Interaction between psychological and pharmacological treatment in cognitive impairment. Can the pattern of neuropsychological improvement obtained with cholinergic drugs be used to infer a cholinergic mechanism in other nootropic drugs? Acute tryptophan depletion reduces kynurenine levels: implications for treatment of impaired visuospatial memory performance in irritable bowel syndrome Cognitive effects of l-deprenyl in Alzheimer's disease Pharmacologic probes of neurotransmitter systems in tardive dyskinesia: implications for clinical management. Rivastigmine but not vardenafil reverses cannabis-induced impairment of verbal memory in healthy humans Piracetam combined with lecithin in the treatment of Alzheimer's disease Pharmaco-electroencephalographic and clinical effects of the cholinergic substance--acetyl-L-carnitine--in patients with organic brain syndrome. Modulation of memory and visuospatial processes by biperiden and rivastigmine in elderly healthy subjects Selegiline versus oxiracetam in patients with Alzheimer-type dementia. Treatment trial of oxiracetam in Alzheimer's disease. Long‐term and high‐dose piracetam treatment of Alzheimer's disease Mirtazapine for chronic breathlessness? A review of mechanistic insights and therapeutic potential [L-acetylcarnitine treatment on fragile X patients hyperactive behaviour]. The effects of acute scopolamine in geriatric depression. 3,4-Diaminopyridine in the treatment of Lambert-Eaton myasthenic syndrome. Positive effects of Cerebrolysin on electroencephalogram slowing, cognition and clinical outcome in patients with postacute traumatic brain injury: an exploratory study Cognitive and biochemical effects of monosodium glutamate and aspartame, administered individually and in combination in male albino mice. Impact of exercise and vitamin B1 intake on hippocampal brain-derived neurotrophic factor and spatial memory performance in a rat model of stress. Piracetam in Alcoholic Psychoses: A Double-Blind, Crossover, Placebo Controlled Study Effect of Piracetam on Recovery and Rehabilitation After Stroke: A Double‐Blind, Placebo‐Controlled Study Contribution of Impaired Parasympathetic Activity to Right Ventricular Dysfunction and Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension Rats and humans paying attention: cross-species task development for translational research.
In contrast to other kinds of psychotropic drugs , nootropics or cognition enhancing drugs may be indicated , not for the direct treatment of the pathology itself , but for improving or restoring the remaining brain functions . Brain functions are normally trained during various kinds of non-medical therapy , such as physiotherapy , speech therapy , occupational therapy , memory training etc ... In research little attention has been paid to the combination of both kinds of therapeutic approaches , probably because of the important method ological difficulties . This combination however , offers various interesting perspectives : L. ISRAEL examined in two placebo-controlled studies the effects of either 160 mg/d of ginkgo biloba extractum ( GBE ) or piracetam 2.4 or 4.8 g/d , combined with a memory training program , in nondemented patients complaining of memory problems . The results of both studies suggest that nootropic drug treatment and memory training have each an effect on different cognitive functions and , hence , are complementary . Some functions , like attention/perception in the GBE study and learning in the piracetam study , seem to benefit from both treatments , suggesting a mutually potentiating effect of drug treatment and training . This potentiation is very clear in the treatment of dyslexic children : in a placebo-controlled study piracetam 3.3 g/d , in combination with normal school teaching and more specific logopedic therapy , allowed a normal progression during the full school year in reading accuracy and reading comprehension , while the placebo treated children getting a similar training progressed only with 50 % . Recently promising results were obtained in the treatment of dysphasic patients with a combination of speech therapy and piracetam 4.8 g/d , especially when given during the first months after the stroke , or otherwise in combination with an intensive speech training . In both double-blind studies the piracetam treated group improved about 60 % more than the group who only got speech therapy and placebo . All these data may be explained by the restorative or enhancing influence of nootropic drugs on neurotransmitter systems closely related to learning and memory functions . E.g. piracetam restores the availability and function of muscarinic and NMDA receptors in aging animals , most probably through a modulation of the psychico-chemical properties of the neuronal membrane such as the membrane fluidity 1 . Enhancement of episodic memory and reduction of intrusion errors are considered as the most characteristic outcome of cholinergic drugs administration in AD patients . 2 . Since the nootropic drugs Piracetam and Oxiracetam are deemed to act through a cholinergic mechanism , we checked whether AD patients treated with these drugs would show the same pattern of neuropsychological improvement . 3 . Results were negative , since ( a ) episodic memory showed a similar degree of improvement both in patients treated with these drugs and in patients treated with placebo ; ( b ) the number of intrusions tended to increase , rather than to decrease , after the treatment period Rationale A visuospatial episodic memory impairment has recently been identified in irritable bowel syndrome . Increased tryptophan metabolism along the kynurenine pathway has also been reported in irritable bowel syndrome , which may play a role in altered cognitive performance as peripheral kynurenine can cross the blood brain barrier and lead to the production of neuroactive metabolites , which modulate glutamatergic and cholinergic signalling , key neurotransmitter systems involved in cognitive function . Objectives Utilising the acute tryptophan depletion ( ATD ) protocol , the aim of this study was to examine if manipulating peripheral levels of tryptophan regulates cognitive performance in irritable bowel syndrome and also to determine for the first time if the ATD protocol alters kynurenine supply to the central nervous system . Methods In this double-blind , placebo-controlled , crossover design study , nine female patients with irritable bowel syndrome and 14 matched female healthy controls participant completed a range of tests from the CANTAB ® following ATD and placebo .  Plasma tryptophan and kynurenine , self-report measures of gastrointestinal symptoms , mood and arousal were determined pre- and post-treatment on each study day . Results Following placebo ( p = 0.016 ) but not ATD ( p > 0.05 ) , patients with irritable bowel syndrome exhibited impaired visuospatial memory performance ( Paired Associates Learning ( PAL ) test ) . In addition , ATD significantly decreased ( p < 0.001 ) and placebo significantly increased ( p < 0.001 ) plasma kynurenine levels in both groups . Conclusions Manipulating peripheral tryptophan and kynurenine levels using ATD modulates hippocampal-mediated cognitive performance in irritable bowel syndrome but not healthy controls . These data may have important implication s for reducing cognitive impairment in irritable bowel syndrome Monoamine neurotransmitter systems , along with cholinergic systems , are known to play important roles in cognition , and are disrupted in at least some patients with dementia of the Alzheimer type ( DAT ) . This suggests that monoamine-enhancing drugs might ameliorate cognitive symptoms in certain patients with DAT .  l-Deprenyl is a monoamine oxidase ( MAO ) inhibitor which may selectively inhibit MAO-B at low doses , while at high doses it nonselectively inhibits MAO-A as well as MAO-B. We studied its effects on several types of cognitive function in 17 patients with DAT . Two doses of l-deprenyl ( 10 mg/day and 40 mg/day ) and placebo were compared in a double-blind , serial treatment design . Episodic learning and memory , knowledge memory , attention , recognition , and performance on a continuous performance task were assessed at baseline and under these drug and placebo conditions . Statistically significant improvement was noted in performance on an episodic memory and learning task requiring complex information processing and sustained conscious effort during treatment with l-deprenyl 10 mg/day . Knowledge memory , intrusions , and other cognitive functions relevant to DAT were not altered by l-deprenyl at either dose Despite the plethora of clinical drug trials in tardive dyskinesia , few consistent findings have emerged . One possible reason for this is that there have been no serious attempts to define the role of major neurotransmitter systems ( dopamine , norepinephrine , acetylcholine , serotonin , GABA ) in one specific population of tardive dyskinesia patients . This study reports a series of five controlled drug trials in a population of patients with persistent tardive dyskinesia ; each drug probed one of four neurotransmitter systems . The intra- and interpatient responses are analyzed and the implication s of the pharmacologic response profiles for the clinical management of tardive dyskinesia are discussed Rationale One of the most often reported cognitive deficits of acute cannabis administration is an impaired recall of previously learned information . Objective The aim of the present study was to determine whether cannabis-induced memory impairment in humans is mediated via glutamatergic or cholinergic pathways . Methods Fifteen occasional cannabis users participated in a double-blind , placebo-controlled , six-way cross-over study . On separate test days , subjects received combinations of pretreatment ( placebo , vardenafil 20 mg or rivastigmine 3 mg ) and treatment ( placebo or 1,376 mg cannabis/kg body weight ) . Cognitive tests were administered immediately after inhalation of treatment was finished and included measures of memory ( visual verbal learning task , prospect i ve memory test , Sternberg memory test ) , perceptual-motor control ( critical tracking task ) , attention ( divided attention task ) and motor impulsivity ( stop signal task ) . Results The results of this study demonstrate that subjects under the influence of cannabis were impaired in all memory tasks , in critical tracking , divided attention and the stop signal task . Pretreatment with rivastigmine attenuated the effect of cannabis on delayed recall and showed a trend towards significance on immediate recall . When cannabis was given in combination with vardenafil , there were no significant interaction effects in any of the tasks . Conclusions The present data therefore suggest that acetylcholine plays an important role in cannabis-induced memory impairment , whereas similar results for glutamate have not been demonstrated in this study Nootropics , a new class of drugs believed to activate mental functions , have been proposed as a treatment for clinical disorders in which cognition is impaired . We therefore administered the nootropic drug piracetam , alone and in combination with phosphatidylcholine ( PC ) , to 18 patients with Alzheimer 's disease ( AD ) , and measured the effects of treatment on a broad range of cognitive functions .  Piracetam was administered according to three double-blind crossover protocol s and a replication study that differed in piracetam dose ( 2.4 to 9.9 g/day ) and whether PC ( 18 g/day ) was administered concurrently . The drug was well tolerated , and there were not toxic side effects . Plasma choline levels rose significantly during piracetam and PC administration ; monoamine metabolites in cerebrospinal fluid were unaffected by treatment . Piracetam , either alone or in combination with PC , did not significantly affect cognition in the AD group as a whole , nor did it improve test performance in any single patient 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 out patients 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 Rationale The central cholinergic system is implicated in cognitive functioning . The dysfunction of this system is expressed in many diseases like Alzheimer 's disease , dementia of Lewy body , Parkinson 's disease and vascular dementia . In recent animal studies , it was found that selective cholinergic modulation affects visuospatial processes even more than memory function . Objective In the current study , we tried to replicate those findings . In order to investigate the acute effects of cholinergic drugs on memory and visuospatial functions , a selective anticholinergic drug , biperiden , was compared to a selective acetylcholinesterase-inhibiting drug , rivastigmine , in healthy elderly subjects . Methods A double-blind , placebo-controlled , r and omised , cross-over study was performed in 16 healthy , elderly volunteers ( eight men , eight women ; mean age 66.1 , SD 4.46 years ) . All subjects received biperiden ( 2 mg ) , rivastigmine ( 3 mg ) and placebo with an interval of 7 days between them . Testing took place 1 h after drug intake ( which was around Tmax for both drugs ) . Subjects were presented with tests for episodic memory ( wordlist and picture memory ) , working memory tasks ( N-back , symbol recall ) and motor learning ( maze task , pursuit rotor ) . Visuospatial abilities were assessed by tests with high visual scanning components ( tangled lines and Symbol Digit Substitution Test ) . Results Episodic memory was impaired by biperiden . Rivastigmine impaired recognition parts of the episodic memory performance . Working memory was non-significantly impaired by biperiden and not affected by rivastigmine .  Motor learning as well as visuospatial processes were impaired by biperiden and improved by rivastigmine . Conclusions These results implicate acetylcholine as a modulator not only of memory but also of visuospatial abilities The efficacy and tolerability of the monoamine oxidase B inhibitor selegiline and of the nootropic agent oxiracetam were compared in a single-blind , controlled , parallel study . The trial involved 22 men and 18 women with mild-to-moderate senile and presenile dementia of the Alzheimer type . The treatments were administered for 90 consecutive days as follows : one 10-mg selegiline tablet once daily and one 800-mg oxiracetam tablet twice daily . Efficacy was evaluated by means of a complex battery of neuropsychological tests , administered monthly for three months , starting from baseline . Safety was evaluated by monitoring adverse drug reactions as well as any pathological changes in hematology , blood chemistry , or liver and kidney function , measured at baseline and again at the conclusion of the study . Analysis of the results demonstrates that , at the dosage used , selegiline is more effective than oxiracetam in improving higher cognitive functions and reducing impairment in daily living . In particular , short- and long-term memory , sustained concentration , attention , verbal fluency , and visuospatial abilities were , for the most part , positively affected by selegiline .  Gastroenteric and systemic tolerability of both drugs was also very good Twenty-four carefully assessed patients with probable Alzheimer 's disease were enrolled in a double-blind , placebo-controlled treatment study of oxiracetam , a nootropic agent reported to improve memory performance in patients with dementia . A broad battery of neuropsychological tests failed to reveal any improvement in the treated group or in any treated patient when individual test scores were analyzed . These findings indicate that oxiracetam is ineffective in reducing cognitive impairment due to Alzheimer 's disease Pre clinical research suggests that piracetam ( a nootropic drug ) may improve cognitive functions , but previous studies have failed to demonstrate a clear benefit for the treatment of Alzheimer 's disease ( AD ) . We report a 1-year , double-blind , placebo-controlled , parallel-group study with a high dose of piracetam ( 8 g/d per os ) in 33 ambulant patients with early probable AD . Thirty subjects completed the 1-year study . No improvement occurred in either group , but our results support the hypothesis that long-term administration of high doses of piracetam might slow the progression of cognitive deterioration in patients with AD . The most significant differences concerned the recall of pictures series and recent incident and remote memory . The drug was well-tolerated ABSTRACT Introduction :  Chronic breathlessness  is a common and distressing symptom of advanced disease with few effective treatments . Central nervous system mechanisms are important in respiratory sensation and control . Consequently , drugs which may modify processing and perception of afferent information in the brain may have a role . Antidepressants have been proposed ; however , current evidence is limited . Of potentially suitable antidepressants , mirtazapine is an attractive option given its tolerability profile , low cost , and wide availability , along with additional potential benefits . Areas covered : The paper provides an overview of the physiology of breathlessness , with an emphasis on central mechanisms , particularly the role of fear circuits and the associated neurotransmitters . It provides a potential rationale for how mirtazapine may improve chronic breathlessness and quality of life in patients with advanced disease . The evidence was identified by a literature search performed in PubMed through to October 2018 . Expert opinion : Currently , there is insufficient evidence to support the routine use of antidepressants for chronic breathlessness in advanced disease . Mirtazapine is a promising c and i date to pursue , with definitive r and omized controlled trials required to determine its efficacy and safety in this setting Hyperactivity is a significant problem for almost all young males affected by fragile X syndrome ( FXS ) , the most common inherited disease causing mental retardation . Therapeutical approaches are actually based on Central Nervous System ( CNS ) stimulants lacking a well defined rationale and efficacy while they further decrease the patient 's limited attention span . A pilot study on 17 fragile X male treated with L-acetylcarnitine ( LAC ) over one year , showed a significant reduction of their hyperactivity behaviour tested by the Conners Abbreviated Parent-Teacher Question naire . LAC use in FXS patients derives from the hypothesis that the biochemical and physiological properties this substance has may preserve brain activity . LAC is a small , hydrosoluble molecule that easily diffuses in the extracellular space and enters any cell in the nervous system through specific transporters . Different cerebral areas use this molecule differently to metabolize glucose and lipids to provide for ATP and neurotrasmitters synthesis . The acetyl group LAC carriers represents a key metabolic signaling element possibly mediating its effect in the CNS . The exogenous administration of LAC may affect brain activity in FXS by : I ) modulation of fuel partitioning for energy production , which at the mithocondrial level is associated with the Kreb 's cycle metabolic role in neurotransmitter synthesis ; II ) remodelling of lipid membrane in terms of LAC actively determining the production of polyunsaturated fatty acids ; III ) preferential effect on the attention component of the cholinergic system which relies on its peculiar modality of communication in the CNS . Based on the above premises an explorative , double-blind , placebo controlled , multicenter study is ongoing . A total population of 160 children from nine European centers will be enrolled . The objective of this study is to determine the effect of LAC on the hyperactive behaviour of FXS children as evaluated by the administration of the Conners Abbreviated Parent Question naire In an intensive multidrug , multidose study , nine elderly depressed patients were administered 0.1 , 0.25 , and 0.5 mg of scopolamine hydrobromide , 1 mg of oral lorazepam , and placebo in a double-blind investigation aim ed at assessing the status of the central cholinergic nervous system in geriatric depression . Significant cognitive and behavioral effects of scopolamine were observed only at the high dose ( 0.5 mg ) , while lower doses and lorazepam showed no significant differences from placebo .  Cognitive deficits caused by scopolamine were in the areas of new learning , access to semantic memory , vigilance , and continuous performance . Behavioral effects consisted of activation , restlessness , and anxiety , but there was no significant effect on depressed mood . These results suggest that elderly depressed patients with mild to moderate cognitive impairment seem to be more similar to previously studied elderly controls rather than to patients with Alzheimer 's disease in their reaction to short-term cholinergic blockade , and suggest that the cognitive and mood changes often seen in geriatric depression may involve factors other than disturbed muscarinic cholinergic mechanisms Lambert-Eaton myasthenic syndrome is characterized by muscle weakness , hyporeflexia , and autonomic dysfunction , which result from impaired release of acetylcholine from cholinergic nerve terminals . It is frequently associated with cancer , it is autoimmune-mediated , and treatment has been unsatisfactory . 3,4-Diaminopyridine enhances the release of acetylcholine . In this prospect i ve , double-blind , placebo-controlled crossover study of 12 patients with Lambert-Eaton myasthenic syndrome ( 7 of whom had cancer ) , 3,4-diaminopyridine in doses up to 100 mg per day was effective in treating both the motor and the autonomic deficits of the syndrome . Muscle strength increased from an average of 70 percent of normal to 81 percent of normal in the upper extremities , and from 45 to 65 percent of normal in the lower extremities . The amplitudes of compound-muscle-action potentials nearly doubled , increasing from an average of 2.9 mV to 5.0 mV in the arm and from 1.6 mV to 3.1 mV in the leg . Autonomic symptoms were relieved . One patient had a seizure after 10 months of treatment , but other side effects from the drug were minimal and dose-related . We conclude that 3,4-diaminopyridine , either alone or in conjunction with other therapies , may be useful in the treatment of Lambert-Eaton myasthenic syndrome The potential effects of Cerebrolysin ( EBEWE Pharma , Unterach , Austria ) , a peptide preparation with neurotrophic activity , on brain bioelectrical activity , cognitive performance and clinical outcome in postacute traumatic brain injury ( TBI ) patients , were investigated in an exploratory study . A decrease in slow electroencephalogram ( EEG ) activity and an increase in fast frequencies were observed after the administration of Cerebrolysin . This EEG-activating effect was not influenced by TBI time course or severity , nor by the chronic treatment with nootropic compounds . Cognitive performance , evaluated with the Syndrome Kurztest test , improved in TBI patients after Cerebrolysin treatment , independent of disease severity , time course or disability . A significant improvement in the patients ' clinical outcome , only evident during the first year after brain trauma , was also found following Cerebrolysin infusions . No relevant changes in biological parameters nor drug-related adverse events were observed . These promising preliminary results suggest that Cerebrolysin might be a useful treatment to improve the recovery of patients with traumatic brain damage , and encourage the conduction of confirmatory clinical trials The present study was design ed to investigate the in vivo effects of monosodium glutamate ( MSG ) and aspartame ( ASM ) individually and in combination on the cognitive behavior and biochemical parameters like neurotransmitters and oxidative stress indices in the brain tissue of mice . Forty male Swiss albino mice were r and omly divided into four groups of ten each and were exposed to MSG and ASM through drinking water for one month . Group I was the control and was given normal tap water . Groups II and III received MSG ( 8 mg/kg ) and ASM ( 32 mg/kg ) respectively dissolved in tap water . Group IV received MSG and ASM together in the same doses . After the exposure period , the animals were subjected to cognitive behavioral tests in a shuttle box and a water maze . Thereafter , the animals were sacrificed and the neurotransmitters and oxidative stress indices were estimated in their forebrain tissue . Both MSG and ASM individually as well as in combination had significant disruptive effects on the cognitive responses , memory retention and learning capabilities of the mice in the order (MSG+ASM)>ASM > MSG . Furthermore , while MSG and ASM individually were unable to alter the brain neurotransmitters and the oxidative stress indices , their combination dose ( MSG+ASM ) decreased significantly the levels of neurotransmitters ( dopamine and serotonin ) and it also caused oxidative stress by increasing the lipid peroxides measured in the form of thiobarbituric acid-reactive substances ( TBARS ) and decreasing the level of total glutathione ( GSH ) . Further studies are required to evaluate the synergistic effects of MSG and ASM on the neurotransmitters and oxidative stress indices and their involvement in cognitive dysfunctions Chronic stress affects brain areas involved in learning and emotional responses through modulation of neurotropic factors or neurotransmitters . Therefore , we investigated the role of exercise and thiamine supplementation on spatial memory and on brain-derived neurotrophic factor ( BDNF ) and acetylcholine ( Ach ) content in the hippocampus of the stressed animals . Male Wistar rats were r and omly assigned to 4 groups ( 8 rats/group ) : control group ; stress group ; swimming and stress group ; and thiamine and stress group . All animals were assessed by a T maze for spatial memory or open field test for locomotion and anxiety . BDNF and Ach were estimated in the hippocampus . Chronic immobilization stress result ed in a significant decrease in BDNF and Ach levels in the hippocampus and impairment in spatial memory functions and decreased basal activity . However , either swimming training or thiamine intake for 30 d was proved to induce a significant increase both in BDNF and Ach in conjunction with improved performance in the T maze , marked anxiolytic effect and enhanced ambulation in the open field test , as compared to the stress group . Interestingly , swimming-exercised rats showed significantly higher levels of BDNF versus thiamine-receiving rats , while thiamine-receiving rats showed higher locomotor activity and less freezing behavior in the open field test compared to the swimming group . It was concluded that decreased BDNF and Ach after stress exposure could be a mechanism for the deleterious actions of stress on memory function ; swimming exercise or vitamin B1 supplementation for 30 d was a protective tool to improve coping with chronic stress by modulating BDNF and Ach content along with enhancement of memory functions and motor activities Introduction Various therapeutic approaches are applied for the treatment of  psychiatric complications in patients suffering from chronic alcoholism , such as in the case of predeliriurn state , in delirium tremens and in alcoholic hallucinosis . One aim is to normalize the basic metabolic functions by means of the administration of infusions containing minerals , vitamins and glucose in order to rehydrate the patient , the other aim is a purely symptomatic treatment using tranquillizers and neuroleptics . Piracetam , a nootrop , may offer another rationale for therapy as it directly activates the higher cortical functions of the brain such as those involved with cognition , memory formation and retrieval , thought and state of consciousness and in the case of toxic aggression it facilitates restoration of normal brain activity .  Piracetam has previously been studied in patients presenting with alcoholic psychosis in several open trials involving a total of about 200 patients ( Aron & Nerot 1975 , De Buck et al 1970 , Delooz 1979 , Marx 1974 , Meyer et al 1979 , Pottier 1973,TuronetaI1971 ) . Our aim was to confirm the therapeutic properties of piracetam in alcoholic psychoses mentioned in the open trials by means of a double-blind , crossover study using placebo as the control agent Summary : The nootropic agent piracetam has been shown to improve learning and memory , and it may , by this means , facilitate recovery and rehabilitation after a stroke . We report the results of a pilot study exploring its effects in patients undergoing rehabilitation after acute cerebral infa rct ion in the carotid artery territory . We compared piracetam and placebo , each given for 12 weeks , in a multicenter , double-blind , r and omized trial of parallel-group design ; testing was performed at baseline ( 6–9 weeks poststroke ) , weeks 5 and 12 , and , in fewer patients , 12 weeks after termination of treatment . St and ardized tests of activities of daily living ( Barthel Index , Kuriansky Test ) , aphasia ( Aachen Aphasia Test ) , and perception ( Rivermead Perception Assessment Battery ) were the primary efficacy variables . Of 158 patients , 137 ( 81 males , 56 females ) were studied after treatment and 88 at 24-week follow-up . Thirty patients on piracetam ( 45 % ) and 37 on placebo ( 53 % ) were aphasic on entry . Both groups , including the subgroups with aphasia , were well matched at baseline for demographic data , stroke sequelae , type and severity of aphasia , and prognostic parameters . Multivariate analysis of Aachen Aphasia subtest scores showed a significant overall improvement relative to baseline in favor of piracetam ( p = 0.02 ) at 12 weeks . This was not seen at 24 weeks when , however , fewer patients were available for evaluation so that we could neither confirm nor deny whether improvement was maintained after cessation of piracetam . We were unable to demonstrate an effect on tests of activities of daily living and could neither confirm nor exclude an effect on perceptual deficit . We have shown an improvement in aphasia in patients undergoing rehabilitation after a stroke after 12 weeks ' treatment with piracetam that requires confirmation in further studies Background : The beneficial effects of parasympathetic stimulation have been reported in left heart failure , but whether it would be beneficial for pulmonary arterial hypertension ( PAH ) remains to be explored . Here , we investigated the relationship between parasympathetic activity and right ventricular ( RV ) function in patients with PAH , and the potential therapeutic effects of pyridostigmine ( PYR ) , an oral drug stimulating the parasympathetic activity through acetylcholinesterase inhibition , in experimental pulmonary hypertension ( PH ) . Methods : Heart rate recovery after a maximal cardiopulmonary exercise test was used as a surrogate for parasympathetic activity . RV ejection fraction was assessed in 112 patients with PAH . Expression of nicotinic ( & agr;-7 nicotinic acetylcholine receptor ) and muscarinic ( muscarinic acetylcholine type 2 receptor ) receptors , and acetylcholinesterase activity were evaluated in RV ( n=11 ) and lungs ( n=7 ) from patients with PAH undergoing heart/lung transplantation and compared with tissue obtained from controls . In addition , we investigated the effects of PYR ( 40 mg/kg per day ) in experimental PH . PH was induced in male rats by SU5416 ( 25 mg/kg subcutaneously ) injection followed by 4 weeks of hypoxia . In a subgroup , sympathetic/parasympathetic modulation was assessed by power spectral analysis . At week 6 , PH status was confirmed by echocardiography , and rats were r and omly assigned to vehicle or treatment ( both n=12 ) . At the end of the study , echocardiography was repeated , with additional RV pressure-volume measurements , along with lung , RV histological , and protein analyses . Results : Patients with PAH with lower RV ejection fraction ( < 41 % ) had a significantly reduced heart rate recovery in comparison with patients with higher RV ejection fraction . In PAH RV sample s , & agr;-7 nicotinic acetylcholine receptor was increased and acetylcholinesterase activity was reduced versus controls . No difference in muscarinic acetylcholine type 2 receptor expression was observed . Chronic PYR treatment in PH rats normalized the cardiovascular autonomic function , demonstrated by an increase in parasympathetic activity and baroreflex sensitivity . PYR improved survival , increased RV contractility , and reduced RV stiffness , RV hypertrophy , RV fibrosis , RV inflammation , and RV & agr;-7 nicotinic acetylcholine receptor and muscarinic acetylcholine type 2 receptor expression , as well . Furthermore , PYR reduced pulmonary vascular resistance , RV afterload , and pulmonary vascular remodeling , which was associated with reduced local and systemic inflammation . Conclusions : RV dysfunction is associated with reduced systemic parasympathetic activity in patients with PAH , with an inadequate adaptive response of the cholinergic system in the RV . Enhancing parasympathetic activity by PYR improved survival , RV function , and pulmonary vascular remodeling in experimental PH Substantial gains have been made on the neurobiology of attention from systems neuroscience work in animal models and human cognitive neuroscience . However , the integration of rodent-based research on the specific neurotransmitter systems that subserve attention with the results from human behavioral and neuroimaging studies has been hampered by the lack of tasks that validly assess attention in both species . To address this issue , an operant sustained attention task that has been extensively used in research on the neurobiology of attention in rats was re design ed and vali date d for use in humans . Although humans showed better performance overall , the two species showed similar effects of several attention-related variables , including the introduction of distractor-related challenge . This task provides a useful tool for integrative , cross-species research and may help to determine how specific neurotransmitter systems contribute to the hemodynamic changes observed in human functional neuroimaging experiments
From the data reported in the literature , it emerges that nootropics may be an effective alternative for strengthening and enhancing cognitive performance in patients with a range of pathologies .
Although nootropics , and specifically the cholinergic precursors , already have a long history behind them , according to recent renewal of interest , they still seem to have a significant therapeutic role .
Drugs with regulatory indications for symptomatic treatment of Alzheimer 's disease , such as cholinesterase inhibitors and memantine , often have transient effects in dementia disorders .
Nootropics represent probably the first " smart drugs " used for the treatment of cognitive deficits .
The aim of this paper is to verify , by a systematic analysis of the literature , the effectiveness of nootropics in this indication .
The analysis was limited to nootropics with cholinergic activity , in view of the role played by acetylcholine in learning and memory .
Acetylcholine was the first neurotransmitter identified in the history of neuroscience and is the main neurotransmitter of the peripheral , autonomic , and enteric nervous systems .