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Combination of Bacopa and Cognitive Training Hypothesized to Improve Age-related Cognitive Decline
Date 12-15-2016
HC# 111651-558
Bacopa (Bacopa monnieri, Plantaginaceae)
Age-related Cognitive Decline

McPhee GM, Downey LA, Noble A, Stough C. Cognitive training and Bacopa monnieri: Evidence for a combined intervention to alleviate age associated cognitive decline. Med Hypotheses. 2016;95:71-76.

It is estimated that worldwide, the percentage of people over 60 will double from 12% to 22% by 2050. Aging is associated with cognitive impairment (age-related cognitive decline [ACD]) that reduces functionality and quality of life. Hence, there is increasing need for more effective treatments of ACD. Research has shown that ACD is associated with a reduction in the activation of previously used neuronal pathways. Cognitive training (CT) has been shown to improve cognitive function by increasing the use of under-utilized neuronal pathways. Traditionally used to improve mental function, several clinical trials have found that bacopa (Bacopa monnieri, Plantaginaceae) aerial plant extract enhances memory and other aspects of cognition. The authors hypothesize that "the combination of these two interventions could improve cognitive outcomes, over and above the effects of administrating these interventions independently."

CT involves cognitive domain-specific games, puzzles, and tasks performed at scheduled intervals, to develop and improve cognitive ability. Systematic reviews and meta-analyses of CT trials have found statistically significant improvements in various aspects of cognition, including immediate and delayed verbal recall, working memory, spatial memory, and verbal and non-verbal memory. Neuroimaging and functional magnetic resonance imaging studies of the brain areas involved in learning and memory show that CT changes activation patterns in older brains, leading to more efficient firing patterns like those observed in younger brains.

The experimental evidence suggests that synaptogenesis (formation of new synapses [connections] between neurons in the brain) occurs in an activity-dependent manner and is initiated via several molecular mechanisms. The tasks involved in CT induce repeated activation of targeted neuronal networks, stimulating increased connectivity between neurons. This activity-dependent synaptic plasticity is evidenced by the upregulation of neurotrophins such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF); protein kinases, such as calcium/calmodulin-dependent protein kinase II (CaMKII), protein kinase A (PKA), and protein kinase C (PKC); cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB); and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB).

Meta-analyses of randomized, controlled trials evaluating the effect of bacopa supplementation in healthy adults have found that bacopa significantly improved delayed recall and several other memory domains of cognition, including free recall of information, associative memory, memory span, and visual memory. These findings suggest that bacopa may enhance the preservation of memories in long-term recall. Individual studies also have reported that bacopa improves processing speed. Another meta-analysis found that compared to modafinil and Asian ginseng (Panax ginseng, Araliaceae) root, bacopa produced the largest and most consistent effect sizes for improved delayed word recall and memory consolidation.

The results of animal studies suggest that bacopa enhances synaptic formation via a number of mechanisms, including modulation of NGF, protein kinases, NF-κB, and CREB. The experimental evidence also indicates that bacopa has significant neuroprotective properties. Taken together, these findings indicate that bacopa stimulates synaptogenesis via neurotrophin activity and exerts neuroprotective effects.

In summary, the extant evidence suggests that CT improves cognitive function by promoting synaptic plasticity and reverting brain functioning back to the more efficient cognitive processing of younger brains. Bacopa promotes synaptogenesis, is neuroprotective, and has been clinically demonstrated to improve memory domains of cognition. The authors conclude that the combination of bacopa supplementation and CT "may theoretically accelerate synaptogenic processes and strengthen this apparent rewiring process." Well-designed clinical studies are needed to evaluate the hypothetical benefits of combined CT and bacopa therapy. As the authors point out, "If successful, a combination of both interventions would be a simple, effective and practical solution to alleviate cognitive deficits in an ever increasing elderly population." One of the authors (A. Noble) is employed by SFI Research Pty Ltd (St Leonards, New South Wales, Australia), a company that produces bacopa extracts and products.

—Heather S. Oliff, PhD

Editorial Note:

There are conflicting opinions regarding the potential benefits of CT. Due to the highly variable results of CT clinical trials (which may be attributed to differences in methodology and CT paradigms), meta-analyses have found the overall effect sizes to be moderate to small.