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Objective: To evaluate for the first time the effects of a combination of sage, rosemary and melissa (Salvia officinalis L., Rosmarinus officinalis L. and Melissa officinalis L.; SRM), traditional European medicines, on verbal recall in normal healthy subjects. To devise a suitable study design for assessing the clinical efficacy of traditional herbal medicines for memory and brain function., Methods: Forty-four normal healthy subjects (mean age 61 ± 9.26y SD; m/f 6/38) participated in this study. A double-blind, randomised, placebo-controlled pilot study was performed with subjects randomised into an active and placebo group. The study consisted of a single 2-week term ethanol extract of SRM that was chemically-characterised using high resolution LC-UV-MS/MS analysis. Immediate and delayed word recall were used to assess memory after taking SRM or placebo (ethanol extract of Myrrhis odorata (L.) Scop.). In addition analysis was performed with subjects divided into younger and older subgroups (≤ 62 years mean age n = 26: SRM n = 10, Placebo n = 16; ≥ 63 years n = 19: SRM n = 13, Placebo n = 6)., Results: Overall there were no significant differences between treatment and placebo change from baseline for immediate or delayed word recall. However subgroup analysis showed significant improvements to delayed word recall in the under 63 year age group (p < 0.0123) with Cohen's effect size d = 0.92. No adverse effects were observed., Conclusion: This pilot study indicates that an oral preparation of SRM at the selected dose and for the period of administration is more effective than a placebo in supported verbal episodic memory in healthy subjects under 63 years of age. Short- and long- term supplementation with SRM extract merits more robust investigation as an adjunctive treatment for patients with Alzheimer's disease and in the general ageing population. The study design proved a simple cost effective trial protocol to test the efficacy of herbal medicines on verbal episodic memory, with future studies including broader cognitive assessment., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Rosemary (Rosmarinus officinalis L.) has traditional reputations that justify investigation for a potential role in reducing widespread cognitive decline in the elderly. A randomized, placebo-controlled, double-blinded, repeated-measures crossover study was conducted to investigate possible acute effects of dried rosemary leaf powder on cognitive performance. Twenty-eight older adults (mean age, 75 years) were tested using the Cognitive Drug Research computerized assessment system 1, 2.5, 4, and 6 hours following a placebo and four different doses of rosemary. Doses were counterbalanced, and there was a 7-day washout between visits. There was a biphasic dose-dependent effect in measures of speed of memory: the lowest dose (750 mg) of rosemary had a statistically significant beneficial effect compared with placebo (P=.01), whereas the highest dose (6,000 mg) had a significant impairing effect (P<.01). There were significant deleterious effects on other measures of cognitive performance, although these were less consistent. Speed of memory is a potentially useful predictor of cognitive function during aging. The positive effect of the dose nearest normal culinary consumption points to the value of further work on effects of low doses over the longer term.

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.)

The aim of the present study was to assess the effects of daily stress perception on cognitive performance and morning basal salivary cortisol and alpha-amylase levels in healthy children aged 9-12. Participants were classified by whether they had low daily perceived stress (LPS, n = 27) or a high daily perceived stress (HPS, n = 26) using the Children Daily Stress Inventory (CDSI). Salivary cortisol and alpha-amylase were measured at awakening and 30 minutes later. Cognitive performance was assessed using the Cognitive Drug Research assessment system. The HPS group exhibited significantly poorer scores on speed of memory (p < .05) and continuity of attention (p < .05) relative to the LPS group. The HPS group also showed significantly lower morning cortisol levels at awakening and at +30 minutes measures in comparison with the LPS group (p < .05), and mean morning cortisol levels were negatively correlated with speed of memory (p < .05) in the 53 participants. No significant differences were observed between both groups in alpha-amylase levels. These findings suggest that daily perceived stress in children may impoverish cognitive performance via its modulating effects on the HPA axis activity.

Objective: To compare executive, memory and visuospatial functioning of DSM-IV anorexia nervosa (AN), bulimia nervosa (BN), and normal controls (NC)., Method: A comparison of women involving: (i) 16 AN with body mass indices (BMI) < or = 17.5 kg/m(2); (ii) 12 AN with BMI > 18.5 kg/m(2) for at least 3 months; (iii) 13 BN; and (iv) 16 NC participants was performed with groups of similar age and intelligence. Groups were assessed with EDE-12, MADRS, HAMA, Cognitive Drug Research (CDR) battery, and Bechara tasks., Results: Significant impairments in CDR Power of Attention were present in underweight AN and BN participants. CDR Morse Tapping was significantly impaired in all clinical groups. The BN and weight-recovered AN groups were significantly impaired on CDR immediate word recall. The BN group alone was significantly impaired on CDR delayed word recall., Conclusion: Attentional impairment is similar in AN and BN. Impaired motor tasks in AN persist after "weight-recovery" and are similar to impairments in BN. BN may be discriminated from AN on word recall., ((c) 2007 by Wiley Periodicals, Inc.)

Objective: Armodafinil is the R-enantiomer of racemic modafinil and has a significantly longer half-life than the S-enantiomer. This study evaluated armodafinil 150 mg/day as an adjunct treatment for residual excessive sleepiness in patients with obstructive sleep apnea/hypopnea syndrome (OSA/HS) who were otherwise well controlled with nasal continuous positive airway pressure (nCPAP). We assessed the ability of armodafinil to improve wakefulness and cognition and reduce fatigue in this population., Methods: In this 12-week, randomized, double-blind study, patients (n=259) received armodafinil (150 mg) or placebo once daily. Efficacy assessments at baseline and weeks 4, 8, and 12 included the Maintenance of Wakefulness Test (MWT), Clinical Global Impression of Change (CGI-C), Cognitive Drug Research battery, Epworth Sleepiness Scale, and Brief Fatigue Inventory., Results: At final visit, mean (SD) MWT sleep latency increased from baseline by 2.3 (7.8) min with armodafinil and decreased by 1.3 (7.1) min in the placebo group (P=0.0003). Armodafinil improved clinical condition (CGI-C, 71% vs. 53% for armodafinil and placebo, respectively; P=0.0069). Armodafinil significantly improved episodic secondary memory (P=0.0102) and patient-estimated wakefulness (P<0.01) and reduced fatigue (P<0.05) compared with placebo. Armodafinil did not adversely affect nCPAP use. The most common adverse event associated with armodafinil was headache. Sleep macroarchitecture was not altered by armodafinil., Conclusion: Adjunct treatment with armodafinil significantly improved alertness, overall clinical condition, and long-term memory. Armodafinil also reduced fatigue and the impact of sleepiness on daily activities in patients with OSA/HS who have residual excessive sleepiness notwithstanding regular use of nCPAP. Armodafinil was well tolerated.

Context: The apolipoprotein E (APOE) epsilon4 allele has been implicated as a significant risk factor in the development of late-onset Alzheimer disease, but the evidence of cognitive sequelae in healthy individuals has been mixed., Objective: To determine if the APOE epsilon4 allele increases susceptibility to lorazepam-induced verbal learning impairment in nondemented older adults., Design: A placebo-controlled crossover design., Setting: A community-based sample of subjects., Participants: Sixty-four cognitively intact and highly educated (>12 years) adults. Twenty-four subjects (mean age, 66.3 years) were carriers of an APOE epsilon4 allele (epsilon4 positive) and 40 (mean age, 66.0 years) were not (epsilon4 negative)., Interventions: All subjects received a single oral dose of placebo and lorazepam (0.5 and 1.0 mg) 1 week apart., Main Outcome Measure: We used the Buschke Selective Reminding Test to assess verbal learning during a 5-hour period after placebo or lorazepam administration., Results: We found a time-related, dose-dependent effect of lorazepam, with long-term recall generally decreasing with higher doses of lorazepam at up to 2.5 hours. At 5 hours, the epsilon4-negative group showed significant improvement in long-term memory, but the epsilon4-positive group demonstrated a persistent deficit. Subsequent analysis revealed that the poor performance at 5 hours was found in an epsilon4-positive subgroup with lower baseline performance., Conclusions: In cognitively intact, older adults, the effect of the APOE epsilon4 allele is not necessarily seen in the immediate response to benzodiazepine challenge. Rather, the APOE epsilon4 allele appears to affect the carrier's ability to recover from a cognitive challenge in a normal fashion, at least in a subgroup of subjects with relatively low baseline performance. This suggests that although carrying an APOE epsilon4 allele increases the risk for cognitive toxic effects, allele status alone is not a sufficient predictor of such effects. Studying the response to and the recovery from cognitive challenges may provide insights into the role of the APOE epsilon4 allele and its interaction with other factors in the development of Alzheimer disease and other age-related cognitive problems.

Hypertension is associated with impairments in cognitive function in older adults, but the nature and extent of these deficits are unclear. Brief cognitive measures lack sensitivity, whereas comprehensive assessments produce numerous variables that are difficult to interpret. The authors performed a principal-components analysis using a computerized cognitive assessment battery and neuropsychological measures of executive function in 506 hypertensive and normotensive older participants. Composite factor scores were used to reanalyze data from 223 untreated participants without vascular complications. The hypertensive group had deficits in Speed of Cognition, Episodic and Working Memory, and Executive Function but not Continuity of Attention. Using composite scores simplified data interpretation and suggested differential effects of hypertension on cognitive performance not clearly evident in individual test results.

Sage (Salvia) has a longstanding reputation in British herbal encyclopaedias as an agent that enhances memory, although there is little evidence regarding the efficacy of sage from systematized trials. Based on known pharmacokinetic and binding properties, it was hypothesised that acute administration of sage would enhance memory in young adult volunteers. Two experiments utilised a placebo-controlled, double-blind, balanced, crossover methodology. In Trial 1, 20 participants received 50, 100 and 150 microl of a standardised essential oil extract of Salvia lavandulaefolia and placebo. In Trial 2, 24 participants received 25 and 50 microl of a standardised essential oil extract of S. lavandulaefolia and placebo. Doses were separated by a 7-day washout period with treatment order determined by Latin squares. Assessment was undertaken using the Cognitive Drug Research computerised test battery prior to treatment and 1, 2.5, 4 and 6 h thereafter. The primary outcome measures were immediate and delayed word recall. The 50 microl dose of Salvia essential oil significantly improved immediate word recall in both studies. These results represent the first systematic evidence that Salvia is capable of acute modulation of cognition in healthy young adults.

Ginkgo biloba has been shown to have chronic memory enhancing effects in healthy subjects and patients with dementia. There is limited research on the acute nootropic effects of Ginkgo biloba in humans. The current study aimed to examine the acute effects of Ginkgo biloba (120 mg) on memory functioning in healthy older volunteers using the cognitive drug research (CDR) battery of memory tests and the Rey auditory verbal learning task (AVLT). The study was a double-blind placebo-controlled design, with each participant tested under both placebo and Ginkgo biloba treatment conditions. Testing was conducted pre- and 90 min post-drug administration for each treatment condition. Treatment conditions were separated by a 7 day wash out period. No acute effects of Ginkgo biloba were found for any of the memory tests examined. The findings suggest that 120 mg of Ginkgo biloba has no acute nootropic effects in healthy older humans., (Copyright 2002 John Wiley & Sons, Ltd.)

The effects of capsules containing 60 mg of a standardised extract of Ginkgo biloba (GK501) and 100 mg of a standardised extract of Panax ginseng (G115) on various aspects of cognitive function were assessed in healthy middle-aged volunteers. A double blind, placebo controlled, 14 week, parallel group, repeated assessment, multi-centre trial of two dosing regimens, 160 mg b.i.d. and 320 mg o.d. was conducted. Two hundred and fifty-six healthy middle-aged volunteers successfully completed the study. On various study days (weeks 0, 4, 8, 12 and 14) the volunteers performed a selection of tests of attention and memory from the Cognitive Drug Research computerised cognitive assessment system prior to morning dosing and again, at 1, 3 and 6 h later. The volunteers also completed questionnaires about mood states, quality of life and sleep quality. The Ginkgo/ginseng combination was found significantly to improve an Index of Memory Quality, supporting a previous finding with the compound. This effect represented an average improvement of 7.5% and reflected improvements to a number of different aspects of memory, including working and long-term memory. This enhancement to memory was seen throughout the 12-week dosing period and also after a 2-week washout. This represents the first substantial demonstration of improvements to the memory of healthy middle-aged volunteers produced by a phytopharmaceutical.

Objectives: To compare the effects of nitrous oxide and midazolam on cognition and mood., Design: A three-way, counterbalanced, cross-over study, using patients receiving conscious sedation for routine dental treatment., Methods: On each of three separate visits, patients performed a computerised test battery to determine baseline cognitive performance. Then, following administration of either midazolam, nitrous oxide, or no drug, patients re-performed the test battery. Finally, patients completed visual analogue scales assessing their subjective mood state., Results: Relative to baseline performance, midazolam administration produced significantly slower reaction times compared with nitrous oxide and no-drug conditions. Furthermore, patients receiving midazolam were impaired in accuracy relative to the other conditions on many of the cognitive tasks, particularly those assessing the recall of information. Patient performance in nitrous oxide and control conditions did not significantly differ. These results could not be explained by differences in mood between the conditions, as subjective mood ratings during midazolam or nitrous oxide administration were very similar., Conclusions: It is important for clinicians to be aware that peri-operative recall of information is reduced in patients who have undergone midazolam sedation. This is an advantage for patients who are anxious, and do not wish to be aware of the operative treatment being performed. However, as the cognitive impairment is enduring, an adult escort and written post-operative instructions should be mandatory for midazolam sedation patients. In contrast, the use of nitrous oxide sedation does not significantly impair higher cognitive tasks and thus patients receiving nitrous oxide sedation can resume normal activities in the post-operative period.

Oxygen administration coinciding with word presentation enhances word recall in humans, suggesting that elevated levels of circulating blood oxygen may be available to neural memory consolidation processes. This double-blind experiment examined the relationship between blood oxygen levels and cognitive performance when oxygen was inspired for 2 min at different times relative to a simple word recall task, forward digit span and backward digit span. Transient hyperoxia, measured by haemoglobin-bound oxygen, was evident following oxygen inspiration. Neither forward nor backward digit span was affected by oxygen administration. Word recall (12 min following word presentation) was enhanced when oxygen was administered 5 min prior to, immediately before or immediately following word presentation; but not 10 min prior to, 5 min following nor 10 min following, word presentation. These data suggest that oxygen administration can selectively enhance aspects of cognitive performance and support a hypothesis whereby supplemental blood oxygen is sequestered by neural mechanisms involved in memory consolidation.

It was recently demonstrated that oxygen administration can improve performance on a simple word recall task in healthy young adults. This study was aimed at determining the impact of various durations of oxygen administration on a wider range of cognitive measures. This was achieved using the Cognitive Drug Research computerised test battery, and employing a double-blind, placebo-controlled crossover design. Over a period of 7 weeks, 20 participants were trained and subsequently assessed on the test battery under several durations of oxygen inhalation; air administered in an identical fashion served as a control. The results provided support for our earlier work in that increases were found in both immediate and delayed word recall. In addition, oxygen administration significantly improved performance on several measures of attention and vigilance. Simple reaction time, choice reaction time, digit vigilance reaction time and picture recognition reaction time were improved in a manner which depended on the duration of oxygen inspired. With the exception of word recall, no significant improvements were found for any measure of accuracy, nor were word recognition, digit memory scanning, or spatial memory improved. These results are discussed in the context of stages of information processing and are consistent with the hypothesis that cognitive performance is "fuel-limited" and can be differentially augmented by increasing the availability of the brain's metabolic resources.

Cognitive task performance was assessed in three groups of young people: 10 regular users of 3,4-methylenedioxymethamphetamine (MDMA) who had taken 'ecstasy' 10 times or more; 10 novice MDMA users who had taken 'ecstasy' one to nine times; and 10 control subjects who had never taken MDMA. A computerized battery of cognitive tasks (Cognitive Drug Research system) was undertaken on a day when subjects were drug free. Performance on the response speed and vigilance measures (simple reaction time, choice reaction time, number vigilance), was similar across the three subgroups. However on immediate word recall and delayed word recall, both groups of MDMA users recalled significantly less words than controls. Animal research has shown that MDMA can lead to serotonergic neurodegeneration, particularly in the hippocampus and frontal cortex. Although the design of this study was far from ideal, these data are consistent with other findings of memory decrements in recreational MDMA users, possibly caused by serotonergic neurotoxicity.

Objectives: This project was conducted to examine whether the computerised analysis of psychomotor responses available from Cognitive Drug Research is appropriate for measuring an effect of low level exposure to mercury in dentists., Methods: A computerised battery of psychomotor tests was given to two groups of dentists (older dentists and trainees) and to two age matched control groups. As well as the psychomotor tests, volunteers were required to complete a questionnaire to identify potential influences on psychomotor performance and to provide a sample for analysis of urinary mercury., Results: Statistical analysis of the results showed that the older dentists had slightly higher concentrations of urinary mercury although most were around background levels and they were all within occupational limits. Five of the psychomotor tests showed no differences between the performance of the four groups. The older dentists showed significantly better performance on the simple reaction time test and significantly poorer performance in the immediate word recall and delayed word recall tests., Conclusions: Poorer performance in memory recall tests confirms previously reported studies. This together with the confirmation that this test system is a practical tool in the occupational setting suggests that a larger study of the effects of mercury exposure on dentists would be appropriate.

Scopolamine produces a satisfactory model of the attentional and secondary memory deficits seen in Alzheimer's disease (AD) that can be used to screen compounds for potential therapeutic usefulness. Physostigmine, which is known to enhance memory in AD, produced marked and widespread antagonism of the scopolamine-induced impairments, indicating the sensitivity of the model and establishing its relevance for the clinical situation. HP 029, a novel anticholinesterase, also exhibited widespread potency in the model, and in an international trial with patients with AD, it subsequently showed improvement on similar measures, demonstrating the predictive use of the scopolamine model.

It is argued that cholinergic drugs have an effect on both attentional and memory aspects of information processing. This thesis is supported by studies with anticholinesterases, cholinolytics, and nicotine.

The present study aimed to systematically assess acute, dose-related behavioural effects of an extract of guaraná plant for the first time in humans. This double-blind, counterbalanced, placebo-controlled study (n = 26) assessed the acute mood and cognitive effects throughout the day of four different doses (37.5mg, 75mg, 150mg and 300mg) of a standardised guaraná extract (PC-102). Assessment included the Cognitive Drug Research computerized test battery and Bond-Lader mood scales. Guaraná improved secondary memory performance and increased alert and content mood ratings. The two lower doses produced more positive cognitive effects than the higher doses. This research supports previous findings of cognitive improvements following 75 mg guaraná and provides the first exploration of different dose effects of guaraná in humans. The findings suggest that the effects cannot be attributed to caffeine alone. [ABSTRACT FROM AUTHOR]

Background: Levodopa (L-dopa) is the gold standard treatment for Parkinson's disease, but a lack of clear efficacy combined with a perceived liability to neuropsychiatric side effects has limited L-dopa use in patients with parkinsonism and dementia. Therefore, the effect of L-dopa on the cognitive profile of dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) is unclear. Aim: To ascertain the acute and long-term effects of L-dopa on aspects of attention and cognition in patients with DLB and PDD, and to compare these with the effects in Parkinson's disease. Method: Baseline cognitive and motor function was assessed off L-dopa in patients with Parkinson's disease (n = 22), PDD (n = 27) and DLB (n = 11) using standard ‘bedside’ measures and a computerised programme detecting reaction times and accuracy. All patients then underwent an acute L-dopa challenge with subsequent subjective and objective analysis of alertness, verbal recall, reaction times and accuracy. The same parameters were measured after 3 months on L-dopa to assess the prolonged effect. Results: Acute L-dopa challenge considerably improved motor function and subjective alertness in all patients without compromising either reaction times or accuracy, but increased fluctuations were noted in both groups with dementia. Neuropsychiatric scores improved in patients with Parkinson's disease both with and without dementia on L-dopa at 3 months. Although patients with Parkinson's disease also had better mean global cognitive function at this time, mean verbal attention and memory deteriorated, and patients with PDD had slower reaction times in some tests. No patient had a marked deterioration over this time. Patients with DLB did not experience any adverse cognitive or neuropsychiatric effects after 3 months of L-dopa treatment. Conclusion: The use of L-dopa in patients with parkinsonism with dementia does not adversely affect cognitive function. [ABSTRACT FROM AUTHOR]

Summary: To assess the effect of the aroma of the essential oil of Roman chamomile (Chamaemelum nobile) and the impact of induced expectancy on mood and cognition in healthy adults, 80 volunteers participated in an independent groups design study. There were four conditions: (1) aroma and arousal expectancy, (2) aroma and sedation expectancy, (3) aroma and no expectancy, and (4) no aroma controls. Expectancy effects were induced by means of a pre-test session where participants were provided with false information from a supposed official source. Pre-test mood scales were completed followed by the Cognitive Drug Research (CDR) battery and a final post-test mood scale. Analysis revealed a significant effect of condition on overall quality of memory (p =0.017), long-term memory (p =0.008) and accuracy of attention (p =0.024). Analysis of the pre to post-test changes in mood revealed significant changes in alertness (p =0.002), and calmness (p =0.00004). The sedative nature of the aroma appeared to combine with induced sedative expectancy to impair cognitive performance to a greater degree than was found for aroma alone. Subjective alertness was influenced by the sedative effect of the aroma which was ameliorated to some degree by the induced arousal expectancy. Similarly, subjective calmness appeared to be influenced by both the sedative effect of the aroma and induced arousal expectancy. [Copyright &y& Elsevier]

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 samples 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 randomized, 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 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. [ABSTRACT FROM AUTHOR]

Summary Flumazenil is traditionally administered intravenously to reverse the adverse effects of over sedation with benzodiazepines. The aim of this study was to test postoperative cognitive and psychomotor recovery from midazolam conscious sedation, following reversal with orally administered flumazenil. It was hypothesised that when administered by the oral route, flumazenil may enhance recovery over a prolonged period, thus increasing safety. Eighteen patients requiring intravenous midazolam sedation for dental treatment completed a randomised, double-blind, crossover trial. Following treatment the patients' sedation was reversed using either flumazenil or saline (asplacebo), administered orally, on alternate appointments. Assessment of mood and cognitive function were undertaken using ClinPhone.cdr®, a highly sensitive and specific computerised battery of cognitive tests administered by telephone prior to sedation and every hour for seven hours post reversal. Results indicate that within 20 min of administration, oral flumazenil is capable of partially reversing some cognitive and psychomotor impairments but the attentional and stimulus discrimination effects of midazolam sedation still remain. [ABSTRACT FROM AUTHOR]

Objectives: To assess the possible effects of flumazenil on cognitive processing, physiology, and mood. Design A double-blind, placebo controlled, four-way cross-over study, using healthy volunteers.Methods: On each of 4 separate visits, 16 participants received 0.5 mg, 2.5 mg, 5.0 mg of flumazenil, or normal saline. They then performed a computerised test battery assessing cognitive function. Measures of pulse rate, arterial oxygen saturation and mean arterial pressure were also taken. Finally, participants completed visual analogue scales assessing their subjective mood state.Results: The majority of cognitive tasks showed dose-dependent declines in performance. Mean arterial pressure was significantly reduced, as was pulse rate. Subjective alertness showed a similar decline.Conclusions: Flumazenil has been clinically described as an agent with few intrinsic properties, whose primary effect lies in its ability to reverse benzodiazepine-induced states. This study has shown that flumazenil does possess intrinsic activity which have a significant effect on cognition, cardiovascular physiology and mood. Clinicians need to be aware of these effects. [ABSTRACT FROM AUTHOR]

In this double-blind, placebo controlled, four-way cross-over trial in 16 healthy elderly volunteers, the acute effects of haloperidol 2 mg, amisulpride 50 mg and 200 mg, were assessed on a range of tests of cognitive function. On each study day, cognitive performance was assessed prior to dosing and at 2, 4, 6, 9, 12 and 24 h after dosing with the following tests from the Cognitive Drug Research computerized assessment system: simple reaction time, digit vigilance task, choice reaction time, visual tracking, Critical Flicker Fusion, body sway, numeric working memory, immediate and delayed word recall, word recognition and self-ratings of mood and alertness. Haloperidol showed a general tendency to impair performance, and although this did not reach significance compared to placebo, for two tasks there were significant impairments with haloperidol compared to amisulpride. Amisulpride 50 mg and 200 mg, was not associated with impairment. In fact, there was some suggestion of improvement over placebo on three measures. The timings of assessment were appropriate for the study compounds. Furthermore, in a recent study in which a smaller number of elderly volunteers was tested on the same cognitive assessment system, a clear profile of acute impairments of haloperidol 3 mg, was identified. This indicates that haloperidol 2 mg, is not a sufficient dose to affect cognitive function in the elderly, supporting the general absence of effects with this dose in the young. Thus, the general absence of cognitive impairments with amisulpride at the doses used in this study suggests that this compound does not impair cognitive function in the elderly. [ABSTRACT FROM AUTHOR]

The cognitive and psychomotor effects of olanzapine (3 mg) were compared with haloperidol (3 mg) and placebo in a double-blind, cross-over study. Fourteen healthy elderly volunteers (>65 years) were randomized to receive once daily medication for 4 days with a 16-day interval between treatment periods. Assessments of attention, memory and motor control were made prior to dosing on each day, at 2, 4, 6 and 8 h after dosing on days 1 and 4, and at 24 and 48 h following the last dose. On day 1, detectable impairment was observed at all time points in both groups. On day 4, haloperidol treated subjects showed increased impairment compared with day 1 and this was sustained throughout the 48 h of testing. Olanzapine treated subjects showed reduced day 4 deficit (compared with day 1), with no significant difference from placebo beyond 6 h post dose. These results suggest that both haloperidol and olanzapine have a measurable initial effect on cognitive and psychomotor function in elderly volunteers. However, acute effects associated with olanzapine decrease with repeated dosing and show substantial adaptation within 4 days. In contrast, effects seen with haloperidol are sustained and increase with repeated dosing over the same period. [ABSTRACT FROM AUTHOR]

The present study was conducted to determine the degree to which impairments in attention accompany the memory deficits produced by scopolamine. Eighteen healthy young volunteers received scopolamine 0·6 mg subcutaneously on three experimental sessions and placebo on three others, On each session, prior to, and 60mm alter injection, the subjects underwent an automated computerized battery of 11 cognitive tasks. The study was run double-blind and the order of treatment conditions over successive visits was counterbalanced between subjects. Scopolamine produced marked and significant decrements on all major aspects of performance from the battery. The drug lowered the efficiency of the detection and processing of information in tests of visual vigilance, rapid information processing. choice reaction, letter cancellation and logical reasoning. These effects were accompanied by a lowering of critical flicker-fusion frequency and subjective alertness. Memory was also impaired on tests of immediate recall, delayed recall, recognition and memory scanning. These findings confirm and extend previous work, demonstrating that scopolamine impairs the selection and evaluation of environmental information, as well as reducing the likelihood of information being subsequently recalled or recognized. Whether the former effects contribute to the latter is not known, but this must be considered a possibility. This potential role of processing deficits in memory loss associated with cholinergic blockade is briefly considered in relation to the cholinergic hypothesis of geriatric memory loss. [ABSTRACT FROM AUTHOR]