In this review article, the authors critically reviewed nootropic agent Brahmi-derived from extract of Bacopa monnieri (EBm). Administration of EBm was seen to protect the cholinergic neurons and reduce anticholinesterase activity comparable to donepezil, rivastigmine, and galantamine. It also reduces hippocampal β-amyloid deposition and stress-induced hippocampal damage. EBm improved the total memory score and maximum improvement was seen in logical memory and paired associate learning in humans and reversed phenytoin-induced memory impairment in experimental model. EBm has not shown any serious clinical, neurological, hematological complications, or vital organs damage in experimental studies.

TITLE: Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract

REFERENCE: Chuenjid Kongkeaw, Piyameth Dilokthornsaku, Phurit Thanarangsarit, Nanteetip Limpeanchob, Norman Scholfield. Journal of Ethnopharmacology, Volume 151, Issue 1, 10 January 2014, Pages 528-535.

Investigators searched published studies on various databases using scientific and common synonyms of Bacopa monnieri, cognitive performance or memory. Randomized, placebo controlled human intervention trials on chronic ≥12 weeks dosing of standardized extracts of Bacopa monnieri without any co-medication were included in this study.

Nine studies met the inclusion criteria using 518 subjects. Meta-analysis of 437 eligible subjects showed improved cognition by shortened Trail B test (−17.9 ms; 95% CI −24.6 to −11.2; p<0.001) and decreased choice reaction time (10.6 ms; 95% CI −12.1 to −9.2; p<0.001).

This meta-analysis suggests that Bacopa monnieri has the potential to improve cognition, particularly speed of attention.

TITLE: Multifaceted therapeutic benefits of Ginkgo biloba L.: chemistry, efficacy, safety, and uses.

The standardized preparation of the Ginkgo leaf extract (EGb 761) contained 2 main bioactive constituents, flavonoid glycosides (24%) and terpene lactones (6%), along with less than 5 ppm of the allergenic component, ginkgolic acid. The Ginkgo leaf extract has been reported to have neuroprotective, anticancer, cardioprotective, stress alleviating, and memory enhancing effects and possible effects on tinnitus, geriatric complaints, and psychiatric disorders.

Pycnogenol is an extract from the bark of the French maritime pine (Pinus pinaster Aiton subsp. atlantica) with known anti-oxidative and neuroprotective effects. This study experimentally assessed the effects of Pycnogenol on AD-related pathology in a ß-amyloidosis mouse model. APP-transgenic mice and controls were treated orally in a pre-onset and post-onset treatment paradigm. Pycnogenol significantly decreased the number of plaques in both treatment paradigms but did not alter levels of soluble Aß or the gene expression of APP-processing enzymes. The authors suggested to evaluate clinically a potential use of Pycnogenol in the prevention or in early stages of mild cognitive impairment (MCI) and AD.

TITLE: Pycnogenol® improves cognitive function, attention, mental performance and specific professional skills in healthy professionals aged 35-55.

This 12-week, product-evaluation registry study aimed to compare the effects of supplementation with French Pine Bark Extract (Pycnogenol®) on cognitive function, attention, and mental performance in healthy professionals with increased oxidative stress in a professional context.

A group of 30 professionals used Pycnogenol®, and 29 acted as comparable controls for a period of 12 weeks. The two registry groups were comparable. Cognitive function, attention, mental performance, sustained attention, memory, executive functions, mood and oxidative stress values were comparable at inclusion. At 12 weeks the improvement in Pycnogenol® subjects was more significant than in controls. Mood parameters (alertness, anxiety, contentedness) also improved in professionals using the supplement. In the evaluation of 12 professional daily tasks all items were improved with Pycnogenol® supplementation.

The authors of this study concluded that Pycnogenol® supplementation for 12 weeks appears to improve cognitive function and oxidative stress in healthy professionals.

TITLE: Phosphatidylserine and the human brain.

The aim of this study was to assess the roles and importance of phosphatidylserine (PS), an endogenous phospholipid and dietary nutrient, in human brain biochemistry, physiology, and function.

127 articles were selected for inclusion for this review study. The authors concluded that Phosphatidylserine is required for healthy nerve cell membranes and myelin. Aging of the human brain is associated with biochemical alterations and structural deterioration that impair neurotransmission. Exogenous PS (300-800 mg/d) is absorbed efficiently in humans, crosses the blood-brain barrier, and safely slows, halts, or reverses biochemical alterations and structural deterioration in nerve cells. It supports human cognitive functions, including the formation of short-term memory, the consolidation of long-term memory, the ability to create new memories, the ability to retrieve memories, the ability to learn and recall information, the ability to focus attention and concentrate, the ability to reason and solve problems, language skills, and the ability to communicate. It also supports locomotor functions, especially rapid reactions and reflexes.

Investigators of this study used functional magnetic resonance imaging (fMRI) to test that l-theanine and caffeine may be bringing about a beneficial effect by increasing attention-related neural resource allocation to target stimuli and decreasing deviation of neural resources to distractors.

Solutions of 200mg of l-theanine, 160mg of caffeine, their combination, or the vehicle (distilled water; placebo) were administered in a randomized 4-way crossover design to 9 healthy adult men. Sixty minutes after administration, a 20-minute fMRI scan was performed while the subjects performed a visual color stimulus discrimination task. l-Theanine and l-theanine-caffeine combination resulted in faster responses to targets compared with placebo (∆=27.8milliseconds, P=.018 and ∆=26.7milliseconds, P=.037, respectively). l-Theanine was associated with decreased fMRI responses to distractor stimuli in brain regions that regulate visual attention, suggesting that l-theanine may be decreasing neural resource allocation to process distractors, thus allowing to attend to targets more efficiently.

The investigators concluded that L-theanine and caffeine may be decreasing deviation of attention to distractors (including mind wandering); thus, enhancing attention to target stimuli.

In this study, twenty-seven participants performed the Sustained Attention to Response Task (SART) over a two-hour session on each of four days, on which they were administered caffeine (50 mg), theanine (100 mg), the combination, or placebo in a double-blind, randomized, cross-over fashion. Concurrently, the investigators recorded oscillatory brain activity through high-density electroencephalography (EEG).

When treated with placebo, participants showed a rise in error rates, a pattern that is commonly observed with increasing time-on-task, whereas after caffeine and theanine ingestion, error rates were significantly reduced.

TITLE: Neuroprotective attributes of L-theanine, a bioactive amino acid of tea, and its potential role in Parkinson’s disease therapeutics.

TITLE: Positive modulation of cognition and mood in the healthy elderly volunteer following the administration of Centella asiatica.

REFERENCE: Wattanathorn J, Mator L, Muchimapura S, Tongun T, Pasuriwong O, Piyawatkul N, Yimtae K, Sripanidkulchai B, Singkhoraard J. J Ethnopharmacol. 2008 Mar 5;116(2):325-32. doi: 10.1016/j.jep.2007.11.038. Epub 2007 Dec 4.

LINK: https://www.ncbi.nlm.nih.gov/pubmed/18191355

Study Synopsis:

Twenty-eight healthy elderly participants received the plant extract of Gotu Kola (Centella asiatica) at various doses ranging 250, 500 and 750 mg once daily for 2 months. Cognitive performance was assessed using the computerized test battery and event-related potential whereas mood was assessed using Bond-Lader visual analogue scales prior to the trial and after single, 1 and 2 months after treatment.

The results showed that the high dose of the plant extract of Gotu Kola (Centella asiatica) enhanced working memory and increased N100 component amplitude of event-related potential. Improvements of self-rated mood were also found following the Centella asiatica treatment. These findings suggest the potential of Centella asiatica to attenuate the age-related decline in cognitive function and mood disorder in the healthy elderly.

TITLE: Centella asiatica (Gotu kola) as a neuroprotectant and its potential role in healthy ageing

·         Centella asiatica is a prospective therapeutic candidate with wholesome health benefits.

·         sIt has the potential of contributing to healthy aging especially as a neuroprotectant.

·         It is used in traditional medicinal systems.

·         It is rich in triterpenes, flavonoids, essential oils, and alkaloids.

TITLE: L-acetylcarnitine treatment of mental decline in the elderly.

REFERENCE: Salvioli G, Neri M. Drugs Exp Clin Res. 1994;20(4):169-76.

The cognitive sphere evaluated by MMSE showed a significant increase in the total score at the end of LAC treatment (p < 0.0001). The Randt Memory Test also revealed that LAC treatment improved the items tested: the total score and the memory index increased significantly and the favourable effect persisted after LAC was discontinued. The emotional-affective area showed a significant improvement in the total score of the GDS after LAC therapy, and the positive results were confirmed by the Hamilton Rating Scale (p < 0.0001).

TITLE: Neuroprotective effects of acetyl-l-carnitine on lipopolysaccharide-induced neuroinflammation in mice: Involvement of brain-derived neurotrophic factor

REFERENCE: FilizKazak, Gul FatmaYarim. Neuroscience Letters, Volume 658, 29 September 2017, Pages 32-36.

·         Acetyl-l-carnitine administration ameliorated LPS-induced neuroinflammation.

·         Acetyl-l-carnitine increased the concentration of BDNF in the brain.

·         Acetyl-l-carnitine may have protective and therapeutic potential for inflammation-related neurodegenerative diseases.

TITLE: Withania somnifera (L.) Dunal ameliorates neurodegeneration and cognitive impairments associated with systemic inflammation.

In this study, the neuroprotective activity of Ashwagandha (Withania somnifera) was elucidated against the inflammation associated neurodegeneration and cognitive impairments induced by systemic LPS administration using in vivo rat model system.

Orally administered ASH-WEX significantly suppressed the cognitive and motor-coordination impairments in rats. On the molecular basis, ASH-WEX supplementation also regulated the expression of various proteins involved in synaptic plasticity and neuronal cell survival. This extensive study using in vivo and in vitro model systems provides first ever pre-clinical evidence that ASH-WEX can be used as a promising natural therapeutic remedial for the prevention of neurodegeneration and cognitive impairments associated with peripheral inflammation and neuroinflammation.

TITLE: Efficacy and Safety of Ashwagandha (Withania somnifera (L.) Dunal) Root Extract in Improving Memory and Cognitive Functions.

LINK: https://www.ncbi.nlm.nih.gov/pubmed/28471731

A prospective, randomized, double-blind, placebo-controlled study was conducted in 50 adults. Subjects were treated with either ashwagandha-root extract (300 mg twice daily) or placebo for eight weeks.

After eight weeks of study, the ashwagandha treatment group demonstrated significant improvements compared with the placebo group in both immediate and general memory. The treatment group also demonstrated significantly greater improvement in executive function, sustained attention, and information-processing speed.

The authors concluded that Ashwagandha may be effective in enhancing both immediate and general memory in people with mild cognitive impairment (MCI) as well as improving executive function, attention, and information processing speed.