Focusing Effect of Acetylcholine on Neuroplasticity in the Human Motor Cortex 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? Pharmaco-electroencephalographic and clinical effects of the cholinergic substance--acetyl-L-carnitine--in patients with organic brain syndrome. Effects of antipsychotic treatment on cognition in healthy subjects Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study Modulation of Mood and Cognitive Performance Following Acute Administration of Single Doses of Melissa Officinalis (Lemon Balm) with Human CNS Nicotinic and Muscarinic Receptor-Binding Properties Increase in the power of human memory in normal man through the use of drugs The expert consensus guideline series. Treatment of dementia and its behavioral disturbances. Introduction: methods, commentary, and summary. [Comparative evaluation of psychoactive drugs used in patients with subacute and chronic cerebrovascular disorders]. Role of acetyl-L-carnitine in the treatment of cognitive deficit in chronic alcoholism. Effects of Cholinergic Drugs and Cognitive Training on Dementia Effects of Cholinergic Drugs and Cognitive Training on Dementia: 2-Year Follow-Up (S)-(+)-mecamylamine (TC-5214): a neuronal nicotinic receptor modulator enters phase III trials as an adjunct treatment for Major Depressive Disorder (MDD). Piracetam combined with lecithin in the treatment of Alzheimer's disease SPECT monitoring of improved cerebral blood flow during long-term treatment of elderly patients with nootropic drugs. Relationship of Cognition to Clinical Response in First-Episode Schizophrenia Spectrum Disorders.
Cholinergic neuromodulation is pivotal for arousal , attention , and cognitive processes . Loss or dysregulation of cholinergic inputs leads to cognitive impairments like those manifested in Alzheimer 's disease . Such dysfunction can be at least partially restored by an increase of acetylcholine ( ACh ) . In animal studies , ACh selectively facilitates long-term excitability changes induced by feed-forward afferent input . Consequently , it has been hypothesized that ACh enhances the signal-to-noise ratio of input processing . However , the neurophysiological foundation for its ability to enhance cognition in humans is not well documented . In this study we explore the effects of rivastigmine , a cholinesterase inhibitor , on global and synapse-specific forms of cortical plasticity induced by transcranial direct current stimulation ( tDCS ) and paired associative stimulation ( PAS ) on 10–12 healthy subjects , respectively .  Rivastigmine essentially blocked the induction of the global excitability enhancement elicited by anodal tDCS and revealed a tendency to first reduce and then stabilize cathodal tDCS-induced inhibitory aftereffects . However , ACh enhanced the synapse-specific excitability enhancement produced by facilitatory PAS and consoli date d the inhibitory PAS-induced excitability diminution . These findings are in line with a cholinergic focusing effect that optimizes the detection of relevant signals during information processing in humans 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 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 Cognitive impairments can be observed in the majority of diseases with disturbed dopamine transmission . They are considered as core symptoms of schizophrenia , a disorder in which they appear to be particularly pronounced . Their neurobiological background is not yet sufficiently investigated , but dopaminergic systems are believed to play a crucial role . The aim of this single-blind , r and omised , placebo-controlled study was to examine the effects of subchronic antidopaminergic treatment on cognitive functions in healthy subjects . In total , 72 healthy volunteers , r and omised into four groups , received one antidopaminergic substance ( aripiprazole , haloperidol or reserpine ) or placebo , respectively , for 7 days . A comprehensive neurocognitive assessment was conducted at baseline , 24 h after the last medication intake and 7 days later . In the Digit Symbol Substitution Test a distinct , statistically significant improvement was measured in the second session in the placebo but not in the medication group . A significant group*time interaction for reaction times in three subtests of the Test battery for Attentional Performance ( TAP ) was also found . Our findings indicate that modulation of dopaminergic systems affects primarily speed of information processing , attention and learning . Absence of effects on other functions , differing from previous reports , may be an expression of a sufficient counter-regulation Abstract Objective To assess the potential of anticholinergic drugs as a cause of  non-degenerative mild cognitive impairment in elderly people . Design Longitudinal cohort study . Setting 63 r and omly selected general practice s in the Montpellier region of southern France . Participants 372 people aged > 60 years without dementia at recruitment . Main outcome measures Anticholinergic burden from drug use , cognitive examination , and neurological assessment . Results 9.2 % of subjects continuously used anticholinergic drugs during the year before cognitive assessment . Compared with non-users , they had poorer performance on reaction time , attention , delayed non-verbal memory , narrative recall , visuospatial construction , and language tasks but not on tasks of reasoning , immediate and delayed recall of wordlists , and implicit memory . Eighty per cent of the continuous users were classified as having mild cognitive impairment compared with 35 % of non-users , and anticholinergic drug use was a strong predictor of mild cognitive impairment ( odds ratio 5.12 , P = 0.001 ) . No difference was found between users and non-users in risk of developing dementia at follow-up after eight years . Conclusions Elderly people taking anticholinergic drugs  had significant deficits in cognitive functioning and were highly likely to be classified as mildly cognitively impaired , although not at increased risk for dementia . Doctors should assess current use of anticholinergic drugs in elderly people with mild cognitive impairment before considering administration of acetylcholinesterase inhibitors Melissa officinalis ( Lemon balm ) is a herbal medicine that has traditionally been attributed with memory-enhancing properties , but which is currently more widely used as a mild sedative and sleep aid . In a previous study it was demonstrated that a commercial Melissa extract led to dose-specific increases in calmness , and dose-dependent decrements in timed memory task performance . However , the extract utilized in that study did not exhibit in vitro cholinergic receptor-binding properties . The current study involved an initial screening of sample s of M. officinalis for human acetylcholinesterase inhibition and cholinergic receptor-binding properties . The cognitive and mood effects of single doses of the most cholinergically active dried leaf were then assessed in a r and omized , placebo-controlled , double-blind , balanced crossover study . Following the in vitro analysis , 20 healthy , young participants received single doses of 600 , 1000 , and 1600 mg of encapsulated dried leaf , or a matching placebo , at 7-day intervals . Cognitive performance and mood were assessed predose and at 1 , 3 , and 6 h postdose using the Cognitive Drug Research computerized assessment battery and Bond – Lader visual analog scales , respectively . In vitro analysis of the chosen extract established IC50 concentrations of 0.18 and 3.47 mg ml−1 , respectively , for the displacement of [3H]-(N)-nicotine and [3H]-(N)-scopolamine from nicotinic and muscarinic receptors in the human cerebral cortex tissue . However , no cholinesterase inhibitory properties were detected . The most notable cognitive and mood effects were improved memory performance and increased ‘ calmness ’ at all postdose time points for the highest ( 1600 mg ) dose . However , while the profile of results was overwhelmingly favorable for the highest dose , decrements in the speed of timed memory task performance and on a rapid visual information-processing task increased with decreasing dose . These results suggest that doses of Melissa officinalis at or above the maximum employed here can improve cognitive performance and mood and may therefore be a valuable adjunct in the treatment of Alzheimer 's disease . The results also suggest that different preparations derived from the same plant species may exhibit different properties depending on the process used for the sample preparation Nootropyl ( Piracetam ) a drug reported to facilitate learning in animals was tested for its effect on man by administering it to normal volunteers . The subjects were given 3 × 4 capsules at 400 mg per day , in a double blind study . Each subject learned series of words presented as stimuli upon a memory drum . No effects were observed after 7 days but after 14 days verbal learning had significantly increased OBJECTIVES New treatment options for dementia and its behavioral disturbances have become available since publication of The Expert Consensus Guidelines on the Treatment of Agitation in Older Persons with Dementia in 1998 . While only 2 cholinesterase inhibitors , donepezil and tacrine , were available in 1998 , 3 new cognitive-enhancing agents have been introduced since that time as well as several new atypical antipsychotics and antidepressants . However , there are still limited data from controlled studies to guide clinicians in choosing among these agents and sequencing and combining treatments . We therefore conducted a new survey study of expert opinion on the treatment of cognitive impairment and behavioral disturbances associated with dementia . METHODS Based on a literature review , a 61- question survey was developed with 1,225 options . Most options were scored using a modified version of the R AND 9-point scale for rating appropriateness of medical decisions . For other options , the experts were asked to write in answers . The survey was sent to 50 North American experts on dementia , 100 % of whom completed it . In analyzing responses to items rated on the 9-point scale , consensus was defined as a nonr and om distribution of scores by chi-square " goodness-of-fit " test . Based on the 95 % confidence interval around the mean , we assigned a categorical rank ( first line/preferred , second line/alternate , third line/usually inappropriate ) to each option . Guidelines indicating preferred treatment strategies were then developed for selected clinical situations . RESULTS For patients at risk for dementia , the experts recommended control of hypertension and diabetes . They also recommended aspirin and would consider a lipid-lowering agent in patients at risk for vascular dementia . Cholinesterase inhibitors were an option for patients with mild cognitive impairment ( i.e. , at risk for Alzheimer 's dementia [ AD ] ) . To slow cognitive impairment in mild/moderate AD , the experts recommended a cholinesterase inhibitor alone or combined with vitamin E. Donepezil and  galantamine  were the preferred cholinesterase inhibitors . The experts recommended combining a cholinesterase inhibitor with a N-methyl-D-aspartate ( NMDA ) antagonist ( e.g. , memantine ) if a patient with mild/moderate dementia has an inadequate response to monotherapy . Control of hypertension and diabetes was the treatment of choice , in patients with mild/moderate vascular or mixed AD/vascular dementia , with aspirin another first-line option . Cholinesterase inhibitors were also a first-line option for mild/moderate mixed AD/vascular dementia . Among nonpharmacological interventions for mild/moderate dementia , the experts recommended caregiver education , supportive therapy for caregivers , referral to day treatment , exercise programs , and respite care . For moderate/severe AD or mixed AD/vascular dementia , the experts recommended combining an NMDA antagonist with a cholinesterase inhibitor . For moderate/severe vascular or mixed AD/vascular dementia , they recommended control of hypertension and diabetes . The experts ' ratings underscore the importance of nonpharmacological strategies aim ed at reducing caregiver burden in more severe dementia . Management of agitation and other behavioral disturbances was another focus of this study . The experts recommended using an atypical antipsychotic for agitation associated with delirium , psychosis , aggression , or anger . They would also consider divalproex to manage anger with a risk of physical aggression . Selective serotonin reuptake inhibitors were recommended for the treatment of depression or anxiety in patients with dementia . Benzodiazepines or atypical antipsychotics were viewed as short-term options for acute anxiety .  Trazodone was recommended for insomnia . The experts also gave recommendations concerning dosage levels , duration of treatment , and choice of medications for patients with different complicating conditions . CONCLUSIONS The experts reached high levels of consensus on key steps in treating dementia and associated behavioral disturbances . Within the limits of expert opinion and with the expectation that new research data will take precedence , these guidelines may provide direction for clinicians offering care to patients with dementia The report is based on 315 patients with subacute and chronic cerebral circulatory disturbances caused mostly by atherosclerosis aged 30 to 82 years , treated for 1 - 6 months . In 90 cases Piracetam ( Nootropil ) was given , 107 received Piritinol ( Encephabol , Enerbol ) , 77 Piriditol , 41 Centrophenoxin . The patients were allocated r and omly to these groups . In the treated patients improvement was achieved in a considerable proportion of cases ( 44 - 82 % ) treated with different drugs . This improvement manifested itself as regression or decreased intensity of neurotic complaints , labyrinthine-cerebellar signs , pyramidal signs , anxiety and fears , improvement of recent memory , attention , psychomotor activity . The best results were obtained with Nootropil , moderately good with Centrophenoxin , Encephabol , and poor with Piriditol .  Drug tolerance was best with Encephabol , while that of other drugs was slightly worse . The only disquieting symptoms was activation of epileptic seizures in several patients treated with Nootropil or Centrophenoxin . The best way of administration was giving the drugs in two doses in the morning hours and at noon . The authors regard as useful the treatment of patients with subacute and chronic cerebral circulatory failure  with psychoenergizing drugs Preliminary data are reported from a multicentred double-blind placebo-controlled study concerned with the effects of acetyl-L-carnitine ( LAC ) on some cognitive deficits of at least one month-abstinent alcoholics . Fifty-five patients , showing impaired performance in at least two out of six mnemonic , praxic and verbal tasks , were r and omly assigned to either LAC 2 g/day or a placebo group .  They were tested by means of a neuropsychological battery exploring the areas of memory , constructional praxia , deductive-logical functions and language . Testing time was on baseline ( T0 ) , after 45 ( T45 ) and 90 ( T90 ) days . On the Rey 's 15 word memory test ( long-term ) , the Wechsler memory scale ( logical memory ) , and the Similarities WAIS subtest , the T90 difference between LAC and the placebo was significant in favour of the former treatment . On the copying drawing test ( simple copy ) , the placebo group did not show any T0-T90 variation , while significant improvement in the LAC group was greater than in the placebo group . As LAC has proved to ameliorate the performance or to accelerate the recovery on tests representative of all cognitive areas explored , it is conceivable that the drug acts diffusely , either at the cholinergic transmission or at the neuronal metabolism level . It is concluded that acetyl-L-carnitine can be a useful and safe therapeutic agent in the subtle cognitive disturbances of chronic alcoholics A study was performed on patients with Alzheimer ’s disease ( AD ) in order to evaluate the efficacy of a combined treatment ( donepezil plus cognitive training ) in both cognitive processes and affective states . Eighty-six subjects , 25 men and 61 women , with an average age of 75.58 years , were studied . Almost all the subjects had a basic educational level .  Donezepil was administered at a dose of 10 mg daily along with cognitive treatment involving images of everyday life and reminiscent music ; the sessions took place on Monday to Friday and lasted three quarters of an hour . The study lasted 12 months . Subjects underwent test-retest with the following tests : Mini-Mental State Examination ( MMSE ) , the cognitive subscale of the Alzheimer ’s Disease Assessment Scale ( ADAS-cog ) ; the Geriatric Depression Scale ( GDS ) and the overall deterioration scale ( FAST ) . The results showed that subjects receiving the combined treatment had a better response than those who did not receive any cognitive training . These subjects ’ MMSE score decreased by 3.24 on average . The affective symptomatology of those receiving only drug treatment improved whereas the cognitive processes did not Several studies have shown that pharmacological and cognitive treatments for Alzheimers ’s disease improve cognitive function for short periods , but fewer studies have evaluated the efficacy of those treatments for longer ( 2-year ) periods . An initial sample of 68 subjects with mild Alzheimer ’s disease underwent clinical and cognitive evaluation . After evaluation , subjects were assigned to four different groups and participated in a 2-year follow-up study . Group 1 ( n = 14 ) received combined drug and cognitive stimulation , group 2 ( n = 20 ) received only drug treatment , group 3 ( n = 14 ) received only cognitive stimulation , and group 4 ( n = 30 ) received no treatment at all . Results confirmed previous investigation , cognitive and  combined stimulation improved patients ’ performance throughout the 1st year ; however , all groups deteriorated gradually throughout the 2nd year of treatment . According to this evidence , it can be concluded that we can not stop cognitive deterioration after 2 years of treatment , although deterioration is greater and its progress faster in patients not receiving any treatment at all Major Depressive Disorder ( MDD ) is a common illness that affects > 40 million people worldwide , and antidepressants are one of the top 5 leading classes of pharmaceuticals with annual sales in excess of $ 20 billion ( 1,2 ) . The current st and ard of care focuses on serotonin−norepinephrine reuptake inhibitors ( SNRI ) and selective serotonin reuptake inhibitors ( SSRI ) ; however , patients often respond poorly . In fact , the National Institute of Mental Health conducted a large-scale STAR*D study and found that 63 % of patients did not achieve remission with the SSRI Citalopram ( 1,3−5 ) . Citalopram was originally developed in Lundbeck in the late 1980s and sold as a racemate . Lundbeck , in collaboration with Forest Laboratories , has recently released an up date d version called Escitalopram ( also known as Lexapro ) , which is the single (S)-enantiomer of the racemic Citalopram , which provided new patent life . In 2009 , Lexapro garnered ∼$2.7 billion in sales in the US ( Figure ​(Figure1)1 ) ( 2 ) . Figure 1 Structures of Citalopram , Escitalopram , and TC-5214 . An alternative hypothesis for depression emerged over 30 years ago and suggests that a cholinergic imbalance ( hypercholinergic tone ) is a major factor in depression , and both clinical and pre clinical studies have implicated neuronal nicotinic cholinergic receptors ( NNRs ) rather than muscarinic receptors ( 5 ) . On the basis of these data , AstraZeneca and Targacept have explored the role of NNR antagonism in depressive disorders and recently announced the initiation of a phase III trial of TC-5214 , (S)-(+)-mecamylamine , as an adjunct therapy with Citalopram . TC-5214 is a low molecular weight ( 167.3 as free base , 203.8 as the HCl salt ) , basic ( pKa = 11.5 ) compound , freely soluble in water . While TC-5214 displays modest selectivity among the NNRs , its antidepressive properties are presumed to be the result of inhibition of the α4β2 NNRs . Pre clinical ly , TC-5214 demonstrated robust efficacy in rodent models of depression ( forced swim and behavioral despair ) and anxiety ( social interaction and light/dark chamber ) . The (S)-enantiomer showed a superior preclincial safety profile compared to that of either the racemic compound or the (R)-enantiomer . Furthermore , TC-5214 was well tolerated in both acute and chronic toxicity tests , displayed no mutagenic potential , and possessed pharmacokinetic properties suitable for development ( 3−5 ) . In 2009 , Targacept conducted a double blind , placebo controlled phase IIb trial in MMD patients with TC-5214  , as an adjunct treatment with Citalopram demonstrated superiority to placebo in both primary and secondary outcome measures ( 3−5 ) . This positive outcome led to a license agreement in December of 2009 with AstraZeneca for the global development and commercialization of TC-5214 . On June 23 , 2010 , AstraZeneca and Targacept announced the enrollment of the first patients in the phase III trial of TC-4214 . Coined the Renaissance Program , the trial will include two fixed dose and two flexible dose phase III studies of TC-5214 as an adjunct treatment for patients with poor response to st and ard SSRI or SNRI therapy . Each fixed dose and flexible dose phase III study will employ an initial open label phase wherein patients diagnosed with MDD receive one of seven marketed SSRIs or SNRIs for eight weeks to assess therapeutic response . Patients that respond poorly will then be r and omized into a double blind , placebo controlled second phase to receive a fixed or a flexible dose of TC-5214 or placebo , twice daily , while continuing the SSRI or SNRI therapy . A change from double blind baseline for TC-5214 on the Montgomery−Asberg Depression Rating Scale ( MADRS ) as compared to placebo is the primary outcome measure . The program will also include a double blind , placebo controlled study for long-term safety . The companies plan completion of the trial in time to file an IND with the FDA in late 2012 ( 3−5 ) . MMD is the leading cause of disability in the US for people 15−44 , and the burden for MDD in the US in 2000 was in excess of $ 83 billion ( 6 ) . When broken down , the workplace burden for lost time is ∼62 % , treatment costs account for ∼31 % , and suicide related costs average 7 % ( 6 ) . For those suffering from MDD with poor response to SSRIs and SNRIs , the phase III data is anxiously awaited 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 PURPOSE In normal aging persons , oxygen and glucose consumption progressively decreases with reduced cerebral blood flow ( CBF ) , which could be responsible for age-related changes in cognitive functions . A data processing model with the use of Tc-99 m SPECT of the human brain has been developed and found to be sensitive for monitoring the effects of drugs that increase CBF . In this study , the effect of two vasodilator drugs ( the combination of pentifylline and nicotinic acid versus piracetam ) was compared with the effect of placebo on CBF . MATERIAL S AND METHODS Thirty elderly volunteers had three different procedures using the Peelproc method to spatially st and ardize and compare CBF patterns by SPECT before and after drug intervention . The 30 patients were divided into five groups of six persons each who were r and omly assigned in a 1:1 ratio to the treatment sequences consisting of three phases : the combination of pentifylline and nicotinic acid ( C ) , piracetam ( N ) , and placebo ( P ) , or C-N-P ; P-N-C ; P-C-N ; N-C-P ; C-P-N ; or N-P-C. Phases 1 to 3 each consisted of a baseline recording of parameters ( day 0 ) , treatment for 60 days ( days 1 to 60 ) , and recording of parameters after treatment ( day 61 ) . RESULTS In elderly human volunteers ( ages , 52 to 70 years ) , after 2 months of oral treatment with a combination of pentifylline and nicotinic acid ( 800 mg pentifylline , 200 mg nicotinic acid daily ) , SPECT results for the Peel-proc program indicated a statistically significant improvement in CBF of the total brain , with a more pronounced improvement in the cerebellum and frontal regions , where a definite shift from abnormal to normal blood flow was detected . Spontaneous communication from most of the volunteers suggested that they experienced an improvement in memory and general well-being from the combination treatment . After 2 months of oral treatment with piracetam ( 2.4 g daily ) in elderly human volunteers , SPECT results indicated a regional improvement in CBF , particularly in the cerebellum . However , no beneficial effects with this drug were spontaneously reported . CONCLUSION The in vivo method to quantitatively monitor the progress of long-term drug therapy on CBF described here could be useful to assess and even direct changes in therapy First-episode schizophrenia ( FES ) spectrum disorders are associated with pronounced cognitive dysfunction across all domains . However , less is known about the course of cognitive functioning , following the first presentation of psychosis , and the relationship of cognition to clinical course during initial treatment . The present longitudinal study examined the magnitude of neurocognitive impairment , using the MATRICS Consensus Cognitive Battery , in patients experiencing their first episode of psychosis at baseline and after 12 weeks of r and omized antipsychotic treatment with either aripiprazole or risperidone .  At baseline , FES patients evidence d marked impairments in cognitive functioning . Notably , performance on the mazes task of planning and reasoning significantly predicted the likelihood of meeting stringent criteria for positive symptom remission during the first 12 weeks of the trial . Performance on indices of general cognitive function , working memory , and verbal learning improved over time , but these improvements were mediated by improvements in both positive and negative symptoms . We did not detect any differential effects of antipsychotic medication assignment ( aripiprazole vs risperidone ) on cognitive functioning . Our results suggest that a brief paper- and -pencil measure reflecting planning/reasoning abilities may index responsivity to antipsychotic medication . However , improvements in cognitive functioning over time were related to clinical symptom improvement , reflecting " pseudospecificity .
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 .