Andrea Zangara

Cognitive Performance and Morning Levels of Salivary Cortisol and α-Amylase in Children Reporting High vs. Low Daily Stress Perception

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.

A pilot investigation into the effect of maca supplementation on physical activity and sexual desire in sportsmen.

AIMS OF THE STUDY Maca (Lepidium meyenii Walp) is consumed both as a sports supplement by strength and endurance athletes, and as a natural stimulant to enhance sexual drive. However, whether or not the postulated benefits of maca consumption are of scientific merit is not yet known. The aim of the study was therefore to investigate the effect of 14 days maca supplementation on endurance performance and sexual desire in trained male cyclists. MATERIALS AND METHODS Eight participants each completed a 40 km cycling time trial before and after 14 days supplementation with both maca extract (ME) and placebo, in a randomised cross-over design. Subjects also completed a sexual desire inventory during each visit. RESULTS ME administration significantly improved 40 km cycling time performance compared to the baseline test (P=0.01), but not compared to the placebo trial after supplementation (P>0.05). ME administration significantly improved the self-rated sexual desire score compared to the baseline test (P=0.01), and compared to the placebo trial after supplementation (P=0.03). CONCLUSIONS 14 days ME supplementation improved 40 km cycling time trial performance and sexual desire in trained male cyclists. These promising results encourage long-term clinical studies involving more volunteers, to further evaluate the efficacy of ME in athletes and normal individuals and also to explore its possible mechanisms of action.

An Acute, Double-Blind, Placebo-Controlled Crossover Study of 320mg and 640mg Doses of a Special Extract of Bacopa monnieri (CDRI 08) on Sustained Cognitive Performance

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

An Acute, Double‐Blind, Placebo‐Controlled Cross‐over Study of 320 mg and 640 mg Doses of Bacopa monnieri (CDRI 08) on Multitasking Stress Reactivity and Mood

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

A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831)

Clinical diagnoses of Attention Deficit Hyperactivity Disorder (ADHD) and the use of prescription medications for its treatment have increased in recent years. Current treatments may involve the administration of amphetamine-type substances, a treatment path many parents are apprehensive to take. Therefore, alternative pharmacological treatments are required. Few nutritional or pharmacological alternatives that reduce ADHD associated symptoms (hyperactivity and inattention) have been subjected to rigorous clinical trials. Bacopa monnieri is a perennial creeping herb. CDRI 08 is a special extract of Bacopa monnieri which has been subjected to hundreds of scientific studies and has been shown in human randomized controlled trials (RCTs) to improve memory, attention, and mood. It is hypothesised that chronic administration of CDRI 08 will improve attention, concentration and behaviour in children with high levels of hyperactivity and/or inattention. This paper reports the protocol for the first 16-week, randomized, placebo-controlled, double-blind, parallel groups trial examining the efficacy and safety of CDRI 08 in male children aged 6–14 years with high levels of inattention and hyperactivity. The primary outcome variable will be the level of hyperactivity and inattention measured by the Conners’ Parent Rating Scale (CPRS). Secondary outcome variables include cognition, mood, sleep, and EEG. Trial registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000827831.

Examining the cognitive effects of a special extract of Bacopa monniera (CDRI08: Keenmnd): a review of ten years of research at Swinburne University.

Bacopa monniera (EBm), an Indian aquatic herb, has been used in traditional Ayurvedic medicine for centuries for indications related to memory and inflammation. More recently specific extracts of EBm have emerged that have been subjected to rigorous in vitro, animal and now human clinical trials. In this paper we discuss some of these studies with special reference to mechanisms and efficacy of a special extract of Bacopa (CDRI08). Studies using this extract indicate that CDRI08 has several modes of action on the human brain. Promising indications for use in humans include improving cognition in the elderly and in patients with neurodegenerative disorders.

Mechanisms, Efficacy, and Safety of Bacopa monnieri (Brahmi) for Cognitive and Brain Enhancement

The plant Bacopa monnieri (water hyssop, Brahmi, thyme-leaved Gratiola, herb of grace, and Indian pennywort) is a perennial, creeping herb native to the wet lands of India, particularly northeast and southern regions. Bacopa is an important plant of Ayurveda, where it is named as Brahmi, after Lord Brahma, the mythological creator of the world and originator of the science of Ayurveda. Bacopa is frequently mentioned in the religious, social, and medical treatises of India since the time of Vedic civilization. Its antiquity can be traced to the time of Athar Ved (the science of well-being) written in 800 BC where Bacopa finds a mention in the very first verse of the third chapter of Athar Samhita (compilation on the factors promoting well-being). More recently researchers have turned their attention to better understanding the mechanisms and efficacy of various extracts of Bacopa monnieri on human conditions. Although extracts of Bacopa have been studied and used to treat various disorders for centuries (pain, epilepsy, and inflammation, amongst many) perhaps the chief therapeutic claim concerning its benefits has been in improving memory. The Indian government has invested significant resources and conducted hundreds of studies examining the mechanisms of action on the brain and at a cellular level. Interestingly this research has uncovered a myriad of possible mechanisms relating to anti-inflammatory, antioxidant, metal chelation, amyloid, and cholinergic effects amongst many others. Although it is not unusual for plant based medicines to have multiple effects on cellular processes, Bacopa monnieri is perhaps one of the most scientifically studied in terms of mechanisms of action. Interestingly these mechanisms seem to comprehensively map on to the biological mechanisms that many researchers have argued underpin cognitive and memory processes. In 1996 a special extract of Bacopa monnieri was launched by the Indian Governments Central Drug Research Institute, Lucknow, termed CDRI 08. It was thought at the time that this particular standardised extract had been subjected to the most research and was the most promising extract for medical conditions. In 2010 the three editors for this special issue attended CDRIs 60th research anniversary where a special one-day symposium on research on CDRI 08 was held. It is this extract of Bacopa monnieri that is the focus of most of the papers in this special issue which reports studies relating to the safety, mechanisms, and efficacy of specific extracts of Bacopa monnieri. Over the last ten years there have been growing scientific studies on this interesting terrestrial herb. As can be seen in Figure 1 the number of publications concerning Bacopa monnieri is steadily growing reflecting increasing scientific interest in this plant for human conditions. Most of these studies reflect scientific endeavours relating to cellular mechanisms. As such these studies are an excellent base to launch larger clinical trials in humans. Although much is known about the mechanisms of Bacopa extracts on the brain there are still significant gaps in our knowledge. For instance, long-term chronic trials in older people are now required to understand whether Bacopa extracts such as CDRI 08 can prevent age-related cognitive decline or even more insidious diseases such as Alzheimers dementia. We note that a number of studies are also currently examining the effect of Bacopa extracts on improving cognitive and behavioural function in younger people. Clearly the next decade will focus on larger clinical trials in humans and expand upon the excellent animal and preclinical work mainly conducted in India. Figure 1 Con Stough Hemant Singh Andrea Zangara

Herbal Cognitive Enhancers: New Developments and Challenges for Therapeutic Applications

Current developments in the search for novel treatments for preserving cognitive function include those for slowing down the progression of the decline in mental ability associated with normal aging as well as treating various dementias. Many natural products possess properties of relevance to the quality of cognitive function, and interest in their use is increasingly driven by a number of factors including the standardization of their production, growing evidence of their mechanisms of action, and improvements in the quality of clinical trials with such products. Of particular interest are products from plants (herbal medicines), due to their potential synergistic complexity and also the ability to interact with multiple mechanisms within the body. However, herbal preparations can vary considerably in their effects and safety, particularly if the ‘seed to patient’ process is not properly controlled and standardized. The challenge is even greater when targeting human cognitive function, a multi faceted process which is demanding to measure and hard to improve. However, good progress is being made in this field; standardized cognitive tests are available and gold-standard experimental designs and methodologies are being increasingly utilised in clinical trials. Encouraging findings are now emerging in treating cognitive aging and dementia with natural products, and the future holds a great promise for this field.

Natural products as cognition enhancing agents

Natural products have a widespread public appeal that appears only to be growing. The fastest growth is in the western world although in lesser economically developed countries the demand remains as strong as ever. This appeal is aided by the almost universal, though completely irrational assumption, that if a product is natural it must be safe. This chapter will consider those naturally-occurring substances that are believed to beneficially affect cognitive function.

The Neurocognitive Effects of Hypericum perforatum Special Extract (Ze 117) during Smoking Cessation

The efficacy and tolerability of current treatments for smoking cessation are relatively poor. More research is required to address the biological mechanisms underpinning nicotine withdrawal and drug treatments for smoking cessation. We assessed the neurocognitive effects of Remotiv® (Hypericum perforatum Special Extract ‐ Ze 117), Nicabate CQ Nicotine Replacement therapy (NRT) and combined NRT/HP during conditions of smoking abstinence in 20 regular smokers aged between 18 and 60 years over a period of 10 weeks during smoking cessation. A Spatial Working Memory (SWM) task was completed at baseline, 4 weeks prior to quitting, as well as at the completion of the study, following the 10 weeks of treatment. Brain activity was recorded during the completion of the SWM task using Steady‐State Probe Topography. Reaction time and accuracy on the SWM task were not found to be significantly different between treatment groups at retest. Differences in SSVEP treatment profiles at retest are discussed, including stronger SSVEP Amplitude increase in posterior‐parietal regions for the HP and NRT groups and greater fronto‐central SSVEP Phase Advance in the HP group. Copyright