Memories naturally degrade with the passing of time. Although the information is initially registered and stored, after a couple of days, weeks, or even years, it is simply erased from storage. The decline of memory function, be it due to normal aging or due to specific medical conditions, greatly affects one’s day-to-day life. Consequently, it is no surprise that the search for ways of improving memory has thousands of years of history.

The vast majority of the retrieval processes (i.e. most of remembering) happens without us even realizing. It is automatic and requires little to no effort or planning. Interestingly, the information that our subconscious identifies as being important or truly relevant tends to be kept in storage for as long as we need it. This can range from a transient need, like the information that you studied for a school exam, to a permanent, primary need, like recognizing your family’s faces and names.

Memory improvement strategies that have been employed throughout the centuries range from simple cognitive exercises and diet modifications to actual pharmaceutical products which influence the molecular pathways at play in memory processes. While many of these strategies have failed to produce any desirable effects, some substances have actually provided with interesting results in different settings.

Nootropics

Nootropics are a group of such substances which show evidence of positively affecting one or more aspects of memory functions. These substances includes not only drugs, but also supplements, “nutraceuticals”, and functional foods.

Notwithstanding the diversity of nootropic compounds, it is possible to summarize their mechanisms of action as follows:

• increasing circulation to the brain
• providing precursors to neurotransmitters
• improving neuronal function
• preventing oxidative neuronal damage
• providing energy sources to the brain.

Perhaps the most famous type of nootropics are racetams, which include various structurally similar compounds, such as piracetam and oxiracetam. Little is known about their precise actions at the molecular level, but there are a few clinical studies indicating their potential when prescribed to individuals with specific memory problems.

For instances, in a study of oxiracetam therapy in patients with senile dementia of Alzheimer type (SDAT) and multi-infarct dementia (MID) of mild to moderate degree, significant improvements were observed. Nootropics are also very popular for being available over-the-counter and for having virtually no undesirable side effects.

Dietary supplements, such as vitamins and omega-3, are considered nootropics as well, thanks to their influence on memory, learning, concentration and decision-making.

Other popular classes of nootropics include:

• stimulants, such as amphetamines and xanthines (e.g. caffeine)
• dopaminergics, affecting the neurotransmitter dopamine or the components of the nervous system that use dopamine. Attributable effects of dopamine are enhancement of attention, alertness, and antioxidant activity
• cholinergics, including acetylcholine precursors and cofactors, and acetylcholinesterase inhibitors
• nutraceuticals, including Bacopa monnieri, isoflavones and Gingko biloba.

One of the nootropic substances that has sparked a lot of scientific curiosity is nicotine. Famously known for its carcinogenic potential and a myriad of other adverse effects on smokers’ health, researchers have long been aware of the ability of nicotine to influence cognitive performance.

For example, difficulty in concentrating is one of the symptoms of nicotine withdrawal, but for a long time this was regarded as a mere relapse factor. Still, as smokers repeatedly reported that one of the reasons they smoke is for the perceived cognitive improvement that smoking gives them, experiments have been attempting, for more than 40 years, to validate these claims and to delineate the conditions under which nicotine might enhance the various domains of human performance.

Biologically, there is a basis for the influence of nicotine in cognitive processes. Nicotine binds to presynaptic nicotinic acetylcholine receptors in the brain, facilitating the release of acetylcholine, dopamine, serotonin, glutamate, and other neurotransmitters known to be involved in these processes.

A meta-analysis of the acute and long-term effects of nicotine on human performance, which looked at the results of a number of studies on the topic, revealed impressive results. Nicotine appears to actually have a significant, positive impact on six domains: fine motor, alerting attention-accuracy, response time (RT), orienting attention-RT, short-term episodic memory-accuracy, and working memory-RT.

Despite these positive effects, it is important to stress that nicotine should not be the nootropic of choice for anyone seeking to improve their memory functions, due to the numerous medical issues it potentiates and the dependence it causes.

As one would expect, like all pharmaceutical products, nootropics have risks as well as benefits. Most of these enhancers are being used with little scientific data to support them, and while some compounds are known to have a good safety profile, others have a risk of unintended side effects that is both high and consequential. It is also important to stress that having an acceptable safety profile is actually dependent on the circumstances under which the product is administered. For example, a drug that restored good cognitive functioning to people with severe dementia but caused serious adverse medical events might be deemed reasonable to prescribe to these patients under the light of its great benefits, but not to healthy individuals who are only seeking enhancement.

Even in terms of practical efficacy, there is much to be said about nootropics. Despite the fact that some studies have shown impressive results, the truth is that there is a lot of heterogeneity (not to mention transiency) in response.

But science is an ever moving field, and recent studies have provided some insight into what might be a revolution in the area of cognitive enhancement. A groundbreaking investigation, published just this year in the renowned journal Science, suggests that there might be a more effective, alternative strategy to stimulate and improve the processes underlying memory formation.

Electromagnetic stimulation

We have known for quite some time now, mainly in the aftermath of very select cases of severe brain injuries which are illuminating by virtue of the impairments they produce, that the hippocampus plays a decisive role in the works of memory. Naturally, the hippocampus does not work on its own, and a team of American researchers took advantage of these complex interactions to test its function.

Using the technique of noninvasive electromagnetic stimulation – never tested in humans before – researchers altered the interactions between the networks of hippocampal and cortical neurons and registered the effects of such modulation on memory. After multiple sessions of electromagnetic stimulation, there was a clear functional increase in the transmission of neural impulses between those neurons. Concomitantly, associate memory performance of the subjects involved improved significantly, persisting about 24 hours after stimulation.

While these results are promising and may constitute a new window into the mechanics of memory formation and memory enhancement, they are also preliminary findings that still leave many questions unanswered. Further investigations, both in healthy individuals and in people with medical issues associated with memory formation, will be necessary for the scientific community to really understand the benefits and risks of electromagnetic stimulation.

References

Greely, H. (2013). Some First Steps Toward Responsible Use of Cognitive-Enhancing Drugs by the Healthy The American Journal of Bioethics, 13 (7), 39-41 DOI: 10.1080/15265161.2013.795823

Gruneberg, M. and Morris, P.E. (1994). Theoretical Aspects of Memory, Volume 2, Routledge.

Heishman SJ, Kleykamp BA, & Singleton EG (2010). Meta-analysis of the acute effects of nicotine and smoking on human performance. Psychopharmacology, 210 (4), 453-69 PMID: 20414766

Rosenbaum RS, Gilboa A, & Moscovitch M (2014). Case studies continue to illuminate the cognitive neuroscience of memory. Annals of the New York Academy of Sciences, 1316, 105-33 PMID: 24871381

Villardita C, Grioli S, Lomeo C, Cattaneo C, & Parini J (1992). Clinical studies with oxiracetam in patients with dementia of Alzheimer type and multi-infarct dementia of mild to moderate degree. Neuropsychobiology, 25 (1), 24-8 PMID: 1603291

Wang JX, Rogers LM, Gross EZ, Ryals AJ, Dokucu ME, Brandstatt KL, Hermiller MS, & Voss JL (2014). Targeted enhancement of cortical-hippocampal brain networks and associative memory. Science (New York, N.Y.), 345 (6200), 1054-7 PMID: 25170153

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