondrial dysfunction may initiate and contribute to the progression of Alzheimer's disease (AD). This study evaluated the neuroprotective effects of S-52, a novel nootropic compound, on Aβ-induced mitochondrial failure. In an established paradigm of moderate cellular injury induced by Aβ, S-52 was observed to attenuate the toxicity of Aβ to energy metabolism, mitochondrial membrane structure, and key enzymes in the electron transport chain and tricarboxylic acid cycle. In addition, S-52 also effectively inhibited reactive oxygen species accumulation dose dependently not only in Aβ-harmed cells but also in unharmed, normal cells. The role of S-52 as a scavenger of free radicals is involved in the antioxidative effect of this compound. The beneficial effects on mitochondria and oxidative stress extend the neuroprotective effects of S-52. The present study provides crucial information for better understanding the beneficial profiles of this compound and discovering novel potential drug candidates for AD therapy. Copyright © 2012 Wiley Periodicals, Inc.

Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity

PubMed Central

Panossian, Alexander; Wikman, Georg

2010-01-01

Adaptogens were initially defined as substances that enhance the “state of non-specific resistance” in stress, a physiological condition that is linked with various disorders of the neuroendocrine-immune system. Studies on animals and isolated neuronal cells have revealed that adaptogens exhibit neuroprotective, anti-fatigue, antidepressive, anxiolytic, nootropic and CNS stimulating activity. In addition, a number of clinical trials demonstrate that adaptogens exert an anti-fatigue effect that increases mental work capacity against a background of stress and fatigue, particularly in tolerance to mental exhaustion and enhanced attention. Indeed, recent pharmacological studies of a number of adaptogens have provided a rationale for these effects also at the molecular level. It was discovered that the stress—protective activity of adaptogens was associated with regulation of homeostasis via several mechanisms of action, which was linked with the hypothalamic-pituitary-adrenal axis and the regulation of key mediators of stress response, such as molecular chaperons (e.g., HSP70), stress-activated c-Jun N-terminal protein kinase 1 (JNK1), Forkhead box O (FOXO) transcription factor DAF-16, cortisol and nitric oxide. PMID:27713248

Aniracetam tested in chronic psychosyndrome after long-term exposure to organic solvents. A randomized, double-blind, placebo-controlled cross-over study with neuropsychological tests.

PubMed

Somnier, F E; Ostergaard, M S; Boysen, G; Bruhn, P; Mikkelsen, B O

1990-01-01

In order to examine if the nootropic drug, aniracetam, was capable of improving cognitive performance, 44 subjects suffering from chronic psychosyndrome after long-term exposure to organic solvents were included in a randomized, double-blind, placebo-controlled, cross-over study. The treatment periods were 3 months with aniracetam 1 g daily and 3 months with placebo. Neuropsychological tests as well as a physical and neurological examination were performed at entry into the study and after each treatment period, together with an evaluation of the subjects' overall condition. Neither the doctors' nor the subjects' own assessment of the overall condition indicated that the trial medication had had any effect. No significant changes in neuropsychological symptoms were observed. A statistically significant difference in favour of antiracetam was found in only 1 of the 19 neuropsychological test measures, namely a test for constructional ability. However, in another test on visuo-spatial function, a statistically significant result was found in favour of placebo. Thus, aniracetam was found to be ineffective in the treatment of subjects suffering from chronic psychosyndrome after long-term exposure to organic solvents.

How does enhancing cognition affect human values? How does this translate into social responsibility?

PubMed

Cabrera, Laura Y

2015-01-01

The past decade has seen a rise in the use of different technologies aimed at enhancing cognition of normal healthy individuals. While values have been acknowledged to be an important aspect of cognitive enhancement practices, the discussion has predominantly focused on just a few values, such as safety, peer pressure, and authenticity. How are values, in a broader sense, affected by enhancing cognitive abilities? Is this dependent on the type of technology or intervention used to attain the enhancement, or does the cognitive domain targeted play a bigger role in how values are affected? Values are not only likely to be affected by cognitive enhancement practices; they also play a crucial role in defining the type of interventions that are likely to be undertaken. This paper explores the way values affect and are affected by enhancing cognitive abilities. Furthermore, it argues that knowledge of the interplay between values and cognitive enhancement makes a strong case for social responsibility around cognitive enhancement practices.

Acetylcholinesterase inhibition in cognition-relevant brain areas of mice treated with a nootropic Amazonian herbal (Marapuama).

PubMed

Figueiró, M; Ilha, J; Pochmann, D; Porciúncula, L O; Xavier, L L; Achaval, M; Nunes, D S; Elisabetsky, E

2010-10-01

The goal of acetylcholinesterase inhibitors (AChEIs) used to treat Alzheimer's patients is an improvement in cholinergic transmission. While currently available AChEIs have limited success, a huge impediment to the development of newer ones is access to the relevant brain areas. Promnesic, anti-amnesic and AChEI properties were identified in a standardized ethanol extract from Ptychopetalum olacoides (POEE), a medicinal plant favored by the elderly in Amazon communities. The purpose of this study was to provide conclusive evidence that orally given POEE induces AChE inhibition in brain areas relevant to cognition. Histochemistry experiments confirmed that the anticholinesterase compound(s) present in POEE are orally bioavailable, inducing meaningful AChE inhibition in the hippocampus CA1 (∼33%) and CA3 (∼20%), and striatum (∼17%). Ellman's colorimetric analysis revealed that G1 and G4 AChE isoforms activities were markedly inhibited (66 and 72%, respectively) in hippocampus and frontal cortex (50 and 63%, respectively), while G4 appeared to be selectively inhibited (72%) in the striatum. Western blotting showed that POEE did not induce significant changes in the AChE immunocontent suggesting that its synthesis is not extensively modified. This study provides definitive proof of meaningful anticholinesterase activity compatible with the observed promnesic and anti-amnesic effects of POEE in mice, reaffirming the potential of this extract for treating neurodegenerative conditions where a hypofunctioning cholinergic neurotransmission is prominent. Adequate assessment of the safety and efficacy of this extract and/or its isolated active compound(s) are warranted. 2010 Elsevier GmbH. All rights reserved.

Comparative evaluation of ethanolic extracts of Bacopa monnieri, Evolvulus alsinoides, Tinospora cordifolia and their combinations on cognitive functions in rats.

PubMed

Gupta, Avneet; Raj, Hem; Karchuli, Manvender Singh; Upmanyu, Neeraj

2013-12-01

The effects of ethanolic extracts of whole plants of Bacopa monnieri (BME), Evolvulus alsinoides (EAE), Tinospora cordifolia (TCE) and their combinations in equal proportion [CEP-1 (BME+EAE), CEP-2 (BME+TCE), CEP-3 (EAE+TCE) and CEP-4 (BME+EAE+TCE)] were tested in amnesic rats using Radial arm maze task performance (RAM) and Barnes maze test at 200 mg/kg p.o. The latency to find food and target hole was observed in RAM and Barnes maze respectively. Cognitive dysfunction was induced by scopolamine (0.3 mg/kg i.p.) treatment. BME, EAE, TCE and their combinations of equal proportion (CEPs) showed significant decrease in latency to find food and target hole in RAM and Barnes maze respectively. Inter comparison among single extract alone treated groups revealed that BME treated animals showed significant difference as compared to EAE and TCE treated animals. All combinations of equal proportion (CEPs) of these extracts showed significant difference in latency to find food and target hole as compared to single extracts treated animals. CEP-1 showed significantly better effect as compared to CEP-2 and CEP-3. Significant difference in latency to find food and target hole was also present between CEP-2 and CEP-3. Effect of CEP-4 was found to be significantly better than CEP-1, CEP-2 and CEP-3 treated rats in both models. From present investigation, it was concluded that ethanolic extract of Bacopa monnieri, Evolvulus alsinoides and Tinospora cordifolia provided better nootropic effect when used in combination.

A NMDA receptor glycine site partial agonist, GLYX-13, simultaneously enhances LTP and reduces LTD at Schaffer collateral-CA1 synapses in hippocampus.

PubMed

Zhang, Xiao-lei; Sullivan, John A; Moskal, Joseph R; Stanton, Patric K

2008-12-01

N-methyl-D-aspartate glutamate receptors (NMDARs) are a key route for Ca2+ influx into neurons important to both activity-dependent synaptic plasticity and, when uncontrolled, triggering events that cause neuronal degeneration and death. Among regulatory binding sites on the NMDAR complex is a glycine binding site, distinct from the glutamate binding site, which must be co-activated for NMDAR channel opening. We developed a novel glycine site partial agonist, GLYX-13, which is both nootropic and neuroprotective in vivo. Here, we assessed the effects of GLYX-13 on long-term synaptic plasticity and NMDAR transmission at Schaffer collateral-CA1 synapses in hippocampal slices in vitro. GLYX-13 simultaneously enhanced the magnitude of long-term potentiation (LTP) of synaptic transmission, while reducing long-term depression (LTD). GLYX-13 reduced NMDA receptor-mediated synaptic currents in CA1 pyramidal neurons evoked by low frequency Schaffer collateral stimulation, but enhanced NMDAR currents during high frequency bursts of activity, and these actions were occluded by a saturating concentration of the glycine site agonist d-serine. Direct two-photon imaging of Schaffer collateral burst-evoked increases in [Ca2+] in individual dendritic spines revealed that GLYX-13 selectively enhanced burst-induced NMDAR-dependent spine Ca2+ influx. Examining the rate of MK-801 block of synaptic versus extrasynaptic NMDAR-gated channels revealed that GLYX-13 selectively enhanced activation of burst-driven extrasynaptic NMDARs, with an action that was blocked by the NR2B-selective NMDAR antagonist ifenprodil. Our data suggest that GLYX-13 may have unique therapeutic potential as a learning and memory enhancer because of its ability to simultaneously enhance LTP and suppress LTD.

Aniracetam reverses memory impairment in rats.

PubMed

Martin, J R; Moreau, J L; Jenck, F

1995-02-01

The pyrrolidinone derivative aniracetam given orally immediately after acquisition of an inhibitory avoidance response reproducibly ameliorated scopolamine-induced amnesia in female rats in an extensive series of test sessions conducted over a 1-year period. In a dose-response experiment it was demonstrated that 50 mg kg-1 was the lowest oral dose of aniracetam to significantly ameliorate scopolamine-induced amnesia. Combined results from these numerous test sessions demonstrated that 50 mg kg-1 aniracetam administered to scopolamine-treated rats resulted in 53% of the animals exhibiting correct passive avoidance responding in the retention evaluation versus 9% of the scopolamine-treated rats given vehicle (in comparison, 64% of the rats injected with vehicle rather than scopolamine in this experimental situation exhibited correct responding in the retention test). There was minimal variation in this pattern of results over the successive 1-month blocks constituting the complete experimental period. Thus, the nootropic compound aniracetam replicably exhibited memory enhancing effects in this animal model of reduced cholinergic function.

Effects of piracetam on behavior and memory in adult zebrafish.

PubMed

Grossman, Leah; Stewart, Adam; Gaikwad, Siddharth; Utterback, Eli; Wu, Nadine; Dileo, John; Frank, Kevin; Hart, Peter; Howard, Harry; Kalueff, Allan V

2011-04-25

Piracetam, a derivative of γ-aminobutyric acid, exerts memory-enhancing and mild anxiolytic effects in human and rodent studies. To examine the drug's behavioral profile further, we assessed its effects on behavioral and endocrine (cortisol) responses of adult zebrafish (Danio rerio)--a novel model species rapidly gaining popularity in neurobehavioral research. Overall, acute piracetam did not affect zebrafish novel tank and light-dark box behavior at mild doses (25-400mg/L), but produced nonspecific behavioral inhibition at 700mg/L. No effects on cortisol levels or inter-/intra-session habituation in the novel tank test were observed for acute or chronic mild non-sedative dose of 200mg/L. In contrast, fish exposed to chronic piracetam at this dose performed significantly better in the cued learning plus-maze test. This observation parallels clinical and rodent literature on the behavioral profile of piracetam, supporting the utility of zebrafish paradigms for testing nootropic agents. Copyright © 2011 Elsevier Inc. All rights reserved.

Neuroprotective properties of nootropic dipeptide GVS-111 in in vitro oxygen-glucose deprivation, glutamate toxicity and oxidative stress.

PubMed

Andreeva, N A; Stel'mashuk, E V; Isaev, N K; Ostrovskaya, R U; Gudasheva, T A; Viktorov, I V

2000-10-01

Argon anoxia and glucose deprivation were used for modeling of ischemic damage in the cultures of cerebellar granule cells. Protective effect of peptide piracetam analogue GVS-111 was demonstrated. GVS-111 prevented neurodegeneration induced by glutamate and oxidative stress. In contrast to GVS-111, piracetam did not attenuate neurocytotoxic effect of glutamate.

JPRS Report - Science & Technology USSR: Life Sciences.

DTIC Science & Technology

1988-06-17

No 6. Nov-Dec 87] 11 Electron Microscopic and Radioautographic Investigation of Bronchi in Chronic Inflammation Upon Exposure to Helium-Neon...87] 22 Functional and Morphological Characteristics of Stress-Protective Action of Piracetam [V. M. Vinogradov, A. A. Klishov et al; FARMAKOLOGIYA...I TOKSIKOLOGIYA No 6, Nov-Dec 87] 23 Comparative Neurophysiological Studies on Nootropic Agents Piracetam and Centrophenoxine [S. V Krapivin, T. A

Acetylcholinesterase inhibitory activity of Thai traditional nootropic remedy and its herbal ingredients.

PubMed

Tappayuthpijarn, Pimolvan; Itharat, Arunporn; Makchuchit, Sunita

2011-12-01

The incidence of Alzheimer disease (AD) is increasing every year in accordance with the increasing of elderly population and could pose significant health problems in the future. The use of medicinal plants as an alternative prevention or even for a possible treatment of the AD is, therefore, becoming an interesting research issue. Acetylcholinesterase (AChE) inhibitors are well-known drugs commonly used in the treatment of AD. The aim of the present study was to screen for AChE inhibitory activity of the Thai traditional nootropic recipe and its herbal ingredients. The results showed that ethanolic extracts of four out of twenty-five herbs i.e. Stephania pierrei Diels. Kaempfera parviflora Wall. ex Baker, Stephania venosa (Blume) Spreng, Piper nigrum L at 0.1 mg/mL showed % AChE inhibition of 89, 64, 59, 50; the IC50 were 6, 21, 29, 30 microg/mL respectively. The other herbs as well as combination of the whole recipe had no synergistic inhibitory effect on AChE activity. However some plants revealed antioxidant activity. More research should have be performed on this local wisdom remedy to verify the uses in scientific term.

[Peptidergic nootropic therapy in cerebral palsy associated with epilepsy].

PubMed

Kholin, A A; Zavadenko, N N; Il Ina, E S; Kolpakchi, L M; Fedonyuk, I D; Bembeeva, R C; Esipova, E S

To assess the efficacy and safety of сortexin in the treatment of children with cerebral palsy (CP) combined with epilepsy. Eighty-four patients (55 boys and 29 girls), aged from 1 to 11 years, with CP combined with epilepsy received cortexin together with antiepileptic drugs (AEDs). Cortexin was administered in doses of 5-10 mg depending on the patient's age and body weight intramuscularly during hospitalization. Cortexin as add-on to AEDs reduced for more than two times the number of seizures, along with improvement of motor function, in 31 (36.9%) patients. The improvement of motor function, but without a significant decrease in epileptic seizures, was achieved in 15 (17.8%) of the patients. Reduction of epileptic seizures frequency (>2 times), but without a significant effect on motor function, was observed in 14 cases (16.7%). Twenty-three patients (27.4%) did not respond the therapy. The aggravation of epileptic seizures during cortexin therapy was observed in only 1 girl with West syndrome (1.2%), and this was significantly lower than the probability of seizures aggravation on AED. Polypeptide nootropic medication cortexin demonstrated efficacy and safety as adjunctive therapy in children with CP combined with epilepsy.

Peptide profiling of Internet-obtained Cerebrolysin using high performance liquid chromatography - electrospray ionization ion trap and ultra high performance liquid chromatography - ion mobility - quadrupole time of flight mass spectrometry.

PubMed

Gevaert, Bert; D'Hondt, Matthias; Bracke, Nathalie; Yao, Han; Wynendaele, Evelien; Vissers, Johannes Petrus Cornelis; De Cecco, Martin; Claereboudt, Jan; De Spiegeleer, Bart

2015-09-01

Cerebrolysin, a parenteral peptide preparation produced by controlled digestion of porcine brain proteins, is an approved nootropic medicine in some countries. However, it is also easily and globally available on the Internet. Nevertheless, until now, its exact chemical composition was unknown. Using high performance liquid chromatography (HPLC) coupled to ion trap and ultra high performance liquid chromatography (UHPLC) coupled to quadrupole-ion mobility-time-of-flight mass spectrometry (Q-IM-TOF MS), combined with UniProt pig protein database search and PEAKS de novo sequencing, we identified 638 unique peptides in an Internet-obtained Cerebrolysin sample. The main components in this sample originate from tubulin alpha- and beta-chain, actin, and myelin basic protein. No fragments of known neurotrophic factors like glial cell-derived neurotrophic factor (GDNF), neurotrophin nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF) were found, suggesting that the activities reported in the literature are likely the result of new, hitherto unknown cryptic peptides with nootropic properties. Copyright © 2015 John Wiley & Sons, Ltd.

Eliminating the Attentional Blink through Binaural Beats: A Case for Tailored Cognitive Enhancement.

PubMed

Reedijk, Susan A; Bolders, Anne; Colzato, Lorenza S; Hommel, Bernhard

2015-01-01

Enhancing human cognitive performance is a topic that continues to spark scientific interest. Studies into cognitive-enhancement techniques often fail to take inter-individual differences into account, however, which leads to underestimation of the effectiveness of these techniques. The current study investigated the effect of binaural beats, a cognitive-enhancement technique, on attentional control in an attentional blink (AB) task. As predicted from a neurocognitive approach to cognitive control, high-frequency binaural beats eliminated the AB, but only in individuals with low spontaneous eye-blink rates (indicating low striatal dopamine levels). This suggests that the way in which cognitive-enhancement techniques, such as binaural beats, affect cognitive performance depends on inter-individual differences.

Distributive justice and cognitive enhancement in lower, normal intelligence.

PubMed

Dunlop, Mikael; Savulescu, Julian

2014-01-01

There exists a significant disparity within society between individuals in terms of intelligence. While intelligence varies naturally throughout society, the extent to which this impacts on the life opportunities it affords to each individual is greatly undervalued. Intelligence appears to have a prominent effect over a broad range of social and economic life outcomes. Many key determinants of well-being correlate highly with the results of IQ tests, and other measures of intelligence, and an IQ of 75 is generally accepted as the most important threshold in modern life. The ability to enhance our cognitive capacities offers an exciting opportunity to correct disabling natural variation and inequality in intelligence. Pharmaceutical cognitive enhancers, such as modafinil and methylphenidate, have been shown to have the capacity to enhance cognition in normal, healthy individuals. Perhaps of most relevance is the presence of an 'inverted U effect' for most pharmaceutical cognitive enhancers, whereby the degree of enhancement increases as intelligence levels deviate further below the mean. Although enhancement, including cognitive enhancement, has been much debated recently, we argue that there are egalitarian reasons to enhance individuals with low but normal intelligence. Under egalitarianism, cognitive enhancement has the potential to reduce opportunity inequality and contribute to relative income and welfare equality in the lower, normal intelligence subgroup. Cognitive enhancement use is justifiable under prioritarianism through various means of distribution; selective access to the lower, normal intelligence subgroup, universal access, or paradoxically through access primarily to the average and above average intelligence subgroups. Similarly, an aggregate increase in social well-being is achieved through similar means of distribution under utilitarianism. In addition, the use of cognitive enhancement within the lower, normal intelligence subgroup negates, or at the very least minimises, several common objections to cognitive enhancement. Subsequently, this paper demonstrates that there is a compelling case for cognitive enhancement use in individuals with lower, normal intelligence.

Original nootropic drug noopept prevents memory deficit in rats with muscarinic and nicotinic receptor blockade.

PubMed

Radionova, K S; Belnik, A P; Ostrovskaya, R U

2008-07-01

Antiamnesic activity of Noopept was studied on the original three-way model of conditioned passive avoidance response, which allows studying spatial component of memory. Cholinoceptor antagonists of both types (scopolamine and mecamylamine) decreased entry latency and reduced the probability for selection of the safe compartment. Noopept abolished the antiamnesic effect of cholinoceptor antagonists and improved spatial preference.

Non Pharmacological Cognitive Enhancers - Current Perspectives.

PubMed

Sachdeva, Ankur; Kumar, Kuldip; Anand, Kuljeet Singh

2015-07-01

Cognition refers to the mental processes involved in thinking, knowing, remembering, judging, and problem solving. Cognitive dysfunctions are an integral part of neuropsychiatric disorders as well as in healthy ageing. Cognitive Enhancers are molecules that help improve aspects of cognition like memory, intelligence, motivation, attention and concentration. Recently, Non Pharmacological Cognitive Enhancers have gained popularity as effective and safe alternative to various established drugs. Many of these Non Pharmacological Cognitive Enhancers seem to be more efficacious compared to currently available Pharmacological Cognitive Enhancers. This review describes and summarizes evidence on various Non Pharmacological Cognitive Enhancers such as physical exercise, sleep, meditation and yoga, spirituality, nutrients, computer training, brain stimulation, and music. We also discuss their role in ageing and different neuro-psychiatric disorders, and current status of Cochrane database recommendations. We searched the Pubmed database for the articles and reviews having the terms 'non pharmacological and cognitive' in the title, published from 2000 till 2014. A total of 11 results displayed, out of which 10 were relevant to the review. These were selected and reviewed. Appropriate cross-references within the articles along with Cochrane reviews were also considered and studied.

Eliminating the Attentional Blink through Binaural Beats: A Case for Tailored Cognitive Enhancement

PubMed Central

Reedijk, Susan A.; Bolders, Anne; Colzato, Lorenza S.; Hommel, Bernhard

2015-01-01

Enhancing human cognitive performance is a topic that continues to spark scientific interest. Studies into cognitive-enhancement techniques often fail to take inter-individual differences into account, however, which leads to underestimation of the effectiveness of these techniques. The current study investigated the effect of binaural beats, a cognitive-enhancement technique, on attentional control in an attentional blink (AB) task. As predicted from a neurocognitive approach to cognitive control, high-frequency binaural beats eliminated the AB, but only in individuals with low spontaneous eye-blink rates (indicating low striatal dopamine levels). This suggests that the way in which cognitive-enhancement techniques, such as binaural beats, affect cognitive performance depends on inter-individual differences. PMID:26089802

Enhancing students’ cognitive skill in Nguyen Tat Thanh high school Hanoi Vietnam through scientific learning material of static electricity

NASA Astrophysics Data System (ADS)

Priyanto, A.; Linuwih, S.; Aji, M. P.; Bich, D. D.

2018-03-01

Scientific learning material is still needed by students at Nguyen Tat Thanh High School (NTT), Hanoi Vietnam in order to enhance the students’ cognitive skill. Cognitive skill represents the level of students’ understanding to the particular material. Students’ cognitive skill can be improved by applying the learning material based on scientific approach as a treatment. The enhancement of students’ cognitive skill can be measured by analyzing the students’ test result collected before and after treatment. The analysis is focused to measure the enhancement or the sifted of cognitive aspects including remembering aspect (C1), understanding aspect (C2), applying aspect (C3), analyzing aspect (C4), and evaluating aspect (C5). According to the analysis the enhancement of cognitive aspects are 8.26% of remembering, 3.26% of understanding, 32.94% of applying, 21.74% of analyzing, and 21.74% of evaluating. The major enhancements are occured at applying, analyzing, and evaluating aspects. Therefore it can be concluded that students’ cognitive skill is enhanced by applying scientific learning material of static electricity.

Cognitive enhancement kept within contexts: neuroethics and informed public policy

PubMed Central

Shook, John R.; Galvagni, Lucia; Giordano, James

2014-01-01

Neurothics has far greater responsibilities than merely noting potential human enhancements arriving from novel brain-centered biotechnologies and tracking their implications for ethics and civic life. Neuroethics must utilize the best cognitive and neuroscientific knowledge to shape incisive discussions about what could possibly count as enhancement in the first place, and what should count as genuinely “cognitive” enhancement. Where cognitive processing and the mental life is concerned, the lived context of psychological performance is paramount. Starting with an enhancement to the mental abilities of an individual, only performances on real-world exercises can determine what has actually been cognitively improved. And what can concretely counts as some specific sort of cognitive improvement is largely determined by the classificatory frameworks of cultures, not brain scans or laboratory experiments. Additionally, where the public must ultimately evaluate and judge the worthiness of individual performance enhancements, we mustn’t presume that public approval towards enhancers will somehow automatically arrive without due regard to civic ideals such as the common good or social justice. In the absence of any nuanced appreciation for the control which performance contexts and public contexts exert over what “cognitive” enhancements could actually be, enthusiastic promoters of cognitive enhancement can all too easily depict safe and effective brain modifications as surely good for us and for society. These enthusiasts are not unaware of oft-heard observations about serious hurdles for reliable enhancement from neurophysiological modifications. Yet those observations are far more common than penetrating investigations into the implications to those hurdles for a sound public understanding of cognitive enhancement, and a wise policy review over cognitive enhancement. We offer some crucial recommendations for undertaking such investigations, so that cognitive enhancers that truly deserve public approval can be better identified. PMID:25538573

Are Prescription Stimulants "Smart Pills"? The Epidemiology and Cognitive Neuroscience of Prescription Stimulant Use by Normal Healthy Individuals

ERIC Educational Resources Information Center

Smith, M. Elizabeth; Farah, Martha J.

2011-01-01

Use of prescription stimulants by normal healthy individuals to enhance cognition is said to be on the rise. Who is using these medications for cognitive enhancement, and how prevalent is this practice? Do prescription stimulants in fact enhance cognition for normal healthy people? We review the epidemiological and cognitive neuroscience…

Treating impaired cognition in schizophrenia: the case for combining cognitive-enhancing drugs with cognitive remediation.

PubMed

Michalopoulou, Panayiota G; Lewis, Shôn W; Wykes, Til; Jaeger, Judith; Kapur, Shitij

2013-08-01

Cognitive impairment is a well-documented feature of schizophrenia and represents a major impediment to the functional recovery of patients. The therapeutic strategies to improve cognition in schizophrenia have either used medications (collectively referred to as 'cognitive-enhancing drugs' in this article) or non-pharmacological training approaches ('cognitive remediation'). Cognitive-enhancing drugs have not as yet been successful and cognitive remediation has shown modest success. Therefore, we may need to explore new therapeutic paradigms to improve cognition in schizophrenia. The optimal approach may require a combination of cognitive-enhancing drugs with cognitive remediation. We review the available data from animal and human studies that provide the conceptual basis, proof-of-concept and illustrations of success of such combination strategies in experimental and clinical paradigms in other conditions. We address the major design issues relevant to the choice of the cognitive-enhancing drugs and cognitive remediation, as well as the timing and the duration of the intervention as will be relevant for schizophrenia. Finally, we address the practical realities of the development and testing of such combined approaches in the real-world clinical situation and conclude that while scientifically attractive, there are several practical difficulties to be overcome for this approach to be clinically feasible. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

The impact of neuroscience on society: cognitive enhancement in neuropsychiatric disorders and in healthy people

PubMed Central

Sahakian, Barbara J.; Bruhl, Annette B.; Cook, Jennifer; Killikelly, Clare; Savulich, George; Piercy, Thomas; Hafizi, Sepehr; Perez, Jesus; Fernandez-Egea, Emilio; Suckling, John; Jones, Peter B.

2015-01-01

In addition to causing distress and disability to the individual, neuropsychiatric disorders are also extremely expensive to society and governments. These disorders are both common and debilitating and impact on cognition, functionality and wellbeing. Cognitive enhancing drugs, such as cholinesterase inhibitors and methylphenidate, are used to treat cognitive dysfunction in Alzheimer's disease and attention deficit hyperactivity disorder, respectively. Other cognitive enhancers include specific computerized cognitive training and devices. An example of a novel form of cognitive enhancement using the technological advancement of a game on an iPad that also acts to increase motivation is presented. Cognitive enhancing drugs, such as methylphenidate and modafinil, which were developed as treatments, are increasingly being used by healthy people. Modafinil not only affects ‘cold’ cognition, but also improves ‘hot’ cognition, such as emotion recognition and task-related motivation. The lifestyle use of ‘smart drugs' raises both safety concerns as well as ethical issues, including coercion and increasing disparity in society. As a society, we need to consider which forms of cognitive enhancement (e.g. pharmacological, exercise, lifelong learning) are acceptable and for which groups (e.g. military, doctors) under what conditions (e.g. war, shift work) and by what methods we would wish to improve and flourish. PMID:26240429

The impact of neuroscience on society: cognitive enhancement in neuropsychiatric disorders and in healthy people.

PubMed

Sahakian, Barbara J; Bruhl, Annette B; Cook, Jennifer; Killikelly, Clare; Savulich, George; Piercy, Thomas; Hafizi, Sepehr; Perez, Jesus; Fernandez-Egea, Emilio; Suckling, John; Jones, Peter B

2015-09-19

In addition to causing distress and disability to the individual, neuropsychiatric disorders are also extremely expensive to society and governments. These disorders are both common and debilitating and impact on cognition, functionality and wellbeing. Cognitive enhancing drugs, such as cholinesterase inhibitors and methylphenidate, are used to treat cognitive dysfunction in Alzheimer's disease and attention deficit hyperactivity disorder, respectively. Other cognitive enhancers include specific computerized cognitive training and devices. An example of a novel form of cognitive enhancement using the technological advancement of a game on an iPad that also acts to increase motivation is presented. Cognitive enhancing drugs, such as methylphenidate and modafinil, which were developed as treatments, are increasingly being used by healthy people. Modafinil not only affects 'cold' cognition, but also improves 'hot' cognition, such as emotion recognition and task-related motivation. The lifestyle use of 'smart drugs' raises both safety concerns as well as ethical issues, including coercion and increasing disparity in society. As a society, we need to consider which forms of cognitive enhancement (e.g. pharmacological, exercise, lifelong learning) are acceptable and for which groups (e.g. military, doctors) under what conditions (e.g. war, shift work) and by what methods we would wish to improve and flourish.

[Asthenic syndrome in clinical course of acute period of brain concussion during complex treatment using nootropic agents].

PubMed

Tkachov, A V

2008-01-01

The comparative analysis of a complex examination of 108 persons aged from 16 till 60 years in acute period of closed craniocerebral injury (CCCT) has been done. Every participants have been divided into 2 groups depending on a nootrop medication they receive in a complex treatment. A control group consisted of 30 practically healthy people. Objective examination by means of tests was done on the 1-st, 10-th that 30-th day of treatment. Patients of 1-st (37 persons) group received piracetam in complex treatment and patients of the 2-nd group (71 persons) pramistar. Patients of the first group received a base treatment (analgetics, tranquilizers, vitamins of group B, magnesium sulfate, diuretic preparations) as well as piracetam at dosage 0.2, two tablets three times per day. The Patients of the 2-nd group received a base treatment as well as pramistar at dosage 0.6, one tablet 2 times per day. Specially developed multiaspects scales and questionnaires, MRT of the brain and EEG have been used for objectification of patient, complaints. During a complex clinico-neuropsychological examination it was found that all cases of concussion of the brain are accompanied by those or other asthenic disorders.

Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam.

PubMed

Ito, I; Tanabe, S; Kohda, A; Sugiyama, H

1990-05-01

1. Allosteric potentiation of the ionotropic quisqualate (iQA) receptor by a nootropic drug aniracetam (1-p-anisoyl-2-pyrrolidinone) was investigated using Xenopus oocytes injected with rat brain mRNA and rat hippocampal slices. 2. Aniracetam potentiates the iQA responses induced in Xenopus oocytes by rat brain mRNA in a reversible manner. This effect was observed above the concentrations of 0.1 mM. Kainate. N-methyl-D-aspartate and gamma-aminobutyric acid responses induced in the same oocytes were not affected. 3. The specific potentiation of iQA responses was accompanied by an increase in the conductance change of iQA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) responses, but the affinity of receptors for agonist and the ion-selectivity of the channels (reversal potentials) were not changed. 4. Aniracetam reversibly potentiated the iQA responses recorded intracellularly from the pyramidal cells in the CA1 region of rat hippocampal slices. The excitatory postsynaptic potentials (EPSPs) in Schaffer collateral-commissural-CA1 synapses were also potentiated by aniracetam. 5. Population EPSPs recorded in the mossy fibre-CA3 synapses as well as Schaffer-commissural synapses were also potentiated by aniracetam. The amplitudes of the potentiation were not changed by the formation of long-term potentiation.

Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam.

PubMed Central

Ito, I; Tanabe, S; Kohda, A; Sugiyama, H

1990-01-01

1. Allosteric potentiation of the ionotropic quisqualate (iQA) receptor by a nootropic drug aniracetam (1-p-anisoyl-2-pyrrolidinone) was investigated using Xenopus oocytes injected with rat brain mRNA and rat hippocampal slices. 2. Aniracetam potentiates the iQA responses induced in Xenopus oocytes by rat brain mRNA in a reversible manner. This effect was observed above the concentrations of 0.1 mM. Kainate. N-methyl-D-aspartate and gamma-aminobutyric acid responses induced in the same oocytes were not affected. 3. The specific potentiation of iQA responses was accompanied by an increase in the conductance change of iQA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) responses, but the affinity of receptors for agonist and the ion-selectivity of the channels (reversal potentials) were not changed. 4. Aniracetam reversibly potentiated the iQA responses recorded intracellularly from the pyramidal cells in the CA1 region of rat hippocampal slices. The excitatory postsynaptic potentials (EPSPs) in Schaffer collateral-commissural-CA1 synapses were also potentiated by aniracetam. 5. Population EPSPs recorded in the mossy fibre-CA3 synapses as well as Schaffer-commissural synapses were also potentiated by aniracetam. The amplitudes of the potentiation were not changed by the formation of long-term potentiation. PMID:1975272

[Ethical aspects of pharmacological cognition enhancement and the use of psychostimulants by children and young persons].

PubMed

Walcher-Andris, Elfriede

2006-03-01

Pharmacological cognition enhancement aims at an improvement of cognitive activity and performance in healthy people by means of appropriate drugs. Ethical implications of this kind of cognition enhancement stand in need of reflection. For a number of reasons, the distinction between treatment and enhancement is fuzzy with regard to Attention Deficit Hyperactivity Disorder (ADHD). In consideration of the growing number methylphenidate prescriptions, one question addressed in this article is whether or not psychostimulants are used not only for therapy but also for cognitive enhancement by children and young people. The possibility of a "grey zone" between treatment and enhancement seems to open the field for medicalization of social and pedagogical problems as well as for "hidden enhancement." In clinical practice, the use of stimulants is associated with certain ethical problems concerning diagnosis, treatment and prevention of ADHD. Some of these problems are associated with the possibility of cognition enhancement. In order to evaluate ethical problems of pharmacological cognition enhancement, short-term and long-term consequences of stimulant use need to be taken into account. This refers to the level of transmitter balance in the learning process, to the level of individual learning strategies as well as to the level of interaction. This raises the question (1) of how well adapted the means of enhancement are with regard to the end of a comprehensive education and socialization, and (2) whether there are justifiable limits to the standardization of behavior and knowledge. (3) Moreover, stipulating an autonomous decision as a minimum prerequisite for legitimate cognition enhancement seems inadequate in the case of children and young persons. Considering the evidence and the many open questions associated with pharmacological cognition enhancement for children and young persons, it is concluded that it is indeed a morally problematic technique.

Medications Used for Cognitive Enhancement in Patients With Schizophrenia, Bipolar Disorder, Alzheimer's Disease, and Parkinson's Disease.

PubMed

Hsu, Wen-Yu; Lane, Hsien-Yuan; Lin, Chieh-Hsin

2018-01-01

Cognitive impairment, which frequently occurs in patients with schizophrenia, bipolar disorder, Alzheimer's disease, and Parkinson's disease, has a significant impact on the daily lives of both patients and their family. Furthermore, since the medications used for cognitive enhancement have limited efficacy, the issue of cognitive enhancement still remains a clinically unsolved challenge. We reviewed the clinical studies (published between 2007 and 2017) that focused on the efficacy of medications used for enhancing cognition in patients with schizophrenia, bipolar disorder, Alzheimer's disease, and Parkinson's disease. Acetylcholinesterase inhibitors and memantine are the standard treatments for Alzheimer's disease and Parkinson's disease. Some studies have reported selective cognitive improvement in patients with schizophrenia following galantamine treatment. Newer antipsychotics, including paliperidone, lurasidone, aripiprazole, ziprasidone, and BL-1020, have also been reported to exert cognitive benefits in patients with schizophrenia. Dopaminergic medications were found to improve language function in patients with Parkinson's disease. However, no beneficial effects on cognitive function were observed with dopamine agonists in patients with schizophrenia. The efficacies of nicotine and its receptor modulators in cognitive improvement remain controversial, with the majority of studies showing that varenicline significantly improved the cognitive function in schizophrenic patients. Several studies have reported that N -methyl-d-aspartate glutamate receptor (NMDAR) enhancers improved the cognitive function in patients with chronic schizophrenia. NMDAR enhancers might also have cognitive benefits in patients with Alzheimer's disease or Parkinson's disease. Raloxifene, a selective estrogen receptor modulator, has also been demonstrated to have beneficial effects on attention, processing speed, and memory in female patients with schizophrenia. Clinical trials with larger sample sizes evaluating comprehensive cognitive domains are warranted to examine the efficacy of medications in cognitive enhancement in patients with schizophrenia, bipolar disorder, Alzheimer's disease, and Parkinson's disease.

Cognitive diversity and moral enhancement.

PubMed

Gyngell, Chris; Easteal, Simon

2015-01-01

One debate in contemporary bioethics centers on whether the development of cognitive enhancement technologies (CETs) will hasten the need for moral enhancement. In this article we provide a new argument in favor of pursuing these enhancement technologies together. The widespread availability of CETs will likely increase population-level cognitive diversity. Different people will choose to enhance different aspects of their cognition, and some won't enhance themselves at all. Although this has the potential to be beneficial for society, it could also result in harms as people become more different from one another. Aspects of our moral psychology make it difficult for people to cooperate and coordinate actions with those who are very different from themselves. These moral failings could be targeted by moral enhancement technologies, which may improve cooperation among individuals. Moral enhancement technologies will therefore help society maximize the benefits, and reduce the costs, associated with widespread access to cognitive enhancements.

Pericortical Enhancement on Delayed Postgadolinium Fluid-Attenuated Inversion Recovery Images in Normal Aging, Mild Cognitive Impairment, and Alzheimer Disease.

PubMed

Freeze, W M; Schnerr, R S; Palm, W M; Jansen, J F; Jacobs, H I; Hoff, E I; Verhey, F R; Backes, W H

2017-09-01

Breakdown of BBB integrity occurs in dementia and may lead to neurodegeneration and cognitive decline. We assessed whether extravasation of gadolinium chelate could be visualized on delayed postcontrast FLAIR images in older individuals with and without cognitive impairment. Seventy-four individuals participated in this study (15 with Alzheimer disease, 33 with mild cognitive impairment, and 26 with normal cognition). We assessed the appearance of pericortical enhancement after contrast administration, MR imaging markers of cerebrovascular damage, and medial temporal lobe atrophy. Three participants who were positive for pericortical enhancement (1 with normal cognition and 2 with mild cognitive impairment) were followed up for approximately 2 years. In vitro experiments with a range of gadolinium concentrations served to elucidate the mechanisms underlying the postcontrast FLAIR signals. Postcontrast pericortical enhancement was observed in 21 participants (28%), including 6 individuals with Alzheimer disease (40%), 10 with mild cognitive impairment (30%), and 5 with normal cognition (19%). Pericortical enhancement was positively associated with age ( P < .02) and ischemic stroke ( P < .05), but not with cognitive status ( P = .3). Foci with enhanced signal remained stable across time in all follow-up cases. The in vitro measurements confirmed that FLAIR imaging is highly sensitive for the detection of low gadolinium concentrations in CSF, but not in cerebral tissue. Postcontrast pericortical enhancement on FLAIR images occurs in older individuals with normal cognition, mild cognitive impairment, and dementia. It may represent chronic focal superficial BBB leakage. Future longitudinal studies are needed to determine its clinical significance. © 2017 by American Journal of Neuroradiology.

Non Pharmacological Cognitive Enhancers – Current Perspectives

PubMed Central

Kumar, Kuldip; Anand, Kuljeet Singh

2015-01-01

Cognition refers to the mental processes involved in thinking, knowing, remembering, judging, and problem solving. Cognitive dysfunctions are an integral part of neuropsychiatric disorders as well as in healthy ageing. Cognitive Enhancers are molecules that help improve aspects of cognition like memory, intelligence, motivation, attention and concentration. Recently, Non Pharmacological Cognitive Enhancers have gained popularity as effective and safe alternative to various established drugs. Many of these Non Pharmacological Cognitive Enhancers seem to be more efficacious compared to currently available Pharmacological Cognitive Enhancers. This review describes and summarizes evidence on various Non Pharmacological Cognitive Enhancers such as physical exercise, sleep, meditation and yoga, spirituality, nutrients, computer training, brain stimulation, and music. We also discuss their role in ageing and different neuro-psychiatric disorders, and current status of Cochrane database recommendations. We searched the Pubmed database for the articles and reviews having the terms ‘non pharmacological and cognitive’ in the title, published from 2000 till 2014. A total of 11 results displayed, out of which 10 were relevant to the review. These were selected and reviewed. Appropriate cross-references within the articles along with Cochrane reviews were also considered and studied. PMID:26393186

Environmental enrichment enhances cognitive flexibility in C57BL/6 mice on a touchscreen reversal learning task.

PubMed

Zeleznikow-Johnston, Ariel; Burrows, Emma L; Renoir, Thibault; Hannan, Anthony J

2017-05-01

Environmental enrichment (EE) is any positive modification of the 'standard housing' (SH) conditions in which laboratory animals are typically held, usually involving increased opportunity for cognitive stimulation and physical activity. EE has been reported to enhance baseline performance of wild-type animals on traditional cognitive behavioural tasks. Recently, touchscreen operant testing chambers have emerged as a way of performing rodent cognitive assays, providing greater reproducibility, translatability and automatability. Cognitive tests in touchscreen chambers are performed over numerous trials and thus experimenters have the power to detect subtle enhancements in performance. We used touchscreens to analyse the effects of EE on reversal learning, visual discrimination and hippocampal-dependent spatial pattern separation and working memory. We hypothesized that EE would enhance the performance of mice on cognitive touchscreen tasks. Our hypothesis was partially supported in that EE induced enhancements in cognitive flexibility as observed in visual discrimination and reversal learning improvements. However, no other significant effects of EE on cognitive performance were observed. EE decreased the activity level of mice in the touchscreen chambers, which may influence the enrichment level of the animals. Although we did not see enhancements on all hypothesized parameters, our testing paradigm is capable of detecting EE-induced improved cognitive flexibility in mice, which has implications for both understanding the mechanisms of EE and improving screening of putative cognitive-enhancing therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Associations between Physical and Cognitive Doping – A Cross-Sectional Study in 2.997 Triathletes

PubMed Central

Dietz, Pavel; Ulrich, Rolf; Dalaker, Robert; Striegel, Heiko; Franke, Andreas G.; Lieb, Klaus; Simon, Perikles

2013-01-01

Purpose This study assessed, for the first time, prevalence estimates for physical and cognitive doping within a single collective of athletes using the randomized response technique (RRT). Furthermore, associations between the use of legal and freely available substances to improve physical and cognitive performance (enhancement) and illicit or banned substances to improve physical and cognitive performance (doping) were examined. Methods An anonymous questionnaire using the unrelated question RRT was used to survey 2,997 recreational triathletes in three sports events (Frankfurt, Regensburg, and Wiesbaden) in Germany. Prior to the survey, statistical power analyses were performed to determine sample size. Logistic regression was used to predict physical and cognitive enhancement and the bootstrap method was used to evaluate differences between the estimated prevalences of physical and cognitive doping. Results 2,987 questionnaires were returned (99.7%). 12-month prevalences for physical and cognitive doping were 13.0% and 15.1%, respectively. The prevalence estimate for physical doping was significantly higher in athletes who also used physical enhancers, as well as in athletes who took part in the European Championship in Frankfurt compared to those who did not. The prevalence estimate for cognitive doping was significantly higher in athletes who also used physical and cognitive enhancers. Moreover, the use of physical and cognitive enhancers were significantly associated and also the use of physical and cognitive doping. Discussion The use of substances to improve physical and cognitive performance was associated on both levels of legality (enhancement vs. doping) suggesting that athletes do not use substances for a specific goal but may have a general propensity to enhance. This finding is important for understanding why people use such substances. Consequently, more effective prevention programs against substance abuse and doping could be developed. PMID:24236038

Cognitive Enhancers for Anxiety Disorders

PubMed Central

Hofmann, Stefan G.; Smits, Jasper A. J.; Asnaani, Anu; Gutner, Cassidy A.; Otto, Michael W.

2010-01-01

Cognitive behavioral therapy is an effective intervention for anxiety disorders. However, a significant number of people do not respond or only show partial response even after an adequate course of the treatment. Recent research has shown that the efficacy of the intervention can be improved by the use of cognitive enhancers that augment the core learning processes of cognitive-behavior therapy. This manuscript provides a review of the current state of cognitive enhancers for the treatment of anxiety disorders. PMID:21134394

Prefrontal electrical stimulation in non-depressed reduces levels of reported negative affects from daily stressors

PubMed Central

Davis, Nick J.

2017-01-01

Advances in neuroscience and pharmacology have led to improvements in the cognitive performance of people with neurological disease and other forms of cognitive decline. These same methods may also afford cognitive enhancement in people of otherwise normal cognitive abilities. “Cosmetic”, or supranormal, cognitive enhancement offers opportunities to enrich our social or financial status, our interactions with others, and the common wealth of our community. It is common to focus on the potential benefits of cognitive enhancement, while being less than clear about the possible drawbacks. Here I examine the harms or side-effects associated with a range of cognitive enhancement interventions. I propose a taxonomy of harms in cognitive enhancement, with harms classified as (neuro)biological, ethical, or societal. Biological harms are those that directly affect the person’s biological functioning, such as when a drug affects a person’s mood or autonomic function. Ethical harms are those that touch on issues such as fairness and cheating, or on erosion of autonomy and coercion. Societal harms are harms that affect whole populations, and which are normally the province of governments, such as the use of enhancement in military contexts. This taxonomy of harms will help to focus the debate around the use and regulation of cognitive enhancement. In particular it will help to clarify the appropriate network of stakeholders who should take an interest in each potential harm, and in minimizing the impact of these harms. PMID:28261075

Extracts and constituents of Leontopodium alpinum enhance cholinergic transmission: Brain ACh increasing and memory improving properties

PubMed Central

Hornick, Ariane; Schwaiger, Stefan; Rollinger, Judith M.; Vo, Nguyen Phung; Prast, Helmut; Stuppner, Hermann

2012-01-01

Leontopodium alpinum (‘Edelweiss’) was phytochemically investigated for constituents that might enhance cholinergic neurotransmission. The potency to increase synaptic availability of acetylcholine (ACh) in rat brain served as key property for the bioguided isolation of cholinergically active compounds using different chromatographic techniques. The dichlormethane (DCM) extract of the root, fractions and isolated constituents were injected i.c.v. and the effect on brain ACh was detected via the push–pull technique. The DCM extract enhanced extracellular ACh concentration in rat brain and inhibited acetylcholinesterase (AChE) in vitro. The extracellular level of brain ACh was significantly increased by the isolated sesquiterpenes, isocomene and 14-acetoxyisocomene, while silphiperfolene acetate and silphinene caused a small increasing tendency. Only silphiperfolene acetate showed in vitro AChE inhibitory activity, thus suggesting the other sesquiterpenes to stimulate cholinergic transmission by an alternative mechanism of action. Isocomene was further investigated with behavioural tasks in mice. It restored object recognition in scopolamine-impaired mice and showed nootropic effects in the T-maze alternation task in normal and scopolamine-treated mice. Additionally, this sesquiterpene reduced locomotor activity of untreated mice in the open field task, while the activity induced by scopolamine was abolished. The enhancement of synaptic availability of ACh, the promotion of alternation, and the amelioration of scopolamine-induced deficit are in accordance with a substance that amplifies cholinergic transmission. Whether the mechanism of action is inhibition of AChE or another pro-cholinergic property remains to be elucidated. Taken together, isocomene and related constituents of L. alpinum deserve further interest as potential antidementia agents in brain diseases associated with cholinergic deficits. PMID:18541221

Is Cognitive Rehabilitation Needed in Verbal Adults with Autism? Insights From Initial Enrollment in a Trial of Cognitive Enhancement Therapy

PubMed Central

Eack, Shaun M.; Bahorik, Amber L.; Hogarty, Susan S.; Greenwald, Deborah P.; Litschge, Maralee Y.; Mazefsky, Carla A.; Minshew, Nancy J.

2013-01-01

Cognitive rehabilitation is an emerging set of potentially effective interventions for the treatment of autism spectrum disorder, yet the applicability of these approaches for “high functioning” adults who have normative levels of intelligence remains unexplored. This study examined the initial cognitive performance characteristics of 40 verbal adults with autism enrolled in a pilot trial of Cognitive Enhancement Therapy to investigate the need for cognitive rehabilitation in this population. Results revealed marked and broad deficits across neurocognitive and social-cognitive domains, despite above-average IQ. Areas of greatest impairment included processing speed, cognitive flexibility, and emotion perception and management. These findings indicate the need for comprehensive interventions designed to enhance cognition among verbal adults with autism who have intact intellectual functioning. PMID:23381484

[Preclinical prognosis of pyracetam and picamilon safety based on acute toxicity data].

PubMed

Bugaeva, L I; Spasov, A A; Verovskiĭ, V E; Iezhitsa, I N

2003-01-01

A comparative acute toxicity test of the nootropic drugs piracetam and picamilon was performed on rats. The study was based on the principles of integral evaluation of the drug effect upon the functional and behavioral state of animals. It was found that the conventional therapeutic index does not coincide with the actual therapeutic activity range. Piracetam and picamilon, while exhibiting significantly different toxicity, are characterized by approximately equal ranges of the therapeutic activity.

The mental cost of cognitive enhancement.

PubMed

Iuculano, Teresa; Cohen Kadosh, Roi

2013-03-06

Noninvasive brain stimulation provides a potential tool for affecting brain functions in the typical and atypical brain and offers in several cases an alternative to pharmaceutical intervention. Some studies have suggested that transcranial electrical stimulation (TES), a form of noninvasive brain stimulation, can also be used to enhance cognitive performance. Critically, research so far has primarily focused on optimizing protocols for effective stimulation, or assessing potential physical side effects of TES while neglecting the possibility of cognitive side effects. We assessed this possibility by targeting the high-level cognitive abilities of learning and automaticity in the mathematical domain. Notably, learning and automaticity represent critical abilities for potential cognitive enhancement in typical and atypical populations. Over 6 d, healthy human adults underwent cognitive training on a new numerical notation while receiving TES to the posterior parietal cortex or the dorsolateral prefrontal cortex. Stimulation to the the posterior parietal cortex facilitated numerical learning, whereas automaticity for the learned material was impaired. In contrast, stimulation to the dorsolateral prefrontal cortex impaired the learning process, whereas automaticity for the learned material was enhanced. The observed double dissociation indicates that cognitive enhancement through TES can occur at the expense of other cognitive functions. These findings have important implications for the future use of enhancement technologies for neurointervention and performance improvement in healthy populations.

Enhancing Exposure Therapy for Anxiety Disorders, Obsessive Compulsive Disorder, and Posttraumatic Stress Disorder

PubMed Central

McGuire, Joseph F.; Lewin, Adam B.; Storch, Eric A.

2014-01-01

Translating findings from basic science, several compounds have been identified that may enhance therapeutic outcomes and/or expedite treatment gains when administered alongside exposure-based treatments. Four of these compounds (referred to as cognitive enhancers) have been evaluated in the context of randomized controlled trials for anxiety disorders (e.g., specific phobias, panic disorder, social anxiety disorder), obsessive compulsive disorder (OCD), and posttraumatic stress disorder (PTSD). These cognitive enhancers include D-cycloserine, yohimbine hydrochloride, glucocorticoids and cortisol, and brain derived neurotrophic factor. There is consistent evidence that cognitive enhancers can enhance therapeutic outcomes and/or expedite treatment gains across anxiety disorders, OCD, and PTSD. Emerging evidence has highlighted the importance of within-session fear habituation and between-session fear learning, which can either enhance fear extinction or reconsolidate of fear responses. Although findings from these trials are promising, there are several considerations that warrant further evaluation prior to wide-spread use of cognitive enhancers in exposure-based treatments. Consistent trial design and large sample sizes are important in future studies of cognitive enhancers. PMID:24972729

Cognitive Enhancement Using ICT and Its Ethical Implications.

PubMed

Doukakis, Spyros; Stamatellos, Giannis; Glinou, Nektaria

2017-01-01

The utilization of digital tools aiming at the cognitive enhancement of students and adults, so that they can achieve better performance and professional or academic success, has increased in recent years. This paper focuses on ICT tools such as computer games, programming languages and educational software as means for cognitive enhancement and attempts to highlight their contributions. Issues of design and the limitations of digital tools are discussed. In the final section, the ethical implications of using educational ICT tools for cognitive enhancement from a virtue ethics perspective are presented.

Analgesic effect of piracetam on peripheral neuropathic pain induced by chronic constriction injury of sciatic nerve in rats.

PubMed

Mehta, Ashish K; Bhati, Yogendra; Tripathi, Chakra D; Sharma, Krishna K

2014-08-01

Despite immense advances in the treatment strategies, management of neuropathic pain remains unsatisfactory. Piracetam is a prototype of nootropic drugs, used to improve cognitive impairment. The present study was designed to investigate the effect of piracetam on peripheral neuropathic pain in rats. Neuropathic pain was induced by the chronic constriction injury of the sciatic nerve. Following this, piracetam was intraperitoneally administered for 2 weeks in doses of 50, 100 and 200 mg/kg, and pain was assessed by employing the behavioural tests for thermal hyperalgesia (hot plate and tail flick tests) and cold allodynia (acetone test). After the induction of neuropathic pain, significant development of thermal hyperalgesia and cold allodynia was observed. The administration of piracetam (50 mg/kg) did not have any significant effect on all the behavioural tests. Further, piracetam (100 mg/kg) also had no effect on the hot plate and tail flick tests; however it significantly decreased the paw withdrawal duration in the acetone test. Piracetam in a dose of 200 mg/kg significantly modulated neuropathic pain as observed from the increased hot plate and tail flick latencies, and decreased paw withdrawal duration (in acetone test). Therefore, the present study suggests the potential use of piracetam in the treatment of neuropathic pain, which merits further clinical investigation.

Enhanced cognitive activity – over and above social or physical activity – is required to protect Alzheimer’s mice against cognitive impairment, reduce Aβ deposition, and increase synaptic immunoreactivity

PubMed Central

Cracchiolo, Jennifer R.; Mori, Takashi; Nazian, Stanley J.; Tan, Jun; Potter, Huntington; Arendash, Gary W.

2007-01-01

Although social, physical, and cognitive activities have each been suggested to reduce the risk of Alzheimer’s Disease (AD), epidemiologic studies cannot determine which activity or combination of activities is most important. To address this question, mutant APP transgenic AD mice were reared long-term in one of four housing conditions (impoverished, social, social+physical, or complete enrichment) from 1½ through 9 months of age. Thus, a stepwise layering of social, physical, and enhanced cognitive activity was created. Behavioral evaluation in a full battery of sensorimotor, anxiety, and cognitive tasks was carried out during the final 5 weeks of housing. Only AD mice raised in complete enrichment (i.e., enhanced cognitive activity) showed: 1) protection against cognitive impairment, 2) decreased brain β-amyloid deposition, and 3) increased hippocampal synaptic immunoreactivity. The protection provided by enhanced cognitive activity spanned multiple cognitive domains (working memory, reference learning, and recognition/identification). Cognitive and neurohistologic benefits of complete enrichment occurred without any changes in blood cytokine or corticosterone levels, suggesting that enrichment-dependent mechanisms do not involve changes in the inflammatory response or stress levels, respectively. These results indicate that the enhanced cognitive activity of complete enrichment is required for cognitive and neurologic benefit to AD mice – physical and/or social activity are insufficient. Thus, our data suggest that humans who emphasize a high lifelong level of cognitive activity (over and above social and physical activities) will attain the maximal environmental protection against AD. PMID:17714960

Cognitive enhancement as a pharmacotherapy target for stimulant addiction.

PubMed

Sofuoglu, Mehmet

2010-01-01

No medications have been proven to be effective for cocaine and methamphetamine addiction. Attenuation of drug reward has been the main strategy for medications development, but this approach has not led to effective treatments. Thus, there is a need to identify novel treatment targets in addition to the brain reward system. To propose a novel treatment strategy for stimulant addiction that will focus on medications enhancing cognitive function and attenuating drug reward. Pre-clinical and clinical literature on potential use of cognitive enhancers for stimulant addiction pharmacotherapy was reviewed. Cocaine and methamphetamine users show significant cognitive impairments, especially in attention, working memory and response inhibition functions. The cognitive impairments seem to be predictive of poor treatment retention and outcome. Medications targeting acetylcholine and norepinephrine are particularly well suited for enhancing cognitive function in stimulant users. Many cholinergic and noradrenergic medications are on the market and have a good safety profile and low abuse potential. These include galantamine, donepezil and rivastigmine (cholinesterase inhibitors), varenicline (partial nicotine agonist), guanfacine (alpha(2)-adrenergic agonist) and atomoxetine (norepinephrine transporter inhibitor). Future clinical studies designed optimally to measure cognitive function as well as drug use behavior would be needed to test the efficacy of these cognitive enhancers for stimulant addiction.

The Importance of the Study of Cognitive Performance Enhancement for U.S. National Security.

PubMed

Malish, Richard G

2017-08-01

The American military is embarking on the 'Third Offset'-a strategy designed to produce seismic shifts in the future of warfare. Central to the approach is the conjoining of humans, technology, and machines to deliver a decisive advantage on the battlefield. Because technology will spread rapidly and globally, tactical overmatch will occur when American operators possess a competitive edge in cognition. Investigation of cognitive enhancing therapeutics is not widely articulated as an adjunct to the Third Offset, yet failure to study promising agents could represent a strategic vulnerability. Because of its legacy of research into therapeutic agents to enhance human-machine interplay, the aerospace medical community represents a front-running candidate to perform this work. Notably, there are strong signals emanating from gambling, academic, and video-gaming enterprises that already-developed stimulants and other agents provide cognitive benefits. These agents should be studied not only for reasons of national security, but also because cognitive enhancement may be a necessary step in the evolution of humankind. To illustrate these points, this article will assert that: 1) the need to preserve and enhance physical and cognitive health will become more and more important over the next century; 2) aeromedical specialists are in a position to take the lead in the endeavor to enhance cognition; 3) signals of enhancement of the type useful to both military and medical efforts exist aplenty in today's society; and 4) the aeromedical community should approach human enhancement research deliberately but carefully.Malish RG. The importance of the study of cognitive performance enhancement for U.S. national security. Aerosp Med Hum Perform. 2017; 88(8):773-778.

[A review of the effects of lithium on cognitive functions: Effects on the neuropsychiatrically challenged CNS].

PubMed

Tsaltas, E; Kontis, D

2009-04-01

Recent data attribute neuroprotective and neurotrophic actions to lithium, leading to expectations of cognitive enhancement action. This hypothesis is at odds with the predominant view of clinical psychiatr y which, on the basis of older clinical data as well as on subjective reports of lithiumtreated patients, associates lithium with cognitive blurring and specific memory deficits. Review of the older data and their integration with more recent clinical and experimental work on the primary effects of lithium on cognitive functioning led us to two central conclusions: (a) Data on the primary cognitive effects of lithium, considered in their entirety, do not support a picture of serious or long-lasting cognitive decline. On the contrary, recent evidence suggests cognitive enhancement under certain conditions. (b) The conditions which appear to promote the emergence of cognitive enhancement under lithium are conditions of challenge to the cognitive systems, such as increased task difficulty resulting in deterioration in the performance of untreated controls. We are suggesting that alternative challenges to cognitive functioning, which therefore would facilitate the emergence of lithium's cognitive enhancement action, include biological insults to the central nervous system (CNS). This second part of our review of the cognitive effects of lithium therefore focuses on studies of its action on cognitive dysfunction associated with functional or biological challenge to the CNS, such as stress, trauma, neurodegenerative and psychiatric disorders.

Do enhanced states exist? Boosting cognitive capacities through an action video-game.

PubMed

Kozhevnikov, Maria; Li, Yahui; Wong, Sabrina; Obana, Takashi; Amihai, Ido

2018-04-01

This research reports the existence of enhanced cognitive states in which dramatic temporary improvements in temporal and spatial aspects of attention were exhibited by participants who played (but not by those who merely observed) action video-games meeting certain criteria. Specifically, Experiments 1 and 2 demonstrate that the attentional improvements were exhibited only by participants whose skills matched the difficulty level of the video game. Experiment 2 showed that arousal (as reflected by the reduction in parasympathetic activity and increase in sympathetic activity) is a critical physiological condition for enhanced cognitive states and corresponding attentional enhancements. Experiment 3 showed that the cognitive enhancements were transient, and were no longer observed after 30 min of rest following video-gaming. Moreover, the results suggest that the enhancements were specific to tasks requiring visual-spatial focused attention, but not distribution of spatial attention as has been reported to improve significantly and durably as a result of long-term video-game playing. Overall, the results suggest that the observed enhancements cannot be simply due to the activity of video-gaming per se, but might rather represent an enhanced cognitive state resulting from specific conditions (heightened arousal in combination with active engagement and optimal challenge), resonant with what has been described in previous phenomenological literature as "flow" (Csikszentmihalyi, 1975) or "peak experiences" (Maslov, 1962). The findings provide empirical evidence for the existence of the enhanced cognitive states and suggest possibilities for consciously accessing latent resources of our brain to temporarily boost our cognitive capacities upon demand. Copyright © 2018 Elsevier B.V. All rights reserved.

Drug treatment of poststroke aphasia.

PubMed

Bakheit, A M O

2004-03-01

Impairment of language function (aphasia) is one of the most common neurological symptoms after stroke. Approximately one in every three patients who have an acute stroke will suffer from aphasia. The estimated incidence and prevalence of stroke in Western Europe is 140 and 800 per 100,000 of the population. Aphasia often results in significant disability and handicap. It is a major obstacle for patients to live independently in the community. When recovery from aphasia occurs, it is usually incomplete and patients are rarely able to return to full employment and other social activities. Currently, the main treatment for aphasia is conventional speech and language therapy. However, the effectiveness of this intervention has not been conclusively demonstrated and empirical observations suggest that spontaneous biological recovery may explain most of the improvement in language function that occurs in aphasics. The generally poor prognosis of the severe forms of poststroke language impairment (Broca, Wernicke and global aphasia), coupled with the limited effectiveness of conventional speech and language therapy has stimulated the search for other treatments that may be used in conjunction with speech and language therapy, including the use of various drugs. Dopamine agonists, piracetam (Nootropil), amphetamines, and more recently donepezil (Aricept), have been used in the treatment of aphasia in both the acute and chronic phase. The justification for the use of drugs in the treatment of aphasia is based on two types of evidence. Some drugs, such as dextroamphetamine (Dexedrine), improve attention span and enhance learning and memory. Learning is an essential mechanism for the acquisition of new motor and cognitive skills, and hence, for recovery from aphasia. Second, laboratory and clinical data suggest that drug treatment may partially restore the metabolic function in the ischemic zone that surrounds the brain lesion and also has a neuroprotective effect following acute brain damage. An example of this is the nootropic agent piracetam. Extensive animal studies have demonstrated the beneficial effects of this and other drugs on neural plasticity, but data on humans are still sparse. This review provides a critical analysis of the current evidence of the effectiveness of these drugs in the treatment of acute and chronic aphasia.

Outsmarted by nootropics? An investigation into the thermal degradation of modafinil, modafinic acid, adrafinil, CRL-40,940 and CRL-40,941 in the GC injector: formation of 1,1,2,2-tetraphenylethane and its tetra fluoro analog.

PubMed

Dowling, Geraldine; Kavanagh, Pierce V; Talbot, Brian; O'Brien, John; Hessman, Gary; McLaughlin, Gavin; Twamley, Brendan; Brandt, Simon D

2017-03-01

2-[(Diphenylmethyl)sulfinyl]acetamide (modafinil) is commonly prescribed for the treatment of narcolepsy. Increasing popularity and off-label use as a cognitive enhancer has resulted in a reputation as an intelligence boosting 'wonder drug'. Common alternatives available from online shops and other retail outlets include 2-[(diphenylmethyl)sulfinyl]-N-hydroxyacetamide (adrafinil), 2-{[bis(4-fluorophenyl)methyl]sulfinyl}acetamide (CRL-40,940), 2-{[bis(4-fluorophenyl)methyl]sulfinyl}-N-hydroxyacetamide (CRL-40,941), and N-methyl-4,4-difluoro-modafinil (modafiendz), respectively. Gas chromatography-mass spectrometry (GC-MS) is a common tool used in forensic and clinical analysis but there is a potential for inducing analysis-related ambiguities. This study reports on the thermal degradation of modafinil, modafinic acid, adrafinil, CRL-40,940, and CRL-40,941 due to exposure to the heated GC injection port dissolved in a variety of solvents. Key degradation products common to modafinil, modafinic acid, and adrafinil analysis included diphenylmethanol and 1,1,2,2-tetraphenylethane (TPE), the latter of which was verified by its synthesis and characterization by x-ray crystallography. The investigated compounds were also characterized by 1 H and 13 C NMR. Diphenylmethane and thiobenzophenone were also identified in some instances. TPE formation was suggested to involve the generation of a benzhydrylium ion and its reaction with the sulfoxide oxygen of the parent compound to give an oxysulfonium intermediate. Correspondingly, the fluorinated TPE analogue was formed during heat-induced degradation of modafiendz, CRL-40,940 and CRL-40,941, respectively. When a mixture of modafinil (non-fluorinated) and modafiendz (fluorinated) were subjected to GC analysis, 4,4'-(2,2-diphenylethane-1,1-diyl)bis(fluorobenzene) was detected as a third cross reaction product in addition to the two expected TPE analogues. These observations served as a reminder that the seemingly straightforward implementation of GC-MS analysis can lead to challenges during routine analysis. Copyright © 2016 John Wiley & Sons, Ltd.

Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders.

PubMed

Malykh, Andrei G; Sadaie, M Reza

2010-02-12

There is an increasing interest in nootropic drugs for the treatment of CNS disorders. Since the last meta-analysis of the clinical efficacy of piracetam, more information has accumulated. The primary objective of this systematic survey is to evaluate the clinical outcomes as well as the scientific literature relating to the pharmacology, pharmacokinetics/pharmacodynamics, mechanism of action, dosing, toxicology and adverse effects of marketed and investigational drugs. The major focus of the literature search was on articles demonstrating evidence-based clinical investigations during the past 10 years for the following therapeutic categories of CNS disorders: (i) cognition/memory; (ii) epilepsy and seizure; (iii) neurodegenerative diseases; (iv) stroke/ischaemia; and (v) stress and anxiety. In this article, piracetam-like compounds are divided into three subgroups based on their chemical structures, known efficacy and intended clinical uses. Subgroup 1 drugs include piracetam, oxiracetam, aniracetam, pramiracetam and phenylpiracetam, which have been used in humans and some of which are available as dietary supplements. Of these, oxiracetam and aniracetam are no longer in clinical use. Pramiracetam reportedly improved cognitive deficits associated with traumatic brain injuries. Although piracetam exhibited no long-term benefits for the treatment of mild cognitive impairments, recent studies demonstrated its neuroprotective effect when used during coronary bypass surgery. It was also effective in the treatment of cognitive disorders of cerebrovascular and traumatic origins; however, its overall effect on lowering depression and anxiety was higher than improving memory. As add-on therapy, it appears to benefit individuals with myoclonus epilepsy and tardive dyskinesia. Phenylpiracetam is more potent than piracetam and is used for a wider range of indications. In combination with a vasodilator drug, piracetam appeared to have an additive beneficial effect on various cognitive disabilities. Subgroup 2 drugs include levetiracetam, seletracetam and brivaracetam, which demonstrate antiepileptic activity, although their cognitive effects are unclear. Subgroup 3 includes piracetam derivatives with unknown clinical efficacies, and of these nefiracetam failed to improve cognition in post-stroke patients and rolipram is currently in clinical trials as an antidepressant. The remaining compounds of this subgroup are at various preclinical stages of research. The modes of action of piracetam and most of its derivatives remain an enigma. Differential effects on subtypes of glutamate receptors, but not the GABAergic actions, have been implicated. Piracetam seems to activate calcium influx into neuronal cells; however, this function is questionable in the light of findings that a persistent calcium inflow may have deleterious impact on neuronal cells. Although subgroup 2 compounds act via binding to another neuronal receptor (synaptic vesicle 2A), some of the subgroup 3 compounds, such as nefiracetam, are similar to those of subgroup 1. Based on calculations of the efficacy rates, our assessments indicate notable improvements in clinical outcomes with some of these agents.

Visuomotor adaptability in older adults with mild cognitive decline.

PubMed

Schaffert, Jeffrey; Lee, Chi-Mei; Neill, Rebecca; Bo, Jin

2017-02-01

The current study examined the augmentation of error feedback on visuomotor adaptability in older adults with varying degrees of cognitive decline (assessed by the Montreal Cognitive Assessment; MoCA). Twenty-three participants performed a center-out computerized visuomotor adaptation task when the visual feedback of their hand movement error was presented in a regular (ratio=1:1) or enhanced (ratio=1:2) error feedback schedule. Results showed that older adults with lower scores on the MoCA had less adaptability than those with higher MoCA scores during the regular feedback schedule. However, participants demonstrated similar adaptability during the enhanced feedback schedule, regardless of their cognitive ability. Furthermore, individuals with lower MoCA scores showed larger after-effects in spatial control during the enhanced schedule compared to the regular schedule, whereas individuals with higher MoCA scores displayed the opposite pattern. Additional neuro-cognitive assessments revealed that spatial working memory and processing speed were positively related to motor adaptability during the regular scheduled but negatively related to adaptability during the enhanced schedule. We argue that individuals with mild cognitive decline employed different adaptation strategies when encountering enhanced visual feedback, suggesting older adults with mild cognitive impairment (MCI) may benefit from enhanced visual error feedback during sensorimotor adaptation. Copyright © 2016 Elsevier B.V. All rights reserved.

Improving Cognitive Processes in Preschool Children: The COGEST Programme

ERIC Educational Resources Information Center

Mayoral-Rodríguez, Silvia; Timoneda-Gallart, Carme; Pérez-Álvarez, Federico; Das, J. P.

2015-01-01

The present study provides empirical evidence to support the hypothesis that pre-school children's cognitive functions can be developed by virtue of a training tool named COGENT (Cognitive Enhancement Training). We assumed that COGENT (COGEST in Spain) which is embedded in speech and language, will enhance the core cognitive processes that are…

Development of the Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills program for adults on the autism spectrum: Results of initial study.

PubMed

Baker-Ericzén, Mary J; Fitch, Meghan A; Kinnear, Mikaela; Jenkins, Melissa M; Twamley, Elizabeth W; Smith, Linda; Montano, Gabriel; Feder, Joshua; Crooke, Pamela J; Winner, Michelle G; Leon, Juan

2018-01-01

The population of adults on the autism spectrum continues to increase, and vocational outcomes are particularly poor. Longitudinal studies of adults with autism spectrum and without intellectual disability have shown consistent and persistent deficits across cognitive, social, and vocational domains, indicating a need for effective treatments of functional disabilities as each impact employment. This initial pilot study is an open trial investigation of the feasibility, acceptability, and initial estimates of outcomes for the newly developed Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills intervention, a manualized "soft skills" curriculum, to enhance both cognitive and social development in adults with autism spectrum. A total of eight adults with autism spectrum, without intellectual disability (78% males), participated in the study. Results support the original hypothesis that adults with autism spectrum can improve both cognitive (i.e. executive functioning) and social cognitive (i.e. social thinking and social communication) abilities. Further Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills was found to be feasible, acceptable, and highly satisfactory for participants and parents. Employment rates more than doubled post-intervention, with an increase from 22% to 56% of participants employed. Conclusion is that Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills has promise as an intervention that can be easily embedded into exiting supported employment vocational training programs to improve cognitive, social, and vocational outcomes.

Development of the Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills program for adults on the autism spectrum: Results of initial study

PubMed Central

Baker-Ericzén, Mary J; Fitch, Meghan A; Kinnear, Mikaela; Jenkins, Melissa M; Twamley, Elizabeth W; Smith, Linda; Montano, Gabriel; Feder, Joshua; Crooke, Pamela J; Winner, Michelle G; Leon, Juan

2018-01-01

The population of adults on the autism spectrum continues to increase, and vocational outcomes are particularly poor. Longitudinal studies of adults with autism spectrum and without intellectual disability have shown consistent and persistent deficits across cognitive, social, and vocational domains, indicating a need for effective treatments of functional disabilities as each impact employment. This initial pilot study is an open trial investigation of the feasibility, acceptability, and initial estimates of outcomes for the newly developed Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills intervention, a manualized “soft skills” curriculum, to enhance both cognitive and social development in adults with autism spectrum. A total of eight adults with autism spectrum, without intellectual disability (78% males), participated in the study. Results support the original hypothesis that adults with autism spectrum can improve both cognitive (i.e. executive functioning) and social cognitive (i.e. social thinking and social communication) abilities. Further Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills was found to be feasible, acceptable, and highly satisfactory for participants and parents. Employment rates more than doubled post-intervention, with an increase from 22% to 56% of participants employed. Conclusion is that Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills has promise as an intervention that can be easily embedded into exiting supported employment vocational training programs to improve cognitive, social, and vocational outcomes. PMID:29034696

Lifestyle use of drugs by healthy people for enhancing cognition, creativity, motivation and pleasure.

PubMed

d'Angelo, L-S Camilla; Savulich, George; Sahakian, Barbara J

2017-10-01

Today, there is continued, and in some cases growing, availability of not only psychoactive substances, including treatments for mental health disorders such as cognitive enhancers, which can enhance or restore brain function, but also 'recreational' drugs such as novel psychoactive substances (NPS). The use of psychoactive drugs has both benefits and risks: whilst new drugs to treat cognitive symptoms in neuropsychiatric or neurodegenerative disorders could have great benefits for many patient groups, the increasing ease of accessibility to recreational NPS and the increasing lifestyle use of cognitive enhancers by healthy people means that the effective management of psychoactive substances will be an issue of increasing importance. Clearly, the potential benefits of cognitive enhancers are large and increasingly relevant, particularly as the population ages, and for this reason, we should continue to devote resources to the development of cognitive enhancers as treatments for neurodegenerative diseases and psychiatric disorders, including Alzheimer's disease, attention deficit hyperactivity disorder and schizophrenia. However, the increasing use of cognitive enhancers by healthy individuals raises safety, ethical and regulatory concerns, which should not be ignored. Similarly, understanding the short- and long-term consequences of the use of NPS, as well as better understanding the motivations and profiles of users could promote more effective prevention and harm reduction measures. Linked Articles This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc. © 2017 The British Pharmacological Society.

Humility pills: building an ethics of cognitive enhancement.

PubMed

Goodman, Rob

2014-06-01

The use of cognition-enhancing drugs (CEDs) appears to be increasingly common in both academic and workplace settings. But many universities and businesses have not yet engaged with the ethical challenges raised by CED use. This paper considers criticisms of CED use with a particular focus on the Accomplishment Argument: an influential set of claims holding that enhanced work is less dignified, valuable, or authentic, and that cognitive enhancement damages our characters. While the Accomplishment Argument assumes a view of authorship based on individual credit-taking, an impersonal or collaborative view is just as possible. This paper considers the benefits of this view-including humility, a value often claimed by critics of enhancement-and argues that such a view is consistent with open CED use. It proposes an ethics of cognitive enhancement based on toleration, transparency, and humility, and it discusses how institutions and individuals can build a culture of open cognitive enhancement. © The Author 2014. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Therapeutic and prophylactic utility of the memory-enhancing drug donepezil hydrochloride on cognition of patients undergoing electroconvulsive therapy: a randomized controlled trial.

PubMed

Prakash, Jyoti; Kotwal, Atul; Prabhu, Hra

2006-09-01

Substantial progress has been made in identifying how the treatment parameters used in electroconvulsive therapy (ECT) impact its cognitive side effects. However, there is limited information regarding the role of memory enhancers in post-ECT cognitive disturbances. We evaluated the therapeutic and prophylactic efficacy of the memory-enhancing drug donepezil hydrochloride on cognition of patients undergoing ECT. A triple blind (the study subjects, clinician assessing the cognition, and the data analyst were unaware of subject allocation for trial assessment) randomized controlled trial was carried out in a General Hospital Psychiatry Unit. Subjects were randomized into 2 groups. One group received ECT with placebo, whereas the other group received ECT and donepezil (a memory-enhancing drug). Study participants were assessed in post-ECT period to analyze cognitive deficits and to compare the differences in 2 groups, as regards recovery of various aspects of cognition. The post-ECT recovery of various components of cognition was more rapid in patients using donepezil as compared to those not given donepezil (P < 0.05). This significant improvement in recovery time among patients receiving donepezil bears therapeutic implication in immediate post-ECT cognitive deficits.

Cognitive enhancement by omega-3 fatty acids from child-hood to old age: findings from animal and clinical studies.

PubMed

Luchtman, Dirk W; Song, Cai

2013-01-01

Omega-(n)-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are major components of neuronal membranes and have a wide range of functions, from modulating synaptic plasticity and neurochemistry, to neuroimmune-modulation and neuroprotection. Thus, it is not surprising that n-3 PUFA are widely acknowledged to have cognitive-enhancing effects. Although clinical evidence is somewhat conflicting, probably in large part due to methodological issues, animal studies have consistently demonstrated that n-3 PUFA are indispensable for proper brain development, may enhance cognitive function in healthy, adult individuals and attenuate cognitive impairment in aging and age-related disorders, such as dementia. This review discusses and integrates up to date evidence from clinical and animal studies investigating the cognitive-enhancing effects of n-3 PUFA during development, child- and adult-hood, as well as old-age with associated neurodegenerative diseases, such as Alzheimer's disease. Furthermore, we cover the major underlying biochemical and neurophysiological mechanisms by which n-3 PUFA mediate these effects on cognition. This article is part of a Special Issue entitled 'Cognitive Enhancers'. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dealing with requests for pharmacological cognitive enhancement from healthy students.

PubMed

Chandramouleeswaran, Susmita; Edwin, Natasha Catherine; Rajaleelan, Wesley

2016-01-01

The use of drugs to enhance cognitive function and academic performance is clearly a global phenomenon, with the reported prevalence of stimulant use among medical students ranging from 15-20%. A multi-institution study from the USA reported a 6.9% lifetime prevalence of non-prescription use of cognitive enhancers among college students. A comprehensive systematic review indicates a 16-29% use of non-prescribed stimulants among all students for reasons that include increasing concentration and alertness. While mental health professionals and guidance counsellors anecdotally recall requests for pharmacological cognitive enhancement from otherwise healthy students, the exact magnitude of this problem in the Indian context is not clear.

The use of methylphenidate among students: the future of enhancement?

PubMed

Outram, Simon M

2010-04-01

During the past few years considerable debate has arisen within academic journals with respect to the use of smart drugs or cognitive enhancement pharmaceuticals. The following paper seeks to examine the foundations of this cognitive enhancement debate using the example of methylphenidate use among college students. The argument taken is that much of the enhancement debate rests upon inflated assumptions about the ability of such drugs to enhance and over-estimations of either the size of the current market for such drugs or the rise in popularity as drugs for enhancing cognitive abilities. This article provides an overview of the empirical evidence that methylphenidate has the ability to significantly improve cognitive abilities in healthy individuals, and examines whether the presumed uptake of the drug is either as socially significant as implied or growing to the extent that it requires urgent regulatory attention. In addition, it reviews the evidence of side-effects for the use of methylphenidate which may be an influential factor in whether an individual decides to use such drugs. The primary conclusions are that neither drug efficacy, nor the benefit-to-risk balance, nor indicators of current or growing demand provide sufficient evidence that methylphenidate is a suitable example of a cognitive enhancer with mass appeal. In light of these empirically based conclusions, the article discusses why methylphenidate might have become seen as a smart drug or cognitive enhancer.

Cognitive Enhancement for Elderly Facing Dementia with the Use of Cognitive Rehabilitation Therapy Techniques and Psychological Treatment. A Case Study.

PubMed

Stratakou, Georgia Dim; Plerou, Antonia

2017-01-01

Psychological therapies in order to provide cognitive enhancement have gained some momentum the last decades. The goal of this case study was to evaluate the effects of a cognitive enhancement training program on daily living activities, cognition, and depression in a demented elderly participant. A 6-month training program was proposed for the participant, whose overall evaluation results suggest significant deficits impairment but whose response rate to the proposed tasks of the treatment was interestingly high. However, additional research is needed to overall evaluate the efficacy of the proposed method to elderly adults.

Can cognitive enhancers reduce the risk of falls in older people with Mild Cognitive Impairment? A protocol for a randomised controlled double blind trial

PubMed Central

2009-01-01

Background Older adults with cognitive problems have a higher risk of falls, at least twice that of cognitively normal older adults. The consequences of falls in this population are very serious: fallers with cognitive problems suffer more injuries due to falls and are approximately five times more likely to be admitted to institutional care. Although the mechanisms of increased fall risk in cognitively impaired people are not completely understood, it is known that impaired cognitive abilities can reduce attentional resource allocation while walking. Since cognitive enhancers, such as cholinesterase inhibitors, improve attention and executive function, we hypothesise that cognitive enhancers may reduce fall risk in elderly people in the early stages of cognitive decline by improving their gait and balance performance due to an enhancement in attention and executive function. Method/Design Double blinded randomized controlled trial with 6 months follow-up in 140 older individuals with Mild Cognitive Impairment (MCI). Participants will be randomized to the intervention group, receiving donepezil, and to the control group, receiving placebo. A block randomization by four and stratification based on fall history will be performed. Primary outcomes are improvements in gait velocity and reduction in gait variability. Secondary outcomes are changes in the balance confidence, balance sway, attention, executive function, and number of falls. Discussion By characterizing and understanding the effects of cognitive enhancers on fall risk in older adults with cognitive impairments, we will be able to pave the way for a new approach to fall prevention in this population. This RCT study will provide, for the first time, information regarding the effect of a medication designed to augment cognitive functioning have on the risk of falls in older adults with Mild Cognitive Impairment. We expect a significant reduction in the risk of falls in this vulnerable population as a function of the reduced gait variability achieved by treatment with cognitive enhancers. This study may contribute to a new approach to prevent and treat fall risk in seniors in early stages of dementia. Trial Registration The protocol for this study is registered with the Clinical Trials Registry, identifier number: NCT00934531 http://www.clinicaltrials.gov PMID:19674471

Piracetam and vinpocetine ameliorate rotenone-induced Parkinsonism in rats.

PubMed

Zaitone, Sawsan A; Abo-Elmatty, Dina M; Elshazly, Shimaa M

2012-01-01

To evaluate the neuroprotective effect of the nootropic drugs, piracetam (PIR) and vinpocetine (VIN), in rotenone-induced Parkinsonism in rats. Sixty male rats were divided into 6 groups of 10 rats each. The groups were administered vehicle, control (rotenone, 1.5 mg/kg/48 h/6 doses, s.c.), PIR (100 and 200 mg/kg/day, p.o.) and VIN (3 and 6 mg/kg/day, p.o.). The motor performance of the rats was evaluated by the open field and pole test. Striatal dopamine level, malondialdehyde (MDA), reduced glutathione (GSH) and tumor necrosis factor-α (TNF-α) were assayed. Histopathological study of the substantia nigra was also done. Results showed that rotenone-treated rats exhibited bradykinesia and motor impairment in the open-field test. In addition, GSH level was decreased whereas MDA and TNF-α increased in striata of rotenone-treated rats as compared to vehicle-treated rats. Marked degeneration of the substantia nigra pars compacta (SNpc) neurons and depletion of striatal dopamine was also observed in the rotenone-treated rats. Treatment with PIR or VIN significantly reversed the locomotor deficits and increased striatal dopamine level. Treatment with VIN significantly (P<0.05) reduced the striatal level of MDA and GSH in comparison to rotenone group whereas TNF-α production was found to be significantly decreased in PIR group (P<0.05). VIN and PIR exhibit neuroprotective activity in rotenone-induced Parkinsonism. Hence, these nootropic agents may be considered as possible candidates in the treatment of Parkinson's disease.

Enhanced Cognitive Rehabilitation to Treat Comorbid TBI and PTSD

DTIC Science & Technology

2017-12-01

13. SUPPLEMENTARY NOTES 14. ABSTRACT This was a randomized controlled treatment study to test a modification of Cognitive Processing Therapy (CPT) for...combination of conditions which often complicates recovery from either condition. Emotional symptoms are likely a main cause of the persistence of post ... tested a modification of CPT in which CPT was enhanced with compensatory cognitive rehabilitation principles detailed in CogSMART. The enhanced CPT

Towards Enhancing Written Communication Skills in the Army: Cognitive and Metacognitive Perspective

DTIC Science & Technology

1987-08-01

Din: 2 Technical Report 755 Towards Enhancing Written Communication Skills in the Army: Cognitive and Metacognitive Perspective (v) Linda Baker O...University of Maryland I Technologies for Skill Acquisition and Retention Training Research Laboratory DTICSELECTE JUL 0 8 1988 H U. S. Army Research...Include Security Classification) Towards Enhancing Written Communication Skills in the Army: Cognitive and Metacognitive Perspective 12. PERSONAL AUTHOR(S

Policy implications of technologies for cognitive enhancement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarewitz, Daniel R.; Karas, Thomas H.

2007-02-01

The Advanced Concepts Group at Sandia National Laboratory and the Consortium for Science, Policy and Outcomes at Arizona State University convened a workshop in May 2006 to explore the potential policy implications of technologies that might enhance human cognitive abilities. The group's deliberations sought to identify core values and concerns raised by the prospect of cognitive enhancement. The workshop focused on the policy implications of various prospective cognitive enhancements and on the technologies/nanotechnology, biotechnology, information technology, and cognitive science--that enable them. The prospect of rapidly emerging technological capabilities to enhance human cognition makes urgent a daunting array of questions, tensions,more » ambitions, and concerns. The workshop elicited dilemmas and concerns in ten overlapping areas: science and democracy; equity and justice; freedom and control; intergenerational issues; ethics and competition; individual and community rights; speed and deliberations; ethical uncertainty; humanness; and sociocultural risk. We identified four different perspectives to encompass the diverse issues related to emergence of cognitive enhancement technologies: (1) Laissez-faire--emphasizes freedom of individuals to seek and employ enhancement technologies based on their own judgment; (2) Managed technological optimism--believes that while these technologies promise great benefits, such benefits cannot emerge without an active government role; (3) Managed technological skepticism--views that the quality of life arises more out of society's institutions than its technologies; and (4) Human Essentialism--starts with the notion of a human essence (whether God-given or evolutionary in origin) that should not be modified. While the perspectives differ significantly about both human nature and the role of government, each encompasses a belief in the value of transparency and reliable information that can allow public discussion and decisions about cognitive enhancement. The practical question is how to foster productive discussions in a society whose attention is notably fragmented and priorities notably diverse. The question of what to talk about remains central, as each of the four perspectives is concerned about different things. Perhaps the key issue for initial clarification as a condition for productive democratic discussion has to do with the intended goals of cognitive enhancement, and the mechanisms for allowing productive deliberation about these goals.« less

Psychostimulants and Cognition: A Continuum of Behavioral and Cognitive Activation

PubMed Central

Wood, Suzanne; Sage, Jennifer R.; Shuman, Tristan

2014-01-01

Psychostimulants such as cocaine have been used as performance enhancers throughout recorded history. Although psychostimulants are commonly prescribed to improve attention and cognition, a great deal of literature has described their ability to induce cognitive deficits, as well as addiction. How can a single drug class be known to produce both cognitive enhancement and impairment? Properties of the particular stimulant drug itself and individual differences between users have both been suggested to dictate the outcome of stimulant use. A more parsimonious alternative, which we endorse, is that dose is the critical determining factor in cognitive effects of stimulant drugs. Herein, we review several popular stimulants (cocaine, amphetamine, methylphenidate, modafinil, and caffeine), outlining their history of use, mechanism of action, and use and abuse today. One common graphic depiction of the cognitive effects of psychostimulants is an inverted U–shaped dose-effect curve. Moderate arousal is beneficial to cognition, whereas too much activation leads to cognitive impairment. In parallel to this schematic, we propose a continuum of psychostimulant activation that covers the transition from one drug effect to another as stimulant intake is increased. Low doses of stimulants effect increased arousal, attention, and cognitive enhancement; moderate doses can lead to feelings of euphoria and power, as well as addiction and cognitive impairment; and very high doses lead to psychosis and circulatory collapse. This continuum helps account for the seemingly disparate effects of stimulant drugs, with the same drug being associated with cognitive enhancement and impairment. PMID:24344115

Use of cognitive enhancement medication among northern Italian university students.

PubMed

Castaldi, Silvana; Gelatti, Umberto; Orizio, Grazia; Hartung, Uwe; Moreno-Londono, Ana Maria; Nobile, Marta; Schulz, Peter J

2012-06-01

This study assesses the use of cognitive enhancement medication among university students in Northern Italy. It was conducted as a cross-sectional analysis on the basis of a paper-and-pencil survey of 77 undergraduate students attending courses in the Faculty of Medicine of the University of Milan, Milano, Italy. Although the share of students who have taken cognitive enhancement medication themselves in the past is still small (16%), the use of these drugs is rather common and freely communicated in some social circles. Enhancing the ability to study outside of the class was students' primary motive for use. Students who think that there is no or an acceptable risk involved in cognitive enhancement medication are more likely to take drugs and dietary supplements than those who perceive the risk as high.

Closing thoughts for cognitive enhancement.

PubMed

Kantak, Kathleen M; Wettstein, Joseph G

2015-01-01

The wide-ranging field of cognition enhancing research along with its ethics as it stands today is summarized. In the forefront are potentially novel drugs and non-pharmacological treatments for cognitive impairment across many different psychiatric and neurologic indications. Today's research will bring new drugs to patients tomorrow, and tomorrow's research will bring new molecular targets to clinical development that should be cognitive domain-specific. There is the likelihood that special populations may be better treated and that personalized medicine for cognitive impairment could become a reality. It is conceivable that with the current research effort, cognition enhancing drugs will become available to wide-ranging populations of people with neuropsychiatric illness and to those that are healthy. In some cultures, there is a push in society to be more intelligent or have more cognitive prowess. Thus, the ethical use of cognitive enhancing drugs should be an area of debate and communication. Neuroethics is a growing field and it intends to bring together key contributors such as physicians, disease experts, regulatory officials, and policy makers to discuss how such medicines can or should be made available. Together with this, one has to consider the possibility that no single medicine or technology will have a great impact on cognition and, therefore, combination therapy of drugs plus other approaches like exercise or transcranial direct-current stimulation may be the path forward. This is another area of scientific inquiry and debate, and the results should be fruitful and helpful to patients. The science of cognition is advancing at a rapid rate, and communication of its progress along with the development of rational and ethical policies for use of cognitive enhancers will be beneficial.

The Mind Bending Quest for Cognitive Enhancers

PubMed Central

Arce, E

2016-01-01

Adequate cognitive functioning is essential for daily activities. When there is an insult to the brain, cognitive abilities can suffer, which, in turn, produce substantial medical and functional impairment. Advances in neurobiology, circuit neuroscience, and clinical assessment technology are converging in a manner that holds promise for the development of new pharmacological agents for cognitive enhancement in neuropsychiatric disease. PMID:27706806

Human Cognitive Enhancement Ethical Implications for Airman-Machine Teaming

DTIC Science & Technology

2017-04-06

34 Psychological Constructs versus Neural Mechanisms: Different Perspectives for Advanced Research of Cognitive Processes and Development of Neuroadaptive...AIR WAR COLLEGE AIR UNIVERSITY HUMAN COGNITIVE ENHANCEMENT ETHICAL IMPLICATIONS FOR AIRMAN-MACHINE TEAMING by William M. Curlin...increasingly challenging adversarial threats. It is hypothesized that by the year 2030, human system operators will be “ cognitively challenged” to keep pace

Are Prescription Stimulants “Smart Pills”?

PubMed Central

Smith, M. Elizabeth; Farah, Martha J.

2013-01-01

Use of prescription stimulants by normal healthy individuals to enhance cognition is said to be on the rise. Who is using these medications for cognitive enhancement, and how prevalent is this practice? Do prescription stimulants in fact enhance cognition for normal healthy people? We review the epidemiological and cognitive neuroscience literatures in search of answers to these questions. Epidemiological issues addressed include the prevalence of nonmedical stimulant use, user demographics, methods by which users obtain prescription stimulants, and motivations for use. Cognitive neuroscience issues addressed include the effects of prescription stimulants on learning and executive function, as well as the task and individual variables associated with these effects. Little is known about the prevalence of prescription stimulant use for cognitive enhancement outside of student populations. Among college students, estimates of use vary widely but, taken together, suggest that the practice is commonplace. The cognitive effects of stimulants on normal healthy people cannot yet be characterized definitively, despite the volume of research that has been carried out on these issues. Published evidence suggests that declarative memory can be improved by stimulants, with some evidence consistent with enhanced consolidation of memories. Effects on the executive functions of working memory and cognitive control are less reliable but have been found for at least some individuals on some tasks. In closing, we enumerate the many outstanding questions that remain to be addressed by future research and also identify obstacles facing this research. PMID:21859174

Should we use Commitment Contracts to Regulate Student use of Cognitive Enhancing Drugs?

PubMed

Danaher, John

2016-10-01

Are universities justified in trying to regulate student use of cognitive enhancing drugs? In this article I argue that they can be, but that the most appropriate kind of regulatory intervention is likely to be voluntary in nature. To be precise, I argue that universities could justifiably adopt a commitment contract system of regulation wherein students are encouraged to voluntarily commit to not using cognitive enhancing drugs (or to using them in a specific way). If they are found to breach that commitment, they should be penalized by, for example, forfeiting a number of marks on their assessments. To defend this model of regulation, I adopt a recently-proposed evaluative framework for determining the appropriateness of enhancement in specific domains of activity, and I focus on particular existing types of cognitive enhancement drugs, not hypothetical or potential forms. In this way, my argument is tailored to the specific features of university education, and common patterns of usage among students. It is not concerned with the general ethical propriety of using cognitive enhancing drugs. © 2016 John Wiley & Sons Ltd.

Will cognitive enhancement create post-persons? The use(lessness) of induction in determining the likelihood of moral status enhancement.

PubMed

Mihailov, Emilian; Dragomir, Alexandru

2018-06-01

The prospect of cognitive enhancement well beyond current human capacities raises worries that the fundamental equality in moral status of human beings could be undermined. Cognitive enhancement might create beings with moral status higher than persons. Yet, there is an expressibility problem of spelling out what the higher threshold in cognitive capacity would be like. Nicholas Agar has put forward the bold claim that we can show by means of inductive reasoning that indefinite cognitive enhancement will probably mark a difference in moral status. The hope is that induction can determine the plausibility of post-personhood existence in the absence of an account of what the higher status would be like. In this article, we argue that Agar's argument fails and, more generally, that inductive reasoning has little bearing on assessing the likelihood of post-personhood in the absence of an account of higher status. We conclude that induction cannot bypass the expressibility problem about post-persons. © 2018 John Wiley & Sons Ltd.

Pharmacological cognitive enhancement: treatment of neuropsychiatric disorders and lifestyle use by healthy people.

PubMed

Sahakian, Barbara J; Morein-Zamir, Sharon

2015-04-01

Neuropsychiatric disorders typically manifest as problems with attentional biases, aberrant learning, dysfunctional reward systems, and an absence of top-down cognitive control by the prefrontal cortex. In view of the cost of common mental health disorders, in terms of distress to the individual and family in addition to the financial cost to society and governments, new developments for treatments that address cognitive dysfunction should be a priority so that all members of society can flourish. Cognitive enhancing drugs, such as cholinesterase inhibitors and methylphenidate, are used as treatments for the cognitive symptoms of Alzheimer's disease and attention deficit hyperactivity disorder. However, these drugs and others, including modafinil, are being increasingly used by healthy people for enhancement purposes. Importantly for ethical and safety reasons, the drivers for this increasing lifestyle use of so-called smart drugs by healthy people should be considered and discussions must occur about how to ensure present and future pharmacological cognitive enhancers are used for the benefit of society. Copyright © 2015 Elsevier Ltd. All rights reserved.

The potential role of dopamine D3 receptor neurotransmission in cognition

PubMed Central

Nakajima, Shinichiro; Gerretsen, Philip; Takeuchi, Hiroyoshi; Caravaggio, Fernando; Chow, Tiffany; Le Foll, Bernard; Mulsant, Benoit; Pollock, Bruce; Graff-Guerrero, Ariel

2013-01-01

Currently available treatments have limited pro-cognitive effects for neuropsychiatric disorders, such as schizophrenia, Parkinson’s disease and Alzheimer’s disease. The primary objective of this work is to review the literature on the role of dopamine D3 receptors in cognition, and propose dopamine D3 receptor antagonists as possible cognitive enhancers for neuropsychiatric disorders. A literature search was performed to identify animal and human studies on D3 receptors and cognition using PubMed, MEDLINE and EMBASE. The search terms included “dopamine D3 receptor” and “cognition”. The literature search identified 164 articles. The results revealed: (1) D3 receptors are associated with cognitive functioning in both healthy individuals and those with neuropsychiatric disorders; (2) D3 receptor blockade appears to enhance while D3 receptor agonism seems to impair cognitive function, including memory, attention, learning, processing speed, social recognition and executive function independent of age; and (3) D3 receptor antagonists may exert their pro-cognitive effect by enhancing the release of acetylcholine in the prefrontal cortex, disinhibiting the activity of dopamine neurons projecting to the nucleus accumbens or prefrontal cortex, or activating CREB signaling in the hippocampus. These findings suggest that D3 receptor blockade may enhance cognitive performance in healthy individuals and treat cognitive dysfunction in individuals with a neuropsychiatric disorder. Clinical trials are needed to confirm these effects. PMID:23791072

Enhancing Warfighter Cognitive Abilities with Transcranial Magnetic Stimulation: A Feasibility Analysis

DTIC Science & Technology

2007-06-01

AFRL-HE-WP-TR-2007-0095 Enhancing Warfighter Cognitive Abilities with Transcranial Magnetic Stimulation : a Feasibility Analysis Jeremy T. Nelson...Abilities with Transcranial N/A Magnetic Stimulation : a Feasibility Analysis 5b. GRANTNUMBER N/A 5c. PROGRAM ELEMENT NUMBER 62202F 6. AUTHOR(S) 5d...feasibility of using transcranial magnetic stimulation (TMS) to enhance warfighter cognitive abilities. An extensive literature review was conducted

Neural correlates of cognitive improvements following cognitive remediation in schizophrenia: a systematic review of randomized trials

PubMed Central

Isaac, Clémence; Januel, Dominique

2016-01-01

Background Cognitive impairments are a core feature in schizophrenia and are linked to poor social functioning. Numerous studies have shown that cognitive remediation can enhance cognitive and functional abilities in patients with this pathology. The underlying mechanism of these behavioral improvements seems to be related to structural and functional changes in the brain. However, studies on neural correlates of such enhancement remain scarce. Objectives We explored the neural correlates of cognitive enhancement following cognitive remediation interventions in schizophrenia and the differential effect between cognitive training and other therapeutic interventions or patients’ usual care. Method We searched MEDLINE, PsycInfo, and ScienceDirect databases for studies on cognitive remediation therapy in schizophrenia that used neuroimaging techniques and a randomized design. Search terms included randomized controlled trial, cognitive remediation, cognitive training, rehabilitation, magnetic resonance imaging, positron emission tomography, electroencephalography, magnetoencephalography, near infrared spectroscopy, and diffusion tensor imaging. We selected randomized controlled trials that proposed multiple sessions of cognitive training to adult patients with a schizophrenia spectrum disorder and assessed its efficacy with imaging techniques. Results In total, 15 reports involving 19 studies were included in the systematic review. They involved a total of 455 adult patients, 271 of whom received cognitive remediation. Cognitive remediation therapy seems to provide a neurobiological enhancing effect in schizophrenia. After therapy, increased activations are observed in various brain regions mainly in frontal – especially prefrontal – and also in occipital and anterior cingulate regions during working memory and executive tasks. Several studies provide evidence of an improved functional connectivity after cognitive training, suggesting a neuroplastic effect of therapy through mechanisms of functional reorganization. Neurocognitive and social-cognitive training may have a cumulative effect on neural networks involved in social cognition. The variety of proposed programs, imaging tasks, and techniques may explain the heterogeneity of observed neural improvements. Future studies would need to specify the effect of cognitive training depending on those variables. PMID:26993787

Facilitatory effects of piracetam on excitability of motor nerve terminals and neuromuscular transmission.

PubMed

Hall, E D; Von Voigtlander, P F

1987-11-01

The possible in vivo facilitatory effects of the pyrrolidine acetamide no-otropic agent piracetam on neuromuscular transmission, were studied based upon reports of enhancement of central cholinergic function. Piracetam was shown to antagonize the lethal effects of the neuromuscular blocking agent hemicholinium-3 (HC-3), in female CF-1 mice when administered in a dose of 100 mg/kg (i.p.) simultaneously with HC-3. A 30 mg/kg (i.p.) dose of piracetam was ineffective by itself, although it potentiated the protective effects of choline (25 mg/kg i.p.). The analogs of piracetam, aniracetam, oxiracetam, pramiracetam and dupracetam also significantly antagonized the lethality of HC-3 at doses over a 30-300 mg/kg range. The acute facilitatory properties of piracetam on neuromuscular transmission were examined in more detail in vivo in the soleus nerve muscle preparation of the cat. A 100 mg/kg (i.v.) dose of piracetam, while having no effect on its own, significantly enhanced the ability of a 200 micrograms/kg (i.v.) dose of edrophonium to produce a potentiation of muscle contraction dependent on repetitive discharges in the soleus motor nerve terminals. In preparations in which the motor nerve terminals of the soleus were in a partially degenerated state as a result of section of the motor axons 48 hr earlier, piracetam acted to restore their sensitivity to edrophonium. Furthermore, in both normal and partially degenerated preparations, piracetam significantly decreased the neuromuscular blocking effects of a 150 micrograms/kg (i.v.) dose of d-tubocurarine. The mechanism of the neuromuscular facilitatory effects of piracetam on neuromuscular transmission is discussed in terms of an enhanced excitability of motor nerve terminals together with an action to increase the synthesis and/or release of acetylcholine.

Effects of peer social interaction on performance during computerized cognitive remediation therapy in patients with early course schizophrenia: A pilot study.

PubMed

Sandoval, Luis R; González, Betzamel López; Stone, William S; Guimond, Synthia; Rivas, Cristina Torres; Sheynberg, David; Kuo, Susan S; Eack, Shaun; Keshavan, Matcheri S

2017-09-04

Recent studies show that computer-based training enhances cognition in schizophrenia; furthermore, socialization has also been found to improve cognitive functions. It is generally believed that non-social cognitive remediation using computer exercises would be a pre-requisite for therapeutic benefits from social cognitive training. However, it is also possible that social interaction by itself enhances non-social cognitive functions; this possibility has scarcely been explored in schizophrenia patients. This pilot study examined the effects of computer-based neurocognitive training, along with social interaction either with a peer (PSI) or without one (N-PSI). We hypothesized that PSI will enhance cognitive performance during computerized exercises in schizophrenia, as compared with N-PSI. Sixteen adult participants diagnosed with schizophrenia or schizoaffective disorder participating in an ongoing trial of Cognitive Enhancement Therapy completed several computerized neurocognitive remediation training sessions (the Orientation Remedial Module©, or ORM), either with a peer or without a peer. We observed a significant interaction between the effect of PSI and performance on the different cognitive exercises (p<0.05). More precisely, when patients performed the session with PSI, they demonstrated better cognitive performances than with N-PSI in the ORM exercise that provides training in processing speed, alertness, and reaction time (the standard Attention Reaction Conditioner, or ARC) (p<0.01, corrected). PSI did not significantly affect other cognitive domains such as target detection and spatial attention. Our findings suggest that PSI could improve cognitive performance, such as processing speed, during computerized cognitive training in schizophrenia. Additional studies investigating the effect of PSI during cognitive remediation are needed to further evaluate this hypothesis. Copyright © 2017. Published by Elsevier B.V.

The Motivational Enhancement Therapy and Cognitive Behavioral Therapy Supplement: 7 Sessions of Cognitive Behavioral Therapy for Adolescent Cannabis Users, Cannabis Youth Treatment (CYT) Series, Volume 2.

ERIC Educational Resources Information Center

Webb, Charles; Scudder, Meleney; Kaminer, Yifrah; Kaden, Ron

This manual, a supplement to "Motivational Enhancement Therapy and Cognitive Behavioral Therapy for Adolescent Cannabis Users: 5 Sessions, Cannabis Youth Treatment (CYT) Series, Volume 1", presents a seven-session cognitive behavioral treatment (CBT7) approach designed especially for adolescent cannabis users. It addresses the implementation and…

Forming Positive Identities to Enhance Mathematics Learning among Adolescents

ERIC Educational Resources Information Center

Mkhize, Duduzile Rosemary

2017-01-01

Learners' participation in mathematics decreases during their transition from primary to high school. This is despite adolescents' cognitive growth equipping them with enhanced cognitive ability; to learn mathematics. Hence low participation in mathematics does not result from cognitive deficiency. Rather, lack of motivation to learn mathematics…

Are prescription stimulants "smart pills"? The epidemiology and cognitive neuroscience of prescription stimulant use by normal healthy individuals.

PubMed

Smith, M Elizabeth; Farah, Martha J

2011-09-01

Use of prescription stimulants by normal healthy individuals to enhance cognition is said to be on the rise. Who is using these medications for cognitive enhancement, and how prevalent is this practice? Do prescription stimulants in fact enhance cognition for normal healthy people? We review the epidemiological and cognitive neuroscience literatures in search of answers to these questions. Epidemiological issues addressed include the prevalence of nonmedical stimulant use, user demographics, methods by which users obtain prescription stimulants, and motivations for use. Cognitive neuroscience issues addressed include the effects of prescription stimulants on learning and executive function, as well as the task and individual variables associated with these effects. Little is known about the prevalence of prescription stimulant use for cognitive enhancement outside of student populations. Among college students, estimates of use vary widely but, taken together, suggest that the practice is commonplace. The cognitive effects of stimulants on normal healthy people cannot yet be characterized definitively, despite the volume of research that has been carried out on these issues. Published evidence suggests that declarative memory can be improved by stimulants, with some evidence consistent with enhanced consolidation of memories. Effects on the executive functions of working memory and cognitive control are less reliable but have been found for at least some individuals on some tasks. In closing, we enumerate the many outstanding questions that remain to be addressed by future research and also identify obstacles facing this research. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

Modafinil combined with cognitive training is associated with improved learning in healthy volunteers--a randomised controlled trial.

PubMed

Gilleen, J; Michalopoulou, P G; Reichenberg, A; Drake, R; Wykes, T; Lewis, S W; Kapur, S

2014-04-01

Improving cognition in people with neuropsychiatric disorders remains a major clinical target. By themselves pharmacological and non-pharmacological approaches have shown only modest effects in improving cognition. In the present study we tested a recently-proposed methodology to combine CT with a 'cognitive-enhancing' drug to improve cognitive test scores and expanded on previous approaches by delivering combination drug and CT, over a long intervention of repeated sessions, and used multiple tasks to reveal the cognitive processes being enhanced. We also aimed to determine whether gains from this combination approach generalised to untrained tests. In this proof of principle randomised-controlled trial thirty-three healthy volunteers were randomised to receive either modafinil or placebo combined with daily cognitive training over two weeks. Volunteers were trained on tasks of new-language learning, working memory and verbal learning following 200 mg modafinil or placebo for ten days. Improvements in trained and untrained tasks were measured. Rate of new-language learning was significantly enhanced with modafinil, and effects were greatest over the first five sessions. Modafinil improved within-day learning rather than between-day retention. No enhancement of gains with modafinil was observed in working memory nor rate of verbal learning. Gains in all tasks were retained post drug-administration, but transfer effects to broad cognitive abilities were not seen. This study shows that combining CT with modafinil specifically elevates learning over early training sessions compared to CT with placebo and provides a proof of principle experimental paradigm for pharmacological enhancement of cognitive remediation. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

[The effect of bemitil on conditioned-reflex memory in normal rats and under stress exposures].

PubMed

Pragina, L L; Tushmalova, N A; Inozemtsev, A N; Smirnov, A V

1999-01-01

The authors studied the effect of the actoprotector bemitil on the conditional-reflex memory of rats and its functional disorder by disturbance of the cause-effect (abatement of the avoidance reaction) or space relations. Intraperitoneal injections of 1.8 mg/kg of bemitil were given daily 30 min before the experiment. The training of animals improved authentically from experiment to experiment. Thus, the drug, possesses the nootropic properties. Exposure to stressogenic factors of various depth demonstrated the stress-protective effect of bemitil.

Cognition-Enhancing Drugs

PubMed Central

Mehlman, Maxwell J

2004-01-01

New drugs that enhance cognition in cognitively healthy individuals present difficult public policy challenges. While their use is not inherently unethical, steps must be taken to ensure that they are safe, that they are widely available to promote equality of opportunity, and that individuals are free to decide whether or not to use them. PMID:15330974

S-phenylpiracetam, a selective DAT inhibitor, reduces body weight gain without influencing locomotor activity.

PubMed

Zvejniece, Liga; Svalbe, Baiba; Vavers, Edijs; Makrecka-Kuka, Marina; Makarova, Elina; Liepins, Vilnis; Kalvinsh, Ivars; Liepinsh, Edgars; Dambrova, Maija

2017-09-01

S-phenylpiracetam is an optical isomer of phenotropil, which is a clinically used nootropic drug that improves physical condition and cognition. Recently, it was shown that S-phenylpiracetam is a selective dopamine transporter (DAT) inhibitor that does not influence norepinephrine (NE) or serotonin (5-HT) receptors. The aim of the present study was to study the effects of S-phenylpiracetam treatment on body weight gain, blood glucose and leptin levels, and locomotor activity. Western diet (WD)-fed mice and obese Zucker rats were treated daily with peroral administration of S-phenylpiracetam for 8 and 12weeks, respectively. Weight gain and plasma metabolites reflecting glucose metabolism were measured. Locomotor activity was detected in an open-field test. S-phenylpiracetam treatment significantly decreased body weight gain and fat mass increase in the obese Zucker rats and in the WD-fed mice. In addition, S-phenylpiracetam reduced the plasma glucose and leptin concentration and lowered hyperglycemia in a glucose tolerance test in both the mice and the rats. S-phenylpiracetam did not influence locomotor activity in the obese Zucker rats or in the WD-fed mice. The results demonstrate that S-phenylpiracetam reduces body weight gain and improves adaptation to hyperglycemia without stimulating locomotor activity. Our findings suggest that selective DAT inhibitors, such as S-phenylpiracetam, could be potentially useful for treating obesity in patients with metabolic syndrome with fewer adverse health consequences compared to other anorectic agents. Copyright © 2017. Published by Elsevier Inc.

Piracetam and aniracetam antagonism of centrally active drug-induced antinociception.

PubMed

Galeotti, N; Ghelardini, C; Bartolini, A

1996-04-01

The effects of the nootropic drugs piracetam and aniracetam on antinociception induced by baclofen, bicuculline, and picrotoxin and on baclofen-induced muscle relaxation were studied in mice. Antinociception was investigated using both the hot plate (thermal stimulus) and abdominal constriction (chemical stimulus) tests. Both behaviour inhibition and muscle relaxation were observed by using the rota-rod test. Piracetam (30 mg/kg, IP) and aniracetam (10 mg/kg, PO) reduced baclofen, bicuculline, and picrotoxin antinociception without modifying analgesia induced by non-GABAergic drugs such as morphine, physostigmine, clomipramine, and diphenhydramine. In this concentration range, piracetam, and aniracetam were also able to reduce the inhibition of rota-rod performance. At higher doses piracetam (100 mg/kg, IP) and aniracetam (100 mg/kg, PO) were able to completely prevent baclofen antinociception. However, when prevention of GABAergic antinociception was complete, piracetam and aniracetam were able to block non-GABAergic antinociception also. comparing the effects of piracetam and aniracetam with those exerted by the GABAB antagonist CGP 35348, a reduction of non-GABAergic analgesia was also observed using higher doses of CGP 35348 (2.5 micrograms per mouse ICV). The present results indicate that piracetam and aniracetam, by preventing both of the investigated effects of baclofen, have some selectivity against GABAB-mediated inhibition. The well-known activity of piracetam and aniracetam on learning and memory might, therefore, depend, at least in part, on the removal of inhibitory GABAB mechanisms that impair attention and cognitive functions.

Inefficacy of piracetam in the prevention of painful crises in children and adolescents with sickle cell disease.

PubMed

Alvim, R C; Viana, M B; Pires, M A S; Franklin, H M O H; Paula, M J; Brito, A C; Oliveira, T F; Rezende, P V

2005-01-01

Analgesia and hydration remain the only safe treatment for painful crises of sickle cell disease; hydroxyurea is effective, but the toxicity is still a problem. Piracetam is a nootropic drug that has reportedly been effective and non-toxic in sickle cell patients, but most studies were not placebo-controlled and included a small number of patients. The present study evaluated the drug in a double-blind crossed placebo-controlled clinical trial in 73 children and adolescents suffering from moderate to severe painful crises for 13 months. Information regarding frequency and severity of pain was acquired through monthly clinical evaluation, visits and house calls, and 4,300 weekly questionnaires filled out by the patients in their domiciles. A monthly pain score was calculated for each patient. Pain was the most frequent adverse manifestation of the disease stressing its significant bio-psycho-social impact. Although nearly all patients and relatives reported a better clinical course throughout the whole study, the drug was ineffective in the prevention of painful crises. This placebo effect may be ascribed to an unplanned and unsystematic 'cognitive-behavioural' management of the children. The pain score in the second semester of the study - both in the experimental and in the control groups - was significantly smaller than that in the first semester. In conclusion, piracetam was found to be ineffective in the prevention of painful crises; a powerful placebo effect due to adequate patient care was demonstrated. Copyright (c) 2005 S. Karger AG, Basel

Digital Learning As Enhanced Learning Processing? Cognitive Evidence for New insight of Smart Learning.

PubMed

Di Giacomo, Dina; Ranieri, Jessica; Lacasa, Pilar

2017-01-01

Large use of technology improved quality of life across aging and favoring the development of digital skills. Digital skills can be considered an enhancing to human cognitive activities. New research trend is about the impact of the technology in the elaboration information processing of the children. We wanted to analyze the influence of technology in early age evaluating the impact on cognition. We investigated the performance of a sample composed of n. 191 children in school age distributed in two groups as users: high digital users and low digital users. We measured the verbal and visuoperceptual cognitive performance of children by n. 8 standardized psychological tests and ad hoc self-report questionnaire. Results have evidenced the influence of digital exposition on cognitive development: the cognitive performance is looked enhanced and better developed: high digital users performed better in naming, semantic, visual memory and logical reasoning tasks. Our finding confirms the data present in literature and suggests the strong impact of the technology using not only in the social, educational and quality of life of the people, but also it outlines the functionality and the effect of the digital exposition in early age; increased cognitive abilities of the children tailor digital skilled generation with enhanced cognitive processing toward to smart learning.

Cognitive enhancing effects of rTMS administered to the prefrontal cortex in patients with depression: A systematic review and meta-analysis of individual task effects.

PubMed

Martin, Donel M; McClintock, Shawn M; Forster, Jane J; Lo, Tin Yan; Loo, Colleen K

2017-11-01

Repetitive transcranial magnetic stimulation (rTMS) is an approved therapeutic treatment of major depressive disorder and has increasing clinical use throughout the world. However, it remains unclear whether an rTMS course for depression may also produce cognitive enhancement. In a recent meta-analysis of sham-controlled randomized controlled studies (RCTs) conducted in patients with neuropsychiatric conditions, no evidence was found for generalized cognitive enhancing effects across cognitive domains with active compared to sham rTMS. Notwithstanding, there remains the possibility of cognitive effects following an rTMS course that are more highly specific, for example, in specific clinical conditions, or at the individual task level. This study aimed to determine whether a therapeutic rTMS course in patients with depression is associated with cognitive enhancing effects at the task level. A systematic review and meta-analysis of outcomes on individual neuropsychological tasks from sham-controlled RCTs where an rTMS course was administered to the dorsolateral prefrontal cortex (DLPFC) in patients with depression. Eighteen studies met the inclusion criteria. Active rTMS treatment showed no specific enhancing effects on the majority of cognitive tasks. Modest effect size improvements with active compared to sham rTMS treatment were found for performance on the Trail Making Test Parts A (g = 0.28, 95% CI = 0.06-0.50) and B (g = 0.26, 95% CI = 0.06-0.47). A therapeutic rTMS course administered to the prefrontal cortex for depression may produce modest cognitive enhancing effects specific to psychomotor speed, visual scanning, and set-shifting ability. © 2017 Wiley Periodicals, Inc.

The influence of offspring, parity, and oxytocin on cognitive flexibility during the postpartum period.

PubMed

Albin-Brooks, Christopher; Nealer, Connor; Sabihi, Sara; Haim, Achikam; Leuner, Benedetta

2017-03-01

Pregnancy and the postpartum period are times of profound behavioral change including alterations in cognitive function. This has been most often studied using hippocampal-dependent tasks assessing spatial learning and memory. However, less is known about the cognitive effects of motherhood for tasks that rely on areas other than the hippocampus. We have previously shown that postpartum females perform better on the extradimensional phase of an attentional set shifting task, a measure of cognitive flexibility which is dependent on the medial prefrontal cortex (mPFC). The present experiments aimed to extend this work by examining the importance of postpartum stage as well as offspring and parity in driving improved mPFC cognitive function during motherhood. We also examined whether the neuropeptide oxytocin, which plays a role in regulating numerous maternal functions, mediates enhanced cognitive flexibility during motherhood. Our results demonstrate that compared to virgin females, cognitive flexibility is enhanced in mothers regardless of postpartum stage and is not affected by parity since both first (primiparous) and second (biparous) time mothers showed the enhancement. Moreover, we found that improved cognitive flexibility in mothers requires the presence of offspring, as removal of the pups abolished the cognitive enhancement in postpartum females. Lastly, using an oxytocin receptor antagonist, we demonstrate that oxytocin signaling in the mPFC is necessary for the beneficial effects of motherhood on cognitive flexibility. Together, these data provide insights into the temporal, experiential and hormonal factors which regulate mPFC-dependent cognitive function during the postpartum period. Copyright © 2017 Elsevier Inc. All rights reserved.

Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorder: Results of an 18-Month Feasibility Study

ERIC Educational Resources Information Center

Eack, Shaun M.; Greenwald, Deborah P.; Hogarty, Susan S.; Bahorik, Amber L.; Litschge, Maralee Y.; Mazefsky, Carla A.; Minshew, Nancy J.

2013-01-01

Adults with autism experience significant impairments in social and non-social information processing for which few treatments have been developed. This study conducted an 18-month uncontrolled trial of Cognitive Enhancement Therapy (CET), a comprehensive cognitive rehabilitation intervention, in 14 verbal adults with autism spectrum disorder to…

Pharmacological Enhancement of Memory and Executive Functioning in Laboratory Animals

PubMed Central

Floresco, Stan B; Jentsch, James D

2011-01-01

Investigating how different pharmacological compounds may enhance learning, memory, and higher-order cognitive functions in laboratory animals is the first critical step toward the development of cognitive enhancers that may be used to ameliorate impairments in these functions in patients suffering from neuropsychiatric disorders. Rather than focus on one aspect of cognition, or class of drug, in this review we provide a broad overview of how distinct classes of pharmacological compounds may enhance different types of memory and executive functioning, particularly those mediated by the prefrontal cortex. These include recognition memory, attention, working memory, and different components of behavioral flexibility. A key emphasis is placed on comparing and contrasting the effects of certain drugs on different cognitive and mnemonic functions, highlighting methodological issues associated with this type of research, tasks used to investigate these functions, and avenues for future research. Viewed collectively, studies of the neuropharmacological basis of cognition in rodents and non-human primates have identified targets that will hopefully open new avenues for the treatment of cognitive disabilities in persons affected by mental disorders. PMID:20844477

Using visual processing training to enhance standard cognitive remediation outcomes in schizophrenia: A pilot study.

PubMed

Contreras, Natalia A; Tan, Eric J; Lee, Stuart J; Castle, David J; Rossell, Susan L

2018-04-01

Approaches to cognitive remediation (CR) that address sensory perceptual skills before higher cognitive skills, have been found to be effective in enhancing cognitive performance in schizophrenia. To date, however, most of the conducted trials have concentrated on auditory processing. The aim of this study was to explore whether the addition of visual processing training could enhance standard cognitive remediation outcomes in a schizophrenia population. Twenty participants were randomised to either receive 20h of computer-assisted cognitive remediation alone or 20h of visual processing training modules and cognitive remediation training. All participants were assessed at baseline and at the end of cognitive remediation training on cognitive and psychosocial (i.e. self-esteem, quality of life) measures. At the end of the study participants across both groups improved significantly in overall cognition and psychosocial functioning. No significant differences were observed between groups on any of the measures. Of potential interest, however, was that the Cohen's d assessing the between group difference in the rates of change were moderate/large for a greater improvement in Visual Learning, Working Memory and Social Cognition for the visual training plus cognitive remediation group. On the basis of our effect sizes on three domains of cognition, we recommend replicating this intervention with a larger sample. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhancing Human Cognition with Cocoa Flavonoids

PubMed Central

Socci, Valentina; Tempesta, Daniela; Desideri, Giovambattista; De Gennaro, Luigi; Ferrara, Michele

2017-01-01

Enhancing cognitive abilities has become a fascinating scientific challenge, recently driven by the interest in preventing age-related cognitive decline and sustaining normal cognitive performance in response to cognitively demanding environments. In recent years, cocoa and cocoa-derived products, as a rich source of flavonoids, mainly the flavanols sub-class, have been clearly shown to exert cardiovascular benefits. More recently, neuromodulation and neuroprotective actions have been also suggested. Here, we discuss human studies specifically aimed at investigating the effects of acute and chronic administration of cocoa flavanols on different cognitive domains, such as executive functions, attention and memory. Through a variety of direct and indirect biological actions, in part still speculative, cocoa and cocoa-derived food have been suggested to possess the potential to counteract cognitive decline and sustain cognitive abilities, particularly among patients at risk. Although still at a preliminary stage, research investigating the relations between cocoa and cognition shows dose-dependent improvements in general cognition, attention, processing speed, and working memory. Moreover, cocoa flavanols administration could also enhance normal cognitive functioning and exert a protective role on cognitive performance and cardiovascular function specifically impaired by sleep loss, in healthy subjects. Together, these findings converge at pointing to cocoa as a new interesting nutraceutical tool to protect human cognition and counteract different types of cognitive decline, thus encouraging further investigations. Future research should include complex experimental designs combining neuroimaging techniques with physiological and behavioral measures to better elucidate cocoa neuromodulatory properties and directly compare immediate versus long-lasting cognitive effects. PMID:28560212

Enhancing Human Cognition with Cocoa Flavonoids.

PubMed

Socci, Valentina; Tempesta, Daniela; Desideri, Giovambattista; De Gennaro, Luigi; Ferrara, Michele

2017-01-01

Enhancing cognitive abilities has become a fascinating scientific challenge, recently driven by the interest in preventing age-related cognitive decline and sustaining normal cognitive performance in response to cognitively demanding environments. In recent years, cocoa and cocoa-derived products, as a rich source of flavonoids, mainly the flavanols sub-class, have been clearly shown to exert cardiovascular benefits. More recently, neuromodulation and neuroprotective actions have been also suggested. Here, we discuss human studies specifically aimed at investigating the effects of acute and chronic administration of cocoa flavanols on different cognitive domains, such as executive functions, attention and memory. Through a variety of direct and indirect biological actions, in part still speculative, cocoa and cocoa-derived food have been suggested to possess the potential to counteract cognitive decline and sustain cognitive abilities, particularly among patients at risk. Although still at a preliminary stage, research investigating the relations between cocoa and cognition shows dose-dependent improvements in general cognition, attention, processing speed, and working memory. Moreover, cocoa flavanols administration could also enhance normal cognitive functioning and exert a protective role on cognitive performance and cardiovascular function specifically impaired by sleep loss, in healthy subjects. Together, these findings converge at pointing to cocoa as a new interesting nutraceutical tool to protect human cognition and counteract different types of cognitive decline, thus encouraging further investigations. Future research should include complex experimental designs combining neuroimaging techniques with physiological and behavioral measures to better elucidate cocoa neuromodulatory properties and directly compare immediate versus long-lasting cognitive effects.

Zingiber officinale Improves Cognitive Function of the Middle-Aged Healthy Women

PubMed Central

Saenghong, Naritsara; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Tongun, Terdthai; Piyavhatkul, Nawanant; Banchonglikitkul, Chuleratana; Kajsongkram, Tanwarat

2012-01-01

The development of cognitive enhancers from plants possessing antioxidants has gained much attention due to the role of oxidative stress-induced cognitive impairment. Thus, this study aimed to determine the effect of ginger extract, or Zingiber officinale, on the cognitive function of middle-aged, healthy women. Sixty participants were randomly assigned to receive a placebo or standardized plant extract at doses of 400 and 800 mg once daily for 2 months. They were evaluated for working memory and cognitive function using computerized battery tests and the auditory oddball paradigm of event-related potentials at three different time periods: before receiving the intervention, one month, and two months. We found that the ginger-treated groups had significantly decreased P300 latencies, increased N100 and P300 amplitudes, and exhibited enhanced working memory. Therefore, ginger is a potential cognitive enhancer for middle-aged women. PMID:22235230

Can noninvasive brain stimulation enhance cognition in neuropsychiatric disorders?

PubMed

Demirtas-Tatlidede, Asli; Vahabzadeh-Hagh, Andrew M; Pascual-Leone, Alvaro

2013-01-01

Cognitive impairment is a core symptom of many neuropsychiatric diseases and a key contributor to the patient's quality of life. However, an effective therapeutic strategy has yet to be developed. Noninvasive brain stimulation techniques, namely transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), are promising techniques that are under investigation for a variety of otherwise treatment-resistant neuropsychiatric diseases. Notably, these tools can induce alterations in neural networks subserving cognitive operations and thus may provide a means for cognitive restoration. The purpose of this article is to review the available evidence concerning cognitive enhancing properties of noninvasive brain stimulation in neuropsychiatry. We specifically focus on major depression, Alzheimer's disease, schizophrenia, autism and attention deficit hyperactivity disorder (ADHD), where cognitive dysfunction is a major symptom and some studies have been completed with promising results. We provide a critical assessment of the available research and suggestions to guide future efforts. This article is part of a Special Issue entitled 'Cognitive Enhancers'. Copyright © 2012 Elsevier Ltd. All rights reserved.

Exercise Induced Neuroplasticity to Enhance Therapeutic Outcomes of Cognitive Remediation in Schizophrenia: Analyzing the Role of Brai nderived Neurotrophic Factor.

PubMed

Campos, Carlos; Rocha, Nuno B F; Lattari, Eduardo; Nardi, Antonio E; Machado, Sergio

2017-01-01

Cognitive impairment is a major manifestation of schizophrenia and a crucial treatment target as these deficits are closely related to patients' functional outcomes. Cognitive remediation is the gold-standard practice to address cognitive deficits in schizophrenia. There is clear evidence stating that cognitive remediation improves cognitive function and promotes structural neuroplastic changes in patients with schizophrenia, with brain-derived neurotrophic factor (BDNF) expression emerging as a potential biomarker for its efficacy. This is particularly important as there is clear evidence relating atypical BDNF expression to cognitive impairment in patients with schizophrenia. Despite the valuable role of cognitive remediation in the management of schizophrenia, there is still a need to develop methods that allow maximizing its efficacy. In this review, we present a hypothesis arguing that cognitive remediation efficacy for patients with schizophrenia can be enhanced by aerobic exercise-induced BDNF upregulation. There have been a few trials reporting that combining aerobic exercise with cognitive training was superior to cognitive training alone to improve cognitive functioning in patients with schizophrenia. Furthermore, there is preliminary evidence suggesting that combined aerobic and cognitive training can increase peripheral BDNF levels. Thereby, engaging in aerobic exercise in close temporal proximity to cognitive remediation may allow achieving a state of neuroplastic readiness in the brain, facilitating cognitive functioning enhancement. Although this hypothesis still lacks evidence, future clinical trials using cognitive remediation for schizophrenia should explore strategies to maximize neuroplasticity and achieve optimal cognitive improvements. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Fluoxetine potentiates methylphenidate-induced gene regulation in addiction-related brain regions: Concerns for use of cognitive enhancers?

PubMed Central

Steiner, Heinz; Van Waes, Vincent; Marinelli, Michela

2009-01-01

Background There is growing use of psychostimulant cognitive enhancers such as methylphenidate (Ritalin). Methylphenidate differs from the psychostimulant cocaine because it does not enhance brain levels of serotonin. We investigated whether exposure to methylphenidate combined with a serotonin-enhancing medication, the prototypical selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac), would produce more “cocaine-like” molecular and behavioral changes. Methods We measured the effects of fluoxetine on gene expression induced by the cognitive enhancer methylphenidate in the striatum and nucleus accumbens of rats, by in situ hybridization histochemistry. We also determined whether fluoxetine modified behavioral effects of methylphenidate. Results Fluoxetine robustly potentiated methylphenidate-induced expression of the transcription factors c-fos and zif 268 throughout the striatum and to some degree in the nucleus accumbens. Fluoxetine also enhanced methylphenidate-induced stereotypical behavior. Conclusions Both potentiated gene regulation in the striatum and the behavioral effects indicate that combining the SSRI fluoxetine with the cognitive enhancer methylphenidate mimics cocaine effects, consistent with an increased risk for substance use disorder. PMID:19931852

A Randomized Clinical Trial of Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorders

DTIC Science & Technology

2015-10-01

This project is focused on conducting the first randomized-controlled trial of Cognitive Enhancement Therapy (CET) in 54 verbal adults with autism ...of the neuroplastic effects of CET on brain function in support of cognitive enhancement in adult autism . Analyses of treatment effects to date...the need and potential for CET to be a significant treatment advance for verbal adults with autism . Importantly, improvements were found in daily life function and in brain circuitry supporting core abilities.

Piracetam and vinpocetine ameliorate rotenone-induced Parkinsonism in rats

PubMed Central

Zaitone, Sawsan A.; Abo-Elmatty, Dina M.; Elshazly, Shimaa M.

2012-01-01

Objective: To evaluate the neuroprotective effect of the nootropic drugs, piracetam (PIR) and vinpocetine (VIN), in rotenone-induced Parkinsonism in rats. Materials and Methods: Sixty male rats were divided into 6 groups of 10 rats each. The groups were administered vehicle, control (rotenone, 1.5 mg/kg/48 h/6 doses, s.c.), PIR (100 and 200 mg/kg/day, p.o.) and VIN (3 and 6 mg/kg/day, p.o.). The motor performance of the rats was evaluated by the open field and pole test. Striatal dopamine level, malondialdehyde (MDA), reduced glutathione (GSH) and tumor necrosis factor-α (TNF-α) were assayed. Histopathological study of the substantia nigra was also done. Results: Results showed that rotenone-treated rats exhibited bradykinesia and motor impairment in the open-field test. In addition, GSH level was decreased whereas MDA and TNF-α increased in striata of rotenone-treated rats as compared to vehicle-treated rats. Marked degeneration of the substantia nigra pars compacta (SNpc) neurons and depletion of striatal dopamine was also observed in the rotenone-treated rats. Treatment with PIR or VIN significantly reversed the locomotor deficits and increased striatal dopamine level. Treatment with VIN significantly (P < 0.05) reduced the striatal level of MDA and GSH in comparison to rotenone group whereas TNF-α production was found to be significantly decreased in PIR group (P < 0.05). Conclusion: VIN and PIR exhibit neuroprotective activity in rotenone-induced Parkinsonism. Hence, these nootropic agents may be considered as possible candidates in the treatment of Parkinson's disease. PMID:23248410

Effects of Cognitive Enhancement Therapy on Employment Outcomes in Early Schizophrenia: Results from a 2-Year Randomized Trial

ERIC Educational Resources Information Center

Eack, Shaun M.; Hogarty, Gerard E.; Greenwald, Deborah P.; Hogarty, Susan S.; Keshavan, Matcheri S.

2011-01-01

Objective: To examine the effects of psychosocial cognitive rehabilitation on employment outcomes in a randomized controlled trial for individuals with early course schizophrenia. Method: Early course schizophrenia outpatients (N = 58) were randomly assigned to cognitive enhancement therapy (CET) or an enriched supportive therapy (EST) control and…

A Cognitive Apprenticeship Approach to Facilitating Web-Based Collaborative Problem Solving

ERIC Educational Resources Information Center

Kuo, Fan-Ray; Hwang, Gwo-Jen; Chen, Szu-Chuang; Chen, Sherry Y.

2012-01-01

Enhancing students' problem-solving abilities has been recognized as an important and challenging issue for technology-enhanced learning. Thus, previous research has attempted to address this issue by developing various mechanisms, among which a cognitive apprenticeship model can particularly enhance students' abilities. However, it is not clear…

The Changing Drug Culture: Use and Misuse of Cognition-Enhancing Drugs.

PubMed

Albertson, Timothy E; Chenoweth, James A; Colby, Daniel K; Sutter, Mark E

2016-02-01

There has been an increase in diagnoses of attention-deficit/hyperactivity disorder (ADHD), with approximately 9% of American children now diagnosed, and a concomitant increase in the use of stimulants (eg, amphetamines, methylphenidate) to manage ADHD. Nonstimulant drugs (eg, atomoxetine, guanfacine, clonidine) also are used, but most patients are treated with stimulants. All of these drugs are effective for management of ADHD, and, overall, use in childhood does not seem to increase the risk of substance abuse later in life. However, widespread use has resulted in prescription stimulants being diverted for nonmedical uses, particularly by high school and college students seeking cognitive enhancement for improved academic performance. Studies of ADHD drugs for improving cognition in patients without ADHD have mixed results, and any improvements appear to be modest and short-term. Other substances also are used for cognitive enhancement. Drugs for Alzheimer disease are being used for mild cognitive impairment, though there is no evidence that they are effective. Creatine may have mild cognition-enhancing properties, but study results often are confounded by the addition of exercise, which by itself is thought to improve cognition. There is no evidence that other supplements, such as vitamins and omega-3 fatty acids, improve cognitive function. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Combining brain stimulation and video game to promote long-term transfer of learning and cognitive enhancement

PubMed Central

Looi, Chung Yen; Duta, Mihaela; Brem, Anna-Katharine; Huber, Stefan; Nuerk, Hans-Christoph; Cohen Kadosh, Roi

2016-01-01

Cognitive training offers the potential for individualised learning, prevention of cognitive decline, and rehabilitation. However, key research challenges include ecological validity (training design), transfer of learning and long-term effects. Given that cognitive training and neuromodulation affect neuroplasticity, their combination could promote greater, synergistic effects. We investigated whether combining transcranial direct current stimulation (tDCS) with cognitive training could further enhance cognitive performance compared to training alone, and promote transfer within a short period of time. Healthy adults received real or sham tDCS over their dorsolateral prefrontal cortices during two 30-minute mathematics training sessions involving body movements. To examine the role of training, an active control group received tDCS during a non-mathematical task. Those who received real tDCS performed significantly better in the game than the sham group, and showed transfer effects to working memory, a related but non-numerical cognitive domain. This transfer effect was absent in active and sham control groups. Furthermore, training gains were more pronounced amongst those with lower baseline cognitive abilities, suggesting the potential for reducing cognitive inequalities. All effects associated with real tDCS remained 2 months post-training. Our study demonstrates the potential benefit of this approach for long-term enhancement of human learning and cognition. PMID:26902664

Combining brain stimulation and video game to promote long-term transfer of learning and cognitive enhancement.

PubMed

Looi, Chung Yen; Duta, Mihaela; Brem, Anna-Katharine; Huber, Stefan; Nuerk, Hans-Christoph; Cohen Kadosh, Roi

2016-02-23

Cognitive training offers the potential for individualised learning, prevention of cognitive decline, and rehabilitation. However, key research challenges include ecological validity (training design), transfer of learning and long-term effects. Given that cognitive training and neuromodulation affect neuroplasticity, their combination could promote greater, synergistic effects. We investigated whether combining transcranial direct current stimulation (tDCS) with cognitive training could further enhance cognitive performance compared to training alone, and promote transfer within a short period of time. Healthy adults received real or sham tDCS over their dorsolateral prefrontal cortices during two 30-minute mathematics training sessions involving body movements. To examine the role of training, an active control group received tDCS during a non-mathematical task. Those who received real tDCS performed significantly better in the game than the sham group, and showed transfer effects to working memory, a related but non-numerical cognitive domain. This transfer effect was absent in active and sham control groups. Furthermore, training gains were more pronounced amongst those with lower baseline cognitive abilities, suggesting the potential for reducing cognitive inequalities. All effects associated with real tDCS remained 2 months post-training. Our study demonstrates the potential benefit of this approach for long-term enhancement of human learning and cognition.

[Adding the perspective of emotion on cognitive rehabilitation].

PubMed

Nakagome, Kazuyuki

2011-01-01

Cognitive rehabilitation has been gradually disseminated in Japan lately. Cognitive rehabilitation is distinct from other psychosocial rehabilitation methods, which aims to enhance cognitive function per se, by various training tools, using paper and pencil tasks, computer games, etc. It stands on the hypothesis that enhancing cognitive function should lead to improvement in social functioning. However, it is becoming clear that cognitive rehabilitation on its own is not strongly effective on social functioning, but rather it appears effective when combined with other methods of rehabilitation. Moreover, it does not treat the emotional problems, which is essential considering the treatment endpoint, to enhance "subjective well-being". Emotional problems arise much often at social interaction in patients with schizophrenia, which can be amended by improving their social cognition as well as social skills. Recently, one of the social cognition training programs has been developed in USA by Penn and his colleagues, named SCIT (Social Cognition and Interaction Training) . The program treats a number of factors involved in social cognition, a) emotion perception, b) attributional style, and c) theory of mind, using various techniques such as Socrates quotes. In previous studies, SCIT showed good effectiveness in various aspects of social cognition for inpatients, whereas the finding was not as clear for outpatients. It may be assumed that integrating SCIT into a cognitive rehabilitation program should alleviate emotional stress the patients often encounter at social interaction in their daily activities. Presumably the next candidate target for psychosocial treatments coming after cognition and emotion should be "intrinsic motivation".

An examination of an enhancing effect of music on attentional abilities in older persons with mild cognitive impairment.

PubMed

Lake, Jessica I; Goldstein, Felicia C

2011-02-01

While the effect of listening to music on cognitive abilities is highly debated, studies reporting an enhancing effect of music in elderly populations appear to be more consistent. In this study, the effects of listening to music on attention in groups of cognitively normal older adults and those with mild cognitive impairment were considered. Participants were exposed to both a music and silence condition, and after each condition performed Digit Span and Coding tasks which require attention for maximal performance. The hypothesis that listening to music, compared to a silence condition, enhances performance was not supported for either group. Various explanations for these findings are considered.

Oral aniracetam treatment in C57BL/6J mice without pre-existing cognitive dysfunction reveals no changes in learning, memory, anxiety or stereotypy

PubMed Central

Reynolds, Conner D.; Jefferson, Taylor S.; Volquardsen, Meagan; Pandian, Ashvini; Smith, Gregory D.; Holley, Andrew J.; Lugo, Joaquin N.

2017-01-01

Background: The piracetam analog, aniracetam, has recently received attention for its cognition enhancing potential, with minimal reported side effects.  Previous studies report the drug to be effective in both human and non-human models with pre-existing cognitive dysfunction, but few studies have evaluated its efficacy in healthy subjects. A previous study performed in our laboratory found no cognitive enhancing effects of oral aniracetam administration 1-hour prior to behavioral testing in naïve C57BL/6J mice. Methods: The current study aims to further evaluate this drug by administration of aniracetam 30 minutes prior to testing in order to optimize any cognitive enhancing effects. In this study, all naïve C57BL/6J mice were tested in tasks of delayed fear conditioning, novel object recognition, rotarod, open field, elevated plus maze, and marble burying. Results: Across all tasks, animals in the treatment group failed to show enhanced learning when compared to controls. Conclusions: These results provide further evidence suggesting that aniracetam conveys no therapeutic benefit to subjects without pre-existing cognitive dysfunction. PMID:29946420

Randomized response estimates for the 12-month prevalence of cognitive-enhancing drug use in university students.

PubMed

Dietz, Pavel; Striegel, Heiko; Franke, Andreas G; Lieb, Klaus; Simon, Perikles; Ulrich, Rolf

2013-01-01

To estimate the 12-month prevalence of cognitive-enhancing drug use. Paper-and-pencil questionnaire that used the randomized response technique. University in Mainz, Germany. A total of 2569 university students who completed the questionnaire. An anonymous, specialized questionnaire that used the randomized response technique was distributed to students at the beginning of classes and was collected afterward. From the responses, we calculated the prevalence of students taking drugs only to improve their cognitive performance and not to treat underlying mental disorders such as attention-deficit-hyperactivity disorder, depression, and sleep disorders. The estimated 12-month prevalence of using cognitive-enhancing drugs was 20%. Prevalence varied by sex (male 23.7%, female 17.0%), field of study (highest in students studying sports-related fields, 25.4%), and semester (first semester 24.3%, beyond first semester 16.7%). To our knowledge, this is the first time that the randomized response technique has been used to survey students about cognitive-enhancing drug use. Using the randomized response technique, our questionnaire provided data that showed a high 12-month prevalence of cognitive-enhancing drug use in German university students. Our study suggests that other direct survey techniques have underestimated the use of these drugs. Drug prevention programs need to be established at universities to address this issue. © 2013 Pharmacotherapy Publications, Inc.

Optogenetic Stimulation of Prefrontal Glutamatergic Neurons Enhances Recognition Memory.

PubMed

Benn, Abigail; Barker, Gareth R I; Stuart, Sarah A; Roloff, Eva V L; Teschemacher, Anja G; Warburton, E Clea; Robinson, Emma S J

2016-05-04

Finding effective cognitive enhancers is a major health challenge; however, modulating glutamatergic neurotransmission has the potential to enhance performance in recognition memory tasks. Previous studies using glutamate receptor antagonists have revealed that the medial prefrontal cortex (mPFC) plays a central role in associative recognition memory. The present study investigates short-term recognition memory using optogenetics to target glutamatergic neurons within the rodent mPFC specifically. Selective stimulation of glutamatergic neurons during the online maintenance of information enhanced associative recognition memory in normal animals. This cognitive enhancing effect was replicated by local infusions of the AMPAkine CX516, but not CX546, which differ in their effects on EPSPs. This suggests that enhancing the amplitude, but not the duration, of excitatory synaptic currents improves memory performance. Increasing glutamate release through infusions of the mGluR7 presynaptic receptor antagonist MMPIP had no effect on performance. These results provide new mechanistic information that could guide the targeting of future cognitive enhancers. Our work suggests that improved associative-recognition memory can be achieved by enhancing endogenous glutamatergic neuronal activity selectively using an optogenetic approach. We build on these observations to recapitulate this effect using drug treatments that enhance the amplitude of EPSPs; however, drugs that alter the duration of the EPSP or increase glutamate release lack efficacy. This suggests that both neural and temporal specificity are needed to achieve cognitive enhancement. Copyright © 2016 Benn et al.

[Peptidergic modulation of the hippocampus synaptic activity].

PubMed

Skrebitskiĭ, V G; Kondratenko, R V; Povarov, I S; Dereviagin, V I

2011-11-01

Effects of two newly synthesized nootropic and anxiolytic dipeptides: Noopept and Selank on inhibitory synaptic transmission in hippocampal CA1 pyramidal cells were investigated using patch-clamp technique in whole-cell configuration. Bath application of Noopept (1 microM) or Selank (2 microM) significantly increased the frequency of spike-dependent spontaneous m1PSCs, whereas spike-independent mlPSCs remained unchanged. It was suggested that both peptides mediated their effect sue to activation of inhibitory interneurons terminating on CA1 pyramidal cells. Results of current clamp recording of inhibitory interneurons residing in stratum radiatum confirmed this suggestion, at least for Noonent.

Design and study of some novel ibuprofen derivatives with potential nootropic and neuroprotective properties.

PubMed

Siskou, Ioanna C; Rekka, Eleni A; Kourounakis, Angeliki P; Chrysselis, Michael C; Tsiakitzis, Kariofyllis; Kourounakis, Panos N

2007-01-15

Six novel ibuprofen derivatives and related structures, incorporating a proline moiety and designed for neurodegenerative disorders, are studied. They possess anti-inflammatory properties and three of them inhibited lipoxygenase. One compound was found to inhibit cyclooxygenase (COX)-2 production in spleenocytes from arthritic rats. The HS-containing compounds are potent antioxidants and one of them protected against glutathione loss after cerebral ischemia/reperfusion. They demonstrated lipid-lowering ability and seem to acquire low gastrointestinal toxicity. Acetylcholinesterase inhibitory activity, found in two of these compounds, may be an asset to their actions.

Quantitative Determination of Vinpocetine in Dietary Supplements.

PubMed

French, John M T; King, Matthew D; McDougal, Owen M

2016-05-01

Current United States regulatory policies allow for the addition of pharmacologically active substances in dietary supplements if derived from a botanical source. The inclusion of certain nootropic drugs, such as vinpocetine, in dietary supplements has recently come under scrutiny due to the lack of defined dosage parameters and yet unproven short- and long-term benefits and risks to human health. This study quantified the concentration of vinpocetine in several commercially available dietary supplements and found that a highly variable range of 0.6-5.1 mg/serving was present across the tested products, with most products providing no specification of vinpocetine concentrations.

[Functional-behavioral profile of new cyclic GABA analogs in acute toxicity tests].

PubMed

Bugaeva, L I; Spasov, A A; Verovskiĭ, V E

2004-01-01

The properties of karphedone and phepyrone--new phenyl derivatives of pyrrolidone possessing nootropic activity--were studied in the course of the acute toxicity tests on rats. The drug effects were evaluated in terms of their integral influence on the state and behavior of test animals. The real therapeutic range and the profit/risk ratio of karphedone were comparable with those of the reference drug pyracetam and exceeded by a factor of 1.3 the corresponding values for phepyrone (irrespective of the LD50 values). The results give grounds for the further preclinical investigation of karphedone.

The promise of a better group future: Cognitive alternatives increase students' self-efficacy and academic performance.

PubMed

Iyer, Aarti; Zhang, Airong; Jetten, Jolanda; Hao, Zhen; Cui, Lijuan

2017-12-01

Drawing on classic social identity theorizing (Tajfel, Differentiation between social groups: Studies in the social psychology of intergroup relations, London, UK, Academic Press, 1978), we propose that low-status minority group members' self-efficacy and performance on intellectual tasks can be enhanced by prompting them to believe in a better future for their group (i.e., increasing awareness of cognitive alternatives to the existing low-status position). Study 1 manipulated cognitive alternatives among 157 migrant workers' children in China, showing that self-efficacy was enhanced in the high compared to the low cognitive alternative condition. Study 2 extended this experimental finding among 114 migrant workers' children: Participants in the high cognitive alternative condition performed better on mathematics and attention tasks than did participants in the low cognitive alternative condition. Results highlight the power of believing in a better future for the collective as a means of enhancing self-efficacy and educational outcomes among members of disadvantaged groups. © 2017 The British Psychological Society.

D-Serine and a glycine transporter inhibitor improve MK-801-induced cognitive deficits in a novel object recognition test in rats.

PubMed

Karasawa, Jun-Ichi; Hashimoto, Kenji; Chaki, Shigeyuki

2008-01-10

Compounds enhancing N-methyl-d-aspartate (NMDA) glutamate receptor function have been reported to improve cognitive deficits. Since cognitive deficits are considered to be the core symptom of schizophrenia, enhancing NMDA receptor function represents a promising approach to treating schizophrenia. In the present study, we investigated whether d-serine or a glycine transporter inhibitor N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine (NFPS), both of which enhance NMDA receptor function, could improve MK-801-induced cognitive deficits in rats, and compared their effects with those of the atypical antipsychotic clozapine and of the typical antipsychotic haloperidol. To assess cognitive function, we used a novel object recognition test in rats that measured spontaneous exploratory activity of a novel object when paired with a familiar object. We then evaluated the effects of the compounds on cognitive deficits induced by treatment with MK-801, the NMDA receptor antagonist. Pretreatment with clozapine (1, 5 mg/kg, i.p.) but not haloperidol (0.03, 0.1 mg/kg, i.p.) significantly improved MK-801-induced cognitive deficits. Pretreatment with D-serine at 800 mg/kg (i.p.) or NFPS (0.3, 1 mg/kg, i.p.) significantly improved MK-801-induced cognitive deficits under this test paradigm. These findings suggest that impaired preference for novel objects induced by MK-801 in the novel object recognition test could be a useful animal model for evaluating the efficacy of compounds targeting the cognitive deficits observed in schizophrenic patients. The results also suggest that enhancing NMDA receptor function is an effective way for treating the cognitive deficits associated with schizophrenia.

Moral and social reasons to acknowledge the use of cognitive enhancers in competitive-selective contexts.

PubMed

Garasic, Mirko D; Lavazza, Andrea

2016-03-29

Although some of the most radical hypothesis related to the practical implementations of human enhancement have yet to become even close to reality, the use of cognitive enhancers is a very tangible phenomenon occurring with increasing popularity in university campuses as well as in other contexts. It is now well documented that the use of cognitive enhancers is not only increasingly common in Western countries, but also gradually accepted as a normal procedure by the media as well. In fact, its implementation is not unusual in various professional contexts and it has its peak in colleges (where the trend has been characterized as "academic doping"). Even when certain restrictions in the legislation of a country are indeed in place (i.e. through prescriptions requirements), they are without doubts easy to overcome. The legitimacy and appropriateness of such restrictions will not be the focus of our investigation. Our concern is instead related to the moral and social reasons to publicly acknowledge the use of cognitive enhancers in competitive-selective contexts. These reasons are linked to a more neutral analysis of contemporary Western society: it is a fact that an increasing number of competitive-selective contexts have a substantial number of contenders using cognitive enhancers. Through the use of five explicative examples, in this paper we want to analyse the problems related to its use. In particular, it will be our aim to show the tension between one of the main argument used by bio-liberals (the use of cognitive enhancers is an eligible procedure that society does not impose on anyone) and the actual implementation of the drugs in competitive, or semi-competitive contexts.

The ethics of elective psychopharmacology

PubMed Central

Mohamed, Ahmed D.; Sahakian, Barbara J.

2012-01-01

Pharmacological cognitive enhancers (PCEs) are used to improve cognitive functions, such as attention, learning, memory and planning in patients with impairments in cognition resulting from traumatic brain injury (TBI) or from neuropsychiatric disorders such as Alzheimer's disease (AD), mild cognitive impairment, schizophrenia, and attention deficit hyperactivity disorder (ADHD). Moreover, PCEs have been shown to improve cognition in healthy volunteers with no psychiatric disorders. This article describes the rationale behind the need for their use in neuropsychiatric patients and illustrates how PCEs can ameliorate cognitive impairments, improve quality of life and wellbeing, and therefore reduce the economic burden associated with these disorders. We also describe evidence that PCEs are being used as cognitive enhancers by healthy people. Crucially, as the lifestyle use of these drugs becomes very popular in the healthy population, a final aim is to present an overview of the current and future neuroethical considerations of enhancing the healthy brain. As information regarding their actual use, benefits and harms in various healthy populations is currently lacking, we propose research that aims to obtain relevant empirical data, monitor the short- and long-term effectiveness and side-effects, and initiate accurate surveys to determine current patterns and quantity of usage of PCE drugs by healthy people. Furthermore, in order to instigate a dialogue between neuroethics and neuropsychopharmacology, we urge scientists to explore and communicate the social and ethical implications of their research to the public. Finally, we discuss and highlight other means of enhancing cognition in both patients and healthy adults, including education and physical exercise. PMID:21396152

Cognitive training and Bacopa monnieri: Evidence for a combined intervention to alleviate age associated cognitive decline.

PubMed

McPhee, Grace M; Downey, Luke A; Noble, Anthony; Stough, Con

2016-10-01

As the elderly population grows the impact of age associated cognitive decline as well as neurodegenerative diseases such as Alzheimer's disease and dementia will increase. Ageing is associated with consistent impairments in cognitive processes (e.g., processing speed, memory, executive function and learning) important for work, well-being, life satisfaction and overall participation in society. Recently, there has been increased effort to conduct research examining methods to improve cognitive function in older citizens. Cognitive training has been shown to improve performance in some cognitive domains; including memory, processing speed, executive function and attention in older adults. These cognitive changes are thought to be related to improvements in brain connectivity and neural circuitry. Bacopa monnieri has also been shown to improve specific domains of cognition, sensitive to age associated cognitive decline (particularly processing speed and memory). These Bacopa monnieri dependent improvements may be due to the increase in specific neuro-molecular mechanisms implicated in the enhancement of neural connections in the brain (i.e. synaptogenesis). In particular, a number of animal studies have shown Bacopa monnieri consumption upregulates calcium dependent kinases in the synapse and post-synaptic cell, crucial for strengthening and growing connections between neurons. These effects have been shown to occur in areas important for cognitive processes, such as the hippocampus. As Bacopa monnieri has shown neuro-molecular mechanisms that encourage synaptogenesis, while cognitive training enhances brain connectivity, Bacopa monnieri supplementation could theoretically enhance and strengthen synaptic changes acquired through cognitive training. Therefore, the current paper hypothesises that the combination of these two interventions could improve cognitive outcomes, over and above the effects of administrating these interventions independently, as an effective treatment to ameliorate age associated cognitive decline. Copyright © 2016 Elsevier Ltd. All rights reserved.

Utility of Nutraceutical Products Marketed for Cognitive and Memory Enhancement

PubMed Central

McDougall, Graham J.; Austin-Wells, Vonnette; Zimmerman, Teena

2008-01-01

This article identifies a convenience sample of 14 memory-enhancing herbal products that were found to be available commercially, examines their active ingredients, states their claims, and evaluates the available evidence to determine their efficacy. The analyses identified four problematic areas. First, a majority of the products use cognitive terminology, which leads consumers to anticipate an intended cognitive benefit. Second, some ingredients are completely homeopathic and contain components not known outside of the homeopathic field. Third, the evidence of treatment efficacy is often contradictory, because products are recommended for purposes other than cognitive or memory loss. Finally, the manufacturers of the product have usually conducted the research on individual products. Until more research is available, it is suggested that holistic nursing professionals exercise caution in recommending nutraceuticals to their patients/clients for the use of cognitive improvement or memory enhancement. PMID:16251490

The Effect of Repetitive Saccade Execution on the Attention Network Test: Enhancing Executive Function with a Flick of the Eyes

ERIC Educational Resources Information Center

Edlin, James M.; Lyle, Keith B.

2013-01-01

The simple act of repeatedly looking left and right can enhance subsequent cognition, including divergent thinking, detection of matching letters from visual arrays, and memory retrieval. One hypothesis is that saccade execution enhances subsequent cognition by altering attentional control. To test this hypothesis, we compared performance…

Implantation of Neuronal Stem Cells Enhances Object Recognition without Increasing Neurogenesis after Lateral Fluid Percussion Injury in Mice

PubMed Central

Ngwenya, Laura B.; Mazumder, Sarmistha; Porter, Zachary R.; Oswald, Duane J.

2018-01-01

Cognitive deficits after traumatic brain injury (TBI) are debilitating and contribute to the morbidity and loss of productivity of over 10 million people worldwide. Cell transplantation has been linked to enhanced cognitive function after experimental traumatic brain injury, yet the mechanism of recovery is poorly understood. Since the hippocampus is a critical structure for learning and memory, supports adult neurogenesis, and is particularly vulnerable after TBI, we hypothesized that stem cell transplantation after TBI enhances cognitive recovery by modulation of endogenous hippocampal neurogenesis. We performed lateral fluid percussion injury (LFPI) in adult mice and transplanted embryonic stem cell-derived neural progenitor cells (NPC). Our data confirm an injury-induced cognitive deficit in novel object recognition, a hippocampal-dependent learning task, which is reversed one week after NPC transplantation. While LFPI alone promotes hippocampal neurogenesis, as revealed by doublecortin immunolabeling of immature neurons, subsequent NPC transplantation prevents increased neurogenesis and is not associated with morphological maturation of endogenous injury-induced immature neurons. Thus, NPC transplantation enhances cognitive recovery early after LFPI without a concomitant increase in neuron numbers or maturation. PMID:29531536

Brief Report: Low-Dose Hydrocortisone Has Acute Enhancing Effects on Verbal Learning in HIV-Infected Men.

PubMed

Rubin, Leah H; Phan, K Luan; Keating, Sheila M; Weber, Kathleen M; Maki, Pauline M

2017-07-01

Glucocorticoids are released in response to stress and alter cognition and brain function through both rapid nongenomic and slow genomic mechanisms. Administration of glucocorticoids in the form of hydrocortisone enhances aspects of learning and memory in individuals with PTSD but impairs these abilities in healthy individuals. We examine the time-dependent effects of glucocorticoids on cognition in HIV-infected men. In a double-blind placebo-controlled crossover study, we examined the time-dependent effects of a single low dose of hydrocortisone [10 mg; low-dose hydrocortisone (LDH)] on cognition in 45 HIV-infected men. Participants were randomized to receive either LDH or placebo and one month later, were given the opposite treatment. At each intervention session, cognition was assessed 30 minutes (assessing nongenomic effects) and 4 hours (assessing genomic effects) after pill administration. Self-reported stress/anxiety and cortisol/cytokines in saliva were measured throughout each session. Compared with placebo, LDH doubled salivary cortisol levels. Cortisol returned to baseline 4 hours postadministration. At the 30-minute assessment, LDH enhanced verbal learning compared with placebo. Greater increases in cortisol were associated with greater enhancements in verbal learning. LDH did not affect subjective stress/anxiety or any other cognitive outcomes at the 30-minute or 4-hour time point. The rapid effects of LDH on verbal learning suggests a nongenomic mechanism by which glucocorticoids can enhance cognition in HIV-infected men. The nonenduring nature of this enhancement may limit its clinical utility but provides insight into mechanisms underlying the effects of acute glucocorticoids on learning.

Swiss University Students' Attitudes toward Pharmacological Cognitive Enhancement.

PubMed

Maier, Larissa J; Liakoni, Evangelia; Schildmann, Jan; Schaub, Michael P; Liechti, Matthias E

2015-01-01

Pharmacological cognitive enhancement (PCE) refers to the nonmedical use of prescription or recreational drugs to enhance cognitive performance. Several concerns about PCE have been raised in the public. The aim of the present study was to investigate students' attitudes toward PCE. Students at three Swiss universities were invited by e-mail to participate in a web-based survey. Of the 29,282 students who were contacted, 3,056 participated. Of these students, 22% indicated that they had used prescription drugs (12%) or recreational substances including alcohol (14%) at least once for PCE. The use of prescription drugs or recreational substances including alcohol prior to the last exam was reported by 16%. Users of pharmacological cognitive enhancers were more likely to consider PCE fair (24%) compared with nonusers (11%). Only a minority of the participants agreed with the nonmedical use of prescription drugs by fellow students when assuming weak (7%) or hypothetically strong efficacy and availability to everyone (14%). Two-thirds (68%) considered performance that is obtained with PCE less worthy of recognition. Additionally, 80% disagreed that PCE is acceptable in a competitive environment. More than half (64%) agreed that PCE in academia is similar to doping in sports. Nearly half (48%) claimed that unregulated access to pharmacological cognitive enhancers increases the pressure to engage in PCE and educational inequality (55%). In conclusion, Swiss students' main concerns regarding PCE were related to coercion and fairness. As expected, these concerns were more prevalent among nonusers than among users of pharmacological cognitive enhancers. More balanced information on PCE should be shared with students, and future monitoring of PCE is recommended.

Swiss University Students’ Attitudes toward Pharmacological Cognitive Enhancement

PubMed Central

Maier, Larissa J.; Liakoni, Evangelia; Schildmann, Jan; Schaub, Michael P.; Liechti, Matthias E.

2015-01-01

Pharmacological cognitive enhancement (PCE) refers to the nonmedical use of prescription or recreational drugs to enhance cognitive performance. Several concerns about PCE have been raised in the public. The aim of the present study was to investigate students’ attitudes toward PCE. Students at three Swiss universities were invited by e-mail to participate in a web-based survey. Of the 29,282 students who were contacted, 3,056 participated. Of these students, 22% indicated that they had used prescription drugs (12%) or recreational substances including alcohol (14%) at least once for PCE. The use of prescription drugs or recreational substances including alcohol prior to the last exam was reported by 16%. Users of pharmacological cognitive enhancers were more likely to consider PCE fair (24%) compared with nonusers (11%). Only a minority of the participants agreed with the nonmedical use of prescription drugs by fellow students when assuming weak (7%) or hypothetically strong efficacy and availability to everyone (14%). Two-thirds (68%) considered performance that is obtained with PCE less worthy of recognition. Additionally, 80% disagreed that PCE is acceptable in a competitive environment. More than half (64%) agreed that PCE in academia is similar to doping in sports. Nearly half (48%) claimed that unregulated access to pharmacological cognitive enhancers increases the pressure to engage in PCE and educational inequality (55%). In conclusion, Swiss students’ main concerns regarding PCE were related to coercion and fairness. As expected, these concerns were more prevalent among nonusers than among users of pharmacological cognitive enhancers. More balanced information on PCE should be shared with students, and future monitoring of PCE is recommended. PMID:26657300

Investigating d-cycloserine as a potential pharmacological enhancer of an emotional bias learning procedure.

PubMed

Woud, Marcella L; Blackwell, Simon E; Steudte-Schmiedgen, Susann; Browning, Michael; Holmes, Emily A; Harmer, Catherine J; Margraf, Jürgen; Reinecke, Andrea

2018-05-01

The partial N-methyl-D-aspartate receptor agonist d-cycloserine may enhance psychological therapies. However, its exact mechanism of action is still being investigated. Cognitive bias modification techniques allow isolation of cognitive processes and thus investigation of how they may be affected by d-cycloserine. We used a cognitive bias modification paradigm targeting appraisals of a stressful event, Cognitive Bias Modification-Appraisal, to investigate whether d-cycloserine enhanced the modification of appraisal, and whether it caused greater reduction in indices of psychopathology. Participants received either 250 mg of d-cycloserine ( n=19) or placebo ( n=19). As a stressor task, participants recalled a negative life event, followed by positive Cognitive Bias Modification-Appraisal training. Before and after Cognitive Bias Modification-Appraisal, appraisals and indices of psychopathology related to the stressor were assessed. Cognitive Bias Modification-Appraisal successfully modified appraisals, but d-cycloserine did not affect appraisals post-training. There were no post-training group differences in frequency of intrusions. Interestingly, d-cycloserine led to a greater reduction in distress and impact on state mood from recalling the event, and lower distress post-training was associated with fewer intrusions. Therefore, d-cycloserine may affect emotional reactivity to recalling a negative event when combined with induction of a positive appraisal style, but via a mechanism other than enhanced learning of the appraisal style.

Impact of contextual factors and substance characteristics on perspectives toward cognitive enhancement.

PubMed

Sattler, Sebastian; Forlini, Cynthia; Racine, Eric; Sauer, Carsten

2013-01-01

Enhancing cognitive performance with substances--especially prescription drugs--is a fiercely debated topic among scholars and in the media. The empirical basis for these discussions is limited, given that the actual nature of factors that influence the acceptability of and willingness to use cognitive enhancement substances remains unclear. In an online factorial survey, contextual and substance-specific characteristics of substances that improve academic performance were varied experimentally and presented to respondents. Students in four German universities rated their willingness to use and moral acceptance of different substances for cognitive enhancement. We found that the overall willingness to use performance enhancing substances is low. Most respondents considered the use of these substances as morally unacceptable. Situational influences such as peer pressure, policies concerning substance use, relative performance level of peers, but also characteristics of the substance, such as perceptions of substance safety, shape the willingness and acceptability of using a substance to enhance academic performance. Among the findings is evidence of a contagion effect meaning that the willingness was higher when the respondents have more CE drug users in their social network. We also found deterrence effects from strong side effects of using the substance, as well as from policy regulations and sanctions. Regulations might activate social norms against usage and sanctions can be seen as costly to users. Moreover, enhancement substances seem to be most tempting to low performers to catch up with others compared to high performers. By identifying contextual factors and substance characteristics influencing the willingness and acceptability of cognitive enhancers, policy approaches could consider these insights to better manage the use of such substances.

The implications of Methylphenidate use by healthy medical students and doctors in South Africa

PubMed Central

2014-01-01

Background The use of medical stimulants to sustain attention, augment memory and enhance intellectual capacity is increasing in society. The use of Methylphenidate for cognitive enhancement is a subject that has received much attention in the literature and academic circles in recent times globally. Medical doctors and medical students appear to be equally involved in the off-label use of Methylphenidate. This presents a potential harm to society and the individual as the long-term side effect profile of this medication is unknown. Discussion The implication of the use of Methylphenidate by medical students and doctors has not been fully explored. This article considers the impact of this use on the traditional role of medicine, society, the patient and suggests a way forward. We discuss the salient philosophy surrounding the use of cognitive enhancement. We query whether there are cognitive benefits to the use of Methylphenidate in healthy students and doctors and whether these benefits would outweigh the risks in taking the medication. Could these benefits lead to tangible outcomes for society and could the off label-use of Methylphenidate potentially undermine the medical profession and the treatment of patients? If cognitive benefits are proven then doctors may be coerced explicitly or implicitly to use the drug which may undermine their autonomy. The increased appeal of cognitive enhancement challenges the traditional role of medicine in society, and calls into question the role of a virtuous life as a contributing factor for achievement. In countries with vast economic disparity such as South Africa an enhancement of personal utility that can be bought may lead to greater inequities. Summary Under the status quo the distribution of methylphenidate is unjust. Regulatory governmental policy must seek to remedy this while minimising the potential for competitive advantage for the enhanced. Public debate on the use of cognitive enhancement is long overdue and must be stimulated. The use of Methylphenidate for cognitive enhancement is philosophically defendable if long-term research can prove that the risks are negligible and the outcomes tangible. PMID:24592964

The implications of methylphenidate use by healthy medical students and doctors in South Africa.

PubMed

Beyer, Chad; Staunton, Ciara; Moodley, Keymanthri

2014-03-04

The use of medical stimulants to sustain attention, augment memory and enhance intellectual capacity is increasing in society. The use of Methylphenidate for cognitive enhancement is a subject that has received much attention in the literature and academic circles in recent times globally. Medical doctors and medical students appear to be equally involved in the off-label use of Methylphenidate. This presents a potential harm to society and the individual as the long-term side effect profile of this medication is unknown. The implication of the use of Methylphenidate by medical students and doctors has not been fully explored. This article considers the impact of this use on the traditional role of medicine, society, the patient and suggests a way forward. We discuss the salient philosophy surrounding the use of cognitive enhancement. We query whether there are cognitive benefits to the use of Methylphenidate in healthy students and doctors and whether these benefits would outweigh the risks in taking the medication. Could these benefits lead to tangible outcomes for society and could the off label-use of Methylphenidate potentially undermine the medical profession and the treatment of patients? If cognitive benefits are proven then doctors may be coerced explicitly or implicitly to use the drug which may undermine their autonomy. The increased appeal of cognitive enhancement challenges the traditional role of medicine in society, and calls into question the role of a virtuous life as a contributing factor for achievement. In countries with vast economic disparity such as South Africa an enhancement of personal utility that can be bought may lead to greater inequities. Under the status quo the distribution of methylphenidate is unjust. Regulatory governmental policy must seek to remedy this while minimising the potential for competitive advantage for the enhanced. Public debate on the use of cognitive enhancement is long overdue and must be stimulated. The use of Methylphenidate for cognitive enhancement is philosophically defendable if long-term research can prove that the risks are negligible and the outcomes tangible.

Crosswords to computers: a critical review of popular approaches to cognitive enhancement.

PubMed

Jak, Amy J; Seelye, Adriana M; Jurick, Sarah M

2013-03-01

Cognitive enhancement strategies have gained recent popularity and have the potential to benefit clinical and non-clinical populations. As technology advances and the number of cognitively healthy adults seeking methods of improving or preserving cognitive functioning grows, the role of electronic (e.g., computer and video game based) cognitive training becomes more relevant and warrants greater scientific scrutiny. This paper serves as a critical review of empirical evaluations of publically available electronic cognitive training programs. Many studies have found that electronic training approaches result in significant improvements in trained cognitive tasks. Fewer studies have demonstrated improvements in untrained tasks within the trained cognitive domain, non-trained cognitive domains, or on measures of everyday function. Successful cognitive training programs will elicit effects that generalize to untrained, practical tasks for extended periods of time. Unfortunately, many studies of electronic cognitive training programs are hindered by methodological limitations such as lack of an adequate control group, long-term follow-up and ecologically valid outcome measures. Despite these limitations, evidence suggests that computerized cognitive training has the potential to positively impact one's sense of social connectivity and self-efficacy.

Cognitive dysfunction in depression - pathophysiology and novel targets.

PubMed

Carvalho, Andre F; Miskowiak, Kamilla K; Hyphantis, Thomas N; Kohler, Cristiano A; Alves, Gilberto S; Bortolato, Beatrice; G Sales, Paulo Marcelo; Machado-Vieira, Rodrigo; Berk, Michael; McIntyre, Roger S

2014-01-01

Major depressive disorder (MDD) is associated with cognitive dysfunction encompassing several domains, including memory, executive function, processing speed and attention. Cognitive deficits persist in a significant proportion of patients even in remission, compromising psychosocial functioning and workforce performance. While monoaminergic antidepressants may improve cognitive performance in MDD, most antidepressants have limited clinical efficacy. The overarching aims of this review were: (1) to synthesize extant literature on putative biological pathways related to cognitive dysfunction in MDD and (2) to review novel neurotherapeutic targets for cognitive enhancement in MDD. We found that reciprocal and overlapping biological pathways may contribute to cognitive dysfunction in MDD, including an hyperactive hypothalamic-pituitary-adrenal axis, an increase in oxidative and nitrosative stress, inflammation (e.g., enhanced production of pro-inflammatory cytokines), mitochondrial dysfunction, increased apoptosis as well as a diminished neurotrophic support. Several promising neurotherapeutic targets were identified such as minocycline, statins, anti-inflammatory compounds, N-acetylcysteine, omega-3 poliunsaturated fatty acids, erythropoietin, thiazolidinediones, glucagon-like peptide-1 analogues, S-adenosyl-l-methionine (SAMe), cocoa flavonols, creatine monohydrate and lithium. Erythropoietin and SAMe had pro-cognitive effects in randomized controlled trials (RCT) involving MDD patients. Despite having preclinical and/or preliminary evidences from trials suggesting possible efficacy as novel cognitive enhancing agents for MDD, no RCT to date was performed for most of the other therapeutic targets reviewed herein. In conclusion, multiple biological pathways are involved in cognitive dysfunction in MDD. RCTs testing genuinely novel pro-cognitive compounds for MDD are warranted.

Reward Motivation Enhances Task Coding in Frontoparietal Cortex

PubMed Central

Etzel, Joset A.; Cole, Michael W.; Zacks, Jeffrey M.; Kay, Kendrick N.; Braver, Todd S.

2016-01-01

Reward motivation often enhances task performance, but the neural mechanisms underlying such cognitive enhancement remain unclear. Here, we used a multivariate pattern analysis (MVPA) approach to test the hypothesis that motivation-related enhancement of cognitive control results from improved encoding and representation of task set information. Participants underwent two fMRI sessions of cued task switching, the first under baseline conditions, and the second with randomly intermixed reward incentive and no-incentive trials. Information about the upcoming task could be successfully decoded from cue-related activation patterns in a set of frontoparietal regions typically associated with task control. More critically, MVPA classifiers trained on the baseline session had significantly higher decoding accuracy on incentive than non-incentive trials, with decoding improvement mediating reward-related enhancement of behavioral performance. These results strongly support the hypothesis that reward motivation enhances cognitive control, by improving the discriminability of task-relevant information coded and maintained in frontoparietal brain regions. PMID:25601237

Cognitive enhancement effects of Bacopa monnieri (Brahmi) on novel object recognition and neuronal density in the prefrontal cortex, striatum and hippocampus in sub-chronic phencyclidine administration rat model of schizophrenia.

PubMed

Wetchateng, Thanitsara; Piyabhan, Pritsana

2015-03-01

Cognitive deficit is a significant problem, which finally occurs in all schizophrenic patients. It can not be attenuated by any antipsychotic drugs. It is well known that changes of neuronal density are correlated with learning and memory deficits. Bacopa monnieri (Brahmi), popularly known as a cognitive enhancer; might be a novel therapeutic agentfor cognitive deficit in schizophrenia by changing cerebral neuronal density. The objective of this study was to determine the effects of Brahmi on attenuation at cognitive deficit and on the neuronal density in the prefrontal cortex, striatum and cornu ammonis subfield 1 (CA1) and 2/3 (CA2/3) of hippocampus in sub-chronic phencyclidine (PCP) rat model of schizophrenia. Rats were assigned to three groups; Group-1: Control, Group-2: PCP administration and Group-3: PCP + Brahmi. Rats were testedfor cognitive ability by using the novel object recognition test. Neuronal density from a serial Nissl stain sections ofthe prefrontal cortex, striatum and hippocampus ofrat model ofschizophrenia were measured by using Image ProPlus software and manual counting. Sub-chronic administration of PCP results in cognitive deficits in novel object recognition task. This occurred alongside significantly increased neuronal density in CA1. The cognitive deficit was recovery to normal in PCP + Brahmi group and it occurred alongside significantly decreased neuronal density in CA1. On the other hand, significantly increased neuronal density was observed in CA2/3 of PCP + Brahmi group compared with PCP alone. Brahmi is a potential cognitive enhancer against schizophrenia. It reduces neuronal density, most likely glutamatergic neuron, which results in neuronal toxicity and cognitive deficit. Therefore, Brahmi has cognitive enhancement effect by reducing glutamatergic neuron in CAI. Moreover, it also has neurogenesis effect in CA2/3, which is needed to be investigated in the further study.

Piracetam improves mitochondrial dysfunction following oxidative stress

PubMed Central

Keil, Uta; Scherping, Isabel; Hauptmann, Susanne; Schuessel, Katin; Eckert, Anne; Müller, Walter E

2005-01-01

Mitochondrial dysfunction including decrease of mitochondrial membrane potential and reduced ATP production represents a common final pathway of many conditions associated with oxidative stress, for example, hypoxia, hypoglycemia, and aging. Since the cognition-improving effects of the standard nootropic piracetam are usually more pronounced under such pathological conditions and young healthy animals usually benefit little by piracetam, the effect of piracetam on mitochondrial dysfunction following oxidative stress was investigated using PC12 cells and dissociated brain cells of animals treated with piracetam. Piracetam treatment at concentrations between 100 and 1000 μM improved mitochondrial membrane potential and ATP production of PC12 cells following oxidative stress induced by sodium nitroprusside (SNP) and serum deprivation. Under conditions of mild serum deprivation, piracetam (500 μM) induced a nearly complete recovery of mitochondrial membrane potential and ATP levels. Piracetam also reduced caspase 9 activity after SNP treatment. Piracetam treatment (100–500 mg kg−1 daily) of mice was also associated with improved mitochondrial function in dissociated brain cells. Significant improvement was mainly seen in aged animals and only less in young animals. Moreover, the same treatment reduced antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, and glutathione reductase) in aged mouse brain only, which are elevated as an adaptive response to the increased oxidative stress with aging. In conclusion, therapeutically relevant in vitro and in vivo concentrations of piracetam are able to improve mitochondrial dysfunction associated with oxidative stress and/or aging. Mitochondrial stabilization and protection might be an important mechanism to explain many of piracetam's beneficial effects in elderly patients. PMID:16284628

Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and α-Synuclein Transgenic Mice.

PubMed

Leon, Julio; Moreno, Arturo J; Garay, Bayardo I; Chalkley, Robert J; Burlingame, Alma L; Wang, Dan; Dubal, Dena B

2017-08-08

Cognitive dysfunction and decreased mobility from aging and neurodegenerative conditions, such as Parkinson and Alzheimer diseases, are major biomedical challenges in need of more effective therapies. Increasing brain resilience may represent a new treatment strategy. Klotho, a longevity factor, enhances cognition when genetically and broadly overexpressed in its full, wild-type form over the mouse lifespan. Whether acute klotho treatment can rapidly enhance cognitive and motor functions or induce resilience is a gap in our knowledge of its therapeutic potential. Here, we show that an α-klotho protein fragment (αKL-F), administered peripherally, surprisingly induced cognitive enhancement and neural resilience despite impermeability to the blood-brain barrier in young, aging, and transgenic α-synuclein mice. αKL-F treatment induced cleavage of the NMDAR subunit GluN2B and also enhanced NMDAR-dependent synaptic plasticity. GluN2B blockade abolished αKL-F-mediated effects. Peripheral αKL-F treatment is sufficient to induce neural enhancement and resilience in mice and may prove therapeutic in humans. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Adaptogenic Activity of Lyophilized Hydroethanol Extract of Pandanus odoratissimus in Swiss Albino Mice

PubMed Central

Jadhav, Pranita P.; Ambavade, Shirishkumar D.; Shelke, Tushar

2014-01-01

Background. The leaves of Pandanus odoratissimus Linn have been widely used in Ayurveda to treat a variety of common and stress related disorders. In the present investigation, hydroethanol extract of leaves of Pandanus odoratissimus Linn (LEPO) were evaluated for antistress activity in normal and stress induced mice. Furthermore, the extract was studied for nootropic (adaptogenic) activity in mice and in vitro antioxidant potential to correlate with its adaptogenic and antistress activity. LEPO (100 and 200 mg/kg p.o) was evaluated against forced swimming endurance stress test, anoxia stress tolerance and immobilization stress and chronic cold resistant stress tests, and biomarkers (serum glucose, Corticosterone, WBC, RBC, and DLC count) to assess the antistress activity in mice. Withania somnifera (WS) (100 mg/kg p.o) was selected as reference standard. The parameters like anoxia stress tolerance time were recorded in anoxia stress and estimation of biochemical marker levels and determination of organs weight were carried out in immobilization stress models. Results. Concomitant treatment with LEPO 200 mg/kg significantly increased in anoxia stress tolerance time. Dose dependent significant reduction in serum glucose, corticosterone, and WBC, RBC, and DLC was observed in immobilisation stress model as compared to stressed group. LEOP 200 mg/kg and WS 100 mg/kg significantly reversed/inhibited the stress induced changes in these parameters. The results from the present study indicate that these values also express that dose dependent significant adaptogenic activity in stressed animals. Conclusion. The present study provides scientific support for the antistress (adaptogenic) and nootropic activities of lyophilized hydroethanol extract of Pandanus odoratissimus Linn and substantiate the traditional claims for the usage of Pandanus in stress induced disorders. PMID:27379263

Candyflipping and Other Combinations: Identifying Drug–Drug Combinations from an Online Forum

PubMed Central

Chary, Michael; Yi, David; Manini, Alex F.

2018-01-01

Novel psychoactive substances (NPS) refer to synthetic compounds or derivatives of more widely known substances of abuse that have emerged over the last two decades. Case reports suggest that users combine substances to achieve desired psychotropic experiences while reducing dysphoria and unpleasant somatic effects. However, the pattern of combining NPS has not been studied on a large scale. Here, we show that posts discussing NPS describe combining nootropics with sedative-hypnotics and stimulants with plant hallucinogens or psychiatric medications. Discussions that mention sedative-hypnotics most commonly also mention hallucinogens and stimulants. We analyzed 20 years of publicly available posts from Lycaeum, an Internet forum dedicated to sharing information about psychoactive substance use. We used techniques from natural language processing and machine learning to identify NPS and correlate patterns of co-mentions of substances across posts. We found that conversations mentioning synthetic hallucinogens tended to divide into those mentioning hallucinogens derived from amphetamine and those derived from ergot. Conversations that mentioned synthetic hallucinogens tended not to mention plant hallucinogens. Conversations that mention bath salts commonly mention sedative-hypnotics or nootropics while more canonical stimulants are discussed with plant hallucinogens and psychiatric medications. All types of substances are frequently compared to MDMA, DMT, cocaine, or atropine when trying to describe their effects. Our results provide the largest analysis to date of online descriptions of patterns of polysubstance use and further demonstrate the utility of social media in learning about trends in substance use. We anticipate this work to lead to a more detailed analysis of the knowledge contained online about the patterns of usage and effects of novel psychoactive substances. PMID:29760666

A study to evaluate the effect of nootropic drug-piracetam on DNA damage in leukocytes and macrophages.

PubMed

Singh, Sarika; Goswami, Poonam; Swarnkar, Supriya; Singh, Sheelendra Pratap; Wahajuddin; Nath, Chandishwar; Sharma, Sharad

2011-11-27

Piracetam is a nootropic drug that protects neurons in neuropathological and age-related diseases and the activation and modulation of peripheral blood cells in patients with neuropathological conditions is well known. Therefore, in the present study, in vivo, ex vivo, and in vitro tests were conducted to investigate the effect of piracetam on leukocytes and macrophages. Lipopolysaccharide (LPS) causes oxidative DNA damage; thus, in the present study, LPS was used as a tool to induce DNA damage. In vivo experiments were conducted on Sprague Dawley rats, and piracetam (600mg/kg, oral) was provided for five consecutive days. On the fifth day, a single injection of LPS (10mg/kg, i.p.) was administered. Three hours after LPS injection, blood leukocytes and peritoneal macrophages were collected and processed, and a variety of different assays were conducted. Ex vivo treatments were performed on isolated rat blood leukocytes, and in vitro experiments were conducted on rat macrophage cell line J774A.1. Cell viability and the level of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and DNA damage were estimated in untreated (control) and piracetam-, LPS- and LPS+piracetam-treated leukocytes and macrophages. In vivo experiments revealed that rats pretreated with piracetam were significantly protected against LPS-induced increases in ROS levels and DNA damage. Ex vivo isolated leukocytes and J774A.1 cells treated with LPS exhibited augmented ROS levels and DNA damage, which were attenuated with piracetam treatment. Thus, the present study revealed the salutary effect of piracetam against LPS-induced oxidative stress and DNA damage in leukocytes and macrophages. Copyright © 2011 Elsevier B.V. All rights reserved.

Suspicious spirits, flexible minds: when distrust enhances creativity.

PubMed

Mayer, Jennifer; Mussweiler, Thomas

2011-12-01

Intuitively, as well as in light of prior research, distrust and creativity appear incompatible. The social consequences of distrust include reluctance to share information, a quality detrimental to creativity in social settings. At the same time, the cognitive concomitants of distrust bear resemblance to creative cognition: Distrust seems to foster thinking about nonobvious alternatives to potentially deceptive appearances. These cognitive underpinnings of distrust hold the provocative implication that distrust may foster creativity. Mirroring these contradictory findings, we suggest that the social versus cognitive consequences of distrust have diverging implications for creativity. We address this question in Study 1 by introducing private/public as a moderating variable for effects of distrust on creativity. Consistent with distrust's social consequences, subliminal distrust (vs. trust) priming had detrimental effects on creative generation presumed to be public. Consistent with distrust's cognitive consequences, though, an opposite tendency emerged in private. Study 2 confirmed a beneficial effect of distrust on private creative generation with a different priming method and pointed to cognitive flexibility as the mediating process. Studies 3 and 4 showed increased category inclusiveness versus increased remote semantic spread after distrust priming, consistent with enhanced cognitive flexibility as a consequence of distrust. Taken together, these results provide evidence for the creativity-enhancing potential of distrust and suggest cognitive flexibility as its underlying mechanism.

Enhancement of human cognitive performance using transcranial magnetic stimulation (TMS)

PubMed Central

Luber, Bruce; Lisanby, and Sarah H.

2014-01-01

Here we review the usefulness of transcranial magnetic stimulation (TMS) in modulating cortical networks in ways that might produce performance enhancements in healthy human subjects. To date over sixty studies have reported significant improvements in speed and accuracy in a variety of tasks involving perceptual, motor, and executive processing. Two basic categories of enhancement mechanisms are suggested by this literature: direct modulation of a cortical region or network that leads to more efficient processing, and addition-by-subtraction, which is disruption of processing which competes or distracts from task performance. Potential applications of TMS cognitive enhancement, including research into cortical function, rehabilitation therapy in neurological and psychiatric illness, and accelerated skill acquisition in healthy individuals are discussed, as are methods of optimizing the magnitude and duration of TMS-induced performance enhancement, such as improvement of targeting through further integration of brain imaging with TMS. One technique, combining multiple sessions of TMS with concurrent TMS/task performance to induce Hebbian-like learning, appears to be promising for prolonging enhancement effects. While further refinements in the application of TMS to cognitive enhancement can still be made, and questions remain regarding the mechanisms underlying the observed effects, this appears to be a fruitful area of investigation that may shed light on the basic mechanisms of cognitive function and their therapeutic modulation. PMID:23770409

Estrogens and Cognition: Friends or Foes?

PubMed Central

Korol, Donna L.; Pisani, Samantha L.

2015-01-01

Estrogens are becoming well known for their robust enhancement on cognition particularly for learning and memory that relies upon functioning of the hippocampus and related neural systems. What is also emerging is that estrogen modulation of cognition is not uniform, at times enhancing yet at other times impairing learning. This review explores the bidirectional effects of estrogens on learning from a multiple memory systems view, focusing on the hippocampus and striatum, whereby modulation by estrogens sorts according to task attributes and neural systems engaged during cognition. We highlight our findings that show the ability to solve hippocampus-sensitive tasks typically improves under relatively high estrogen status while the ability to solve striatum-sensitive tasks degrades with estrogen exposures. Though constrained by dose and timing of exposure, these opposing enhancements and impairments of cognition can be observed following treatments with different estrogenic compounds including the hormone estradiol, the isoflavone genistein found in soybeans, and agonists that are selective for specific estrogen receptors, suggesting that activation of a single receptor type is sufficient to produce the observed shifts in learning strategies. Using this multi-dimensional framework will allow us to extend our thinking of the relationship between estrogens and cognition to other brain regions and cognitive functions. PMID:26149525

Improving Temporal Cognition by Enhancing Motivation

PubMed Central

Avlar, Billur; Kahn, Julia B.; Jensen, Greg; Kandel, Eric R.; Simpson, Eleanor H.; Balsam, Peter D.

2015-01-01

Increasing motivation can positively impact cognitive performance. Here we employed a cognitive timing task that allows us to detect changes in cognitive performance that are not influenced by general activity or arousal factors such as the speed or persistence of responding. This approach allowed us to manipulate motivation using three different methods; molecular/genetic, behavioral and pharmacological. Increased striatal D2Rs resulted in deficits in temporal discrimination. Switching off the transgene improved motivation in earlier studies, and here partially rescued the temporal discrimination deficit. To manipulate motivation behaviorally, we altered reward magnitude and found that increasing reward magnitude improved timing in control mice and partially rescued timing in the transgenic mice. Lastly, we manipulated motivation pharmacologically using a functionally selective 5-HT2C receptor ligand, SB242084, which we previously found to increase incentive motivation. SB242084 improved temporal discrimination in both control and transgenic mice. Thus, while there is a general intuitive belief that motivation can affect cognition, we here provide a direct demonstration that enhancing motivation, in a variety of ways, can be an effective strategy for enhancing temporal cognition. Understanding the interaction of motivation and cognition is of clinical significance since many psychiatric disorders are characterized by deficits in both domains. PMID:26371378

Evidence for circulatory benefits of resveratrol in humans.

PubMed

Wong, Rachel H X; Coates, Alison M; Buckley, Jonathan D; Howe, Peter R C

2013-07-01

Impairments of endothelial function, which can be assessed noninvasively by flow-mediated dilation (FMD) of the brachial artery, contribute to the development of cardiovascular disease. Associations between FMD and cognition suggest a vascular component in the loss of cognitive function. Certain vasoactive nutrients that have been shown to improve FMD may also have the potential to enhance cerebral perfusion and cognition. Preclinical studies show that trans-resveratrol can enhance nitric oxide bioavailability, thereby increasing endothelium-dependent vasodilation. We have now shown that acute administration of resveratrol elicits dose-dependent increases of FMD with greater potency than other vasoactive nutrients and that this benefit is sustained following regular consumption. We describe the potential implications of this vasodilator benefit of resveratrol and its role in enhancing cerebrovascular and cognitive functions. © 2013 New York Academy of Sciences.

Hypothalamic-pituitary-adrenal axis physiology and cognitive control of behavior in stress inoculated monkeys.

PubMed

Parker, Karen J; Buckmaster, Christine L; Lindley, Steven E; Schatzberg, Alan F; Lyons, David M

2012-01-01

Monkeys exposed to stress inoculation protocols early in life subsequently exhibit diminished neurobiological responses to moderate psychological stressors and enhanced cognitive control of behavior during juvenile development compared to non-inoculated monkeys. The present experiments extended these findings and revealed that stress inoculated monkeys: (a) mount neurobiological responses equivalent to non-inoculated monkeys when the stressor is of sufficient intensity, and (b) continue to exhibit enhanced cognitive control as young adults compared to non-inoculated monkeys. These results suggest that stress inoculation protocols alter the appraisal of and response to moderate stressors as less threatening and permanently enhance cognitive control, at least through early adulthood. These data therefore support the notion that the stress inoculation phenotype reflects stress resilience rather than stress pathology.

A turtle cognition research demonstration enhances visitor engagement and keeper-animal relationships.

PubMed

Alba, Andrew C; Leighty, Katherine A; Pittman Courte, Victoria L; Grand, Alison P; Bettinger, Tamara L

2017-07-01

Environmental enrichment techniques present animals with cognitive challenges while providing them opportunities to make choices and exert control over their environment. In this way, cognitive research and training is enriching to animals and can be used as a form of enrichment in zoos and aquariums. Cognitive research demonstrations also provide an opportunity to enhance visitor experience, as well as foster interactions between animals and keepers. We investigated how cognitive research sessions involving eastern box turtles (Terrapene carolina carolina) at Disney's Animal Kingdom ® impacted both the rate of visitors coming to the exhibit and the amount of time they spent engaged. Further, we used a questionnaire to assess the impact of keeper participation in these sessions on their relationships with and perceptions of the turtles. While visitation rate to the exhibit was not impacted, cognitive research sessions held visitor attention for longer than keeper interpretation or at times during which no keepers or researchers were present. We also found that keepers that had worked with the turtles for longer and keepers that regularly participated in cognitive research sessions reported stronger bonds with the turtles. Our research suggests that use of cognitive research and training demonstrations for guest viewing in zoos and aquariums may enhance visitor learning opportunities by increasing the amount of time they spend at the exhibit. Our study also provides evidence that participation in such demonstrations by zoo and aquarium professionals can be related to improved keeper-animal bonds, potentially resulting in better husbandry and enhanced animal welfare. © 2017 Wiley Periodicals, Inc.

Neurocognitive Enhancement or Impairment? A Systematic Meta-Analysis of Prescription Stimulant Effects on Processing Speed, Decision-Making, Planning, and Cognitive Perseveration

PubMed Central

Marraccini, Marisa E.; Weyandt, Lisa L.; Rossi, Joseph S.; Gudmundsdottir, Bergljot Gyda

2016-01-01

Increasing numbers of adults, particularly college students, are misusing prescription stimulants primarily for cognitive/academic enhancement, so it is critical to explore whether empirical findings support neurocognitive benefits of prescription stimulants. Previous meta-analytic studies have supported small benefits from prescription stimulants for the cognitive domains of inhibitory control and memory; however, no meta-analytic studies have examined the effects on processing speed or the potential impairment on other domains of cognition, including planning, decision-making, and cognitive perseveration. Therefore, the present study conducted a meta-analysis of the available literature examining the effects of prescription stimulants on specific measures of processing speed, planning, decision-making, and cognitive perseveration among healthy adult populations. The meta-analysis results indicated a positive influence of prescription stimulant medication on processing speed accuracy, with an overall mean effect size of g = 0.282 (95% CI 0.077, 0.488; n = 345). Neither improvements nor impairments were revealed for planning time, planning accuracy, advantageous decision-making, or cognitive perseveration; however findings are limited by the small number of studies examining these outcomes. Findings support that prescription stimulant medication may indeed act as a neurocognitive enhancer for accuracy measures of processing speed without impeding other areas of cognition. Considering that adults are already engaging in illegal use of prescription stimulants for academic enhancement, as well as the potential for stimulant misuse to have serious side effects, the establishment of public policies informed by interdisciplinary research surrounding this issue, whether restrictive or liberal, is of critical importance. PMID:27454675

Multimodal Cognitive Enhancement Therapy for Patients with Mild Cognitive Impairment and Mild Dementia: A Multi- Center, Randomized, Controlled, Double-Blind, Crossover Trial.

PubMed

Han, Ji Won; Lee, Hyeonggon; Hong, Jong Woo; Kim, Kayoung; Kim, Taehyun; Byun, Hye Jin; Ko, Ji Won; Youn, Jong Chul; Ryu, Seung-Ho; Lee, Nam-Jin; Pae, Chi-Un; Kim, Ki Woong

2017-01-01

We developed and evaluated the effect of Multimodal Cognitive Enhancement Therapy (MCET) consisting of cognitive training, cognitive stimulations, reality orientation, physical therapy, reminiscence therapy, and music therapy in combination in older people with mild cognitive impairment (MCI) or mild dementia. This study was a multi-center, double-blind, randomized, placebo-controlled, two-period cross-over study (two 8-week treatment phases separated by a 4-week wash-out period). Sixty-four participants with MCI or dementia whose Clinical Dementia Rating was 0.5 or 1 were randomized to the MCET group or the mock-therapy (placebo) group. Outcomes were measured at baseline, week 9, and week 21. Fifty-five patients completed the study. Mini-Mental State Examination (effect size = 0.47, p = 0.013) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (effect size = 0.35, p = 0.045) scores were significantly improved in the MCET compared with mock-therapy group. Revised Memory and Behavior Problems Checklist frequency (effect size = 0.38, p = 0.046) and self-rated Quality of Life - Alzheimer's Disease (effect size = 0.39, p = 0.047) scores were significantly improved in the MCET compared with mock-therapy. MCET improved cognition, behavior, and quality of life in people with MCI or mild dementia more effectively than conventional cognitive enhancing activities did.

Enhancing cognition with video games: a multiple game training study.

PubMed

Oei, Adam C; Patterson, Michael D

2013-01-01

Previous evidence points to a causal link between playing action video games and enhanced cognition and perception. However, benefits of playing other video games are under-investigated. We examined whether playing non-action games also improves cognition. Hence, we compared transfer effects of an action and other non-action types that required different cognitive demands. We instructed 5 groups of non-gamer participants to play one game each on a mobile device (iPhone/iPod Touch) for one hour a day/five days a week over four weeks (20 hours). Games included action, spatial memory, match-3, hidden- object, and an agent-based life simulation. Participants performed four behavioral tasks before and after video game training to assess for transfer effects. Tasks included an attentional blink task, a spatial memory and visual search dual task, a visual filter memory task to assess for multiple object tracking and cognitive control, as well as a complex verbal span task. Action game playing eliminated attentional blink and improved cognitive control and multiple-object tracking. Match-3, spatial memory and hidden object games improved visual search performance while the latter two also improved spatial working memory. Complex verbal span improved after match-3 and action game training. Cognitive improvements were not limited to action game training alone and different games enhanced different aspects of cognition. We conclude that training specific cognitive abilities frequently in a video game improves performance in tasks that share common underlying demands. Overall, these results suggest that many video game-related cognitive improvements may not be due to training of general broad cognitive systems such as executive attentional control, but instead due to frequent utilization of specific cognitive processes during game play. Thus, many video game training related improvements to cognition may be attributed to near-transfer effects.

Cognitive Remediation: A New Generation of Psychosocial Interventions for People with Schizophrenia

PubMed Central

Eack, Shaun M.

2013-01-01

Schizophrenia is a mental health condition characterized by broad impairments in cognition, which place profound limitations on functional recovery. Social work has an enduring legacy in pioneering the development of novel psychosocial interventions for people with schizophrenia, and this article introduces cognitive remediation, the latest advance in psychosocial treatments for the disorder designed to improve cognition. First, an overview of the nature of cognitive impairments and their functional consequences in schizophrenia is presented, followed by a description of the theoretical basis and key practice principles of cognitive remediation. Next, the latest biopsychosocial evidence for the efficacy of cognitive remediation in schizophrenia is critically reviewed. Finally, a model cognitive remediation program, Cognitive Enhancement Therapy, which was developed and evaluated by a social work-led multidisciplinary team is presented. Cognitive Enhancement Therapy represents a significant advance in cognitive remediation for schizophrenia, and uses a unique holistic approach that extends beyond traditional neurocognitive training to facilitate the achievement of adult social-cognitive milestones and broader functional recovery. It is concluded that cognitive remediation represents an effective next generation of psychosocial interventions that social workers can use to help improve the lives of many people who live with schizophrenia. PMID:23252315

Genetic enhancement of cognition in a kindred with cone–rod dystrophy due to RIMS1 mutation

PubMed Central

Sisodiya, Sanjay M; Thompson, Pamela J; Need, Anna; Harris, Sarah E; Weale, Michael E; Wilkie, Susan E; Michaelides, Michel; Free, Samantha L; Walley, Nicole; Gumbs, Curtis; Gerrelli, Dianne; Ruddle, Piers; Whalley, Lawrence J; Starr, John M; Hunt, David M; Goldstein, David B; Deary, Ian J; Moore, Anthony T

2007-01-01

Background The genetic basis of variation in human cognitive abilities is poorly understood. RIMS1 encodes a synapse active‐zone protein with important roles in the maintenance of normal synaptic function: mice lacking this protein have greatly reduced learning ability and memory function. Objective An established paradigm examining the structural and functional effects of mutations in genes expressed in the eye and the brain was used to study a kindred with an inherited retinal dystrophy due to RIMS1 mutation. Materials and methods Neuropsychological tests and high‐resolution MRI brain scanning were undertaken in the kindred. In a population cohort, neuropsychological scores were associated with common variation in RIMS1. Additionally, RIMS1 was sequenced in top‐scoring individuals. Evolution of RIMS1 was assessed, and its expression in developing human brain was studied. Results Affected individuals showed significantly enhanced cognitive abilities across a range of domains. Analysis suggests that factors other than RIMS1 mutation were unlikely to explain enhanced cognition. No association with common variation and verbal IQ was found in the population cohort, and no other mutations in RIMS1 were detected in the highest scoring individuals from this cohort. RIMS1 protein is expressed in developing human brain, but RIMS1 does not seem to have been subjected to accelerated evolution in man. Conclusions A possible role for RIMS1 in the enhancement of cognitive function at least in this kindred is suggested. Although further work is clearly required to explore these findings before a role for RIMS1 in human cognition can be formally accepted, the findings suggest that genetic mutation may enhance human cognition in some cases. PMID:17237123

Enhancement of numeric cognition in children with low achievement in mathematic after a non-instrumental musical training.

PubMed

Ribeiro, Fabiana Silva; Santos, Flávia H

2017-03-01

Studies suggest that musical training enhances spatial-temporal reasoning and leads to greater learning of mathematical concepts. The aim of this prospective study was to verify the efficacy of a Non-Instrumental Musical Training (NIMT) on the Numerical Cognition systems in children with low achievement in math. For this purpose, we examined, with a cluster analysis, whether children with low scores on Numerical Cognition would be grouped in the same cluster at pre and post-NIMT. Participants were primary school children divided into two groups according to their scores on an Arithmetic test. Results with a specialized battery of Numerical Cognition revealed improvements for Cluster 2 (children with low achievement in math) especially for number production capacity compared to normative data. Besides, the number of children with low scores in Numerical Cognition decreased at post-NIMT. These findings suggest that NIMT enhances Numerical Cognition and seems to be a useful tool for rehabilitation of children with low achievement in math. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pointing and tracing gestures may enhance anatomy and physiology learning.

PubMed

Macken, Lucy; Ginns, Paul

2014-07-01

Currently, instructional effects generated by Cognitive load theory (CLT) are limited to visual and auditory cognitive processing. In contrast, "embodied cognition" perspectives suggest a range of gestures, including pointing, may act to support communication and learning, but there is relatively little research showing benefits of such "embodied learning" in the health sciences. This study investigated whether explicit instructions to gesture enhance learning through its cognitive effects. Forty-two university-educated adults were randomly assigned to conditions in which they were instructed to gesture, or not gesture, as they learnt from novel, paper-based materials about the structure and function of the human heart. Subjective ratings were used to measure levels of intrinsic, extraneous and germane cognitive load. Participants who were instructed to gesture performed better on a knowledge test of terminology and a test of comprehension; however, instructions to gesture had no effect on subjective ratings of cognitive load. This very simple instructional re-design has the potential to markedly enhance student learning of typical topics and materials in the health sciences and medicine.

Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands--A review.

PubMed

Jongkees, Bryant J; Hommel, Bernhard; Kühn, Simone; Colzato, Lorenza S

2015-11-01

Consuming the amino-acid tyrosine (TYR), the precursor of dopamine (DA) and norepinephrine (NE), may counteract decrements in neurotransmitter function and cognitive performance. However, reports on the effectiveness of TYR supplementation vary considerably, with some studies finding beneficial effects, whereas others do not. Here we review the available cognitive/behavioral studies on TYR, to elucidate whether and when TYR supplementation can be beneficial for performance. The potential of using TYR supplementation to treat clinical disorders seems limited and its benefits are likely determined by the presence and extent of impaired neurotransmitter function and synthesis. Likewise, the potential of TYR supplementation for enhancing physical exercise seems minimal as well, perhaps because the link between physical exercise and catecholamine function is mediated by many other factors. In contrast, TYR does seem to effectively enhance cognitive performance, particularly in short-term stressful and/or cognitively demanding situations. We conclude that TYR is an effective enhancer of cognition, but only when neurotransmitter function is intact and DA and/or NE is temporarily depleted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cognitive effects of two nutraceuticals Ginseng and Bacopa benchmarked against modafinil: a review and comparison of effect sizes

PubMed Central

Neale, Chris; Camfield, David; Reay, Jonathon; Stough, Con; Scholey, Andrew

2013-01-01

Over recent years there has been increasing research into both pharmaceutical and nutraceutical cognition enhancers. Here we aimed to calculate the effect sizes of positive cognitive effect of the pharmaceutical modafinil in order to benchmark the effect of two widely used nutraceuticals Ginseng and Bacopa (which have consistent acute and chronic cognitive effects, respectively). A search strategy was implemented to capture clinical studies into the neurocognitive effects of modafinil, Ginseng and Bacopa. Studies undertaken on healthy human subjects using a double‐blind, placebo‐controlled design were included. For each study where appropriate data were included, effect sizes (Cohen's d) were calculated for measures showing significant positive and negative effects of treatment over placebo. The highest effect sizes for cognitive outcomes were 0.77 for modafinil (visuospatial memory accuracy), 0.86 for Ginseng (simple reaction time) and 0.95 for Bacopa (delayed word recall). These data confirm that neurocognitive enhancement from well characterized nutraceuticals can produce cognition enhancing effects of similar magnitude to those from pharmaceutical interventions. Future research should compare these effects directly in clinical trials. PMID:23043278

Pharmacological cognitive enhancement-how neuroscientific research could advance ethical debate.

PubMed

Maslen, Hannah; Faulmüller, Nadira; Savulescu, Julian

2014-01-01

THERE ARE NUMEROUS WAYS PEOPLE CAN IMPROVE THEIR COGNITIVE CAPACITIES: good nutrition and regular exercise can produce long-term improvements across many cognitive domains, whilst commonplace stimulants such as coffee temporarily boost levels of alertness and concentration. Effects like these have been well-documented in the medical literature and they raise few (if any) ethical issues. More recently, however, clinical research has shown that the off-label use of some pharmaceuticals can, under certain conditions, have modest cognition-improving effects. Substances such as methylphenidate and modafinil can improve capacities such as working memory and concentration in some healthy individuals. Unlike their more mundane predecessors, these methods of "cognitive enhancement" are thought to raise a multitude of ethical issues. This paper presents the six principal ethical issues raised in relation to pharmacological cognitive enhancers (PCEs)-issues such as whether: (1) the medical safety-profile of PCEs justifies restricting or permitting their elective or required use; (2) the enhanced mind can be an "authentic" mind; (3) individuals might be coerced into using PCEs; (4), there is a meaningful distinction to be made between the treatment vs. enhancement effect of the same PCE; (5) unequal access to PCEs would have implications for distributive justice; and (6) PCE use constitutes cheating in competitive contexts. In reviewing the six principal issues, the paper discusses how neuroscientific research might help advance the ethical debate. In particular, the paper presents new arguments about the contribution neuroscience could make to debates about justice, fairness, and cheating, ultimately concluding that neuroscientific research into "personalized enhancement" will be essential if policy is to be truly informed and ethical. We propose an "ethical agenda" for neuroscientific research into PCEs.

Impact of Contextual Factors and Substance Characteristics on Perspectives toward Cognitive Enhancement

PubMed Central

Sattler, Sebastian; Forlini, Cynthia; Racine, Éric; Sauer, Carsten

2013-01-01

Enhancing cognitive performance with substances–especially prescription drugs–is a fiercely debated topic among scholars and in the media. The empirical basis for these discussions is limited, given that the actual nature of factors that influence the acceptability of and willingness to use cognitive enhancement substances remains unclear. In an online factorial survey, contextual and substance-specific characteristics of substances that improve academic performance were varied experimentally and presented to respondents. Students in four German universities rated their willingness to use and moral acceptance of different substances for cognitive enhancement. We found that the overall willingness to use performance enhancing substances is low. Most respondents considered the use of these substances as morally unacceptable. Situational influences such as peer pressure, policies concerning substance use, relative performance level of peers, but also characteristics of the substance, such as perceptions of substance safety, shape the willingness and acceptability of using a substance to enhance academic performance. Among the findings is evidence of a contagion effect meaning that the willingness was higher when the respondents have more CE drug users in their social network. We also found deterrence effects from strong side effects of using the substance, as well as from policy regulations and sanctions. Regulations might activate social norms against usage and sanctions can be seen as costly to users. Moreover, enhancement substances seem to be most tempting to low performers to catch up with others compared to high performers. By identifying contextual factors and substance characteristics influencing the willingness and acceptability of cognitive enhancers, policy approaches could consider these insights to better manage the use of such substances. PMID:23940757

Effects of pharmacological treatments on hippocampal NCAM1 and ERK2 expression in epileptic rats with cognitive dysfunction

PubMed Central

Kong, Qingxia; Min, Xia; Sun, Ran; Gao, Jianying; Liang, Ruqing; Li, Lei; Chu, Xu

2016-01-01

The present study aimed to investigate the effects of various pharmacological agents on the hippocampal expression of neural cell adhesion molecule 1 (NCAM1) and extracellular signal-regulated kinase 2 (ERK2) in epileptic rats with cognitive dysfunction. The experiments were conducted using 120 Wistar rats: 20 controls and 100 with pilocarpine-induced status epilepticus (SE). The SE rats were randomly assigned to 5 groups (n=20/group) that received daily treatments for 1 month with one of the following: (i) saline (no effect on epilepsy); (ii) carbamazepine (an anticonvulsant); (iii) oxcarbazepine (an anticonvulsant); (iv) aniracetam (a nootropic); or (v) donepezil (an acetylcholinesterase inhibitor). Spatial learning and memory were assessed using a Morris Water Maze (MWM). Hippocampal tissue was assessed for NCAM1 and ERK2 messenger RNA (mRNA) expression by reverse transcription polymerase chain reaction, and protein expression by immunochemistry. The results revealed that SE rats had significantly poorer MWM performances compared with controls (P<0.01). Performance in SE rats was improved with donepezil treatment (P<0.01), but declined with carbamazepine (P<0.01). Compared with controls, saline-treated SE rats exhibited increased hippocampal NCAM1 mRNA expression (P<0.01). Among SE rats, NCAM1 mRNA expression was highest in those treated with donepezil, followed by aniracetam-, saline-, oxcarbazepine- and carbamazepine-treated rats. Compared to controls, saline-treated SE rats exhibited decreased hippocampal ERK2 mRNA expression (P<0.01). Among SE rats, ERK2 mRNA expression was highest in those treated with donepezil, followed by aniracetam, saline, oxcarbazepine and carbamazepine. NCAM1 and ERK2 protein expression levels were parallel to those of the mRNA. In saline-treated SE rats, hippocampal ERK2 expression was decreased and NCAM1 expression was increased; thus, these two molecules may be involved in the impairment of spatial memory. Carbamazepine augmented this impairment, whereas donepezil was found to ameliorate the dysfunction associated with epilepsy. In conclusion, ERK2 and NCAM1 have significant roles in impairment of spatial memory in SE rats. Carbamazepine may increase this impairment, while donepezil may decrease this impairment. PMID:27588125

Video game training does not enhance cognitive ability: A comprehensive meta-analytic investigation.

PubMed

Sala, Giovanni; Tatlidil, K Semir; Gobet, Fernand

2018-02-01

As a result of considerable potential scientific and societal implications, the possibility of enhancing cognitive ability by training has been one of the most influential topics of cognitive psychology in the last two decades. However, substantial research into the psychology of expertise and a recent series of meta-analytic reviews have suggested that various types of cognitive training (e.g., working memory training) benefit performance only in the trained tasks. The lack of skill generalization from one domain to different ones-that is, far transfer-has been documented in various fields of research such as working memory training, music, brain training, and chess. Video game training is another activity that has been claimed by many researchers to foster a broad range of cognitive abilities such as visual processing, attention, spatial ability, and cognitive control. We tested these claims with three random-effects meta-analytic models. The first meta-analysis (k = 310) examined the correlation between video game skill and cognitive ability. The second meta-analysis (k = 315) dealt with the differences between video game players and nonplayers in cognitive ability. The third meta-analysis (k = 359) investigated the effects of video game training on participants' cognitive ability. Small or null overall effect sizes were found in all three models. These outcomes show that overall cognitive ability and video game skill are only weakly related. Importantly, we found no evidence of a causal relationship between playing video games and enhanced cognitive ability. Video game training thus represents no exception to the general difficulty of obtaining far transfer. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Cognitive Bias as a Mediator in the Relation Between Fear-Enhancing Parental Behaviors and Anxiety Symptoms in Children: A Cross-Sectional Study.

PubMed

Fliek, Lorraine; Dibbets, Pauline; Roelofs, Jeffrey; Muris, Peter

2017-02-01

The present cross-sectional study explored the relations between fear-enhancing parenting behaviors (modeling and threat information transmission) and children's cognitive biases and anxiety symptoms. Participants were 258 children aged 7-12 years (132 boys and 126 girls), and their mothers (n = 199) and/or fathers (n = 117). Children and parents completed the Parental Enhancement of Anxious Cognitions questionnaire, which measures parental modeling and threat information transmission, while children also filled in a scale for assessing anxiety symptoms. In addition, children conducted a number of computerized tasks for measuring confirmation and interpretation bias. The data indicated that both biases mediated the relationship between threat information transmission (of both parents) and children's anxiety symptoms. Only interpretation bias significantly mediated the relationship between modeling (of mothers) and anxiety symptoms. These findings give partial support for the hypothesis that cognitive biases play a mediating role in the relation between fear-enhancing parental behaviors and children's anxiety symptoms.

Converging technologies: a critical analysis of cognitive enhancement for public policy application.

PubMed

Makridis, Christos

2013-09-01

This paper investigates cognitive enhancement, specifically biological cognitive enhancement (BCE), as a converging technology, and its implications for public policy. With an increasing rate of technological advancements, the legal, social, and economic frameworks lag behind the scientific advancements that they support. This lag poses significant challenges for policymakers if it is not dealt with sufficiently within the right analytical context. Therefore, the driving question behind this paper is, "What contingencies inform the advancement of biological cognitive enhancement, and what would society look like under this set of assumptions?" The paper is divided into five components: (1) defining the current policy context for BCEs, (2) analyzing the current social and economic outcomes to BCEs, (3) investigating the context of cost-benefit arguments in relation to BCEs, (4) proposing an analytical model for evaluating contingencies for BCE development, and (5) evaluating a simulated policy, social, technological, and economic context given the contingencies. In order to manage the risk and uncertainty inherent in technological change, BCEs' drivers must be scrutinized and evaluated.

Mechanisms for Robust Cognition.

PubMed

Walsh, Matthew M; Gluck, Kevin A

2015-08-01

To function well in an unpredictable environment using unreliable components, a system must have a high degree of robustness. Robustness is fundamental to biological systems and is an objective in the design of engineered systems such as airplane engines and buildings. Cognitive systems, like biological and engineered systems, exist within variable environments. This raises the question, how do cognitive systems achieve similarly high degrees of robustness? The aim of this study was to identify a set of mechanisms that enhance robustness in cognitive systems. We identify three mechanisms that enhance robustness in biological and engineered systems: system control, redundancy, and adaptability. After surveying the psychological literature for evidence of these mechanisms, we provide simulations illustrating how each contributes to robust cognition in a different psychological domain: psychomotor vigilance, semantic memory, and strategy selection. These simulations highlight features of a mathematical approach for quantifying robustness, and they provide concrete examples of mechanisms for robust cognition. © 2014 Cognitive Science Society, Inc.

The importance of need for cognition and educational experience in enhanced and standard substance abuse treatment.

PubMed

Czuchry, Michael; Dansereau, Donald F

2004-06-01

The current study examined the relationship between need for cognition (i.e., cognitive motivation or "will") and educational experience (i.e., cognitive ability or "skill") to perceived improvements during treatment of probationers receiving residential treatment within the criminal justice system. Probationers were randomly assigned to either receive motivational activities developed by the authors (the "enhanced" condition), or treatment as usual (but with access to general reading materials in lieu of the motivational activities). Need for cognition and educational experience were assessed and used as blocking variables, and ratings of progress were assessed midway and toward the end of treatment. The results indicate that both need for cognition and educational experience are important predictors of improvement during treatment, and that the motivational activities developed by the authors were particularly valuable for clients with lower levels of need for cognition.

Integrating psychopharmacology and cognitive remediation to treat cognitive dysfunction in the psychotic disorders.

PubMed

Medalia, Alice; Opler, Lewis A; Saperstein, Alice M

2014-04-01

Cognitive deficits are a prominent and enduring aspect of schizophrenia, which pose a significant barrier to achieving functional goals. The most promising intervention for treating cognitive impairment is cognitive remediation (CR), a behaviorally based therapy associated with medium effect sizes for cognitive and functional outcomes. However, there is a sizeable group of nonresponders whose CR outcomes become limited when the therapeutic approach fails to address individual differences in baseline cognition, motivation variables, and the extent to which CR offers opportunities for generalization. This speaks to a need to develop cognitive interventions that are both personalized and scalable. Emerging data suggest that specific pharmacological agents have the potential to enhance and accelerate behaviorally based CR effects. This article will review the rationale and preliminary evidence to support combining CR and pharmacotherapy. We will review crucial aspects of cognitive interventions that offer the most promise for improving not only cognitive outcomes, but also for enhancing improvement in real-world functioning. Finally, we will address methodological issues to be considered for future research on combined pharmacological and CR interventions.

Virtual reality training to enhance behavior and cognitive function among children with attention-deficit/hyperactivity disorder: brief report.

PubMed

Shema-Shiratzky, Shirley; Brozgol, Marina; Cornejo-Thumm, Pablo; Geva-Dayan, Karen; Rotstein, Michael; Leitner, Yael; Hausdorff, Jeffrey M; Mirelman, Anat

2018-05-17

To examine the feasibility and efficacy of a combined motor-cognitive training using virtual reality to enhance behavior, cognitive function and dual-tasking in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Fourteen non-medicated school-aged children with ADHD, received 18 training sessions during 6 weeks. Training included walking on a treadmill while negotiating virtual obstacles. Behavioral symptoms, cognition and gait were tested before and after the training and at 6-weeks follow-up. Based on parental report, there was a significant improvement in children's social problems and psychosomatic behavior after the training. Executive function and memory were improved post-training while attention was unchanged. Gait regularity significantly increased during dual-task walking. Long-term training effects were maintained in memory and executive function. Treadmill-training augmented with virtual-reality is feasible and may be an effective treatment to enhance behavior, cognitive function and dual-tasking in children with ADHD.

Bacopa monnieri (Brahmi) Enhanced Cognitive Function and Prevented Cognitive Impairment by Increasing VGLUT2 Immunodensity in Prefrontal Cortex of Sub-Chronic Phencyclidine Rat Model of Schizophrenia.

PubMed

Piyabhan, Pritsana; Wetchateng, Thanitsara

2015-04-01

Glutamatergic hypofunction is affected in schizophrenia. The decrement ofpresynaptic glutamatergic marker remarkably vesicular glutamate transporter type 1 (VGLUT1) indicates the deficit ofglutamatergic and cognitive function in schizophrenic brain. However there have been afew studies in VGLUT2. Brahmi, a traditional herbal medicine, might be a new frontier of cognitive deficit treatment and prevention in schizophrenia by changing cerebral VGLUT2 density. To study cognitive enhancement- and neuroprotective-effects of Brahmi on novel object recognition task and cerebral VGLUT2 immunodensity in sub-chronic phencyclidine (PCP) rat model of schizophrenia. Cognitive enhancement effect study; rats were assigned to three groups; Group-1: Control, Group-2: PCP administration and Group-3: PCP + Brahmi. Neuroprotective effect study; rats were assigned to three groups; Group-1: Control, Group-2: PCP administration and Group-3: Brahmi + PCP Discrimination ratio (DR) representing cognitive ability was obtained from novel object recognition task. VGLUT2 immunodensity was measured in prefrontal cortex, striatum, cornu ammonis fields 1 (CA1) and 2/3 (CA2/3) of hippocampus using immunohistochemistry. DR was significantly reduced in PCP group compared with control. This occurred alongside VGLUT2 reduction in prefrontal cortex, but not in striatum, CA1 or CA2/3. Both PCP + Brahmi and Brahmi + PCP groups showed an increased DR score up to normal, which occurred alongside a significantly increased VGLUT2 immunodensity in the prefrontal cortex, compared with PCP group. The decrement of VGLUT2 density in prefrontal cortex resulted in cognitive deficit in rats receiving PCP. Interestingly, receiving Brahmi after PCP administration can restore this cognitive deficit by increasing VGLUT2 density in prefrontal cortex. This investigation is defined as Brahmi's cognitive enhancement effect. Additionally, receiving Brahmi before PCP administration can also prevent cognitive impairment by elevating VGLUT2 density in prefrontal cortex. This observation indicates neuroprotective effect of Brahmi. Therefore, Brahmi could be a new frontier of restoration and prevention of cognitive deficit in schizophrenia.

Hand Matters: Left-Hand Gestures Enhance Metaphor Explanation

ERIC Educational Resources Information Center

Argyriou, Paraskevi; Mohr, Christine; Kita, Sotaro

2017-01-01

Research suggests that speech-accompanying gestures influence cognitive processes, but it is not clear whether the gestural benefit is specific to the gesturing hand. Two experiments tested the "(right/left) hand-specificity" hypothesis for self-oriented functions of gestures: gestures with a particular hand enhance cognitive processes…

[Preclinical study of noopept toxicity].

PubMed

Kovalenko, L P; Smol'nikova, N M; Alekseeva, S V; Nemova, E P; Sorokina, A V; Miramedova, M G; Kurapova, S P; Sidorina, E I; Kulakova, A V; Daugel'-Dauge, N O

2002-01-01

Within the framework of a preclinical investigation, the new nootrope drug noopept (N-phenyl-acetyl-L-propyl-glycine ethylate) was tested for chronic toxicity upon peroral administration in a dose of 10 or 100 mg/kg over 6 months in both male and female rabbits. The results of observations showed that noopept administered in this dose range induced no irreversible pathologic changes in the organs and systems studied and exhibited no allergenic, immunotoxic, and mutagen activity. The drug affected neither the generative function nor the antenatal or postnatal progeny development. Noopept produced a dose-dependent suppression of inflammation reaction to concanavalin A and stimulated the cellular and humoral immune response in mice.

[Characteristics of antiischemic and nootropic properties of ademol in a rat model of acute brain ischemia].

PubMed

Khodakivs'kyĭ, O A

2013-01-01

In experiments with the rat model of acute disorder of encephalic circulation (bilateral carotid occlusion) it was found that introduction of derivate of adamantan 1-adamantiloxy-3-morfolino-2 propanol (under conventional name ademol) in the dose 2 mg/kg intraabdominal in treatment regimen (in an hour after reconstruction of insult and further 1 time every 24 hours during 21 days) was accompanied by a recovery of mnemotropic properties and is more effective than cytikolin, resulting in a decreased lethality and neurological deficiency in acute and recovery periods of insults. The data received proved the usefulness of development of ademol based cerebroprotective remedy.

Nootropic effect of meadowsweet (Filipendula vulgaris) extracts.

PubMed

Shilova, I V; Suslov, N I

2015-03-01

The effects of the extracts of the aboveground parts of Filipendula vulgaris Moench on the behavior and memory of mice after hypoxic injury and their physical performance in the open-field test were studied using the models of hypoxia in a sealed volume, conditioned passive avoidance response (CPAR), and forced swimming with a load. The extracts improved animal resistance to hypoxia, normalized orientation and exploration activities, promoted CPAR retention after hypoxic injury, and increased physical performance. Aqueous extract of meadowsweet had the most pronounced effect that corresponded to the effect of the reference drug piracetam. These effects were probably caused by modulation of hippocampal activity.

Quantitative determination of vinpocetine in dietary supplements

PubMed Central

French, John M. T.; King, Matthew D.

2017-01-01

Current United States regulatory policies allow for the addition of pharmacologically active substances in dietary supplements if derived from a botanical source. The inclusion of certain nootropic drugs, such as vinpocetine, in dietary supplements has recently come under scrutiny due to the lack of defined dosage parameters and yet unproven short- and long-term benefits and risks to human health. This study quantified the concentration of vinpocetine in several commercially available dietary supplements and found that a highly variable range of 0.6–5.1 mg/serving was present across the tested products, with most products providing no specification of vinpocetine concentrations. PMID:27319129

A yoga program for cognitive enhancement.

PubMed

Brunner, Devon; Abramovitch, Amitai; Etherton, Joseph

2017-01-01

Recent studies suggest that yoga practice may improve cognitive functioning. Although preliminary data indicate that yoga improves working memory (WM), high-resolution information about the type of WM subconstructs, namely maintenance and manipulation, is not available. Furthermore, the association between cognitive enhancement and improved mindfulness as a result of yoga practice requires empirical examination. The aim of the present study is to assess the impact of a brief yoga program on WM maintenance, WM manipulation and attentive mindfulness. Measures of WM (Digit Span Forward, Backward, and Sequencing, and Letter-Number Sequencing) were administered prior to and following 6 sessions of yoga (N = 43). Additionally, the Mindfulness Attention Awareness Scale was administered to examine the potential impact of yoga practice on mindfulness, as well as the relationships among changes in WM and mindfulness. Analyses revealed significant improvement from pre- to post- training assessment on both maintenance WM (Digit Span Forward) and manipulation WM (Digit Span Backward and Letter-Number Sequencing). No change was found on Digit Span Sequencing. Improvement was also found on mindfulness scores. However, no correlation was observed between mindfulness and WM measures. A 6-session yoga program was associated with improvement on manipulation and maintenance WM measures as well as enhanced mindfulness scores. Additional research is needed to understand the extent of yoga-related cognitive enhancement and mechanisms by which yoga may enhance cognition, ideally by utilizing randomized controlled trials and more comprehensive neuropsychological batteries.

Action Video Gaming and Cognitive Control: Playing First Person Shooter Games Is Associated with Improved Action Cascading but Not Inhibition

PubMed Central

Steenbergen, Laura; Sellaro, Roberta; Stock, Ann-Kathrin; Beste, Christian; Colzato, Lorenza S.

2015-01-01

There is a constantly growing interest in developing efficient methods to enhance cognitive functioning and/or to ameliorate cognitive deficits. One particular line of research focuses on the possibly cognitive enhancing effects that action video game (AVG) playing may have on game players. Interestingly, AVGs, especially first person shooter games, require gamers to develop different action control strategies to rapidly react to fast moving visual and auditory stimuli, and to flexibly adapt their behaviour to the ever-changing context. This study investigated whether and to what extent experience with such videogames is associated with enhanced performance on cognitive control tasks that require similar abilities. Experienced action videogame-players (AVGPs) and individuals with little to no videogame experience (NVGPs) performed a stop-change paradigm that provides a relatively well-established diagnostic measure of action cascading and response inhibition. Replicating previous findings, AVGPs showed higher efficiency in response execution, but not improved response inhibition (i.e. inhibitory control), as compared to NVGPs. More importantly, compared to NVGPs, AVGPs showed enhanced action cascading processes when an interruption (stop) and a change towards an alternative response were required simultaneously, as well as when such a change had to occur after the completion of the stop process. Our findings suggest that playing AVGs is associated with enhanced action cascading and multi-component behaviour without affecting inhibitory control. PMID:26655929

Action Video Gaming and Cognitive Control: Playing First Person Shooter Games Is Associated with Improved Action Cascading but Not Inhibition.

PubMed

Steenbergen, Laura; Sellaro, Roberta; Stock, Ann-Kathrin; Beste, Christian; Colzato, Lorenza S

2015-01-01

There is a constantly growing interest in developing efficient methods to enhance cognitive functioning and/or to ameliorate cognitive deficits. One particular line of research focuses on the possibly cognitive enhancing effects that action video game (AVG) playing may have on game players. Interestingly, AVGs, especially first person shooter games, require gamers to develop different action control strategies to rapidly react to fast moving visual and auditory stimuli, and to flexibly adapt their behaviour to the ever-changing context. This study investigated whether and to what extent experience with such videogames is associated with enhanced performance on cognitive control tasks that require similar abilities. Experienced action videogame-players (AVGPs) and individuals with little to no videogame experience (NVGPs) performed a stop-change paradigm that provides a relatively well-established diagnostic measure of action cascading and response inhibition. Replicating previous findings, AVGPs showed higher efficiency in response execution, but not improved response inhibition (i.e. inhibitory control), as compared to NVGPs. More importantly, compared to NVGPs, AVGPs showed enhanced action cascading processes when an interruption (stop) and a change towards an alternative response were required simultaneously, as well as when such a change had to occur after the completion of the stop process. Our findings suggest that playing AVGs is associated with enhanced action cascading and multi-component behaviour without affecting inhibitory control.

Video game training enhances cognitive control in older adults.

PubMed

Anguera, J A; Boccanfuso, J; Rintoul, J L; Al-Hashimi, O; Faraji, F; Janowich, J; Kong, E; Larraburo, Y; Rolle, C; Johnston, E; Gazzaley, A

2013-09-05

Cognitive control is defined by a set of neural processes that allow us to interact with our complex environment in a goal-directed manner. Humans regularly challenge these control processes when attempting to simultaneously accomplish multiple goals (multitasking), generating interference as the result of fundamental information processing limitations. It is clear that multitasking behaviour has become ubiquitous in today's technologically dense world, and substantial evidence has accrued regarding multitasking difficulties and cognitive control deficits in our ageing population. Here we show that multitasking performance, as assessed with a custom-designed three-dimensional video game (NeuroRacer), exhibits a linear age-related decline from 20 to 79 years of age. By playing an adaptive version of NeuroRacer in multitasking training mode, older adults (60 to 85 years old) reduced multitasking costs compared to both an active control group and a no-contact control group, attaining levels beyond those achieved by untrained 20-year-old participants, with gains persisting for 6 months. Furthermore, age-related deficits in neural signatures of cognitive control, as measured with electroencephalography, were remediated by multitasking training (enhanced midline frontal theta power and frontal-posterior theta coherence). Critically, this training resulted in performance benefits that extended to untrained cognitive control abilities (enhanced sustained attention and working memory), with an increase in midline frontal theta power predicting the training-induced boost in sustained attention and preservation of multitasking improvement 6 months later. These findings highlight the robust plasticity of the prefrontal cognitive control system in the ageing brain, and provide the first evidence, to our knowledge, of how a custom-designed video game can be used to assess cognitive abilities across the lifespan, evaluate underlying neural mechanisms, and serve as a powerful tool for cognitive enhancement.

Neurocognitive enhancement or impairment? A systematic meta-analysis of prescription stimulant effects on processing speed, decision-making, planning, and cognitive perseveration.

PubMed

Marraccini, Marisa E; Weyandt, Lisa L; Rossi, Joseph S; Gudmundsdottir, Bergljot Gyda

2016-08-01

Increasing numbers of adults, particularly college students, are misusing prescription stimulants primarily for cognitive/academic enhancement, so it is critical to explore whether empirical findings support neurocognitive benefits of prescription stimulants. Previous meta-analytic studies have supported small benefits from prescription stimulants for the cognitive domains of inhibitory control and memory; however, no meta-analytic studies have examined the effects on processing speed or the potential impairment on other domains of cognition, including planning, decision-making, and cognitive perseveration. Therefore, the present study conducted a meta-analysis of the available literature examining the effects of prescription stimulants on specific measures of processing speed, planning, decision-making, and cognitive perseveration among healthy adult populations. The meta-analysis results indicated a positive influence of prescription stimulant medication on processing speed accuracy, with an overall mean effect size of g = 0.282 (95% CI [0.077, 0.488]; n = 345). Neither improvements nor impairments were revealed for planning time, planning accuracy, advantageous decision-making, or cognitive perseveration; however, findings are limited by the small number of studies examining these outcomes. Findings support that prescription stimulant medication may indeed act as a neurocognitive enhancer for accuracy measures of processing speed without impeding other areas of cognition. Considering that adults are already engaging in illegal use of prescription stimulants for academic enhancement, as well as the potential for stimulant misuse to have serious side effects, the establishment of public policies informed by interdisciplinary research surrounding this issue, whether restrictive or liberal, is of critical importance. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Estrogens and cognition: Friends or foes?: An evaluation of the opposing effects of estrogens on learning and memory.

PubMed

Korol, Donna L; Pisani, Samantha L

2015-08-01

This article is part of a Special Issue "Estradiol and cognition". Estrogens are becoming well known for their robust enhancement on cognition particularly for learning and memory that relies upon functioning of the hippocampus and related neural systems. What is also emerging is that estrogen modulation of cognition is not uniform, at times enhancing yet at other times impairing learning. This review explores the bidirectional effects of estrogens on learning from a multiple memory systems view, focusing on the hippocampus and striatum, whereby modulation by estrogens sorts according to task attributes and neural systems engaged during cognition. We highlight our findings showing that the ability to solve hippocampus-sensitive tasks typically improves under relatively high estrogen status while the ability to solve striatum-sensitive tasks degrades with estrogen exposures. Though constrained by dose and timing of exposure, these opposing enhancements and impairments of cognition can be observed following treatments with different estrogenic compounds including the hormone estradiol, the isoflavone genistein found in soybeans, and agonists that are selective for specific estrogen receptors, suggesting that activation of a single receptor type is sufficient to produce the observed shifts in learning strategies. Using this multi-dimensional framework will allow us to extend our thinking of the relationship between estrogens and cognition to other brain regions and cognitive functions. Copyright © 2015 Elsevier Inc. All rights reserved.

Green tea and cocoa enhance cognition in Lymnaea

PubMed Central

Swinton, Erin; de Freitas, Emily; Swinton, Cayley; Shymansky, Tamila; Hiles, Emily; Zhang, Jack; Rothwell, Cailin; Lukowiak, Ken

2018-01-01

ABSTRACT A flavonoid, (-)-epicatechi (Epi), enhances long-term memory (LTM) formation in Lymnaea and reverses memory obstruction caused by stress. Many foods contain substantial amounts of Epi, (e.g. green tea and cocoa). In humans eating such foods may directly or indirectly enhance cognition. We directly test whether operant conditioning training Lymnaea in these natural foods result in the same effects as training snails in pure Epi. We found that exposure to products containing high concentrations of Epi (e.g. green tea and cocoa) during training enhanced memory formation and could even reverse a learning and memory deficit brought about by stress. Epi can be photo-inactivated by exposure to ultraviolet light. We found that following photo-inactivation of Epi, memory enhancement did not occur. Photo-inactivation of foods containing Epi (e,g. green tea) blocked their ability to enhance LTM. Our data are thus consistent with the hypothesis that dietary sources of Epi can have positive benefits on cognitive ability and be able to reverse memory aversive states. PMID:29497476

Design of a Cognitive Tool to Enhance Problemsolving Performance

ERIC Educational Resources Information Center

Lee, Youngmin; Nelson, David

2005-01-01

The design of a cognitive tool to support problem-solving performance for external representation of knowledge is described. The limitations of conventional knowledge maps are analyzed in proposing the tool. The design principles and specifications are described. This tool is expected to enhance learners problem-solving performance by allowing…

Does Tracing Worked Examples Enhance Geometry Learning?

ERIC Educational Resources Information Center

Hu, Fang-Tzu; Ginns, Paul; Bobis, Janette

2014-01-01

Cognitive load theory seeks to generate novel instructional designs through a focus on human cognitive architecture including a limited working memory; however, the potential for enhancing learning through non-visual or non-auditory working memory channels is yet to be evaluated. This exploratory experiment tested whether explicit instructions to…

Children's Friendships and Learning in School: Cognitive Enhancement through Social Interaction?

ERIC Educational Resources Information Center

Kutnick, Peter; Kington, Alison

2005-01-01

Background: Recent literature has identified that children's performance on cognitive (or problem-solving) tasks can be enhanced when undertaken as a joint activity among pairs of pupils. Performance on this "social" activity will require quality relationships between pupils, leading some researchers to argue that friendships are characterized by…

Alcohol Treatment and Cognitive-Behavioral Therapy: Enhancing Effectiveness by Incorporating Spirituality and Religion

ERIC Educational Resources Information Center

Hodge, David R.

2011-01-01

Cognitive-behavioral therapy (CBT) is an effective modality for the treatment of alcoholism. Given widespread interest in incorporating spirituality into professional treatment, this article orients practitioners to spiritually modified CBT, an approach that may enhance outcomes with some spiritually motivated clients. More specifically, by…

Metabolic Enhancer Piracetam Attenuates the Translocation of Mitochondrion-Specific Proteins of Caspase-Independent Pathway, Poly [ADP-Ribose] Polymerase 1 Up-regulation and Oxidative DNA Fragmentation.

PubMed

Verma, Dinesh Kumar; Gupta, Sonam; Biswas, Joyshree; Joshi, Neeraj; Sivarama Raju, K; Wahajuddin, Mu; Singh, Sarika

2018-03-12

Piracetam, a nootropic drug, has been clinically used for decades; however, its mechanism of action still remains enigmatic. The present study was undertaken to evaluate the role of mitochondrion-specific factors of caspase-independent pathway like apoptotic-inducing factor (AIF) and endonuclease-G (endo-G) in piracetam-induced neuroprotection. N2A cells treated with lipopolysaccharide (LPS) exhibited significant cytotoxicity, impaired mitochondrial activity, and reactive oxygen species generation which was significantly attenuated with piracetam co-treatment. Cells co-treated with LPS and piracetam exhibited significant uptake of piracetam in comparison to only piracetam-treated cells as estimated by liquid chromatography-mass spectrometry (LC-MSMS). LPS treatment caused significant translocation of AIF and endonuclease-G in neuronal N2A cells which were significantly attenuated with piracetam co-treatment. Significant over-expression of proinflammatory cytokines was also observed after treatment of LPS to cells which was inhibited with piracetam co-treatment demonstrating its anti-inflammatory property. LPS-treated cells exhibited significant oxidative DNA fragmentation and poly [ADP-ribose] polymerase-1 (PARP-1) up-regulation in nucleus, both of which were attenuated with piracetam treatment. Antioxidant melatonin but not z-VAD offered the inhibited LPS-induced DNA fragmentation indicating the involvement of oxidative DNA fragmentation. Further, we did not observe the altered caspase-3 level after LPS treatment initially while at a later time point, significantly augmented level of caspase-3 was observed which was not inhibited with piracetam treatment. In total, our findings indicate the interference of piracetam in mitochondrion-mediated caspase-independent pathway, as well as its anti-inflammatory and antioxidative properties. Graphical Abstract Graphical abstract indicating the novel interference of metabolic enhancer piracetam (P) in neuronal death mechanisms.

Enhancing Neuroplasticity to Augment Cognitive Remediation in Schizophrenia.

PubMed

Jahshan, Carol; Rassovsky, Yuri; Green, Michael F

2017-01-01

There is a burgeoning need for innovative treatment strategies to improve the cognitive deficits in schizophrenia. Cognitive remediation (CR) is effective at the group level, but the variability in treatment response is large. Given that CR may depend on intact neuroplasticity to produce cognitive gains, it is reasonable to combine it with strategies that harness patients' neuroplastic potential. In this review, we discuss two non-pharmacological approaches that can enhance neuroplasticity and possibly augment the effects of CR in schizophrenia: physical exercise and transcranial direct current stimulation (tDCS). Substantial body of evidence supports the beneficial effect of physical exercise on cognition, and a handful of studies in schizophrenia have shown that physical exercise in conjunction with CR has a larger impact on cognition than CR alone. Physical exercise is thought to stimulate neuroplasticity through the regulation of central growth factors, and current evidence points to brain-derived neurotrophic factor as the potential underlying mechanism through which physical exercise might enhance the effectiveness of CR. tDCS has emerged as a potential tool for cognitive enhancement and seems to affect the cellular mechanisms involved in long-term potentiation (LTP). A few reports have demonstrated the feasibility of integrating tDCS with CR in schizophrenia, but there are insufficient data to determine if this multimodal approach leads to incremental performance gain in patients. Larger randomized controlled trials are necessary to understand the mechanisms of the combined tDCS-CR intervention. Future research should take advantage of new developments in neuroplasticity paradigms to examine the effects of these interventions on LTP.

Effects of modafinil on non-verbal cognition, task enjoyment and creative thinking in healthy volunteers.

PubMed

Müller, U; Rowe, J B; Rittman, T; Lewis, C; Robbins, T W; Sahakian, B J

2013-01-01

Modafinil, a putative cognitive enhancing drug, has previously been shown to improve performance of healthy volunteers as well as patients with attention deficit disorder and schizophrenia, mainly in tests of executive functions. The aim of this study was to investigate the effects of modafinil on non-verbal cognitive functions in healthy volunteers, with a particular focus on variations of cognitive load, measures of motivational factors and the effects on creative problem-solving. A double-blind placebo-controlled parallel design study evaluated the effect of 200 mg of modafinil (N = 32) or placebo (N = 32) in non-sleep deprived healthy volunteers. Non-verbal tests of divergent and convergent thinking were used to measure creativity. A new measure of task motivation was used, together with more levels of difficulty on neuropsychological tests from the CANTAB battery. Improvements under modafinil were seen on spatial working memory, planning and decision making at the most difficult levels, as well as visual pattern recognition memory following delay. Subjective ratings of enjoyment of task performance were significantly greater under modafinil compared with placebo, but mood ratings overall were not affected. The effects of modafinil on creativity were inconsistent and did not reach statistical significance. Modafinil reliably enhanced task enjoyment and performance on several cognitive tests of planning and working memory, but did not improve paired associates learning. The findings confirm that modafinil can enhance aspects of highly demanding cognitive performance in non-sleep deprived individuals. This article is part of a Special Issue entitled 'Cognitive Enhancers'. Copyright © 2012 Elsevier Ltd. All rights reserved.

Methylphenidate as a cognitive enhancer in healthy young people

PubMed Central

Batistela, Silmara; Bueno, Orlando Francisco Amodeo; Vaz, Leonardo José; Galduróz, José Carlos Fernandes

2016-01-01

ABSTRACT The so-called cognitive enhancers have been widely and increasingly used by healthy individuals who seek improvements in cognitive performance despite having no pathologies. One drug used for this purpose is methylphenidate, a first-line drug for the treatment of attention deficit hyperactivity disorder (ADHD). Objective: The aim of the present study was to test the effect of acute administration of varying doses of methylphenidate (10 mg, 20 mg, 40 mg and placebo) on a wide range of cognitive functions in healthy young people. Methods: A total of 36 young university students and graduates participated in the study. The participants underwent tests of attention and of episodic, and working memory. Results: No differences in performance were observed on any of the tests. There was a dose-dependent (40 mg > placebo) effect on self-reported wellbeing. Conclusions: According to the recent literature, psychostimulant medications, such as methylphenidate, improve performance when cognitive processes are below an optimal level, which was not the case for the subjects of the present study. We suggest the impression that methylphenidate enhances cognitive performance in healthy young people, justifying its use, may be due to improvements in subjective wellbeing promoted by the drug. PMID:29213444

Cognitive effects of two nutraceuticals Ginseng and Bacopa benchmarked against modafinil: a review and comparison of effect sizes.

PubMed

Neale, Chris; Camfield, David; Reay, Jonathon; Stough, Con; Scholey, Andrew

2013-03-01

Over recent years there has been increasing research into both pharmaceutical and nutraceutical cognition enhancers. Here we aimed to calculate the effect sizes of positive cognitive effect of the pharmaceutical modafinil in order to benchmark the effect of two widely used nutraceuticals Ginseng and Bacopa (which have consistent acute and chronic cognitive effects, respectively). A search strategy was implemented to capture clinical studies into the neurocognitive effects of modafinil, Ginseng and Bacopa. Studies undertaken on healthy human subjects using a double-blind, placebo-controlled design were included. For each study where appropriate data were included, effect sizes (Cohen's d) were calculated for measures showing significant positive and negative effects of treatment over placebo. The highest effect sizes for cognitive outcomes were 0.77 for modafinil (visuospatial memory accuracy), 0.86 for Ginseng (simple reaction time) and 0.95 for Bacopa (delayed word recall). These data confirm that neurocognitive enhancement from well characterized nutraceuticals can produce cognition enhancing effects of similar magnitude to those from pharmaceutical interventions. Future research should compare these effects directly in clinical trials. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

The value and pitfalls of speculation about science and technology in bioethics: the case of cognitive enhancement.

PubMed

Racine, Eric; Martin Rubio, Tristana; Chandler, Jennifer; Forlini, Cynthia; Lucke, Jayne

2014-08-01

In the debate on the ethics of the non-medical use of pharmaceuticals for cognitive performance enhancement in healthy individuals there is a clear division between those who view "cognitive enhancement" as ethically unproblematic and those who see such practices as fraught with ethical problems. Yet another, more subtle issue, relates to the relevance and quality of the contribution of scholarly bioethics to this debate. More specifically, how have various forms of speculation, anticipatory ethics, and methods to predict scientific trends and societal responses augmented or diminished this contribution? In this paper, we use the discussion of the ethics of cognitive enhancement to explore the positive and negative contribution of speculation in bioethics scholarship. First, we review and discuss how speculation has relied on different sets of assumptions regarding the non-medical use of stimulants, namely: (1) terminology and framing; (2) scientific aspects such as efficacy and safety; (3) estimates of prevalence and consequent normalization; and (4) the need for normative reflection and regulatory guidelines. Second, three methodological guideposts are proposed to alleviate some of the pitfalls of speculation: (1) acknowledge assumptions more explicitly and identify the value attributed to assumptions; (2) validate assumptions with interdisciplinary literature; and (3) adopt a broad perspective to promote more comprehensive reflection. We conclude that, through the examination of the controversy about cognitive enhancement, we can employ these methodological guideposts to enhance the value of contributions from bioethics and minimize potential epistemic and practical pitfalls in this case and perhaps in other areas of bioethical debate.

Patterns of Substance Use During Cognitive Enhancement Therapy: An 18-Month Randomized Feasibility Study.

PubMed

Eack, Shaun M; Hogarty, Susan S; Bangalore, Srihari S; Keshavan, Matcheri S; Cornelius, Jack R

2016-01-01

Substance use problems are common among people with schizophrenia, as are significant cognitive impairments. Because of potential shared neurobiological pathways, it is possible that cognitive remediation interventions may be associated with improvements in both substance use and cognition. This study examined the impact of cognitive remediation on alcohol and cannabis use and the cognitive correlates of changes in substance use among outpatients with schizophrenia. Individuals with schizophrenia who were receiving outpatient services at a psychiatric clinic and had moderate or higher addiction severity scores (N = 31) were randomized to 18 months of cognitive enhancement therapy (n = 22) or usual care (n = 9). Cognitive enhancement therapy is a cognitive remediation approach that integrates computer-based training in attention, memory, and problem solving with a group-based social cognition curriculum. Usual care was provided to all participants and consisted of routine psychiatric care. Primary outcomes included days of alcohol and cannabis use, assessed with the Timeline Followback method every six months and modeled using penalized quasi-likelihood growth curves. Participants were on average 38.23 (SD = 13.44) years of age, had been ill for 14.19 (SD = 11.28) years, and were mostly male (n = 22, 71%), and about half were Caucasian (n = 16, 52%). Temporal patterns of substance use days were highly variable and followed nonlinear trajectories. Intent-to-treat analyses indicated that, compared to patients only receiving usual care, those receiving cognitive enhancement therapy were significantly less likely to use alcohol (OR = .22; 95% CI: .05, .90; p = .036), but not cannabis (OR = 1.89; 95% CI: .02, 142.99; p = .774) over time, and they reduced their alcohol use at significantly accelerated rates (OR = 1.02; 95% CI: 1.01, 1.03; p = .003). Changes in cognition were variably associated with substance use outcomes, although improvements in visual learning and reasoning and problem solving were both consistently related to reduced alcohol and cannabis use. Cognitive remediation may be effective for improving some substance use problems in schizophrenia. Visual learning and problem-solving deficits may be particularly important targets of such interventions, given their association with reduced alcohol and cannabis use. This study is registered at clinicaltrials.gov under #NCT01292577.

Learning a Foreign Language: A New Path to Enhancement of Cognitive Functions

ERIC Educational Resources Information Center

Shoghi Javan, Sara; Ghonsooly, Behzad

2018-01-01

The complicated cognitive processes involved in natural (primary) bilingualism lead to significant cognitive development. Executive functions as a fundamental component of human cognition are deemed to be affected by language learning. To date, a large number of studies have investigated how natural (primary) bilingualism influences executive…

A Novel Approach to Treating Anxiety and Enhancing Executive Skills in an Older Adult with Parkinson’s Disease

PubMed Central

Mohlman, Jan; Reel, Dorian Hunter; Chazin, Daniel; Ong, Diana; Georgescu, Bianca; Tiu, Jade; Dobkin, Roseanne D.

2010-01-01

Scientific interest in the nonmotoric symptoms of Parkinson’s disease (PD) has increased dramatically, and psychiatric symptoms (e.g., cognitive impairment, anxiety and mood disorders) are now considered prime targets for treatment optimization. Psychiatric complications in PD are quite common, affecting as many as 60 to 80% of patients. This study describes the case of a 74 year-old male with PD who presented with complaints of anxiety and trouble with memory and attention. A combined cognitive behavior therapy and cognitive enhancement intervention was delivered in ten 90-to-120 minute sessions. The patient showed a reduction in anxiety symptoms that was of sufficient magnitude to meet criteria for ‘responder’ status. His cognitive skills were mostly unchanged, despite the rigorous rehabilitation practice. Implications for treatment and strategies for enhancing therapeutic benefits are discussed. PMID:20419071

Enhanced Cognitive Rehabilitation to Treat Comorbid TBI and PTSD

DTIC Science & Technology

2016-10-01

therapeutic approaches and tests a modification of cognitive processing therapy (CPT), an empirically supported treatment for PTSD, in which CPT is...been organized into a manualized treatment, Cognitive Symptom Management and Rehabilitation Therapy (CogSMART), which teaches Veterans ways to...the Effects of Cognitive Processing Therapy on Psychological, Neuropsychological, and Speech Symptoms in Comorbid PTSD and TBI, Cognitive and

PDE4 as a target for cognition enhancement

PubMed Central

Richter, Wito; Menniti, Frank S.; Zhang, Han-Ting; Conti, Marco

2014-01-01

Introduction The second messengers cAMP and cGMP mediate fundamental aspects of brain function relevant to memory, learning and cognitive functions. Consequently, cyclic nucleotide phosphodiesterases (PDEs), the enzymes that inactivate the cyclic nucleotides, are promising targets for the development of cognition-enhancing drugs. Areas covered PDE4 is the largest of the eleven mammalian PDE families. This review covers the properties and functions of the PDE4 family, highlighting procognitive and memory-enhancing effects associated with their inactivation. Expert opinion PAN-selective PDE4 inhibitors exert a number of memory- and cognition-enhancing effects and have neuroprotective and neuroregenerative properties in preclinical models. The major hurdle for their clinical application is to target inhibitors to specific PDE4 isoforms relevant to particular cognitive disorders to realize the therapeutic potential while avoiding side effects, in particular emesis and nausea. The PDE4 family comprises four genes, PDE4A-D, each expressed as multiple variants. Progress to date stems from characterization of rodent models with selective ablation of individual PDE4 subtypes, revealing that individual subtypes exert unique and non-redundant functions in the brain. Thus, targeting specific PDE4 subtypes, as well as splicing variants or conformational states, represents a promising strategy to separate the therapeutic benefits from the side effects of PAN-PDE4 inhibitors. PMID:23883342

Cognitive training and selective attention in the aging brain: an electrophysiological study.

PubMed

O'Brien, Jennifer L; Edwards, Jerri D; Maxfield, Nathan D; Peronto, Carol L; Williams, Victoria A; Lister, Jennifer J

2013-11-01

Age-related deficits in selective attention are hypothesized to result from decrements in inhibition of task-irrelevant information. Speed of processing (SOP) training is an adaptive cognitive intervention designed to enhance processing speed for attention tasks. The effectiveness of SOP training to improve cognitive and everyday functional performance is well documented. However, underlying mechanisms of these training benefits are unknown. Participants completed a visual search task evaluated using event-related potentials (ERPs) before and after 10 weeks of SOP training or no contact. N2pc and P3b components were evaluated to determine SOP training effects on attentional resource allocation and capacity. Selective attention to a target was enhanced after SOP training compared to no training. N2pc and P3b amplitudes increased after training, reflecting attentional allocation and capacity enhancement, consistent with previous studies demonstrating behavioral improvements in selective attention following SOP training. Changes in ERPs related to attention allocation and capacity following SOP training support the idea that training leads to cognitive enhancement. Specifically, we provide electrophysiological evidence that SOP training may be successful in counteracting age-related declines in selective attention. This study provides important evidence of the underlying mechanisms by which SOP training improves cognitive function in older adults. Published by Elsevier Ireland Ltd.

Targeting Alertness to Improve Cognition in Older Adults: A Preliminary Report of Benefits in Executive Function and Skill Acquisition

PubMed Central

Van Vleet, Thomas M.; DeGutis, Joseph M.; Merzenich, Michael M.; Simpson, Gregory V.; Zomet, Ativ; Dabit, Sawsan

2016-01-01

Efficient self-regulation of alertness declines with age exacerbating normal declines in performance across multiple cognitive domains, including learning and skill acquisition. Previous cognitive intervention studies have shown that it is possible to enhance alertness in patients with acquired brain injury and marked attention impairments, and that this benefit generalizes to improvements in more global cognitive functions. In the current preliminary studies, we sought to test whether this approach, that targets both tonic (over a period of minutes) and phasic (moment-to-moment) alertness, can improve key executive functioning declines in older adults, and enhance the rate of skill acquisition. The results of both experiments 1 and 2 demonstrate that, compared to active control training, alertness training significantly enhanced performance in several validated executive function measures. In experiment 2, alertness training significantly improved skill acquisition compared to active control training in a well-characterized speed of processing task, with the largest benefits shown in the most challenging speed of processing blocks. The results of the current study suggest that targeting intrinsic alertness in cognitive training provides a novel approach to improve executive functions in older adults and may be a useful adjunct treatment to enhance benefits gained in other clinically validated treatments. PMID:27372902

Enhanced neural activation with blueberry supplementation in mild cognitive impairment.

PubMed

Boespflug, Erin L; Eliassen, James C; Dudley, Jonathan A; Shidler, Marcelle D; Kalt, Wilhelmina; Summer, Suzanne S; Stein, Amanda L; Stover, Amanda N; Krikorian, Robert

2018-05-01

Preclinical studies have shown that blueberry supplementation can improve cognitive performance and neural function in aged animals and have identified associations between anthocyanins and such benefits. Preliminary human trials also suggest cognitive improvement in older adults, although direct evidence of enhancement of brain function has not been demonstrated. In this study, we investigated the effect of blueberry supplementation on regional brain activation in older adults at risk for dementia. In a randomized, double-blind, placebo-controlled trial we performed pre- and post-intervention functional magnetic resonance imaging during a working memory (WM) task to assess the effect of blueberry supplementation on blood oxygen level-dependent (BOLD) signal in older adults with mild cognitive impairment, a risk condition for dementia. Following daily supplementation for 16 weeks, blueberry-treated participants exhibited increased BOLD activation in the left pre-central gyrus, left middle frontal gyrus, and left inferior parietal lobe during WM load conditions (corrected P < 0.01). There was no clear indication of WM enhancement associated with blueberry supplementation. Diet records indicated no between-group difference in anthocyanin consumption external to the intervention. These data demonstrate, for the first time, enhanced neural response during WM challenge in blueberry-treated older adults with cognitive decline and are consistent with prior trials showing neurocognitive benefit with blueberry supplementation in this at-risk population.

Enhancing Cognition with Video Games: A Multiple Game Training Study

PubMed Central

Oei, Adam C.; Patterson, Michael D.

2013-01-01

Background Previous evidence points to a causal link between playing action video games and enhanced cognition and perception. However, benefits of playing other video games are under-investigated. We examined whether playing non-action games also improves cognition. Hence, we compared transfer effects of an action and other non-action types that required different cognitive demands. Methodology/Principal Findings We instructed 5 groups of non-gamer participants to play one game each on a mobile device (iPhone/iPod Touch) for one hour a day/five days a week over four weeks (20 hours). Games included action, spatial memory, match-3, hidden- object, and an agent-based life simulation. Participants performed four behavioral tasks before and after video game training to assess for transfer effects. Tasks included an attentional blink task, a spatial memory and visual search dual task, a visual filter memory task to assess for multiple object tracking and cognitive control, as well as a complex verbal span task. Action game playing eliminated attentional blink and improved cognitive control and multiple-object tracking. Match-3, spatial memory and hidden object games improved visual search performance while the latter two also improved spatial working memory. Complex verbal span improved after match-3 and action game training. Conclusion/Significance Cognitive improvements were not limited to action game training alone and different games enhanced different aspects of cognition. We conclude that training specific cognitive abilities frequently in a video game improves performance in tasks that share common underlying demands. Overall, these results suggest that many video game-related cognitive improvements may not be due to training of general broad cognitive systems such as executive attentional control, but instead due to frequent utilization of specific cognitive processes during game play. Thus, many video game training related improvements to cognition may be attributed to near-transfer effects. PMID:23516504

CAN NONINVASIVE BRAIN STIMULATION ENHANCE COGNITION IN NEUROPSYCHIATRIC DISORDERS?

PubMed Central

Demirtas-Tatlidede, Asli; Vahabzadeh-Hagh, Andrew M.; Pascual-Leone, Alvaro

2013-01-01

Cognitive impairment is a core symptom of many neuropsychiatric diseases and a key contributor to the patient’s quality of life. However, an effective therapeutic strategy has yet to be developed. Noninvasive brain stimulation techniques, namely transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), are promising techniques that are under investigation for a variety of otherwise treatment-resistant neuropsychiatric diseases. Notably, these tools can induce alterations in neural networks subserving cognitive operations and thus may provide a means for cognitive restoration. The purpose of this article is to review the available evidence concerning cognitive enhancing properties of noninvasive brain stimulation in neuropsychiatry. We specifically focus on major depression, Alzheimer’s disease, schizophrenia, autism and attention deficit hyperactivity disorder (ADHD), where cognitive dysfunction is a major symptom and some studies have been completed with promising results. We provide a critical assessment of the available research and suggestions to guide future efforts. PMID:22749945

Emotional Enhancement Effect of Memory: Removing the Influence of Cognitive Factors

ERIC Educational Resources Information Center

Sommer, Tobias; Glascher, Jan; Moritz, Steffen; Buchel, Christian

2008-01-01

According to the modulation hypothesis, arousal is the crucial factor in the emotional enhancement of memory (EEM). However, the multifactor theory of the EEM recently proposed that cognitive characteristics of emotional stimuli, e.g., relatedness and distinctiveness, also play an important role. The current study aimed to investigate the…

The Impact of a Technology-Enhanced Math Performance Task on Student Cognitive Engagement in Mathematics

ERIC Educational Resources Information Center

Guerreiro, Meg

2017-01-01

Technology may play a critical role in impacting student engagement, specifically within an assessment context. Using a mixed methods approach, I examined the relationship between varying degrees of technology-enhancements applied in a mathematics performance task on the outcome of student cognitive engagement. Using a counterbalanced…

Cognitive Enhancement and Beyond: Recommendations from the Bioethics Commission.

PubMed

Allen, Anita L; Strand, Nicolle K

2015-10-01

Media outlets are reporting that cognitive enhancement is reaching epidemic levels, but evidence is lacking and ethical questions remain. The US Presidential Commission for the Study of Bioethical Issues (Bioethics Commission) has examined the issue, and we lay out the commission's findings and their relevance for the scientific community. Published by Elsevier Ltd.

Accounting for Immediate Emotional Memory Enhancement

ERIC Educational Resources Information Center

Talmi, Deborah; McGarry, Lucy M.

2012-01-01

Memory for emotional events is usually very good even when tested shortly after study, before it is altered by the influence of emotional arousal on consolidation. Immediate emotion-enhanced memory may stem from the influence of emotion on cognitive processes at encoding and retrieval. Our goal was to test which cognitive factors are necessary and…

The Potential Relevance of Cognitive Neuroscience for the Development and Use of Technology-Enhanced Learning

ERIC Educational Resources Information Center

Howard-Jones, Paul; Ott, Michela; van Leeuwen, Theo; De Smedt, Bert

2015-01-01

There is increasing interest in the application of cognitive neuroscience in educational thinking and practice, and here we review findings from neuroscience that demonstrate its potential relevance to technology-enhanced learning (TEL). First, we identify some of the issues in integrating neuroscientific concepts into TEL research. We caution…

A single low-dose of hydrocortisone enhances cognitive functioning in HIV-infected women.

PubMed

Rubin, Leah H; Phan, K Luan; Keating, Sheila M; Maki, Pauline M

2018-06-14

Low-dose hydrocortisone (LDH) enhances aspects of learning and memory in select populations including patients with PTSD and HIV-infected men. HIV-infected women show impairments in learning and memory, but the cognitive effects of LDH in HIV-infected women are unknown. Double-blind, placebo-controlled, cross-over study examining the time-dependent effects of a single low-dose administration of hydrocortisone (10 mg oral) on cognition in 36 HIV-infected women. Participants were first randomized to LDH or placebo and then received the opposite treatment one month later. Cognitive performance was assessed 30 minutes and 4 hours after pill administration to assess, respectively nongenomic and genomic effects. Self-reported stress/anxiety and salivary cortisol were assessed throughout sessions. LDH significantly increased salivary cortisol levels versus placebo; levels returned to baseline 4-hours post-administration. At the 30-minute assessment, LDH enhanced verbal learning and delayed memory, working memory, behavioral inhibition, and visuospatial abilities. At the 4-hour assessment, LDH enhanced verbal learning and delayed memory compared to placebo. LDH-induced cognitive benefits related to reductions in cytokines and to a lesser extent to increases in cortisol. The extended benefits from 30 minutes to 4 hours of a single administration of LDH on learning and delayed memory suggest that targeting the HPA axis may have potential clinical utility in HIV-infected women. These findings contrast with our findings in HIV-infected men who showed improved learning only at the 30-minute assessment. Larger, longer-term studies are underway to verify possible cognitive enhancing effects of LDH and the clinical significance of these effects in HIV.

Cognitive enhancement therapy for adult autism spectrum disorder: Results of an 18-month randomized clinical trial.

PubMed

Eack, Shaun M; Hogarty, Susan S; Greenwald, Deborah P; Litschge, Maralee Y; Porton, Shannondora A; Mazefsky, Carla A; Minshew, Nancy J

2018-03-01

Cognitive remediation is a promising approach to treating core cognitive deficits in adults with autism, but rigorously controlled trials of comprehensive interventions that target both social and non-social cognition over a sufficient period of time to impact functioning are lacking. This study examined the efficacy of cognitive enhancement therapy (CET) for improving core cognitive and employment outcomes in adult autism. Verbal adult outpatients with autism spectrum disorder (N = 54) were randomized to an 18-month, single-blind trial of CET, a cognitive remediation approach that integrates computer-based neurocognitive training with group-based training in social cognition, or an active enriched supportive therapy (EST) comparison focused on psychoeducation and condition management. Primary outcomes were composite indexes of neurocognitive and social-cognitive change. Competitive employment was a secondary outcome. Intent-to-treat analyses indicated that CET produced significant differential increases in neurocognitive function relative to EST (d = .46, P = .013). Both CET and EST were associated with large social-cognitive improvements, with CET demonstrating an advantage at 9 (d = .58, P = 0.020), but not 18 months (d = .27, P = 0.298). Effects on employment indicated that participants treated with CET were significantly more likely to gain competitive employment than those in EST, OR = 6.21, P = 0.023, which was mediated by cognitive improvement. CET is a feasible and potentially effective treatment for core cognitive deficits in adult autism spectrum disorder. The treatment of cognitive impairments in this population can contribute to meaningful improvements in adult outcomes. Autism Res 2018, 11: 519-530. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Cognitive enhancement therapy (CET), an 18-month cognitive remediation intervention designed to improve thinking and social understanding, was found to be more effective than supportive therapy at improving mental quickness, attention, and employment in adults living with autism. Social understanding was equally improved in CET and supportive therapy. Cognitive remediation interventions are feasible and may confer significant functional benefits to adults with autism. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorder: Results of an 18-Month Feasibility Study

PubMed Central

Eack, Shaun M.; Greenwald, Deborah P.; Hogarty, Susan S.; Bahorik, Amber L.; Litschge, Maralee Y.; Mazefsky, Carla A.; Minshew, Nancy J.

2013-01-01

Adults with autism experience significant impairments in social and non-social information processing for which few treatments have been developed. This study conducted an 18-month uncontrolled trial of Cognitive Enhancement Therapy (CET), a comprehensive cognitive rehabilitation intervention, in 14 verbal adults with autism spectrum disorder to investigate its feasibility, acceptability, and initial efficacy in treating these impairments. Results indicated that CET was satisfying to participants, with high treatment attendance and retention. Effects on cognitive deficits and social behavior were also large (d = 1.40 to 2.29) and statistically significant (all p < .001). These findings suggest that CET is a feasible, acceptable, and potentially effective intervention for remediating the social and non-social cognitive impairments in verbal adults with autism. PMID:23619953

Effects of Cognitive Enhancement Therapy on Employment Outcomes in Early Schizophrenia: Results From a Two-Year Randomized Trial

PubMed Central

Eack, Shaun M.; Hogarty, Gerard E.; Greenwald, Deborah P.; Hogarty, Susan S.; Keshavan, Matcheri S.

2013-01-01

Objective To examine the effects of psychosocial cognitive rehabilitation on employment outcomes in a randomized controlled trial for individuals with early course schizophrenia. Method Early course schizophrenia outpatients (N = 58) were randomly assigned to Cognitive Enhancement Therapy (CET) or an Enriched Supportive Therapy (EST) control and treated for two years. Comprehensive data on cognition and employment were collected annually. Results Individuals treated with CET were significantly more likely to be competitively employed, had greater earnings from employment, and were more satisfied with their employment status by the end of treatment compared to EST recipients. Mediator analyses revealed that improvements in both social and non-social cognition mediated the CET effects on employment. Conclusion CET can help facilitate employment in early schizophrenia, by addressing the cognitive impairments that limit functioning in the disorder. Inclusion of cognitive rehabilitation in social work practice can support more optimal functional recovery from schizophrenia. PMID:23885163

The neurobiology of modafinil as an enhancer of cognitive performance and a potential treatment for substance use disorders

PubMed Central

Mereu, Maddalena; Bonci, Antonello; Newman, Amy Hauck; Tanda, Gianluigi

2013-01-01

Rationale and Objectives Modafinil (MOD) and its R-enantiomer (R-MOD) are approved medications for narcolepsy and other sleep disorders. They have also been used, off label, as cognitive enhancers in populations of patients with mental disorders, including substance abusers that demonstrate impaired cognitive function. A debated non-medical use of MOD in healthy individuals to improve intellectual performance is raising questions about its potential abuse liability in this population. Results and Conclusions MOD has low micromolar affinity for the dopamine transporter (DAT). Inhibition of dopamine (DA) reuptake via the DAT explains the enhancement of DA levels in several brain areas, an effect shared with psychostimulants like cocaine, methylphenidate and the amphetamines. However, its neurochemical effects and anatomical pattern of brain area activation differ from typical psychostimulants and are consistent with its beneficial effects on cognitive performance processes such as attention, learning, and memory. At variance with typical psychostimulants, MOD shows very low, if any, abuse liability, in spite of its use as a cognitive enhancer by otherwise healthy individuals. Finally, recent clinical studies have focused on the potential use of MOD as a medication for treatment of drug abuse, but have not shown consistent outcomes. However, positive trends in several result measures suggest that medications that improve cognitive function, like MOD or R-MOD, may be beneficial for treatment of substance use disorders in certain patient populations. PMID:23934211

Training Working Memory in Childhood Enhances Coupling between Frontoparietal Control Network and Task-Related Regions.

PubMed

Barnes, Jessica J; Nobre, Anna Christina; Woolrich, Mark W; Baker, Kate; Astle, Duncan E

2016-08-24

Working memory is a capacity upon which many everyday tasks depend and which constrains a child's educational progress. We show that a child's working memory can be significantly enhanced by intensive computer-based training, relative to a placebo control intervention, in terms of both standardized assessments of working memory and performance on a working memory task performed in a magnetoencephalography scanner. Neurophysiologically, we identified significantly increased cross-frequency phase amplitude coupling in children who completed training. Following training, the coupling between the upper alpha rhythm (at 16 Hz), recorded in superior frontal and parietal cortex, became significantly coupled with high gamma activity (at ∼90 Hz) in inferior temporal cortex. This altered neural network activity associated with cognitive skill enhancement is consistent with a framework in which slower cortical rhythms enable the dynamic regulation of higher-frequency oscillatory activity related to task-related cognitive processes. Whether we can enhance cognitive abilities through intensive training is one of the most controversial topics of cognitive psychology in recent years. This is particularly controversial in childhood, where aspects of cognition, such as working memory, are closely related to school success and are implicated in numerous developmental disorders. We provide the first neurophysiological account of how working memory training may enhance ability in childhood, using a brain recording technique called magnetoencephalography. We borrowed an analysis approach previously used with intracranial recordings in adults, or more typically in other animal models, called "phase amplitude coupling." Copyright © 2016 Barnes et al.

Training Working Memory in Childhood Enhances Coupling between Frontoparietal Control Network and Task-Related Regions

PubMed Central

Barnes, Jessica J.; Nobre, Anna Christina; Woolrich, Mark W.; Baker, Kate

2016-01-01

Working memory is a capacity upon which many everyday tasks depend and which constrains a child's educational progress. We show that a child's working memory can be significantly enhanced by intensive computer-based training, relative to a placebo control intervention, in terms of both standardized assessments of working memory and performance on a working memory task performed in a magnetoencephalography scanner. Neurophysiologically, we identified significantly increased cross-frequency phase amplitude coupling in children who completed training. Following training, the coupling between the upper alpha rhythm (at 16 Hz), recorded in superior frontal and parietal cortex, became significantly coupled with high gamma activity (at ∼90 Hz) in inferior temporal cortex. This altered neural network activity associated with cognitive skill enhancement is consistent with a framework in which slower cortical rhythms enable the dynamic regulation of higher-frequency oscillatory activity related to task-related cognitive processes. SIGNIFICANCE STATEMENT Whether we can enhance cognitive abilities through intensive training is one of the most controversial topics of cognitive psychology in recent years. This is particularly controversial in childhood, where aspects of cognition, such as working memory, are closely related to school success and are implicated in numerous developmental disorders. We provide the first neurophysiological account of how working memory training may enhance ability in childhood, using a brain recording technique called magnetoencephalography. We borrowed an analysis approach previously used with intracranial recordings in adults, or more typically in other animal models, called “phase amplitude coupling.” PMID:27559180

Atomoxetine in abstinent cocaine users: Cognitive, subjective and cardiovascular effects.

PubMed

DeVito, Elise E; Herman, Aryeh I; Konkus, Noah S; Zhang, Huiping; Sofuoglu, Mehmet

2017-08-01

No pharmacotherapies are approved for the treatment of cocaine use disorders (CUD). Behavioral treatments for CUD are efficacious for some individuals, but recovery rates from CUD remain low. Cognitive impairments in CUD have been linked with poorer clinical outcomes. Cognitive enhancing pharmacotherapies have been proposed as promising treatments for CUD. Atomoxetine, a norepinephrine transporter inhibitor, shows potential as a treatment for CUD based on its efficacy as a cognitive enhancer in other clinical populations and impact on addictive processes in preclinical and human laboratory studies. In this randomized, double-blind, crossover study, abstinent individuals with CUD (N=39) received placebo, 40 and 80mg atomoxetine, over three sessions. Measures of attention, response inhibition and working memory; subjective medication effects and mood; and cardiovascular effects were collected. Analyses assessed acute, dose-dependent effects of atomoxetine. In addition, preliminary analyses investigating the modulation of atomoxetine dose effects by sex were performed. Atomoxetine increased heart rate and blood pressure, was rated as having positive and negative subjective drug effects, and had only modest effects on mood and cognitive enhancement. Copyright © 2017. Published by Elsevier Inc.

Improvement of spatial memory function in APPswe/PS1dE9 mice after chronic inhibition of phosphodiesterase type 4D.

PubMed

Sierksma, A S R; van den Hove, D L A; Pfau, F; Philippens, M; Bruno, O; Fedele, E; Ricciarelli, R; Steinbusch, H W M; Vanmierlo, T; Prickaerts, J

2014-02-01

Phosphodiesterase type 4 inhibitors (PDE4-Is) have received increasing attention as cognition-enhancers and putative treatment strategies for Alzheimer's disease (AD). By preventing cAMP breakdown, PDE4-Is can enhance intracellular signal transduction and increase the phosphorylation of cAMP response element-binding protein (CREB) and transcription of proteins related to synaptic plasticity and associated memory formation. Unfortunately, clinical development of PDE4-Is has been seriously hampered by emetic side effects. The new isoform-specific PDE4D-I, GEBR-7b, has shown to have beneficial effects on memory at non-emetic doses. The aim of the current study was to investigate chronic cognition-enhancing effects of GEBR-7b in a mouse model of AD. To this extent, 5-month-old (5M) APPswe/PS1dE9 mice received daily subcutaneous injections with GEBR-7b (0.001 mg/kg) or vehicle for a period of 3 weeks, and were tested on affective and cognitive behavior at 7M. We demonstrated a cognition-enhancing potential in APPswe/PS1dE9 mice as their spatial memory function at 7M in the object location test was improved by prior GEBR-7b treatment. APPswe/PS1dE9 mice displayed lower levels of CREB phosphorylation, which remained unaltered after chronic GEBR-7b treatment, and higher levels of tau in the hippocampus. Hippocampal brain-derived neurotrophic factor levels and synaptic densities were not different between experimental groups and no effects were observed on hippocampal GSK3β and tau phosphorylation or Aβ levels. In conclusion, GEBR-7b can enhance spatial memory function in the APPswe/PS1dE9 mouse model of AD. Although the underlying mechanisms of its cognition-enhancing potential remain to be elucidated, PDE4D inhibition appears an interesting novel therapeutic option for cognitive deficits in AD. Copyright © 2013 Elsevier Ltd. All rights reserved.

tDCS over the left prefrontal cortex enhances cognitive control for positive affective stimuli.

PubMed

Vanderhasselt, Marie-Anne; De Raedt, Rudi; Brunoni, Andre R; Campanhã, Camila; Baeken, Chris; Remue, Jonathan; Boggio, Paulo S

2013-01-01

Transcranial Direct Current Stimulation (tDCS) is a neuromodulation technique with promising results for enhancing cognitive information processes. So far, however, research has mainly focused on the effects of tDCS on cognitive control operations for non-emotional material. Therefore, our aim was to investigate the effects on cognitive control considering negative versus positive material. For this sham-controlled, within-subjects study, we selected a homogeneous sample of twenty-five healthy participants. By using behavioral measures and event related potentials (ERP) as indexes, we aimed to investigate whether a single session of anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) would have specific effects in enhancing cognitive control for positive and negative valenced stimuli. After tDCS over the left DLPFC (and not sham control stimulation), we observed more negative N450 amplitudes along with faster reaction times when inhibiting a habitual response to happy compared to sad facial expressions. Gender did not influence the effects of tDCS on cognitive control for emotional information. In line with the Valence Theory of side-lateralized activity, this stimulation protocol might have led to a left dominant (relative to right) prefrontal cortical activity, resulting in augmented cognitive control specifically for positive relative to negative stimuli. To verify that tDCS induces effects that are in line with all aspects of the well known Valence Theory, future research should investigate the effects of tDCS over the left vs. right DLPFC on cognitive control for emotional information.

Current trends in the empirical study of cognitive remediation for schizophrenia.

PubMed

Saperstein, Alice M; Kurtz, Matthew M

2013-06-01

Cognitive remediation (CR) for schizophrenia is a learning-based behavioural skills training intervention designed to enhance neuro and (or) social cognitive skills, with the ultimate goal of generalization to improve psychosocial outcomes. This review summarizes conceptual approaches to CR for schizophrenia and the evidence for efficacy in clinical research settings. Four issues are at the forefront of ongoing research: the identification of techniques that produce the largest cognitive change, delineation of techniques that enhance transfer of cognitive skills to functional skills, the identification of CR methods that can be personalized to meet the specific cognitive and functional needs of each individual, and, all the while, ensuring that when CR methods are developed in a research setting, they remain scalable for delivery in the larger clinical community. In response to these issues, 3 prominent research trends have emerged: the rise of a new generation of computerized restorative cognitive training, the integration of CR with skills training to promote generalization, and the application of techniques to enhance motivation and learning during CR. As data on the neural basis of learning in people with schizophrenia become available, new technologies that harness the ability of the brain to make sustainable, functional changes may be integrated within a therapeutic context that promotes a personalized approach to learning. The development of transportable and scalable methods of CR that maximize the ability of people with schizophrenia to improve cognition will help them achieve personal goals for recovery.

Putative cognitive enhancers in preclinical models related to schizophrenia: the search for an elusive target.

PubMed

Barak, Segev; Weiner, Ina

2011-08-01

Several developments have converged to drive what may be called "the cognitive revolution" in drug discovery in schizophrenia (SCZ), including the emphasis on cognitive deficits as a core disabling aspect of SCZ, the increasing consensus that cognitive deficits are not treated satisfactorily by the available antipsychotic drugs (APDs), and the failure of animal models to predict drug efficacy for cognitive deficits in clinical trials. Consequently, in recent years, a paradigm shift has been encouraged in animal modeling, triggered by the NIMH sponsored Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative, and intended to promote the development and use of behavioral measures in animals that can generate valid (clinically relevant) measures of cognition and thus promote the identification of cognition enhancers for SCZ. Here, we provide a non-exhaustive survey of the effects of putative cognition enhancers (PCEs) representing 10 pharmacological targets as well as antipsychotic drugs (APDs), on SCZ-mimetic drugs (NMDA antagonists, muscarinic antagonist scopolamine and dopaminergic agonist amphetamine), in several tasks considered to measure cognitive processes/domains that are disrupted in SCZ (the five choice serial reaction time task, sustain attention task, working and/or recognition memory (delayed (non)matching to sample, delayed alternation task, radial arm maze, novel object recognition), reversal learning, attentional set shifting, latent inhibition and spatial learning and memory). We conclude that most of the available models have no capacity to distinguish between PCEs and APDs and that there is a need to establish models based on tasks whose perturbations lead to performance impairments that are resistant to APDs, and/or to accept APDs as a "weak gold standard". Several directions derived from the surveyed data are suggested. Copyright © 2011 Elsevier Inc. All rights reserved.

Cognitive Impairment in Chronic Alcoholics: Some Cause for Optimism.

ERIC Educational Resources Information Center

Goldman, Mark S.

1983-01-01

It appears that, although the cognitive functioning of many alcoholics remains impaired even after drinking has stopped, considerable recovery can occur. New findings now suggest the possibility of reducing cognitive dysfunction and enhancing alcoholism treatment outcomes. (CMG)

Cognitive Psychology and College-Level Pedagogy: Two Siblings that Rarely Communicate.

ERIC Educational Resources Information Center

Matlin, Margaret W.

2002-01-01

Following an introduction on the literature on cognitive psychology and pedagogy, provides an annotated bibliography listing several dozen resources that have explored how principles of cognitive psychology can be used to enhance college-level pedagogy. (EV)

The Impact of Motivational "World-View" on Engagement in a Cognitive Acceleration Programme

ERIC Educational Resources Information Center

McLellan, Ros

2006-01-01

Cognitive Acceleration through Science Education (CASE) is an intervention programme conducted during Years 7 and 8 in the United Kingdom (aged 11-13 years), which has reported remarkable success in enhancing cognitive development and in raising academic achievement. Critics, however, have questioned whether a purely cognitive mechanism can…

Understanding the Technology Enhanced Learning Environments from a Cognitive Perspective

ERIC Educational Resources Information Center

Kok, Ayse

2009-01-01

This conceptual paper discusses some principles for powerful learning environments based on a cognitive perspective. Throughout the paper, it is argued that the accommodation of different individual cognitive preferences is crucial for its alignment with the human cognitive architecture. The paper concludes that in order to be aligned with the…

Promoting Conceptual Development in Physics Teacher Education: Cognitive-Historical Reconstruction of Electromagnetic Induction Law

ERIC Educational Resources Information Center

Mantyla, Terhi

2013-01-01

In teaching physics, the history of physics offers fruitful starting points for designing instruction. I introduce here an approach that uses historical cognitive processes to enhance the conceptual development of pre-service physics teachers' knowledge. It applies a method called cognitive-historical approach, introduced to the cognitive sciences…

Cognitive Restructuring in the Treatment of Social Phobia: Efficacy and Mode of Action.

ERIC Educational Resources Information Center

Taylor, Steven; Woody, Sheila; Koch, William J.; McLean, Peter; Paterson, Randy J.; Anderson, Kent W.

1997-01-01

Examines whether cognitive restructuring (CR) contributes to treatment efficacy and investigates its mode of action for therapeutic effects. Results, based on 60 persons with generalized social phobia, indicate that CR reduced social phobia and negative social cognitions and increased positive cognitions. CR did not enhance the effects of…

Habitual exercise is associated with cognitive control and cognitive reappraisal success.

PubMed

Giles, Grace E; Cantelon, Julie A; Eddy, Marianna D; Brunyé, Tad T; Urry, Heather L; Mahoney, Caroline R; Kanarek, Robin B

2017-12-01

Habitual exercise is associated with enhanced domain-general cognitive control, such as inhibitory control, selective attention, and working memory, all of which rely on the frontal cortex. However, whether regular exercise is associated with more specific aspects of cognitive control, such as the cognitive control of emotion, remains relatively unexplored. The present study employed a correlational design to determine whether level of habitual exercise was related to performance on the Stroop test measuring selective attention and response inhibition, the cognitive reappraisal task measuring cognitive reappraisal success, and associated changes in prefrontal cortex (PFC) oxygenation using functional near-infrared spectroscopy. 74 individuals (24 men, 50 women, age 18-32 years) participated. Higher habitual physical activity was associated with lower Stroop interference (indicating greater inhibitory control) and enhanced cognitive reappraisal success. Higher habitual exercise was also associated with lower oxygenated hemoglobin (O 2 Hb) in the PFC in response to emotional information. However, NIRS data indicated that exercise was not associated with cognitive control-associated O 2 Hb in the PFC. Behaviorally, the findings support and extend the previous findings that habitual exercise relates to more successful cognitive control of neutral information and cognitive reappraisal of emotional information. Future research should explore whether habitual exercise exerts causal benefits to cognitive control and PFC oxygenation, as well as isolate specific cognitive control processes sensitive to change through habitual exercise.

Evidence supporting a role for astrocytes in the regulation of cognitive flexibility and neuronal oscillations through the Ca2+ binding protein S100β.

PubMed

Brockett, Adam T; Kane, Gary A; Monari, Patrick K; Briones, Brandy A; Vigneron, Pierre-Antoine; Barber, Gabriela A; Bermudez, Andres; Dieffenbach, Uma; Kloth, Alexander D; Buschman, Timothy J; Gould, Elizabeth

2018-01-01

The medial prefrontal cortex (mPFC) is important for cognitive flexibility, the ability to switch between two task-relevant dimensions. Changes in neuronal oscillations and alterations in the coupling across frequency ranges have been correlated with attention and cognitive flexibility. Here we show that astrocytes in the mPFC of adult male Sprague Dawley rats, participate in cognitive flexibility through the astrocyte-specific Ca2+ binding protein S100β, which improves cognitive flexibility and increases phase amplitude coupling between theta and gamma oscillations. We further show that reduction of astrocyte number in the mPFC impairs cognitive flexibility and diminishes delta, alpha and gamma power. Conversely, chemogenetic activation of astrocytic intracellular Ca2+ signaling in the mPFC enhances cognitive flexibility, while inactivation of endogenous S100β among chemogenetically activated astrocytes in the mPFC prevents this improvement. Collectively, our work suggests that astrocytes make important contributions to cognitive flexibility and that they do so by releasing a Ca2+ binding protein which in turn enhances coordinated neuronal oscillations.

Cognitive training in Parkinson disease: cognition-specific vs nonspecific computer training.

PubMed

Zimmermann, Ronan; Gschwandtner, Ute; Benz, Nina; Hatz, Florian; Schindler, Christian; Taub, Ethan; Fuhr, Peter

2014-04-08

In this study, we compared a cognition-specific computer-based cognitive training program with a motion-controlled computer sports game that is not cognition-specific for their ability to enhance cognitive performance in various cognitive domains in patients with Parkinson disease (PD). Patients with PD were trained with either a computer program designed to enhance cognition (CogniPlus, 19 patients) or a computer sports game with motion-capturing controllers (Nintendo Wii, 20 patients). The effect of training in 5 cognitive domains was measured by neuropsychological testing at baseline and after training. Group differences over all variables were assessed with multivariate analysis of variance, and group differences in single variables were assessed with 95% confidence intervals of mean difference. The groups were similar regarding age, sex, and educational level. Patients with PD who were trained with Wii for 4 weeks performed better in attention (95% confidence interval: -1.49 to -0.11) than patients trained with CogniPlus. In our study, patients with PD derived at least the same degree of cognitive benefit from non-cognition-specific training involving movement as from cognition-specific computerized training. For patients with PD, game consoles may be a less expensive and more entertaining alternative to computer programs specifically designed for cognitive training. This study provides Class III evidence that, in patients with PD, cognition-specific computer-based training is not superior to a motion-controlled computer game in improving cognitive performance.

Evaluating a cognitive/ecological program for the prevention of aggression among urban children.

PubMed

Huesmann, L R; Maxwell, C D; Eron, L; Dahlberg, L L; Guerra, N G; Tolan, P H; VanAcker, R; Henry, D

1996-01-01

The Metropolitan Area Child Study (MACS) is a multifaceted school- and family-based intervention and evaluation study designed to prevent and understand the development of aggressive behavior. The multifaceted interventions are grounded in combined social-cognitive and ecologic theories. Social-cognitive theories contend that cognitive scripts, attributions, and beliefs acquired early in life mediate the effects of ecological factors that influence the development of antisocial behavior. Prevention programs aimed at these cognitions must address multiple dimensions of the child's environment including family, peer, school, and community. The program has three levels of intervention delivered in two-year segments: (1) Level 1: a general enhancement classroom intervention that stresses culturally sensitive student and teacher interaction involving instructional and classroom management strategies and a social-cognitive curriculum that mitigates aggressive development; (2) Level 2: intensive small-group sessions designed to change children's cognitions and enhance peer relationship skills for at-risk children added to the general classroom enhancement program; and (3) Level 3: a one-year family relationship intervention that stresses parenting skill building and emotional responsiveness in family interactions added to the general enhancement and small-group training conditions. Sixteen Chicago-area schools are randomly assigned (four each) to a control group or one of the three intervention levels. Individual child assessment, peer assessments, classroom behavioral observations, and archival data are collected before the interventions begin, during the interventions, at the end of each intervention, and at a follow-up point. The pretests indicate that the children on average have higher levels of aggression than found nationally and elevated clinical levels of other psychopathologies. Across the four intervention levels there are no significant differences in ethnic composition, socio-economic status (SES), aggressive behavior, and normative beliefs about aggression.

Transcranial direct current stimulation can enhance working memory in Huntington's disease.

PubMed

Eddy, Clare M; Shapiro, Kimron; Clouter, Andrew; Hansen, Peter C; Rickards, Hugh E

2017-07-03

Transcranial direct current stimulation (tDCS) combined with a cognitive task can enhance targeted aspects of cognitive functioning in clinical populations. The movement disorder Huntington's disease (HD) is associated with progressive cognitive impairment. Deficits in working memory (WM) can be apparent early in the disease and impact functional capacity. We investigated whether tDCS combined with cognitive training could improve WM in patients with HD, and if baseline clinical or cognitive measures may predict efficacy. Twenty participants with HD completed this crossover trial, undergoing 1.5mA anodal tDCS over left dorsolateral prefrontal cortex and sham stimulation on separate visits. Participants and assessor were blinded to condition order, which was randomised across participants. All participants completed baseline clinical and cognitive assessments. Pre- and post-stimulation tasks included digit reordering, computerised n-back tests and a Stroop task. During 15min of tDCS/sham stimulation, participants practiced 1- and 2-back WM tasks. Participants exhibited an increase in WM span on the digit re-ordering span task from pre- to post-stimulation after tDCS, but not after sham stimulation. Gains in WM were positively related to motor symptom ratings and negatively associated with verbal fluency scores. Patients with more severe motor symptoms showed greatest improvement, suggesting that motor symptom ratings may help identify patients who are most likely to benefit from tDCS. Dorsolateral prefrontal tDCS appears well tolerated in HD and enhances WM span compared to sham stimulation. Our findings strongly encourage further investigation of the extent to which tDCS combined with cognitive training could enhance everyday function in HD. ClinicalTrials.gov; NCT02216474 Brain stimulation in Movement Disorders; https://clinicaltrials.gov/ct2/show/NCT02216474. Copyright © 2017 Elsevier Inc. All rights reserved.

Reward Motivation Enhances Task Coding in Frontoparietal Cortex.

PubMed

Etzel, Joset A; Cole, Michael W; Zacks, Jeffrey M; Kay, Kendrick N; Braver, Todd S

2016-04-01

Reward motivation often enhances task performance, but the neural mechanisms underlying such cognitive enhancement remain unclear. Here, we used a multivariate pattern analysis (MVPA) approach to test the hypothesis that motivation-related enhancement of cognitive control results from improved encoding and representation of task set information. Participants underwent two fMRI sessions of cued task switching, the first under baseline conditions, and the second with randomly intermixed reward incentive and no-incentive trials. Information about the upcoming task could be successfully decoded from cue-related activation patterns in a set of frontoparietal regions typically associated with task control. More critically, MVPA classifiers trained on the baseline session had significantly higher decoding accuracy on incentive than non-incentive trials, with decoding improvement mediating reward-related enhancement of behavioral performance. These results strongly support the hypothesis that reward motivation enhances cognitive control, by improving the discriminability of task-relevant information coded and maintained in frontoparietal brain regions. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Using the Cognitive Apprenticeship Model with a Chat Tool to Enhance Online Collaborative Learning

ERIC Educational Resources Information Center

Rodríguez-Bonces, Mónica; Ortiz, Kris

2016-01-01

In Colombia, many institutions are in the firm quest of virtual learning environments to improve instruction, and making the most of online tools is clearly linked to offering quality learning. Thus, the purpose of this action research was to identify how the Cognitive Apprenticeship Model enhances online collaborative learning by using a chat…

Emotion Regulation Enhancement of Cognitive Behavior Therapy for College Student Problem Drinkers: A Pilot Randomized Controlled Trial

ERIC Educational Resources Information Center

Ford, Julian D.; Grasso, Damion J.; Levine, Joan; Tennen, Howard

2018-01-01

This pilot randomized clinical trial tested an emotion regulation enhancement to cognitive behavior therapy (CBT) with 29 college student problem drinkers with histories of complex trauma and current clinically significant traumatic stress symptoms. Participants received eight face-to-face sessions of manualized Internet-supported CBT for problem…

Hypnosis as an Adjunct to Cognitive-Behavioral Psychotherapy for Obesity: A Meta-analytic Reappraisal.

ERIC Educational Resources Information Center

Allison, David B.; Faith, Myles S.

1996-01-01

A meta-analysis for six weight-loss studies comparing the efficacy of cognitive-behavior therapy (CBT) alone to CBT plus hypnotherapy. Notes that "the addition of hypnosis substantially enhanced treatment outcome." Concludes that the addition of hypnosis to CBT for weight loss results in, at most, a small enhancement of treatment…

Enrichment Effects on Adult Cognitive Development: Can the Functional Capacity of Older Adults Be Preserved and Enhanced?

PubMed

Hertzog, Christopher; Kramer, Arthur F; Wilson, Robert S; Lindenberger, Ulman

2008-10-01

In this monograph, we ask whether various kinds of intellectual, physical, and social activities produce cognitive enrichment effects-that is, whether they improve cognitive performance at different points of the adult life span, with a particular emphasis on old age. We begin with a theoretical framework that emphasizes the potential of behavior to influence levels of cognitive functioning. According to this framework, the undeniable presence of age-related decline in cognition does not invalidate the view that behavior can enhance cognitive functioning. Instead, the course of normal aging shapes a zone of possible functioning, which reflects person-specific endowments and age-related constraints. Individuals influence whether they function in the higher or lower ranges of this zone by engaging in or refraining from beneficial intellectual, physical, and social activities. From this point of view, the potential for positive change, or plasticity, is maintained in adult cognition. It is an argument that is supported by newer research in neuroscience showing neural plasticity in various aspects of central nervous system functioning, neurochemistry, and architecture. This view of human potential contrasts with static conceptions of cognition in old age, according to which decline in abilities is fixed and individuals cannot slow its course. Furthermore, any understanding of cognition as it occurs in everyday life must make a distinction between basic cognitive mechanisms and skills (such as working-memory capacity) and the functional use of cognition to achieve goals in specific situations. In practice, knowledge and expertise are critical for effective functioning, and the available evidence suggests that older adults effectively employ specific knowledge and expertise and can gain new knowledge when it is required. We conclude that, on balance, the available evidence favors the hypothesis that maintaining an intellectually engaged and physically active lifestyle promotes successful cognitive aging. First, cognitive-training studies have demonstrated that older adults can improve cognitive functioning when provided with intensive training in strategies that promote thinking and remembering. The early training literature suggested little transfer of function from specifically trained skills to new cognitive tasks; learning was highly specific to the cognitive processes targeted by training. Recently, however, a new generation of studies suggests that providing structured experience in situations demanding executive coordination of skills-such as complex video games, task-switching paradigms, and divided attention tasks-train strategic control over cognition that does show transfer to different task environments. These studies suggest that there is considerable reserve potential in older adults' cognition that can be enhanced through training. Second, a considerable number of studies indicate that maintaining a lifestyle that is intellectually stimulating predicts better maintenance of cognitive skills and is associated with a reduced risk of developing Alzheimer's disease in late life. Our review focuses on longitudinal evidence of a connection between an active lifestyle and enhanced cognition, because such evidence admits fewer rival explanations of observed effects (or lack of effects) than does cross-sectional evidence. The longitudinal evidence consistently shows that engaging in intellectually stimulating activities is associated with better cognitive functioning at later points in time. Other studies show that meaningful social engagement is also predictive of better maintenance of cognitive functioning in old age. These longitudinal findings are also open to important rival explanations, but overall, the available evidence suggests that activities can postpone decline, attenuate decline, or provide prosthetic benefit in the face of normative cognitive decline, while at the same time indicating that late-life cognitive changes can result in curtailment of activities. Given the complexity of the dynamic reciprocal relationships between stimulating activities and cognitive function in old age, additional research will be needed to address the extent to which observed effects validate a causal influence of an intellectually engaged lifestyle on cognition. Nevertheless, the hypothesis that an active lifestyle that requires cognitive effort has long-term benefits for older adults' cognition is at least consistent with the available data. Furthermore, new intervention research that involves multimodal interventions focusing on goal-directed action requiring cognition (such as reading to children) and social interaction will help to address whether an active lifestyle enhances cognitive function. Third, there is a parallel literature suggesting that physical activity, and aerobic exercise in particular, enhances older adults' cognitive function. Unlike the literature on an active lifestyle, there is already an impressive array of work with humans and animal populations showing that exercise interventions have substantial benefits for cognitive function, particularly for aspects of fluid intelligence and executive function. Recent neuroscience research on this topic indicates that exercise has substantial effects on brain morphology and function, representing a plausible brain substrate for the observed effects of aerobic exercise and other activities on cognition. Our review identifies a number of areas where additional research is needed to address critical questions. For example, there is considerable epidemiological evidence that stress and chronic psychological distress are negatively associated with changes in cognition. In contrast, less is known about how positive attributes, such as self-efficacy, a sense of control, and a sense of meaning in life, might contribute to preservation of cognitive function in old age. It is well known that certain personality characteristics such as conscientiousness predict adherence to an exercise regimen, but we do not know whether these attributes are also relevant to predicting maintenance of cognitive function or effective compensation for cognitive decline when it occurs. Likewise, more information is needed on the factors that encourage maintenance of an active lifestyle in old age in the face of elevated risk for physiological decline, mechanical wear and tear on the body, and incidence of diseases with disabling consequences, and whether efforts to maintain an active lifestyle are associated with successful aging, both in terms of cognitive function and psychological and emotional well-being. We also discuss briefly some interesting issues for society and public policy regarding cognitive-enrichment effects. For example, should efforts to enhance cognitive function be included as part of a general prevention model for enhancing health and vitality in old age? We also comment on the recent trend of business marketing interventions claimed to build brain power and prevent age-related cognitive decline, and the desirability of direct research evidence to back claims of effectiveness for specific products. © 2009 Association for Psychological Science.

Moral Enhancement Should Target Self-Interest and Cognitive Capacity.

PubMed

Ahlskog, Rafael

2017-01-01

Current suggestions for capacities that should be targeted for moral enhancement has centered on traits like empathy, fairness or aggression. The literature, however, lacks a proper model for understanding the interplay and complexity of moral capacities, which limits the practicability of proposed interventions. In this paper, I integrate some existing knowledge on the nature of human moral behavior and present a formal model of prosocial motivation. The model provides two important results regarding the most friction-free route to moral enhancement. First, we should consider decreasing self-interested motivation rather than increasing prosociality directly. Second, this should be complemented with cognitive enhancement. These suggestions are tested against existing and emerging evidence on cognitive capacity, mindfulness meditation and the effects of psychedelic drugs and are found to have sufficient grounding for further theoretical and empirical exploration. Furthermore, moral effects of the latter two are hypothesized to result from a diminished sense of self with subsequent reductions in self-interest.

The regulation of cognitive enhancement devices: extending the medical model

PubMed Central

Maslen, Hannah; Douglas, Thomas; Cohen Kadosh, Roi; Levy, Neil; Savulescu, Julian

2014-01-01

This article presents a model for regulating cognitive enhancement devices (CEDs). Recently, it has become very easy for individuals to purchase devices which directly modulate brain function. For example, transcranial direct current stimulators are increasingly being produced and marketed online as devices for cognitive enhancement. Despite posing risks in a similar way to medical devices, devices that do not make any therapeutic claims do not have to meet anything more than basic product safety standards. We present the case for extending existing medical device legislation to cover CEDs. Medical devices and CEDs operate by the same or similar mechanisms and pose the same or similar risks. This fact coupled with the arbitrariness of the line between treatment and enhancement count in favour of regulating these devices in the same way. In arguing for this regulatory model, the paper highlights potential challenges to its implementation, and suggests solutions. PMID:25243073

[Drug dependence test on a cerebral insufficiency improver, aniracetam].

PubMed

Kuwahara, A; Kubota, A; Hakkei, M; Nakamura, K

1987-01-01

Aniracetam, 1-p-anisoyl-2-pyrrolidinone, is known to be a nootropic or cognitive activator. Aniracetam protects against memory and learning deficits without causing effects on motor function and the autonomic nervous system. A drug dependence study on aniracetam utilizing the intragastric route of administration was performed in male cynomolgus monkeys. The behavioral observation test after acute administration revealed that aniracetam at the dose of 25-400 mg/kg did not change the gross behavior. In the self-administration initiation test, animals were exposed to two or three unit doses of aniracetam and references for a total available period of 7 weeks. Aniracetam at the dose of 25, 50 and 75 mg/kg/injection did not initiate self-administration in the respective group of 4, 4 and 2 animals. In the study with d-methamphetamine hydrochloride at the dose of 0.1 mg/kg/injection, 1 out of 4 animals started to consistently self-administer the drug. Self-administration of cocaine hydrochloride at the dose of 10 mg/kg/injection was confirmed in 3 out of 5 animals, and these 3 animals died from overdosing later. In the physical dependence direct induction test, animals received aniracetam (50 mg/kg) and sodium pentobarbital (25 mg/kg: the dose inducing intermediate CNS depression) intragastrically twice a day for 31 consecutive days. Abrupt withdrawal of aniracetam did not elicit abstinent signs (including changes in appetite and body weight) in all 6 animals, whereas withdrawal of pentobarbital produced typical abstinent behavioral signs and decreases in appetite and body weight. In conclusion, aniracetam was confirmed to develop neither physical dependence nor psychic dependence in cynomolgus monkeys.

Do cognitive training strategies improve motor and positive psychological skills development in soccer players? Insights from a systematic review.

PubMed

Slimani, Maamer; Bragazzi, Nicola Luigi; Tod, David; Dellal, Alexandre; Hue, Olivier; Cheour, Foued; Taylor, Lee; Chamari, Karim

2016-12-01

Soccer players are required to have well-developed physical, technical and cognitive abilities. The present systematic review, adhering to Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines, examined the effects of cognitive training strategies on motor and positive psychological skills development in soccer performance and identified the potential moderators of the "cognitive training-soccer performance" relationship. Thirteen databases were systematically searched using keywords related to psychological or cognitive training in soccer players. The review is based on 18 studies, employing 584 soccer players aged 7-39 years. Cognitive strategies, particularly imagery, appear to improve sports performance in soccer players. Regarding imagery, the combination of two different types of cognitive imagery training (i.e., cognitive general and cognitive specific) has a positive influence on soccer performance during training, whereas motivational imagery (i.e., motivational general-arousal, motivational general-mastery and motivational specific) enhance competition performance. Younger soccer players employ cognitive general and cognitive specific imagery techniques to a greater extent than older soccer players. Combined cognitive training strategies were more beneficial than a single cognitive strategy relative to motor skills enhancement in elite (particularly midfielders) and amateur (i.e., when practising complex and specific soccer skills in precompetitive period) soccer players. In conclusion, it appears that there are differences in cognitive/psychological training interventions, and their efficacy, according to whether they are directed towards training or competition, and the age, standard and playing position of the players.

Treatment of Functional Impairment in Patients with Bipolar Disorder.

PubMed

Sanchez-Moreno, Jose; Martinez-Aran, Anabel; Vieta, Eduard

2017-01-01

Traditionally, functional impairment has received little attention in bipolar disorder, despite the fact that many patients experience significant impairments in daily life. In the last decade, research has changed its focus from clinical remission to functional recovery in bipolar patients as a priority. A literature review of this topic will allow us provide an overview of the relevance of functional impairment as well as the potential factors that can predict or contribute to low functioning in bipolar disorder (BD). Treatment approaches should consider not only euthymia as a goal but also cognitive and functional improvement of patients with such a complex disorder. Functional remediation and psychoeducation among psychological interventions may help to enhance functioning. The combination of cognitive enhancers and cognitive/functional remediation programs may help in improving cognitive and functional impairments. Early interventions are essential to prevent cognitive deficits and disability.

Lithium and cognitive enhancement: leave it or take it?

PubMed

Tsaltas, Eleftheria; Kontis, Dimitris; Boulougouris, Vasileios; Papadimitriou, George N

2009-01-01

Lithium is established as an effective treatment of acute mania, bipolar and unipolar depression and as prophylaxis against bipolar disorder. Accumulating evidence is also delineating a neuroprotective and neurotrophic role for lithium. However, its primary effects on cognitive functioning remain ambiguous. The aim of this paper is to review and combine the relevant translational studies, focusing on the putative cognitive enhancement properties of lithium, specifically on learning, memory, and attention. These properties are also discussed in reference to research demonstrating a protective action of lithium against cognitive deficits induced by various challenges to the nervous system, such as stress, trauma, neurodegenerative disorders, and psychiatric disorders. It is suggested on the basis of the evidence that the cognitive effects of lithium are best expressed and should, therefore, be sought under conditions of functional or biological challenge to the nervous system.

Study of the deposition process of vinpocetine on the surface of porous silicon

NASA Astrophysics Data System (ADS)

Lenshin, A. S.; Polkovnikova, Yu. A.; Seredin, P. V.

Currently the most prospective way in pharmacotherapy is the obtaining of nanoparticles involving pharmaceutical substances. Application of porous inorganic materials on the basis of silicon is among the main features in solving of this problem. The present work is concerned with the problem of the deposition of pharmaceutical drug with nootropic activity - vinpocetine - into porous silicon. Silicon nanoparticles were obtained by electrochemical anodic etching of Si plates. The process of vinpocetine deposition was studied in dependence of the deposition time. As a result of the investigations it was found that infrared transmission spectra of porous silicon with the deposited vinpocetine revealed the absorption bands characteristic of vinpocetine substance.

Creative Design of Digital Cognitive Games: Application of Cognitive Toys and Isomorphism

ERIC Educational Resources Information Center

Sedig, Kamran; Haworth, Robert

2012-01-01

Digital cognitive games (DCGs) are games whose primary purpose is to mediate (i.e., support, develop, and enhance) cognitive activities such as problem solving, decision making, planning, and critical reasoning. As these games increase in popularity and usage, more attention should be paid to their design. Currently, there is a lack of design…

Employing Cognitive Chunking Techniques to Enhance Sight-Reading Performance of Undergraduate Group-Piano Students

ERIC Educational Resources Information Center

Pike, Pamela D.; Carter, Rebecca

2010-01-01

The purpose of this study was to compare the effect of cognitive chunking techniques among first-semester group-piano music majors. The ability to group discrete pieces of information into larger, more meaningful chunks is essential for efficient cognitive processing. Since reading keyboard music and playing the piano is a cognitively complex…

Enhanced/Operator Machine Interface Phase I

DTIC Science & Technology

1997-12-22

investigation proposes an adaptive OMI technique using a cognitive task analysis (CTA) approach derived from research by several experts in the Cognitive...Science field. The research reveals that adaptive interfaces have not been widely implemented due to the difficulty of the cognitive task analysis . Moreover

Non-invasive brain stimulation can induce paradoxical facilitation. Are these neuroenhancements transferable and meaningful to security services?

PubMed Central

Levasseur-Moreau, Jean; Brunelin, Jerome; Fecteau, Shirley

2013-01-01

For ages, we have been looking for ways to enhance our physical and cognitive capacities in order to augment our security. One potential way to enhance our capacities may be to externally stimulate the brain. Methods of non-invasive brain stimulation (NIBS), such as repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES), have been recently developed to modulate brain activity. Both techniques are relatively safe and can transiently modify motor and cognitive functions outlasting the stimulation period. The purpose of this paper is to review data suggesting that NIBS can enhance motor and cognitive performance in healthy volunteers. We frame these findings in the context of whether they may serve security purposes. Specifically, we review studies reporting that NIBS induces paradoxical facilitation in motor (precision, speed, strength, acceleration endurance, and execution of daily motor task) and cognitive functions (attention, impulsive behavior, risk-taking, working memory, planning, and deceptive capacities). Although transferability and meaningfulness of these NIBS-induced paradoxical facilitations into real-life situations are not clear yet, NIBS may contribute at improving training of motor and cognitive functions relevant for military, civil, and forensic security services. This is an enthusiastic perspective that also calls for fair and open debates on the ethics of using NIBS in healthy individuals to enhance normal functions. PMID:23966923

Environmental enrichment improves learning and memory and long-term potentiation in young adult rats through a mechanism requiring mGluR5 signaling and sustained activation of p70s6k.

PubMed

Hullinger, Rikki; O'Riordan, Kenneth; Burger, Corinna

2015-11-01

Previous studies from our lab have demonstrated that mild cognitive impairments identified early in life are predictive of cognitive deficits that develop with age, suggesting that enhancements in cognition at an early age can provide a buffer against age-related cognitive decline. Environmental enrichment has been shown to improve learning and memory in the rodent, but the impact of enrichment on synaptic plasticity and the molecular mechanisms behind enrichment are not completely understood. To address these unresolved issues, we have housed 2-month old rats in environmentally enriched (EE), socially enriched (SE), or standard housing (SC) and conducted tests of learning and memory formation at various time intervals. Here we demonstrate that animals that have been exposed to one month of social or environmental enrichment demonstrate enhanced learning and memory relative to standard housed controls. However, we have found that after 4months EE animals perform better than both SE and SC groups and demonstrate an enhanced hippocampal LTP. Our results demonstrate that this LTP is dependent on mGluR5 signaling, activation of ERK and mTOR signaling cascades, and sustained phosphorylation of p70s6 kinase, thus providing a potential target mechanism for future studies of cognitive enhancement in the rodent. Copyright © 2015 Elsevier Inc. All rights reserved.

Enhanced Emotional Empathy after Mineralocorticoid Receptor Stimulation in Women with Borderline Personality Disorder and Healthy Women

PubMed Central

Wingenfeld, Katja; Kuehl, Linn K; Janke, Katrin; Hinkelmann, Kim; Dziobek, Isabel; Fleischer, Juliane; Otte, Christian; Roepke, Stefan

2014-01-01

The mineralocorticoid receptor (MR) is highly expressed in the hippocampus and prefrontal cortex. MR have an important role in appraisal processes and in modulating stress-associated emotional reactions but it is not known whether the MR affects empathy. Borderline personality disorder (BPD) is characterized by disturbed emotion regulation and alterations in empathy. In the current study, we examined whether stimulation of the MR enhances empathy in patients with BPD and healthy individuals. In a placebo-controlled study, we randomized 38 women with BPD and without psychotropic medication, and 35 healthy women to either placebo or 0.4 mg fludrocortisone, an MR agonist. Subsequently, all participants underwent two tests of social cognition, the Multifaceted Empathy Test (MET) and the Movie for the Assessment of Social Cognition (MASC), measuring cognitive and emotional facets of empathy. Eighteen BPD patients and 18 healthy women received placebo, whereas 20 BPD patients and 17 healthy women received fludrocortisone. In the MET, fludrocortisone enhanced emotional empathy across groups, whereas cognitive empathy was not affected. In the MASC, no effect of fludrocortisone could be revealed. In both tests, BPD patients and healthy women did not differ significantly in cognitive and emotional empathy and in their response to fludrocortisone. Stimulation of MR enhanced emotional empathy in healthy women and in BPD patients. Whether fludrocortisone might have a therapeutic role in psychotherapeutic processes, remains to be elucidated. PMID:24535100

Cognitive Enhancement Therapy Improves Resting-State Functional Connectivity in Early Course Schizophrenia

PubMed Central

Eack, Shaun M.; Newhill, Christina E.; Keshavan, Matcheri S.

2016-01-01

Objective Cognitive remediation is emerging as an effective psychosocial intervention for addressing untreated cognitive and functional impairments in persons with schizophrenia, and might achieve its benefits through neuroplastic changes in brain connectivity. This study seeks to examine the effects of cognitive enhancement therapy (CET) on fronto-temporal brain connectivity in a randomized controlled trial with individuals in the early course of schizophrenia. Method Stabilized, early course outpatients with schizophrenia or schizoaffective disorder (N = 41) were randomly assigned to CET (n = 25) or an active enriched supportive therapy (EST) control (n = 16) and treated for 2 years. Functional MRI data were collected annually, and pseudo resting-state functional connectivity analysis was used to examine differential changes in fronto-temporal connectivity between those treated with CET compared with EST. Results Individuals receiving CET evidenced significantly less functional connectivity loss between the resting-state network and the left dorsolateral prefrontal cortex as well as significantly increased connectivity with the right insular cortex compared to EST (all corrected p < .01). These neural networks are involved in emotion processing and problem-solving. Increased connectivity with the right insula significantly mediated CET effects on improved emotion perception (z′ = −1.96, p = .021), and increased connectivity with the left dorsolateral prefrontal cortex mediated CET-related improvements in emotion regulation (z′ = −1.71, p = .052). Conclusions These findings provide preliminary evidence that CET, a psychosocial cognitive remediation intervention, may enhance connectivity between frontal and temporal brain regions implicated in problem-solving and emotion processing in service of cognitive enhancement in schizophrenia. PMID:27713804

Brain enhancement through cognitive training: a new insight from brain connectome.

PubMed

Taya, Fumihiko; Sun, Yu; Babiloni, Fabio; Thakor, Nitish; Bezerianos, Anastasios

2015-01-01

Owing to the recent advances in neurotechnology and the progress in understanding of brain cognitive functions, improvements of cognitive performance or acceleration of learning process with brain enhancement systems is not out of our reach anymore, on the contrary, it is a tangible target of contemporary research. Although a variety of approaches have been proposed, we will mainly focus on cognitive training interventions, in which learners repeatedly perform cognitive tasks to improve their cognitive abilities. In this review article, we propose that the learning process during the cognitive training can be facilitated by an assistive system monitoring cognitive workloads using electroencephalography (EEG) biomarkers, and the brain connectome approach can provide additional valuable biomarkers for facilitating leaners' learning processes. For the purpose, we will introduce studies on the cognitive training interventions, EEG biomarkers for cognitive workload, and human brain connectome. As cognitive overload and mental fatigue would reduce or even eliminate gains of cognitive training interventions, a real-time monitoring of cognitive workload can facilitate the learning process by flexibly adjusting difficulty levels of the training task. Moreover, cognitive training interventions should have effects on brain sub-networks, not on a single brain region, and graph theoretical network metrics quantifying topological architecture of the brain network can differentiate with respect to individual cognitive states as well as to different individuals' cognitive abilities, suggesting that the connectome is a valuable approach for tracking the learning progress. Although only a few studies have exploited the connectome approach for studying alterations of the brain network induced by cognitive training interventions so far, we believe that it would be a useful technique for capturing improvements of cognitive functions.

Brain enhancement through cognitive training: a new insight from brain connectome

PubMed Central

Taya, Fumihiko; Sun, Yu; Babiloni, Fabio; Thakor, Nitish; Bezerianos, Anastasios

2015-01-01

Owing to the recent advances in neurotechnology and the progress in understanding of brain cognitive functions, improvements of cognitive performance or acceleration of learning process with brain enhancement systems is not out of our reach anymore, on the contrary, it is a tangible target of contemporary research. Although a variety of approaches have been proposed, we will mainly focus on cognitive training interventions, in which learners repeatedly perform cognitive tasks to improve their cognitive abilities. In this review article, we propose that the learning process during the cognitive training can be facilitated by an assistive system monitoring cognitive workloads using electroencephalography (EEG) biomarkers, and the brain connectome approach can provide additional valuable biomarkers for facilitating leaners’ learning processes. For the purpose, we will introduce studies on the cognitive training interventions, EEG biomarkers for cognitive workload, and human brain connectome. As cognitive overload and mental fatigue would reduce or even eliminate gains of cognitive training interventions, a real-time monitoring of cognitive workload can facilitate the learning process by flexibly adjusting difficulty levels of the training task. Moreover, cognitive training interventions should have effects on brain sub-networks, not on a single brain region, and graph theoretical network metrics quantifying topological architecture of the brain network can differentiate with respect to individual cognitive states as well as to different individuals’ cognitive abilities, suggesting that the connectome is a valuable approach for tracking the learning progress. Although only a few studies have exploited the connectome approach for studying alterations of the brain network induced by cognitive training interventions so far, we believe that it would be a useful technique for capturing improvements of cognitive functions. PMID:25883555

Enhancing CBT for Chronic Insomnia: A Randomised Clinical Trial of Additive Components of Mindfulness or Cognitive Therapy.

PubMed

Wong, Mei Yin; Ree, Melissa J; Lee, Christopher W

2016-09-01

Although cognitive behavioural therapy (CBT) for insomnia has resulted in significant reductions in symptoms, most patients are not classified as good sleepers after treatment. The present study investigated whether additional sessions of cognitive therapy (CT) or mindfulness-based therapy (MBT) could enhance CBT in 64 participants with primary insomnia. All participants were given four sessions of standard CBT as previous research had identified this number of sessions as an optimal balance between therapist guidance and patient independence. Participants were then allocated to further active treatment (four sessions of CT or MBT) or a no further treatment control. The additional treatments resulted in significant improvements beyond CBT on self-report and objective measures of sleep and were well tolerated as evidenced by no dropouts from either treatment. The effect sizes for each of these additional treatments were large and clinically significant. The mean scores on the primary outcome measure, the Insomnia Severity Index, were 5.74 for CT and 6.69 for MBT, which are within the good-sleeper range. Treatment effects were maintained at follow-up. There were no significant differences between CT and MBT on any outcome measure. These results provide encouraging data on how to enhance CBT for treatment of insomnia. Copyright © 2015 John Wiley & Sons, Ltd. CBT treatments for insomnia can be enhanced using recent developments in cognitive therapy. CBT treatments for insomnia can be enhanced using mindfulness-based treatments. Both cognitive therapy and mindfulness produce additional clinically significant change. Copyright © 2015 John Wiley & Sons, Ltd.

Enhancing Innovation and Underlying Neural Mechanisms Via Cognitive Training in Healthy Older Adults

PubMed Central

Chapman, Sandra B.; Spence, Jeffrey S.; Aslan, Sina; Keebler, Molly W.

2017-01-01

Non-invasive interventions, such as cognitive training (CT) and physical exercise, are gaining momentum as ways to augment both cognitive and brain function throughout life. One of the most fundamental yet little studied aspects of human cognition is innovative thinking, especially in older adults. In this study, we utilize a measure of innovative cognition that examines both the quantity and quality of abstracted interpretations. This randomized pilot trial in cognitively normal adults (56–75 years) compared the effect of cognitive reasoning training (SMART) on innovative cognition as measured by Multiple Interpretations Measure (MIM). We also examined brain changes in relation to MIM using two MRI-based measurement of arterial spin labeling (ASL) to measure cerebral blood flow (CBF) and functional connectivity MRI (fcMRI) to measure default mode and central executive network (CEN) synchrony at rest. Participants (N = 58) were randomized to the CT, physical exercise (physical training, PT) or control (CN) group where CT and PT groups received training for 3 h/week over 12 weeks. They were assessed at baseline-, mid- and post-training using innovative cognition and MRI measures. First, the CT group showed significant gains pre- to post-training on the innovation measure whereas the physical exercise and control groups failed to show significant gains. Next, the CT group showed increased CBF in medial orbitofrontal cortex (mOFC) and bilateral posterior cingulate cortex (PCC), two nodes within the Default Mode Network (DMN) compared to physical exercise and control groups. Last, significant correlations were found between innovation performance and connectivity of two major networks: CEN (positive correlation) and DMN (negative correlation). These results support the view that both the CEN and DMN are important for enhancement of innovative cognition. We propose that neural mechanisms in healthy older adults can be modified through reasoning training to better subserve enhanced innovative cognition. PMID:29062276

Seven Pervasive Statistical Flaws in Cognitive Training Interventions

PubMed Central

Moreau, David; Kirk, Ian J.; Waldie, Karen E.

2016-01-01

The prospect of enhancing cognition is undoubtedly among the most exciting research questions currently bridging psychology, neuroscience, and evidence-based medicine. Yet, convincing claims in this line of work stem from designs that are prone to several shortcomings, thus threatening the credibility of training-induced cognitive enhancement. Here, we present seven pervasive statistical flaws in intervention designs: (i) lack of power; (ii) sampling error; (iii) continuous variable splits; (iv) erroneous interpretations of correlated gain scores; (v) single transfer assessments; (vi) multiple comparisons; and (vii) publication bias. Each flaw is illustrated with a Monte Carlo simulation to present its underlying mechanisms, gauge its magnitude, and discuss potential remedies. Although not restricted to training studies, these flaws are typically exacerbated in such designs, due to ubiquitous practices in data collection or data analysis. The article reviews these practices, so as to avoid common pitfalls when designing or analyzing an intervention. More generally, it is also intended as a reference for anyone interested in evaluating claims of cognitive enhancement. PMID:27148010

COGNITIVE-ENHANCING PROPERTIES OF MORINDA LUCIDA (RUBIACEAE) AND PELTOPHORUM PTEROCARPUM (FABACEAE) IN SCOPOLAMINE-INDUCED AMNESIC MICE.

PubMed

O, Elufioye Taiwo; Halimah A, Hameed

2017-01-01

Cognitive disorders associated with aging have been successfully managed by African traditional medical practitioners using various plants. This study evaluated the cognitive enhancing potentials of Morinda lucida (L) Rubiaceae and Peltophorum pterocarpum (DC) ex. K Heyne in scopolamine induced amnesic animals. The anti-amnesic activity of the ethyl acetate extracts of Morinda lucida and Peltophorum pterocarpum at doses of 4 mg/kg, 6 mg/kg and 8 mg/kg were assessed in scopolamine induced amnesic mice using Morris water maze test model. Effect of the extracts on the histology of the hippocampus was also evaluated. The ethyl acetate extract of Morinda lucida and Peltophorum pterocarpum ameliorated scopolamine induced memory deficit in the animals under study. There was no effect of the extract on the histology of the hippocampus. However, there was an increase in the density of cells in the hippocampus of treated group as compared to the untreated. Morinda lucida and Peltophorum pterocarpum showed considerable enhancement of cognition in scopolamine induced amnesic mice.

Curcumin Enhances Neurogenesis and Cognition in Aged Rats: Implications for Transcriptional Interactions Related to Growth and Synaptic Plasticity

PubMed Central

Mitchell, E. Siobhan; Xiu, Jin; Tiwari, Jyoti K.; Hu, Yinghe; Cao, Xiaohua; Zhao, Zheng

2012-01-01

Background Curcumin has been demonstrated to have many neuroprotective properties, including improvement of cognition in humans and neurogenesis in animals, yet the mechanism of such effects remains unclear. Methodology We assessed behavioural performance and hippocampal cell proliferation in aged rats after 6- and 12-week curcumin-fortified diets. Curcumin enhanced non-spatial and spatial memory, as well as dentate gyrate cell proliferation as compared to control diet rats. We also investigated underlying mechanistic pathways that might link curcumin treatment to increased cognition and neurogenesis via exon array analysis of cortical and hippocampal mRNA transcription. The results revealed a transcriptional network interaction of genes involved in neurotransmission, neuronal development, signal transduction, and metabolism in response to the curcumin treatment. Conclusions The results suggest a neurogenesis- and cognition-enhancing potential of prolonged curcumin treatment in aged rats, which may be due to its diverse effects on genes related to growth and plasticity. PMID:22359574

Therapeutic mechanisms of Mindfulness-Oriented Recovery Enhancement for internet gaming disorder: Reducing craving and addictive behavior by targeting cognitive processes.

PubMed

Li, Wen; Garland, Eric L; Howard, Matthew O

2018-03-22

Internet gaming disorder (IGD) is characterized by signs and symptoms similar to substance use and gambling disorders, and associated with psychosocial impairments. Research suggests that maladaptive gaming-related cognitions and coping may be implicated in IGD; therefore, interventions for IGD need to target these underlying mechanisms. Mindfulness-based treatment is effective in changing maladaptive cognitive processes and increasing adaptive coping among people with addictions. This study used data from an RCT of Mindfulness-Oriented Recovery Enhancement (MORE) for IGD to further examine changes in maladaptive gaming-related cognitions and positive reappraisal as mediators of the effects of MORE on IGD signs/symptoms. Participants (N = 30, Age M = 25.0, SD  = 5.4) were randomized to 8-weekly sessions of MORE or a support group (SG) control condition. IGD severity, levels of craving for video game playing, maladaptive gaming-related cognitions, and positive reappraisal were measured at pre-and posttreatment, and 3-month follow-up. Multivariate path analyses revealed that effects of MORE in reducing IGD and craving were statistically mediated by changes in maladaptive gaming-related cognitions. Though changes in positive reappraisal did not significantly mediate effects of MORE on IGD or craving, MORE enhanced positive reappraisal to a significantly greater extent than the SG at posttreatment. Findings suggest that effects of mindfulness treatment in reducing maladaptive gaming-related cognitions might lead to reductions in IGD severity and cravings for video game playing. This cognitive mechanism should be evaluated in a future, full-scale RCT.

Cognitive and Physical Fatigue Tasks Enhance Pain, Cognitive Fatigue and Physical Fatigue in People with Fibromyalgia

PubMed Central

Dailey, Dana L; Keffala, Valerie J; Sluka, Kathleen A

2014-01-01

Objective Fibromyalgia is a condition characterized by chronic widespread muscle pain and fatigue. The primary objective of this study was to determine if pain, perceived cognitive fatigue, and perceived physical fatigue were enhanced in participants with fibromyalgia compared to healthy controls during a cognitive fatigue task, a physical fatigue task and a dual fatigue task. Methods Twenty four people with fibromyalgia and 33 healthy controls completed pain, fatigue and function measures. A cognitive fatigue task (Controlled Oral Word Association Test) and physical fatigue task (Valpar peg test) were done individually and combined for a dual fatigue task. Resting pain, perceived cognitive fatigue and perceived physical fatigue were assessed during each task using visual analogue scales. Function was assessed with shoulder range of motion and grip. Results People with fibromyalgia had significantly higher increases in pain, cognitive fatigue and physical fatigue when compared to healthy controls after completion of a cognitive fatigue task, a physical fatigue task, or a dual fatigue task (p<0.01). People with fibromyalgia performed equivalently on measures of physical performance and cognitive performance on the physical and cognitive fatigue tasks, respectively. Conclusions These data show that people with fibromyalgia show larger increases in pain, perceived cognitive fatigue and perceived physical fatigue to both cognitive and physical fatigue tasks compared to healthy controls. The increases in pain and fatigue during cognitive and physical fatigue tasks could influence subject participation in daily activities and rehabilitation. PMID:25074583

Family Day Care: Guidelines Designed to Enhance Cognitive Learning within the Home Environment Based on Piagetian Theory.

ERIC Educational Resources Information Center

Parr, Carolyn M.

The purpose of this guidebook is to help persons interested in establishing a family day care program in their homes set up a quality learning environment that enhances children's cognitive development through play. Following a literature review showing the importance of play in Piaget's theory of child development, the author describes a…

Development of Web-Based Learning Environment Model to Enhance Cognitive Skills for Undergraduate Students in the Field of Electrical Engineering

ERIC Educational Resources Information Center

Lakonpol, Thongmee; Ruangsuwan, Chaiyot; Terdtoon, Pradit

2015-01-01

This research aimed to develop a web-based learning environment model for enhancing cognitive skills of undergraduate students in the field of electrical engineering. The research is divided into 4 phases: 1) investigating the current status and requirements of web-based learning environment models. 2) developing a web-based learning environment…

The Effect of Insulin and Insulin-Like Growth Factors on Hippocampus- and Amygdala-Dependent Long-Term Memory Formation

ERIC Educational Resources Information Center

Stern, Sarah A.; Chen, Dillon Y.; Alberini, Cristina M.

2014-01-01

Recent work has reported that the insulin-like growth factor 2 (IGF2) promotes memory enhancement. Furthermore, impaired insulin or IGF1 functions have been suggested to play a role in the pathogenesis of neurodegeneration and cognitive impairments, hence implicating the insulin/IGF system as an important target for cognitive enhancement and/or…

Self-Enhancement on a Self-Categorization Leash: Evidence for a Dual-Process Model of First-and Third-Person Perceptions

ERIC Educational Resources Information Center

Zhang, Jinguang

2010-01-01

Research suggests that first- and third-person perceptions are driven by the motive to self-enhance and cognitive processes involving the perception of social norms. This article proposes and tests a dual-process model that predicts an interaction between cognition and motivation. Consistent with the model, Experiment 1 (N = 112) showed that…

A Randomized Trial of Mindfulness-Based Cognitive Therapy for Children: Promoting Mindful Attention to Enhance Social-Emotional Resiliency in Children

ERIC Educational Resources Information Center

Semple, Randye J.; Lee, Jennifer; Rosa, Dinelia; Miller, Lisa F.

2010-01-01

Mindfulness-based cognitive therapy for children (MBCT-C) is a manualized group psychotherapy for children ages 9-13 years old, which was developed specifically to increase social-emotional resiliency through the enhancement of mindful attention. Program development is described along with results of the initial randomized controlled trial. We…

Cognitive Enhancers for Facilitating Drug Cue Extinction: Insights from Animal Models

PubMed Central

Nic Dhonnchadha, Bríd Áine; Kantak, Kathleen M.

2011-01-01

Given the success of cue exposure (extinction) therapy combined with a cognitive enhancer for reducing anxiety, it is anticipated that this approach will prove more efficacious than exposure therapy alone in preventing relapse in individuals with substance use disorders. Several factors may undermine the efficacy of exposure therapy for substance use disorders, but we suspect that neurocognitive impairments associated with chronic drug use are an important contributing factor. Numerous insights on these issues are gained from research using animal models of addiction. In this review, the relationship between brain sites whose learning, memory and executive functions are impaired by chronic drug use and brain sites that are important for effective drug cue extinction learning is explored first. This is followed by an overview of animal research showing improved treatment outcome for drug addiction (e.g. alcohol, amphetamine, cocaine, heroin) when explicit extinction training is conducted in combination with acute dosing of a cognitive-enhancing drug. The mechanism by which cognitive enhancers are thought to exert their benefits is by facilitating consolidation of drug cue extinction memory after activation of glutamatergic receptors. Based on the encouraging work in animals, factors that may be important for the treatment of drug addiction are considered. PMID:21295059

The diffusion of performance and image-enhancing drugs (PIEDs) on the internet: the abuse of the cognitive enhancer piracetam.

PubMed

Corazza, Ornella; Bersani, Francesco Saverio; Brunoro, Roberto; Valeriani, Giuseppe; Martinotti, Giovanni; Schifano, Fabrizio

2014-12-01

Performance and image-enhancing drugs (PIEDs), also known as "lifestyle drugs," are increasingly sold on the Internet to enhance cognitive as well as sexual, muscular, attentive, and other natural capacities. Our analysis focuses on the misuse of the cognitive enhancer piracetam. A literature review was carried out in PsychInfo and Pubmed database. Considering the absence of peer-reviewed data, review of additional sources of unstructured information from the Internet was carried out between February 2012 and July 2013. Additional searches were conducted using the Global Public Health Intelligence Network (GPHIN), a secure Internet-based early warning system developed by Health Canada and the World Health Organization (WHO), which monitors media reports in six languages, Arabic, Chinese, English, French, Russian, and Spanish. Piracetam is sold via illicit online pharmacies with no need of prescription at low prices. Buyers, mainly healthy individuals, purchase the product to enhance study- and work-related performances as well as for recreational purposes. Its nonmedical use is often associated with the occurrence of side effects such as hallucinations, psychomotor agitation, dysphoria, tiredness, dizziness, memory loss, headache, and severe diarrhoea; moreover, several users declared to have neither felt any cognitive improvement nor psychedelic effects. This is a new and fast-growing trend of abuse that needs to be extensively monitored and studied also by using near real-time and unstructured sources of information such as Internet news and online reports in order to acquire rapid knowledge and understanding. Products sold online might be counterfeits and this enhances related health risks.

Program of arithmetic improvement by means of cognitive enhancement: an intervention in children with special educational needs.

PubMed

Deaño, Manuel Deaño; Alfonso, Sonia; Das, Jagannath Prasad

2015-03-01

This study reports the cognitive and arithmetic improvement of a mathematical model based on the program PASS Remedial Program (PREP), which aims to improve specific cognitive processes underlying academic skills such as arithmetic. For this purpose, a group of 20 students from the last four grades of Primary Education was divided into two groups. One group (n=10) received training in the program and the other served as control. Students were assessed at pre and post intervention in the PASS cognitive processes (planning, attention, simultaneous and successive processing), general level of intelligence, and arithmetic performance in calculus and solving problems. Performance of children from the experimental group was significantly higher than that of the control group in cognitive process and arithmetic. This joint enhancement of cognitive and arithmetic processes was a result of the operationalization of training that promotes the encoding task, attention and planning, and learning by induction, mediation and verbalization. The implications of this are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Brain plasticity and motor practice in cognitive aging.

PubMed

Cai, Liuyang; Chan, John S Y; Yan, Jin H; Peng, Kaiping

2014-01-01

For more than two decades, there have been extensive studies of experience-based neural plasticity exploring effective applications of brain plasticity for cognitive and motor development. Research suggests that human brains continuously undergo structural reorganization and functional changes in response to stimulations or training. From a developmental point of view, the assumption of lifespan brain plasticity has been extended to older adults in terms of the benefits of cognitive training and physical therapy. To summarize recent developments, first, we introduce the concept of neural plasticity from a developmental perspective. Secondly, we note that motor learning often refers to deliberate practice and the resulting performance enhancement and adaptability. We discuss the close interplay between neural plasticity, motor learning and cognitive aging. Thirdly, we review research on motor skill acquisition in older adults with, and without, impairments relative to aging-related cognitive decline. Finally, to enhance future research and application, we highlight the implications of neural plasticity in skills learning and cognitive rehabilitation for the aging population.

Performance Enhancement with Low Stress and Anxiety Modulated by Cognitive Flexibility

PubMed Central

Park, Hyung Woo; Kee, Baik Seok; Na, Churl; Na, Do-Hyun E.; Zaichkowsky, Leonard

2011-01-01

Objective The purpose of this study was to compare cognitive flexibility abilities, stress, and anxiety between starters and non-starter athletes. Methods A total of 30 male professional-soccer and 40 professional-baseball athletes were recruited. Wisconsin Card Sorting Test (WCST) and Trail Making Test A & B (TMT A & B) were administered to assess cognitive flexibility during competition. The Korean version of the STAI form Y (STAI-KY) and Visual analogue scale for anxiety and stress were used to assess the anxiety and stress. Results The starter group had better cognitive function (fewer perseverative errors and rapid TMTB times) (Z=3.32, p<0.01; Z=2.20, p=0.03, respectively) and lower stress and anxiety (F=4.34, p=0.01; F=6.61, p<0.01, respectively) during competition than the non-starter group. Conclusion The better cognitive performances were negatively correlated with stress and anxiety. Current results suggested that cognitive flexibility would enhance human performance by modulation of the anxiety and stress during competition. PMID:21994509

Neural Correlates for Intrinsic Motivational Deficits of Schizophrenia; Implications for Therapeutics of Cognitive Impairment

PubMed Central

Takeda, Kazuyoshi; Sumiyoshi, Tomiki; Matsumoto, Madoka; Murayama, Kou; Ikezawa, Satoru; Matsumoto, Kenji; Nakagome, Kazuyuki

2018-01-01

The ultimate goal of the treatment of schizophrenia is recovery, a notion related to improvement of cognitive and social functioning. Cognitive remediation therapies (CRT), one of the most effective cognition enhancing methods, have been shown to moderately improve social functioning. For this purpose, intrinsic motivation, related to internal values such as interest and enjoyment, has been shown to play a key role. Although the impairment of intrinsic motivation is one of the characteristics of schizophrenia, its neural mechanisms remain unclear. This is related to the lack of feasible measures of intrinsic motivation, and its response to treatment. According to the self-determination theory (SDT), not only intrinsic motivation, but extrinsic motivation has been reported to enhance learning and memory in healthy subjects to some extent. This finding suggests the contribution of different types of motivation to potentiate the ability of the CRT to treat cognitive impairment of schizophrenia. In this paper, we provide a review of psychological characteristics, assessment methods, and neural correlates of intrinsic motivation in healthy subjects and patients with schizophrenia. Particularly, we focus on neuroimaging studies of intrinsic motivation, including our own. These considerations are relevant to enhancement of functional outcomes of schizophrenia. PMID:29922185

Neural Correlates for Intrinsic Motivational Deficits of Schizophrenia; Implications for Therapeutics of Cognitive Impairment.

PubMed

Takeda, Kazuyoshi; Sumiyoshi, Tomiki; Matsumoto, Madoka; Murayama, Kou; Ikezawa, Satoru; Matsumoto, Kenji; Nakagome, Kazuyuki

2018-01-01

The ultimate goal of the treatment of schizophrenia is recovery, a notion related to improvement of cognitive and social functioning. Cognitive remediation therapies (CRT), one of the most effective cognition enhancing methods, have been shown to moderately improve social functioning. For this purpose, intrinsic motivation, related to internal values such as interest and enjoyment, has been shown to play a key role. Although the impairment of intrinsic motivation is one of the characteristics of schizophrenia, its neural mechanisms remain unclear. This is related to the lack of feasible measures of intrinsic motivation, and its response to treatment. According to the self-determination theory (SDT), not only intrinsic motivation, but extrinsic motivation has been reported to enhance learning and memory in healthy subjects to some extent. This finding suggests the contribution of different types of motivation to potentiate the ability of the CRT to treat cognitive impairment of schizophrenia. In this paper, we provide a review of psychological characteristics, assessment methods, and neural correlates of intrinsic motivation in healthy subjects and patients with schizophrenia. Particularly, we focus on neuroimaging studies of intrinsic motivation, including our own. These considerations are relevant to enhancement of functional outcomes of schizophrenia.

Pretreatment with 5-hydroxymethyl-2-furaldehyde blocks scopolamine-induced learning deficit in contextual and spatial memory in male mice.

PubMed

Lee, Younghwan; Gao, Qingtao; Kim, Eunji; Lee, Younghwa; Park, Se Jin; Lee, Hyung Eun; Jang, Dae Sik; Ryu, Jong Hoon

2015-07-01

5-Hydroxymethyl-2-furaldehyde (5-HMF) is a compound derived from the dehydration of certain sugars. The aim of the present study was to evaluate the effect of 5-HMF on the cognitive impairment induced by scopolamine, a muscarinic receptor antagonist. To measure various cognitive functions, we conducted the step-through passive avoidance task, the Y-maze task and the Morris water maze task. A single administration of 5-HMF (5 or 10mg/kg, p.o.) significantly attenuates scopolamine-induced cognitive impairment in these behavioral tasks without changes in locomotor activity, and the effect of 5-HMF on scopolamine-induced cognitive impairment was significantly reversed by a sub-effective dose of MK-801, an NMDA receptor antagonist. In addition, a single administration of 5-HMF (10mg/kg, p.o.) enhanced the cognitive performance of normal naïve mice in the passive avoidance task. Furthermore, Western blot analysis revealed that the levels of phosphorylated Ca(2+)/calmodulin-dependent protein kinase II-α (CaMKII) and extracellular signal-regulated kinases (ERK) were significantly enhanced by the single administration of 5-HMF in the hippocampal tissues. Taken together, the present study suggests that 5-HMF may block scopolamine-induced learning deficit and enhance cognitive function via the activation of NMDA receptor signaling, including CaMKII and ERK, and would be an effective candidate against cognitive disorders, such as Alzheimer's disease. Copyright © 2015. Published by Elsevier Inc.

Longitudinal functional brain imaging study in early course schizophrenia before and after cognitive enhancement therapy.

PubMed

Keshavan, Matcheri S; Eack, Shaun M; Prasad, Konasale M; Haller, Chiara S; Cho, Raymond Y

2017-05-01

Schizophrenia is characterized by impaired -social and non social cognition both of which lead to functional deficits. These deficits may benefit from cognitive remediation, but the neural underpinnings of such improvements have not been clearly delineated. We conducted a functional magnetic resonance (fMRI) study in early course schizophrenia patients randomly assigned to cognitive enhancement therapy (CET) or enriched supportive therapy (EST) and treated for two years. Imaging data over three time points including fMRI blood oxygen level dependent (BOLD) data were acquired during performance of a cognitive control paradigm, the Preparing to Overcome Prepotency (POP) task, and functional connectivity data, were analyzed. During the two years of treatment, CET patients showed a continual increase in BOLD activity in the right dorsolateral prefrontal cortex (DLPFC), whereas EST patients tended to show no change in prefrontal brain function throughout treatment. Increases in right DLPFC activity were modestly associated with improved neurocognition (β = .14, p = .041), but not social cognition. Functional connectivity analyses showed reduced connectivity between the DLPFC and the anterior cingulate cortex (ACC) in CET compared to EST over the two years of treatment, which was associated with neurocognitive improvement. These findings suggest that CET leads to enhanced neural activity in brain regions mediating cognitive control and increased efficiency in prefrontal circuits; such changes may be related to the observed therapeutic effects of CET on neurocognitive function. Copyright © 2017. Published by Elsevier Inc.

Systematic review of clinical trials assessing pharmacological properties of Salvia species on memory, cognitive impairment and Alzheimer's disease.

PubMed

Miroddi, Marco; Navarra, Michele; Quattropani, Maria C; Calapai, Fabrizio; Gangemi, Sebastiano; Calapai, Gioacchino

2014-06-01

Salvia officinalis L. and Salvia lavandulaefolia L. have a longstanding use as traditional herbal remedies that can enhance memory and improve cognitive functions. Pharmacological actions of S. officinalis and S. lavandulaefolia on healthy subjects and on patients suffering of cognitive decline have been investigated. Aim of this review was to summarize published clinical trials assessing effectiveness and safety of S. officinalis and S. lavandulaefolia in the enhancement of cognitive performance in healthy subjects and neurodegenerative illnesses. Furthermore, to purchase a more complete view on safety of S. officinalis and S. lavandulaefolia, we collected and discussed articles regarding toxicity and adverse reactions. Eight clinical studies investigating on acute effects of S. officinalis on healthy subjects were included in the review. Six studies investigated on the effects of S. officinalis and S. lavandaeluaefolia on cognitive performance in healthy subjects. The two remaining were carried out to study the effects of sage on Azheimer's disease. Our review shows that S. officinalis and S. lavandulaefolia exert beneficial effects by enhancing cognitive performance both in healthy subjects and patients with dementia or cognitive impairment and is safe for this indication. Unfortunately, promising beneficial effects are debased by methodological issues, use of different herbal preparations (extracts, essential oil, use of raw material), lack of details on herbal products used. We believe that sage promising effects need further higher methodological standard clinical trials. © 2014 John Wiley & Sons Ltd.

Training-induced improvement of response selection and error detection in aging assessed by task switching: effects of cognitive, physical, and relaxation training.

PubMed

Gajewski, Patrick D; Falkenstein, Michael

2012-01-01

Cognitive control functions decline with increasing age. The present study examines if different types of group-based and trainer-guided training effectively enhance performance of older adults in a task switching task, and how this expected enhancement is reflected in changes of cognitive functions, as measured in electrophysiological brain activity (event-related potentials). One hundred forty-one healthy participants aged 65 years and older were randomly assigned to one of four groups: physical training (combined aerobic and strength training), cognitive training (paper-pencil and computer-aided), relaxation and wellness (social control group), and a control group that did not receive any intervention. Training sessions took place twice a week for 90 min for a period of 4 months. The results showed a greater improvement of performance for attendants of the cognitive training group compared to the other groups. This improvement was evident in a reduction of mixing costs in accuracy and intraindividual variability of speed, indexing improved maintenance of multiple task sets in working memory, and an enhanced coherence of neuronal processing. These findings were supported by event-related brain potentials which showed higher amplitudes in a number of potentials associated with response selection (N2), allocation of cognitive resources (P3b), and error detection (Ne). Taken together, our findings suggest neurocognitive plasticity of aging brains which can be stimulated by broad and multilayered cognitive training and assessed in detail by electrophysiological methods.

Modulatory Effects of Modafinil on Neural Circuits Regulating Emotion and Cognition

PubMed Central

Rasetti, Roberta; Mattay, Venkata S; Stankevich, Beth; Skjei, Kelsey; Blasi, Giuseppe; Sambataro, Fabio; Arrillaga-Romany, Isabel C; Goldberg, Terry E; Callicott, Joseph H; Apud, José A; Weinberger, Daniel R

2010-01-01

Modafinil differs from other arousal-enhancing agents in chemical structure, neurochemical profile, and behavioral effects. Most functional neuroimaging studies to date examined the effect of modafinil only on information processing underlying executive cognition, but cognitive enhancers in general have been shown to have pronounced effects on emotional behavior, too. We examined the effect of modafinil on neural circuits underlying affective processing and cognitive functions. Healthy volunteers were enrolled in this double-blinded placebo-controlled trial (100 mg/day for 7 days). They underwent BOLD fMRI while performing an emotion information-processing task that activates the amygdala and two prefrontally dependent cognitive tasks—a working memory (WM) task and a variable attentional control (VAC) task. A clinical assessment that included measurement of blood pressure, heart rate, the Hamilton anxiety scale, and the profile of mood state (POMS) questionnaire was also performed on each test day. BOLD fMRI revealed significantly decreased amygdala reactivity to fearful stimuli on modafinil compared with the placebo condition. During executive cognition tasks, a WM task and a VAC task, modafinil reduced BOLD signal in the prefrontal cortex and anterior cingulate. Although not statistically significant, there were trends for reduced anxiety, for decreased fatigue-inertia and increased vigor-activity, as well as decreased anger-hostility on modafinil. Modafinil in low doses has a unique physiologic profile compared with stimulant drugs: it enhances the efficiency of prefrontal cortical cognitive information processing, while dampening reactivity to threatening stimuli in the amygdala, a brain region implicated in anxiety. PMID:20555311

Training-Induced Improvement of Response Selection and Error Detection in Aging Assessed by Task Switching: Effects of Cognitive, Physical, and Relaxation Training

PubMed Central

Gajewski, Patrick D.; Falkenstein, Michael

2012-01-01

Cognitive control functions decline with increasing age. The present study examines if different types of group-based and trainer-guided training effectively enhance performance of older adults in a task switching task, and how this expected enhancement is reflected in changes of cognitive functions, as measured in electrophysiological brain activity (event-related potentials). One hundred forty-one healthy participants aged 65 years and older were randomly assigned to one of four groups: physical training (combined aerobic and strength training), cognitive training (paper–pencil and computer-aided), relaxation and wellness (social control group), and a control group that did not receive any intervention. Training sessions took place twice a week for 90 min for a period of 4 months. The results showed a greater improvement of performance for attendants of the cognitive training group compared to the other groups. This improvement was evident in a reduction of mixing costs in accuracy and intraindividual variability of speed, indexing improved maintenance of multiple task sets in working memory, and an enhanced coherence of neuronal processing. These findings were supported by event-related brain potentials which showed higher amplitudes in a number of potentials associated with response selection (N2), allocation of cognitive resources (P3b), and error detection (Ne). Taken together, our findings suggest neurocognitive plasticity of aging brains which can be stimulated by broad and multilayered cognitive training and assessed in detail by electrophysiological methods. PMID:22593740

Cognitive Enhancement in Infants Associated with Increased Maternal Fruit Intake During Pregnancy: Results from a Birth Cohort Study with Validation in an Animal Model.

PubMed

Bolduc, Francois V; Lau, Amanda; Rosenfelt, Cory S; Langer, Steven; Wang, Nan; Smithson, Lisa; Lefebvre, Diana; Alexander, R Todd; Dickson, Clayton T; Li, Liang; Becker, Allan B; Subbarao, Padmaja; Turvey, Stuart E; Pei, Jacqueline; Sears, Malcolm R; Mandhane, Piush J

2016-06-01

In-utero nutrition is an under-studied aspect of cognitive development. Fruit has been an important dietary constituent for early hominins and humans. Among 808 eligible CHILD-Edmonton sub-cohort subjects, 688 (85%) had 1-year cognitive outcome data. We found that each maternal daily serving of fruit (sum of fruit plus 100% fruit juice) consumed during pregnancy was associated with a 2.38 point increase in 1-year cognitive development (95% CI 0.39, 4.37; p<0.05). Consistent with this, we found 30% higher learning Performance index (PI) scores in Drosophila offspring from parents who consumed 30% fruit juice supplementation prenatally (PI: 85.7; SE 1.8; p<0.05) compared to the offspring of standard diet parents (PI: 65.0 SE 3.4). Using the Drosophila model, we also show that the cyclic adenylate monophosphate (cAMP) pathway may be a major regulator of this effect, as prenatal fruit associated cognitive enhancement was blocked in Drosophila rutabaga mutants with reduced Ca(2+)-Calmodulin-dependent adenylyl cyclase. Moreover, gestation is a critical time for this effect as postnatal fruit intake did not enhance cognitive performance in either humans or Drosophila. Our study supports increased fruit consumption during pregnancy with significant increases in infant cognitive performance. Validation in Drosophila helps control for potential participant bias or unmeasured confounders. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Recent and past musical activity predicts cognitive aging variability: direct comparison with general lifestyle activities.

PubMed

Hanna-Pladdy, Brenda; Gajewski, Byron

2012-01-01

Studies evaluating the impact of modifiable lifestyle factors on cognition offer potential insights into sources of cognitive aging variability. Recently, we reported an association between extent of musical instrumental practice throughout the life span (greater than 10 years) on preserved cognitive functioning in advanced age. These findings raise the question of whether there are training-induced brain changes in musicians that can transfer to non-musical cognitive abilities to allow for compensation of age-related cognitive declines. However, because of the relationship between engagement in general lifestyle activities and preserved cognition, it remains unclear whether these findings are specifically driven by musical training or the types of individuals likely to engage in greater activities in general. The current study controlled for general activity level in evaluating cognition between musicians and nomusicians. Also, the timing of engagement (age of acquisition, past versus recent) was assessed in predictive models of successful cognitive aging. Seventy age and education matched older musicians (>10 years) and non-musicians (ages 59-80) were evaluated on neuropsychological tests and general lifestyle activities. Musicians scored higher on tests of phonemic fluency, verbal working memory, verbal immediate recall, visuospatial judgment, and motor dexterity, but did not differ in other general leisure activities. Partition analyses were conducted on significant cognitive measures to determine aspects of musical training predictive of enhanced cognition. The first partition analysis revealed education best predicted visuospatial functions in musicians, followed by recent musical engagement which offset low education. In the second partition analysis, early age of musical acquisition (<9 years) predicted enhanced verbal working memory in musicians, while analyses for other measures were not predictive. Recent and past musical activity, but not general lifestyle activities, predicted variability across both verbal and visuospatial domains in aging. These findings are suggestive of different use-dependent adaptation periods depending on cognitive domain. Furthermore, they imply that early age of musical acquisition, sustained and maintained during advanced age, may enhance cognitive functions and buffer age and education influences.

Cognitive Function as a Trans-Diagnostic Treatment Target in Stimulant Use Disorders

PubMed Central

Sofuoglu, Mehmet; DeVito, Elise E.; Waters, Andrew J.; Carroll, Kathleen M.

2016-01-01

Stimulant use disorder is an important public health problem, with an estimated 2.1 million current users in the United States alone. No pharmacological treatments are approved by the U.S. Food and Drug Administration (FDA) for stimulant use disorder and behavioral treatments have variable efficacy and limited availability. Most individuals with stimulant use disorder have other comorbidities, most with overlapping symptoms and cognitive impairments. The goal of this article is to present a rationale for cognition as a treatment target in stimulant use disorder, and to outline potential treatment approaches. Rates of lifetime comorbid psychiatric disorders among people with stimulant use disorders are estimated at 65% - 73%, with the most common being mood disorders (13% - 64%) and anxiety disorders (21% - 50%), as well as non-substance induced psychotic disorders (under 10%). There are several models of addictive behavior, but the dual process model particularly highlights the relevance of cognitive impairments and biases to the development and maintenance of addiction. This model explains addictive behavior as a balance between automatic processes and executive control, which in turn are related to individual (genetics, comorbid disorders, psychosocial factors) and other (craving, triggers, drug use) factors. Certain cognitive impairments, such as attentional bias and approach bias, are most relevant to automatic processes, while sustained attention, response inhibition, and working memory are primarily related to executive control. These cognitive impairments and biases are also common in disorders frequently comorbid with stimulant use disorder, and predict poor treatment retention and clinical outcomes. As such, they may serve as feasible trans-diagnostic treatment targets. There are promising pharmacological, cognitive, and behavioral approaches that aim to enhance cognitive function. Pharmacotherapies target cognitive impairments associated with executive control and include cholinesterase inhibitors (e.g., galantamine, rivastigmine) and monoamine transporter inhibitors (e.g., modafinil, methylphenidate). Cognitive behavioral therapy and cognitive rehabilitation also enhance executive control, while cognitive bias modification targets impairments associated with automatic processes. Cognitive enhancements to improve treatment outcomes is a novel and promising strategy, but its clinical value for the treatment of stimulant use disorder, with or without other psychiatric comorbidities, remains to be determined in future studies. PMID:26828702

Is it time to revisit the role of psychedelic drugs in enhancing human creativity?

PubMed

Sessa, B

2008-11-01

Human creativity is difficult to define and measure, but it is undoubtedly an important cognitive process. This makes it an interesting challenge for modern neuroscientific exploration - especially given the current interest in developing cognitive enhancers for commercial and clinical uses. There are similarities between the typical traits of creative people and the subjective psychological characteristics of the psychedelic (hallucinogenic) drug experience. This phenomenon was studied in a number of small trials and case studies in the 1960s. Results were inconclusive, and the quality of these studies - by modern research standards - was merely anecdotal. Nevertheless, with today's current renaissance in psychedelic drug research and the growing interest in cognitive enhancing drugs, now may be the time to re-visit these studies with contemporary research methods.

Improving the Quality of Online Discussion: The Effects of Strategies Designed Based on Cognitive Load Theory Principles

ERIC Educational Resources Information Center

Darabi, Aubteen; Jin, Li

2013-01-01

This article focuses on heavy cognitive load as the reason for the lack of quality associated with conventional online discussion. Using the principles of cognitive load theory, four online discussion strategies were designed specifically aiming at reducing the discussants' cognitive load and thus enhancing the quality of their online discussion.…

Brief Report: Is Cognitive Rehabilitation Needed in Verbal Adults with Autism? Insights from Initial Enrollment in a Trial of Cognitive Enhancement Therapy

ERIC Educational Resources Information Center

Eack, Shaun M.; Bahorik, Amber L.; Hogarty, Susan S.; Greenwald, Deborah P.; Litschge, Maralee Y.; Mazefsky, Carla A.; Minshew, Nancy J.

2013-01-01

Cognitive rehabilitation is an emerging set of potentially effective interventions for the treatment of autism spectrum disorder, yet the applicability of these approaches for "high functioning" adults who have normative levels of intelligence remains unexplored. This study examined the initial cognitive performance characteristics of 40…

Cognitive reserve: implications for assessment and intervention.

PubMed

Stern, Yaakov

2013-01-01

The concept of reserve is used to explain the observation that some individuals function better than others in the presence of brain pathology. This article reviews the concept of reserve from its theoretical basis to the implication of reserve for clinical practice. A distinction between brain reserve, referring to individual differences in the anatomic substrate, and cognitive reserve, referring to differences in the flexibility or adaptivity of cognitive networks, is useful. Epidemiologic evidence indicates that a set of life exposures including higher educational and occupational attainment, and engaging in leisure activities is associated with a lower risk of incident dementia, suggesting that these life exposures may enhance cognitive reserve. This provides a basis for controlled clinical studies that can test specific exposures that may enhance reserve. The concept of cognitive reserve also has important implications for clinical practice in terms of diagnosis and prognosis. © 2013 S. Karger AG, Basel.

Learning a Foreign Language: A New Path to Enhancement of Cognitive Functions.

PubMed

Shoghi Javan, Sara; Ghonsooly, Behzad

2018-02-01

The complicated cognitive processes involved in natural (primary) bilingualism lead to significant cognitive development. Executive functions as a fundamental component of human cognition are deemed to be affected by language learning. To date, a large number of studies have investigated how natural (primary) bilingualism influences executive functions; however, the way acquired (secondary) bilingualism manipulates executive functions is poorly understood. To fill this gap, controlling for age, gender, IQ, and socio-economic status, the researchers compared 60 advanced learners of English as a foreign language (EFL) to 60 beginners on measures of executive functions involving Stroop, Wisconsin Card Sorting Task (WCST) and Wechsler's digit span tasks. The results suggested that mastering English as a foreign language causes considerable enhancement in two components of executive functions, namely cognitive flexibility and working memory. However, no significant difference was observed in inhibitory control between the advanced EFL learners and beginners.

Cognitive Reserve: Implications for Assessment and Intervention

PubMed Central

Stern, Yaakov

2014-01-01

The concept of reserve is used to explain the observation that some individuals function better than others in the presence of brain pathology. This paper reviews the concept of reserve from its theoretical basis to the implication of reserve for clinical practice. A distinction between brain reserve, referring to individual differences in the anatomic substrate, and cognitive reserve, referring to differences in the flexibility or adaptivity of cognitive networks, is useful. Epidemiologic evidence indicates that a set of life exposures including higher educational and occupational attainment, and engaging in leisure activities is associated with a lower risk of incident dementia, suggesting that these life exposures may enhance cognitive reserve. This provides a basis for controlled clinical studies can test specific exposures that may enhance reserve. The concept of cognitive reserve also has important implications for clinical practice in terms of diagnosis and prognosis. PMID:23941972

Perceptual Training Strongly Improves Visual Motion Perception in Schizophrenia

ERIC Educational Resources Information Center

Norton, Daniel J.; McBain, Ryan K.; Ongur, Dost; Chen, Yue

2011-01-01

Schizophrenia patients exhibit perceptual and cognitive deficits, including in visual motion processing. Given that cognitive systems depend upon perceptual inputs, improving patients' perceptual abilities may be an effective means of cognitive intervention. In healthy people, motion perception can be enhanced through perceptual learning, but it…