The impact of blackcurrant juice on attention, mood and brain wave spectral activity in young healthy volunteers.

There is a growing body of evidence from randomized controlled trials which indicates that consumption of berries has a positive effect upon the cognitive function of healthy adults. It has been recommended that studies combining cognitive and physiological measures be undertaken in order to strengthen the evidence base for the putative effects of flavonoid consumption on cognitive outcomes. This pilot study utilized a randomized, double-blind and placebo controlled crossover design to assess the influence of the acute administration of anthocyanin-rich blackcurrant juice, standardized at 500 mg of polyphenols, on mood and attention. Additionally, this trial used electroencephalography (EEG) to assess if any changes in cognitive performance are associated with changes in localized prefrontal cortex neuronal activity in nine healthy young adults. Outcomes from the pilot EEG data highlight an anxiolytic effect of the consumption of a single serve blackcurrant juice, as indexed by a suppression of α spectral power, and an increase in the slow wave δ and θ spectral powers. There was also an indication of greater alertness and lower fatigue, as indexed by an increase in ß power and suppression of α spectral power. Outcomes from the CogTrack™ system indicated a small acute increase in reaction times during the digit vigilance task.

A randomised double-blind placebo-controlled pilot trial of a combined extract of sage, rosemary and melissa, traditional herbal medicines, on the enhancement of memory in normal healthy subjects, including influence of age.

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.

Serum 25-hydroxyvitamin D and cognitive decline in the very old: the Newcastle 85+ Study.

BACKGROUND AND PURPOSE: Studies investigating the association between 25-hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking. METHODS: Cross-sectional (baseline) and prospective data (up to 3 years follow-up) from 775 participants in the Newcastle 85+ Study were analysed for global (measured by the Standardized Mini-Mental State Examination) and attention-specific (measured by the attention battery of the Cognitive Drug Research test) cognitive performance in relation to season-specific 25(OH)D quartiles. RESULTS: Those in the lowest and highest season-specific 25(OH)D quartiles had an increased risk of impaired prevalent (1.66, 95% confidence interval 1.06-2.60, P = 0.03; 1.62, 95% confidence interval 1.02-2.59, P = 0.04, respectively) but not incident global cognitive functioning or decline in functioning compared with those in the middle quartiles adjusted for sociodemographic, health and lifestyle confounders. Random effects models showed that participants belonging to the lowest and highest 25(OH)D quartiles, compared with those in the middle quartiles, had overall slower (log-transformed) attention reaction times for Choice Reaction Time (lowest, ß = 0.023, P = 0.01; highest, ß = 0.021, P = 0.02), Digit Vigilance Task (lowest, ß = 0.009, P = 0.05; highest, ß = 0.01, P = 0.02) and Power of Attention (lowest, ß = 0.017, P = 0.02; highest, ß = 0.022, P = 0.002) and greater Reaction Time Variability (lowest, ß = 0.021, P = 0.02; highest, ß = 0.02, P = 0.03). The increased risk of worse global cognition and attention amongst those in the highest quartile was not observed in non-users of vitamin D supplements/medication. CONCLUSION: Low and high season-specific 25(OH)D quartiles were associated with prevalent cognitive impairment and poorer overall performance in attention-specific tasks over 3 years in the very old, but not with global cognitive decline or incident impairment.

An examination of the effects of the antioxidant Pycnogenol on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population.

The study examines the effects of the antioxidant flavonoid Pycnogenol on a range of cognitive and biochemical measures in healthy elderly individuals. The study used a double-blind, placebo-controlled, matched-pair design, with 101 elderly participants (60-85 years) consuming a daily dose of 150 mg of Pycnogenol for a three-month treatment period. Participants were assessed at baseline, then at 1, 2, and 3 months of the treatment. The control (placebo) and Pycnogenol groups were matched by age, sex, body mass index, micronutrient intake, and intelligence. The cognitive tasks comprised measures of attention, working memory, episodic memory, and psychomotor performance. The biological measures comprised levels of clinical hepatic enzymes, serum lipid profile, human growth hormone, and lipid peroxidation products. Statistically significant interactions were found for memory-based cognitive variables and lipid peroxidation products, with the Pycnogenol group displaying improved working memory and decreased concentrations of F2-isoprostanes relative to the control group.

Improved cognitive performance in human volunteers following administration of guarana (Paullinia cupana) extract: comparison and interaction with Panax ginseng.

Extracts from the plant guarana (Paullinia cupana) feature as putatively stimulating ingredients in a number of foods, drinks and dietary/herbal supplements. To date, little research in humans has examined the potential psychoactive effects of these extracts. Extracts of Panax ginseng, which are often sold in combination with guarana, contain similar potentially active components, and have been shown to modulate cognitive performance. In this double-blind, counterbalanced, placebo-controlled study, the cognitive and mood effects of separate single doses of: 75 mg of a dried ethanolic extract of guarana (approx 12% caffeine), 200 mg of Panax ginseng (G115), and their combination (75 mg/200 mg), were assessed in 28 healthy young (18-24) participants. On each day of the study (separated by a 7-day washout), cognitive performance and subjective mood were assessed pre-dose and at 1, 2.5, 4 and 6 h post-dose using the Cognitive Drug Research computerised assessment battery, Serial subtraction tasks and Bond-Lader mood scales. In comparison to placebo, all three treatments resulted in improved task performance throughout the day. In the case of guarana, improvements were seen across 'attention' tasks (but with some evidence of reduced accuracy), and on a sentence verification task. While also increasing the speed of attention task performance, both ginseng and the ginseng/guarana combination also enhanced the speed of memory task performance, with little evidence of modulated accuracy. Guarana and the combination, and to a lesser extent ginseng, also led to significant improvements in serial subtraction task performance. These results provide the first demonstration in humans of the psychoactive effects of guarana, and confirmation of the psychoactive properties of ginseng. Given the low caffeine content (9 mg) of this dose of guarana extract, the effects are unlikely to be attributable to its caffeine content.

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.

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 IC(50) concentrations of 0.18 and 3.47 mg ml(-1), respectively, for the displacement of [(3)H]-(N)-nicotine and [(3)H]-(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.

Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm).

Melissa officinalis (lemon balm) is a traditional herbal medicine, which enjoys contemporary usage as a mild sedative, spasmolytic and antibacterial agent. It has been suggested, in light of in vitro cholinergic binding properties, that Melissa extracts may effectively ameliorate the cognitive deficits associated with Alzheimer's disease. To date, no study has investigated the effects on cognition and mood of administration of Melissa to healthy humans. The present randomised, placebo-controlled, double-blind, balanced-crossover study investigated the acute effects on cognition and mood of a standardised extract of M. officinalis. Twenty healthy, young participants received single doses of 300, 600 and 900 mg of M. officinalis (Pharmaton) or a matching placebo at 7-day intervals. Cognitive performance was assessed using the Cognitive Drug Research (CDR) computerised test battery and two serial subtraction tasks immediately prior to dosing and at 1, 2.5, 4 and 6 h thereafter. In vitro IC(50) concentrations for the displacement of [3H]-(N)-nicotine and [3H]-(N)-scopolamine from nicotinic and muscarinic receptors in human occipital cortex tissue were also calculated. Results, utilising the cognitive factors previously derived from the CDR battery, included a sustained improvement in Accuracy of Attention following 600 mg of Melissa and time- and dose-specific reductions in both Secondary Memory and Working Memory factors. Self-rated "calmness," as assessed by Bond-Lader mood scales, was elevated at the earliest time points by the lowest dose, whilst "alertness" was significantly reduced at all time points following the highest dose. Both nicotinic and muscarinic binding were found to be low in comparison to the levels found in previous studies.

Modulation of cognition and mood following administration of single doses of Ginkgo biloba, ginseng, and a ginkgo/ginseng combination to healthy young adults.

It has previously been demonstrated in separate studies that single doses of Ginkgo biloba, Panax ginseng, and a combination of the two extracts can improve different aspects of cognitive performance in healthy young volunteers. The present study directly compared the effects of single doses of G. biloba, ginseng, and a product combining the two on aspects of mood and cognitive performance in the same cohort of healthy, young adult volunteers. The study followed a randomised placebo-controlled, double-blind, balanced, cross-over design. Twenty participants received 360 mg of ginkgo, 400 mg of ginseng, 960 mg of a product combining the two extracts, and a matching placebo. Treatment order was dictated by random allocation to a Latin square, with a 7-day wash-out period between treatments. Cognitive testing comprised completion of the Cognitive Drug Research (CDR) computerised assessment battery and two serial subtraction mental arithmetic tasks. Mood was assessed with Bond-Lader visual analogue scales. Following a baseline cognitive assessment, further test sessions took place 1, 2.5, 4, and 6 h after the day's treatment was taken. The results largely supported previous findings. All three treatments were associated with improved secondary memory performance on the CDR battery, with the ginseng condition evincing some improvement in the speed of performing memory tasks and in the accuracy of attentional tasks. Following ginkgo and the ginkgo/ginseng combination performance of both the Serial Threes and Serial Sevens, subtraction tasks was also improved at the later testing sessions. No modulation of the speed of performing attention tasks was evident. Improvements in self-rated mood was also found following ginkgo and to a lesser extent the combination product.

Dose dependent changes in cognitive performance and mood following acute administration of Ginseng to healthy young volunteers.

Recent evidence suggests that chronic administration of Ginseng can improve cognitive performance in animals and in humans. No previous study has examined the possibility of cognitive effects following single doses of Ginseng in healthy adults. The present study investigated whether acute administration of Ginseng (G115, Pharmaton SA) had any consistent effect on mood and four aspects of cognitive performance ("Quality of Memory", "Speed of Memory", "Quality of Attention" and "Speed of Attention") that can be derived by factor analysis of the Cognitive Drug Research computerised assessment battery. The study followed a placebo-controlled, double-blind, balanced, crossover design. Twenty healthy young adult volunteers received 200, 400, and 600 mg of G115, and a matching placebo, in counterbalanced order, with a 7 day wash-out period between treatments. Following a baseline cognitive assessment, further test sessions took place 1, 2.5, 4 and 6 h after the day's treatment. The most striking result was a significant improvement in "Quality of Memory" and the associated "Secondary Memory" factor at all time points following 400 mg of Ginseng. Both the 200 and 600 mg doses were associated with a significant decrement of the "Speed of Attention" factor at later testing times only. Subjective ratings of alertness were also reduced 6 h following the two lowest doses. To the best of our knowledge this represents the first demonstration of a modulation of mood and cognitive performance by acute administration of Ginseng.

Differential, dose dependent changes in cognitive performance following acute administration of a Ginkgo biloba/Panax ginseng combination to healthy young volunteers.

We have previously shown differential cognitive improvements following single doses of Ginkgo biloba and of Ginseng. There is also evidence that chronic administration of a combination of standardised extracts of Ginkgo biloba and Panax ginseng may improve aspects of cognitive performance both in pathological populations and the healthy middle aged. No investigation has thus far looked either at the cognitive effects of single doses of such a combination, nor the effects of the combination on healthy young volunteers. The present study investigated whether acute administration of a combination of standardised extracts of Ginkgo biloba (GK501, Pharmaton SA) and Ginseng (G115, Pharmaton SA) had any consistent effect on mood and aspects of cognitive performance ("quality of memory", "secondary memory", "working memory", "speed of memory", "quality of attention" and "speed of attention") that can be derived by factor analysis of the cognitive drug research computerised assessment battery. The study followed a placebo-controlled, double blind, balanced, crossover design. Twenty healthy young adult volunteers received 320, 640, and 960 mg of the combination, and a matching placebo, in an order dictated by random allocation to a Latin square, and with a seven-day wash-out period between treatments. Following a baseline cognitive assessment, further test sessions took place 1, 2.5,4 and 6 h after the day's treatment. The most striking result was a dose-dependent improvement in performance on the "quality of memory" factor for the highest dose. Further analysis revealed that this effect was differentially targeted at the secondary memory rather than the working memory component. There was also a dose dependent decrement in performance of the "speed of attention" factor for both the 320 and 640 mg doses. These results are discussed in the context of previous findings within this series of studies.

The dose-dependent cognitive effects of acute administration of Ginkgo biloba to healthy young volunteers.

RATIONALE: Chronic administration of extracts from the leaves of the tree Ginkgo biloba is known to improve aspects of cognitive performance. However, little is known about the effects of acute doses of Ginkgo on coherent cognitive domains. Recent factor analysis of test measures from subtasks of the Cognitive Drug Research (CDR) computerised assessment battery has revealed that four primary cognitive 'factors' corresponding to speed of attention, accuracy of attention, speed of memory and quality of memory can be useful to describe cognitive function changes. OBJECTIVE: The present study aimed at assessing whether acute administration of Ginkgo biloba had any consistent effect on the four CDR factors. METHODS: The study utilised a placebo-controlled, multi-dose, double-blind, balanced, crossover design. Twenty participants received 120 mg, 240 mg and 360 mg of a standardised extract of Ginkgo (GK501, Pharmaton, SA) or a matching placebo. Cognitive performance was assessed using the CDR computerised test battery immediately prior to dosing and at 1, 2.5, 4 and 6 h thereafter. The primary outcome measures were the four aspects of cognitive performance, which have previously been derived by factor analysis of CDR subtests. RESULTS: Compared with the placebo, administration of Ginkgo produced a number of significant changes on the performance measures. The most striking of these was a dose-dependent improvement of the 'speed of attention' factor following both 240 mg and 360 mg of the extract, which was evident at 2.5 h and was still present at 6 h. Additionally, there were a number of time- and dose-specific changes (both positive and negative) in performance of the other factors. CONCLUSIONS: We conclude that acute administration of Ginkgo biloba is capable of producing a sustained improvement in attention in healthy young volunteers.

The memory enhancing effects of a Ginkgo biloba/Panax ginseng combination in healthy middle-aged volunteers.

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.

The cognitive, subjective, and physical effects of a ginkgo biloba/panax ginseng combination in healthy volunteers with neurasthenic complaints.

We evaluated the effects of a Ginkgo biloba/ginseng combination on cognitive function in this 90-day, double-blind, placebo-controlled, parallel-group study. Sixty-four healthy volunteers (aged 40 to 65 years), selected on the basis of fulfilling the ICD-10 F48.0 criteria for neurasthenia, were assigned randomly to four equal dosing groups, receiving 80, 160, or 320 mg of the combination b.i.d. or placebo. Assessments were performed on the day before dosing, and again at Days 1, 30, and 90 at 1 hour after the morning dose and 1 hour after the afternoon dose. The assessments included the Cognitive Drug Research (CDR) computerized assessment system, the Vienna Determination Unit, cycle ergometry, and various questionnaires. The treatments were well tolerated by all volunteers. On Day 90 at 1 hour post morning dosing, dose-related improvements were seen on the CDR tests, the 320 mg dose being significantly superior to placebo. These effects, however, were reversed 1 hour after the afternoon dose, possibly suggesting that a longer inter-dosing interval would be preferable. The 80-mg dose produced a significant benefit on the ergometry assessment of heart rate at maximum load. There were also several supporting changes from other assessments, including an advantage of 320 mg over placebo on the global score from the Symptom Checklist-90-revised (SCL-90-R) at Day 90.

A double-blind, placebo controlled study of Ginkgo biloba extract ('tanakan') in elderly outpatients with mild to moderate memory impairment.

Thirty-one patients over the age of 50 years and showing a mild to moderate degree of memory impairment entered a 6-month double-blind, placebo controlled, parallel group design study to assess the effects of a standardized Ginkgo biloba extract (containing 24% flavonoid glycosides and 6% terpenes) on cognitive function. Patients were allocated at random to receive oral doses of 40 mg Ginkgo biloba extract or identical placebo 3-times daily. Assessments were made at baseline and after 12 and 24 weeks of treatment using a range of psychometric tests. Efficacy data were available for 27 patients (15 in the placebo group and 12 in the active treatment group). Statistical analysis of the data as compared to baseline suggests that Ginkgo biloba extract had a beneficial effect on cognitive function in this group of patients. Performance on the Digit Copying sub-test of the Kendrick battery was significantly improved at both 12 and 24 weeks, while the median speed of response on a computerized version of a classification task also showed a significant superiority over placebo at 24 weeks.

Facilitation of learning and state dependency with nicotine.

Two studies of nicotine and memory encoding were carried out using a state-dependent design. The first experiment used cigarettes and involved memory for stimuli that could not be encoded phonemically or semantically. The results of this recognition study show that nicotine was facilitating the input of non-phonemicably encodable and non-semanticably encodable information to storage and that nicotine produced state-dependent learning. The second study used nicotine tablets and involved memory for concrete words. The results of the free recall study show that nicotine produced state-dependent learning, that nicotine was facilitating the input of information to storage, but there was no evidence that associative processes had been changed by nicotine. These findings give no support for the suggestion that a cholinergic system in the brain is controlling the encoding of intrinsic cues relating to phonemic and semantic properties of things but not those involving mnemonic encoding by mental imagery, but rather that the cholinergic system is non-specifically involved in encoding.

Smoking as a coping strategy.

People in modern society use an ever increasing variety of psychoactive substances to help them cope with the increasing amount of stress they experience in the course of their lives. A survey was undertaken to investigate the role of smoking as a coping strategy and the relationship between smoking, the other coping strategies available, and personality in an undergraduate student population. There seemed to be three distinct subgroups in this population as defined by their preferred coping strategy: those who seek help from their friends when faced by problems, those who seek "expert advice," and those who attempt to solve their problems alone; often with the use of drugs. Those falling in the third category, that of self-help, were more likely to self-medicate with a wide variety of psychoactive substances. If they were smokers then they smoked more cigarettes and chose their brand on the basis of strength of a cigarette. There was no evidence for different personality types tending to smoke in different situations and no evidence for any link between extraversion or neuroticism and substance use or coping.