cognitionrewired-blog

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Nootropics and Neurotransmitters 101 : an infographic

credits to nootropicdaily.com

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Music & The Brain - An Under-appreciated Relationship

The idea that music can affect what we think and feel is intuitively obvious. We all know what happens to us when we hear certain types of music. Soul makes us want to move, metal makes us want to fight, and classical music often seems to help us concentrate.  So is the idea that music influences our thoughts and emotions really that controversial? Yes and no. 

People do accept that music has the ability to alter our mental state. They even accept that music can alter our executive cognitive faculties (attention, focus, learning, motor control, etc). 

But when I tell people that music can actually change the physical architecture of the brain, they’re usually loathe to accept it. They assume I’m getting carried away, or that I’ve been overly impressed with shaky science. But neither of these is true; I’ve simply read some recent, ground-breaking studies which show - amazingly - that music can actually cause physical changes in the brain.

Instead of making more unqualified comments, I’ll jump right into the studies that have impressed me so much!

The Studies

This paper was published in the Journal of Neuroscience in 2013. 

It details a study in which researchers took musicians which had either received their musical training at an early or late age. They matched the participants for years of total training. They then performed diffusion imaging scans on their brains to see if there were any differences in physical structure between those who received their training at a young age (before 7) and those who started their training much later.

The results were really quite incredible - to me at least!

Here is how the researchers summed up their findings: “We found that early-trained musicians had greater connectivity in the posterior midbody/isthmus of the corpus callosum and that fractional anisotropy in this region was related to age of onset of training and sensorimotor synchronization performance.”

That is pretty damn astounding. 

Early musical training can have a dramatic effect on the physical development of the human brain. Furthermore, it can have an effect on an area of the brain that is absolutely vital for higher cognitive functioning. 

The corpus callosum is the communication channel between the left and right sides of the brain. It is a thick band of fibres that act as ‘telephone cables’ between the two hemispheres.

Communication between the two hemispheres of the brain is necessary for pretty much every higher cognitive faculty humans possess. Strengthening the communication channel between the two sides of the brain will help with everything from hand-eye co-ordination to creative thinking. Allowing diffuse areas of the brain to better communicate with one another will facilitate memory formation, recall, and verbal fluidity. 

That musical training can bring about such a profound change is really something. 

Going Forward

The cognitive neuroscience of music is a burgeoning field of enquiry. But it has already turned up some absolutely fascinating finds. We hope more researchers get interested in this field and start investigating how more of us can use music to enhance not only our cognitive performance, but our long-term mental health as well!

In the meantime, I know that my children will definitely be giving the violin or piano a try from a very young age. There’s definitely nothing to lose from trying. 

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Why Don’t They Care About BDNF?

There’s been a lot of very interesting discussion about Brain Derived Neurotrophic Factor lately.

Some people on Reddit were questioning why this topic isn’t more discussed online. They were quite rightly questioning the lack of attention given to BDNF by supplement manufacturers.

Indeed, few brain supplements today include any kind of BDNF-stimulating content.

Hell, very few try to stimulate neurotrophic factors of any kind.

But before we get into why this might be the case, or how it can be rectified, let’s take a step back.

What is BDNF?

What is a neurotrophic factor?

Can these things actually be targeted through supplementation?

Would we even want it if it were possible?

Let’s get into it.

What Is BDNF?

Brain Derived Neurotrophic Factor (BDNF) is a naturally-occurring protein.

It is a member of the neurotrophin family of growth factors. You may be familiar with Nerve Growth Factor (NGF); this is often thought of as the prototypical growth factor, both because it was the first to be described and because it seems to have the broadest action.

Neurotrophic factors are responsible for the growth, maintenance, proliferation, differentiation, and death of brain cells.

Almost all neurotrophic factors are small proteins or peptides, and BDNF is no different.

It is neurotrophic factors that dictate which type of cell your developing neurons will become. To some degree, neurotrophic factors can differentiate mature neurons too.

They control how well maintained your neurons are, how quickly they grow, how quickly they proliferate, and when they die.

They dictate everything from dendrite pruning to axon growth.

So yeah, they’re pretty important.

I actually can’t think of a single molecule that has a more profound effect on the physical brain than neurotrophic factors – the possible exception being acetylcholine.

 What Does BDNF Do?

So what about BDNF in particular?

Well, BDNF seems to be directly responsible for the regulation of the growth of select neurons and synapses.

The presence of BDNF tells certain neurons and synaptic cells that they need to grow, repair themselves, and proliferate.

It is also directly responsible for neuron differentiation; it tells your brain cells exactly what they’re going to be when they grow up.

Most importantly, as far as I’m concerned, is where it operates.

BDNF seems to be concentrated in the hippocampus, basal forebrain, and the cortex – areas critical for memory, learning, and higher, abstract thought.

So if you were going to try to target these cognitive faculties through neurotrophic factors, then BDNF would be the one to use.

 Can It Be Targeted Through Supplements?

You may not think that something like BDNF can be manipulated with simple dietary interventions.

After all, if certain foods were able to amplify brain cell growth and development, you’d think we’d have figured that out by now, right?

Well, maybe we have – we just aren’t conscious of it.

It’s possible that we owe the rapid development of our big brains in part to certain substances found naturally in a healthy, balanced diet.

Preliminary research seems to suggest this might be right. There are some common, everyday herbs, minerals and amino acids that seem to significantly increase the expression of BDNF in human beings.

For example, this study looked at the role magnesium plays in the regulation of depression. The conclusion here is pretty straightforward: “For the first time, the present results demonstrate the antidepressant-like activity of magnesium in the OB animal model of depression and indicate the potential involvement of the AMPA/BDNF pathway in this activity.”

It seems that magnesium may increase the amount of BDNF present in the brain. The researchers noted that this link was sound. Whether or not BDNF or some other protein helped with the depression is neither here nor there as far as I’m concerned. I’m more interested in the BDNF itself, and that seems to be reliably increased with magnesium.

Interestingly, another study found that BDNF might be preserved by Bacopa monnieri supplementation. Here the researchers gave rats Bacopa monnieri extract on a daily basis and measured their cognitive performance after subjecting them to random stressful events.

They found a pretty remarkable link: “Daily administration of the graded doses of BM extract during the 4-week period of CUS significantly suppressed behavioral changes and attenuated the CUS-induced decrease in BDNF protein and mRNA levels in the hippocampus and frontal cortex.”

So while magnesium seems to boost BDNF levels, Bacopa monnieri supplementation may well prevent it from being depressed due to chronic stress.

What would that mean practically?

It would mean eating more walnuts, spinach, almonds, black beans, and making sure you take your multivitamins.

It would also mean supplementing with Bacopa monnieri. This is fairly simple – this stuff is in most nootropic supplements these days.

 So Why Does Nobody Care?

The answer to this is quite simple: supplement manufacturers are not at the cutting edge of research.

Or to put it another way, they don’t care about BDNF!

It isn’t that it doesn’t work.

It’s just that most of their customers don’t know about BDNF, what it can do, or that it can be influenced.

Most won’t even know it exists.

They therefore have little incentive to start investing serious money researching how to best influence BDNF through their supplements.

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No work or love will flourish out of guilt, fear, or hollowness of heart, just as no valid plans for the future can be made by those who have no capacity for living now.

Alan Watts

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Sorry if it’s a dumb question. I’m just wondering why this isn’t more discussed? Although there are some side effects… Shouldn’t increasing BDNF be everyone’s objective (if their goal is to improve their lives?)​I try to read about it here… although there’s a limited amount of discussion threads on what can be done to raise BDNF via /r/Nootropics

[cognitionrewired-blog]

Apoaequorin & The Dangers Of Post-Hoc Analysis

A new supplement is causing quite a stir at the moment.

You’ve probably heard of it; it’s called Prevagen.

To look at the commercials, ads, and testimonials, you’d think we had just discovered the cure for dementia, Alzheimer’s, even occasional memory loss.

The makers claim that it is able to significantly improve memory function in people living with mild cognitive decline.

They’re quite explicit that Prevagen isn’t a cure for serious cognitive decline. Yet there are definitely insinuations that it can help older people beginning to show signs of age-related memory loss.

The manufacturers say that it helps with mental clarity, focus, and overall cognition. 

They claim that their patented ingredient – apoaequorin – is a revolutionary new substance that is going to turn the nootropics world upside down.

They say that it has substantial scientific backing.

Yet this same company are currently being sued by the United States government over false claims.

The charge is that Prevagen’s claims are false. According to Uncle Sam, Prevagen is claiming to do things that it has never been shown to do. The makers are claiming things that have no basis in reality.

Prevagen deny these charges – I believe they intend to challenge in court.

So what’s going on here?

Who’s right?

Is Prevagen making claims it shouldn’t be?

Or is the US government being overzealous in taking legal action against this company?

Let’s find out.

Let’s take a look at the evidence offered by Prevagen and see if it is fair to draw the same conclusions that they are.

 The Study

To support the claim that Prevagen helps restore memory function and prevent age-related cognitive impairment, the manufacturer provides just a single study on the main ingredient – apoaequorin.

Not one meta-analysis; we mean a single, standalone study.

Here it is in case you want to see it – it’s hosted on their website and nowhere else; big surprise!

That in itself would be enough to make us sceptical.

But the lack of follow-up studies isn’t even the most ridiculous thing about this whole business.

The thing that leaves me most confused is the fact that the study doesn’t even conclude in their favour!

If you take a look at the study conclusion, you’ll see the following: “No statistically significant results were observed over the entire study population”.

You will then see a table showing the results of the various cognition tests issued to the participants’ sub groups. The annotation reads: “In the AD8 0-2 and AD8 0-1 subgroups, no statistically significant differences were noted in Baseline values between the Experimental and Control groups in any of the nine variables. The randomization was successful.”

No difference between those given apoaequorin and those given plain rice flour capsules.

No difference whatsoever.

In fact, the table shows that some participants must have scored LOWER on the cognition tests after being given apoaequorin!

So at best, this substance does nothing, and at worst, it hinders cognitive function!

How then can Prevagen be using this study to sell their product?

How can they be using this to back up their fantastical claims?

The answer is that they are using a very clever (and extremely dishonest) for of data analysis.

 Post Hoc Analysis & False Conclusions

If you read the details of the study linked above, you might notice something curious. The study itself was carried out between December 2009 and April 2011. Yet the publication date reads August 2016, and it was published on the Prevagen website in early 2017.

Why the hiatus?

As we’ve mentioned, the research found no statistically significant difference in cognitive function between groups given apoaequorin and those given placebo.

But the full results stamen reads as follows: “While no statistically significant results were observed over the entire study population, there were statistically significant results in the AD8 0-1 and AD8 0-2 subgroups. These subgroups contain individuals with either minimal or no cognitive impairment, and are the appropriate population for a dietary supplement intended to support people with mild memory loss associated with aging.”

Clearly, the guys at Prevagen undertook a post hoc analysis of the original data.

A post hoc analysis is when you go back and take another look at a data set with new parameters that weren’t originally specified.

Or to put it another way, it’s where you look at a data set and do your best to find a relationship that the original researchers weren’t looking for.  

They obviously did this in the hope of finding some kind of positive relationship between apoaequorin supplementation and improved cognitive function.

The problem here is that it is almost impossible NOT to find some kind of correlation when you look hard enough and long enough at a data set.

The longer you look at a data set, the more likely it becomes that you will find something…it’s almost inevitable. Correlations exist everywhere, whereas causal relationships do not!

This is why the US FDA does not accept post hoc analyses when considering pharmaceuticals.

Every substance can eventually be shown to positively influence some aspect of health and longevity if we go by post hoc analyses. If we look at a study done on inhalers for long enough, I’m sure we’ll find that they have some sort of correlation with back pain, or near sightedness, or liking spaghetti.

Sometimes post hoc analyses can be useful when they identify an interesting relationship that needs further examination.

But until further study is done, I’m afraid they mean pretty much nothing from a scientific point of view.

[cognitionrewired-blog]

The Unsung Power Of Phosphatidylserine

It is amazing to me how little credit we give phosphatidylserine (PS).

This simple phospholipid has the power to support brain cell formation and to regulate proper brain cell cycling.

Its benefits have been demonstrated beyond a reasonable doubt. Scientific study after scientific study have been publishing attesting to its immense potential as a cognitive enhancer.

So many studies have found the same thing that I have no problem telling people that it definitely works – unlike so many other substances, PS actually supports brain function. 

It is relatively easy to get hold of, and it is seemingly very safe to consume – even long-term.

Yet only a minority of people are using this stuff.

Many people could benefit from PS supplementation, but by and large these people have no idea that this is the case.

So let’s take a look at phosphatidylserine and see why this stuff really deserves to be in everybody’s stack.

A Look At The Science

I don’t make any claims about supplements unless I’m able to back them up with empirical evidence.

I don’t just regurgitate the claims made by manufacturers.

I don’t look for bloggers who back up what I want to believe and use them as references.

That’s a totally irresponsible way to approach brain supplementation. Doing that will inevitably see you losing a lot of money, and might even put your health at risk.

If you limit yourself to the latest scientific research, you’ll be in a much better position to make good decisions.

Thankfully, phosphatidylserine has a lot of hard, independent scientific backing.

First of all, let’s look at ameliorating cognitive decline.

This study found that 300mg of PS supplementation was able to significantly reduce the memory complaints of older Japanese people. The authors concluded: “Soy-PS used in this study is considered as safety food ingredient and 6 months of Soy-PS supplementation could improve the memory functions of the elderly with memory complaints.”

Another study, published in Psychopharmacology Bulletin in 1992, looked at PS and its ability to slow down the progression of Alzheimer’s Disease. The authors found the following: “Results suggest that phosphatidylserine may be a promising candidate for study in the early stages of AD.”

The authors noted that the best results were observed in people with less severe cognitive impairment. Phosphatidylserine’s effects are increasingly limited when you are dealing with more and more advanced cognitive impairment.

It is important to note that these researchers do not suggest that PS may be a cure for Alzheimer’s Disease. This is an incredibly complex disease that we don’t yet fully understand, and there is no known cure. It just seems that PS might help ameliorate some of the symptoms of AD.

So what about younger people?

Well, phosphatidylserine has actually been shown to have a meaningful impact on cognitive function in young people too.

This study, published in the Journal of Human Nutrition and Dietetics in 2014, looked at whether phosphatidylserine supplementation had any impact on the symptoms of children with ADHD.

The results were fascinating: “PS significantly improved ADHD symptoms and short-term auditory memory in children. PS supplementation might be a safe and natural nutritional strategy for improving mental performance in young children suffering from ADHD.”

Another study looked at the effects of PS supplementation on resistance-trained, college-aged men. As this study looked at healthy volunteers between the ages of 18 and 30, it may prove to be more enlightening to the people reading this article!

These researchers reached very similar conclusions to the other studies looking at PS and cognitive function: “PS supplementation significantly increased cognitive function prior to exercise. Improved cognitive function could benefit athletes and non-athletes alike. PS did not appear to affect mood or endocrine response prior to or following resistance exercise.”

So it looks like PS really works.

But why?

What does it do?

 What Phosphatidylserine Does

PS has multiple different functions in the body.

Of these, the most commonly discussed is its role in cell membrane formation.

Phosphatidylserine is found in great abundance in cell membranes.

It actually covers your nerve cell membranes, as well as the myelin sheaths which wrap around the axons projecting from your neurons.

These axons are basically the “communication cables” between neurons. As you can see from the diagram below, they lead from the neuron to the synaptic terminals, which transfer electro-chemical signals from their neuro to another neuron or to another effector cell.

  That phosphatidylserine forms a large proportion of this myelin sheath, as well as forming an important part of the cell membrane itself, is no small matter.

Without sufficient levels of PS, we simply couldn’t produce enough of the neurons, axons, or protective myelin sheaths. We would therefore leave our brain operating under its potential capacity.

As this study states, the importance of PS for general cognitive function is well known. Its role as a raw material in the construction of brain nerve cells (or neurons) is a major reason for this. Supplementation with PS is an effective way to ensure that we have enough of the stuff to keep our brains operating at 100% capacity.

In the words of the study authors: “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.”

The authors went on to say: “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.”

  But what’s more interesting to me is the fact that PS seems to be involved in cell signalling.

More specifically, PS is thought to play a role in apoptosis (programmed cell death).

As this article explains, phosphatidylserine seems to be at least partly responsible for the triggering of cell destruction.

Basically, when cells are ready to end their life cycle, phosphatidylserine begins to appear on the outer leaf of the cell’s membrane: “Exposure of phosphatidylserine on the outer leaflet of the plasma membrane is a surface change common to many apoptotic cells.”

Phagocytes (immune cells) seem to recognize the appearance of PS on the outside of the membrane, and they begin to “attack” the cell, destroying it and ending its life cycle.

This is really fascinating to me right now.

If PS is involved in making sure that apoptosis occurs properly and at the right time, then it definitely ranks among the best natural nootropics in existence.

Properly functioning apoptosis is absolutely necessary if you want to stay healthy and functional for as long as possible.

If your brain cells aren’t dying when they need to, then you will have gradually have more and more degraded brain cells carrying out your cognitive functions. If these cells aren’t destroyed and removed, then new, healthy, more efficient cells can’t be grown in their place!

More work is needed here, obviously.

That’s always true.

But as it stands, PS looks like it is going to turn out to be one of the most effective natural nootropic substances in existence.

It is safe and well tolerated.

You don’t need large amounts to see benefits.

It is relatively cheap and widely available.

That more people don’t use this substance to enhance long-term cognitive performance is a total mystery, and a tragedy!