Aging, brain function and memory loss are on the minds of every Baby Boomer in America. Millions of dollars are being spent on cosmetic surgery, organic food, brain training, exercise equipment and numerous other modalities that make us look and feel younger. So I thought it would be germane to mention a report I came across that reports the results of a new clinical study evaluating a "modernized" version of a previously helpful nutritional supplement called phosphatidylserine (PS). PS is a naturally occurring nutrient that lives in the membranes of cells. Approximately half of the PS in the body is located in the brain, much of it being in the mitochondria -- the power generating centers of each cell. When PS wears out it must be replaced or recycled.

Because of the vital roles played by PS, it was first made available as a nutritional supplement in the 1990s. At that time it was obtained from the brains of cows (the cerebral cortex) and was called BC-PS (Bovine Cortex PhosphatidylSerine). BC-PS is no longer on the market because of the risk of transmitting infectious agents such as the organism responsible for the production of Mad Cow Disease. PS supplements on the market today are derived from soy.

There was great interest in BC-PS because of the general medical support for its memory-enhancing properties. The PS currently available from soy doesn't generally share such robust clinical support. In fact, many of the products on the market have based their memory claims on the BC-PS literature. One might question whether those results can be applied to the soy-based PS. Many experts in brain research and alternative medicine have serious doubts about the validity of that leap of faith. Lloyd Horrocks, Professor Emeritus of Medical Biochemistry at the Ohio State University, believes "The fatty acids in BC-PS are mostly made up of DHA (docosahexaenoic acid -- an omega 3 fatty acid found in cold water fish) and arachidonic acid (an essential fatty acid in the omega 6 class) while the fatty acids from soy-derived PS are made mostly from oleic, linolenic and linoleic acids." Hence, the chemical composition of soy-derived PS is dramatically different from that of BC-PS, the product that was studied for cognitive benefits.

In addition to being chemically different, BC-PS is not pure phosphatidylserine. It is a mixture of many components of bovine cerebral cortex containing other fats. Thus, it is like comparing apples and oranges while evaluating soy PS and BC-PS. However, there is a new PS product on the market that has DHA complexed with a PS backbone making it much more biochemically like the BC-PS but without the risk of Mad Cow Disease. It is called PS-DHA and is manufactured by Enzymotec.

Scientific findings based on the usage of their novel form of PS-DHA were recently presented at a conference (the 25th Conference of Alzheimer's Disease International). The study was a double-blind, placebo-controlled trial that evaluated the efficacy of PS-DHA in healthy elderly individuals who had memory complaints but had not been diagnosed with Alzheimer's disease or any form of dementia. The dose tested was 300 mg of PS-DHA versus placebo. The trial period was 15 weeks. The Rey Auditory Verbal Learning Test and the Clinicians' Global Impression of Change scale were used. 53% of the patients in the PS-DHA group showed improved immediate recall (P=0.05) versus the placebo group. It was noted that the treatment was well-tolerated. The researchers concluded that PS-DHA had benefit and may improve short-term memory in this group of subjects.

This is a nutrient that should be evaluated by other scientists for similar cognitive benefits and might eventually be identified as a product that could be considered for inclusion in a supplemental program of brain health.

Alzheimer's disease is the most common form of dementia -- a progressive disease in which memory and thought processes become severely impaired.

Senile plaques are typical microscopic features seen in the brain tissue of patients with Alzheimer's disease. They are large aggregates of folded amyloid fibrils.  In 1985 amyloid beta was discovered. It is a chain of about 40-42 amino acids (the building blocks of proteins) linked end to end. Amyloid consists of clumps of this proteinaceous material.  As such, senile plaques have long been considered the primary killers of brain cells in this disorder. They were first discovered by Blocq and Marinescu in 1892. In 1906 Alzheimer first made the connection between plaques and dementia. In the 1970s M. Franke showed their association with dementing disease when the density of plaques in the frontal lobes was greater than 200/cubic millimeter. 

In the minds of researchers, the nexus between senile plaques and Alzheimer's disease became so entrenched that they were believed to actually cause the disease. Based on this theory of causation, medications were developed to remove the plaques. However, during drug trials designed to remove these plaques from the brain (such as the recent study testing bapineuzumab, which decreased plaques by 25%),  the patients' ability to think and reason got no better in spite of the decrease in plaques caused by the drug therapy.

This type of results have demonstrated to researchers that plaques are not the chief toxin responsible for Alzheimer's disease.  Moreover, not only are plaques not the cause of Alzheimer's disease, but it now appears that scientists are beginning to think they are a good thing!

According to Adrian Ivinson, director of the Harvard NeuroDiscovery Center in Boston, plaques actually appear to sequester all that amyloid. He went on to suggest that small particles of amyloid, called oligomers, rather than the large plaques, are the truly toxic substance. So it seems that like the capsule, or surrounding membrane, of a collection of pus, the plaque actually is protective rather than being the causative factor in Alzheimer's disease as has been believed all along. This insight has dramatically changed the way scientists view Alzheimer's disease and what they feel may be the optimal way to treat it.  I guess one take home message is that merely because something happens to share proximity with what causes a disease, it might not be the actual culprit.

It is worth taking a moment, in this context, to consider other diseases where related circumstances may have clouded scientific thinking in a similar fashion. Consider the cholesterol theory of heart disease. According to those who believe it, the build up of cholesterol in the blood somehow damages the arterial wall in very specific locations, in spite of the fact that the concentration of cholesterol is identical throughout the vascular tree. Could there be other factors that are producing injury to the lining membranes of blood vessels and that, once damaged, the cholesterol is deposited secondarily in the blood vessel wall in an attempt to repair the damage. If this is the case, then attention must be paid to other potential causes of vascular disease than cholesterol!

A good friend of mine, Alvaro Fernandez, and his associate Elkhonon Goldberg -- the co-founders of www.sharpbrains.com -- have just published a guide to brain fitness aptly entitled The SharpBrains Guide to Brain Fitness. (ISBN 9780982362907) It is written for the lay reader with information of interest for scientists and professionals as well.

In it they debunk brain and brain fitness myths, discuss neuroplasticity (the ability of the brain to continuously rewire itself based on real-time input) and what can be done to modulate how our brains work, go into lifestyle choices and how they interact with the "Four Pillars of Brain Maintenance" -- nutrition, stress management, physical exercise and mental stimulation. They define the distinction between mental exercise and mental activity and why that is important for people of all ages -- children, stressed business executives or housewives and even Baby Boomers and their parents.

They then wade into the rapidly evolving (and often confusing) field of computerized brain training software and provide a checklist for how to evaluate various products on the market, what they "train," levels of scientific substantiation each has provided, who might benefit from what and even discuss whether the different products are "on-line" or require CDs or other devices to run them. They even provide their "21 Quick Picks." The target groups include those of us interested in general brain health, verbal or auditory training, tools for ADD/ADHD, autism, dyslexia, training tools for strokes or TBI (traumatic brain injury), enhancing visual information processing  for the older driver and even programs for improving performance while flying military aircraft. There is literally something for everyone!

Topics that were of particular interest to me were (1) the concept of neuroscience-driven schools where the focus is on learning "how to learn" and (2) the ability of several instructional tools that by enhancing working memory -- the ability to keep several bits of information "on-line" for simultaneous analysis -- are able to "generalize" their benefit by actually augmenting fluid intelligence (the skill set that enables one to perform better in unfamiliar or untrained scenarios), something that was previously felt to be untrainable.

While you're at it, check out their web site www.sharpbrains.com.

Brain starvation has been discussed on numerous occasions in this blog. What it means is that the brain doesn't get enough of the proper nutrients for optimal function. In this case, we are referring to the primary brain fuel glucose (the "sugar" that is measured in the blood when blood sugar tests are performed). This is important because when brain cells (or neurons as they are called by medical doctors) don't receive enough glucose to fuel their metabolic needs, certain adverse consequences occur.

One of these is an increase in the production of the sticky clumps of proteins in the brain called beta-amyloid fibrils, which turn into senile plaques -- the postulated culprits behind the development of Alzheimer disease. When they build up, inflammation develops that leads to the loss of neuronal function and ultimately death of neurons throughout the brain. This is what causes memory loss, confusion, difficulty thinking and even behavioral changes.

Most currently available drugs that treat this horrible disease don't address this critical issue and, in part, because of this they are not very effective. However, there is an alternative approach that we have talked about previously that can offer help. By being turned into ketone bodies (an additional type of brain fuel), compounds called medium chain triglycerides (MCTs) can "bridge the energy gap" caused by the fall off in the ability of the brain to effectively utilize glucose. This is especially helpful in persons on insulin therapy for Type 2, or adult-onset, diabetes. In this condition, insulin overdoses can lead to confusion and fuzzy thinking due to the excessive fall in blood glucose (and subsequently brain glucose) they cause. MCTs in the diet can ameliorate these symptoms.

A new medical food (an FDA-regulated food like product) called Axona has recently been released by the company Accera for the nutritional treatment of Alzheimer disease. It is a powder that is prescribed by a physician and is administered once a day -- usually in the morning -- after being dissolved in water. It is a product that contains MCTs and generates ketone bodies when it is consumed. It has been tested and shown to improve cognition in this group of patients. The only significant side effects are related to mild abdominal distress and it may be used safely with other Alzheimer medications. The web site for further information is www.about-axona.com.

Tau proteins carry out very important functions in the brain. Especially in brain cells or neurons. They are akin to spot welds on cellular scaffolds that form tracks that shuttle other vital molecules to and fro within nerve cells. Their activity is governed by other cellular communicators called "phosphate groups." They attach to the tau proteins and enable them to perform their unique task. However, under certain circumstances the assembly line that regulates where and how many phosphate groups are attached runs amok. Under these conditions more and more phosphate groups are attached end to end, and instead of enhancing the activity of tau proteins, they create problems.

One type of problem with these "hyper-phosphorylated" tau proteins is that they accumulate and form masses called neuro-fibrillary tangles (NFTs). These NFTs are a purported cause of Alzheimer disease.

Based on these observations, findings made by researchers at McGill University in Canada offer new hope for the early diagnosis and treatment of Alzheimer disease. In a study published in the Journal of Biological Chemistry on May 15, they reported that the addition of a single phosphate group to a specific amino acid (protein building block) in tau proteins is a principal cause of Alzheimer disease.

Normal tau proteins only contain three or four phosphate groups, but the abnormal tau proteins can contain 20 to 25 additional phosphates. What the McGill scientists discovered was that the addition of a single phosphate group to a certain amino group (Serine 202) was the primary culprit responsible for the changes seen in Alzheimer disease.

This is important for two reasons. The first is that brain scans could be developed to identify that change. The second is that the enzyme that adds the phosphate to that specific amino group could become the target for drug therapy. Together, these suggest that early diagnosis and treatment may be at hand!

Evidence is accumulating that over-eating -- frequently associated with the development of obesity and diabetes -- is intimately associated with the development of memory disorders and more ominous conditions such as Mild Cognitive Impairment and even neurodegenerative disorders such as Alzheimer disease. For these reasons, I was interested to see a recent posting describing new research that investigated the link between dietary composition and appetite.

Researchers measured the levels of insulin and GLP-1 (short for Glucagon-like peptide-1) following two different types of meal. The meals differed in what is called GI (Glycemic Index). GI is a parameter that describes how various types of carbohydrate foods affect the body's blood sugar levels in the hours following their ingestion. High GI carbohydrates (including bread, cakes, cookies and cornflakes) markedly elevate blood glucose levels following a meal. Low GI carbohydrates increase blood glucose levels much less when consumed. They include most vegetables and non-starchy fruits. Low GI carbohydrates are usually broken down and digested more slowly than high GI foods thus releasing sugar into the bloodstream more slowly.

A low GI diet is known to cause reduced appetite, but the precise mechanisms behind this effect were not known. To address this, Dr. Reza Norouzy and colleagues at King's College London looked at the impact of a single low versus high GI meal on gut hormone levels in twelve healthy volunteers. Each subject was given a medium grade GI dinner the night before, fasted and then was randomly provided either a low (46) or high (66) GI meal for breakfast. Blood samples were taken every thirty minutes for 150 minutes and blood levels of the gut hormone GLP-1 and insulin were measured.

Volunteers who consumed the low GI breakfast had GLP-1 levels that were 20% higher than those eating the high GI meal. They also had 38% lower insulin levels over the same time interval. It is known that GLP-1 potently decreases appetite. These studies show for the first time that a low GI meal elevates GLP-1 levels and these are associated with diminished appetite. This observation provides a physiological mechanism to explain how a low GI meal makes you feel fuller than a high GI meal.

This insight might be used to guide food choices that diminish appetite and (hopefully) help us all maintain optimal weight and brain function at any age.

Deterioration and loss of the microscopic connections between brain cells (referred to as synapses) underlies the memory loss and other mental dysfunction seen in Alzheimer disease. The culprit behind all of this damage and destruction is believed to be soluble beta amyloid fibrils. They bind to specific sites on nerve cell membranes (the outer coatings of the nerve cells) in the region of synaptic connections. In so doing, they trigger the production of inflammation and subsequent damage to the tiny nerve cell connections. As they are lost, the nerve cells become functionally disconnected and can't perform the computer-like computations that are the basis for every thought we have.

This information is not particularly new. However, the observation that a protective mechanism exists that can shield nerve cells from the beta amyloid toxins is. The exciting thing about this finding is that it can prevent the deleterious changes from happening before symptoms develop! The savior in all of this drama is the hormone insulin. It so happens that insulin in the brain prevents the binding of beta amyloid fibrils to the receptors they must interact with to cause damage to the synaptic connections.

The proposed mechanism behind the insulin protective effect is not one of insulin interfering with the binding of beta amyloid to its receptors, but the actual down-regulation, or reduction , in the number of beta amyloid binding sites on the nerve cell membranes. To cause this reduction in beta amyloid binding sites, insulin must first bind to insulin receptors on the same nerve cell and produce an insulin signal within the nerve cell. The end result of this complex process is the loss of beta amyloid binding sites in the synaptic region. Without the binding sites, beta amyloid is almost helpless.

The novel finding that insulin mitigates synaptic vulnerability suggests that mechanisms that enhance brain insulin signaling, which declines with aging and diabetes, could potentially slow the onset or development of Alzheimer disease. In brain cells grown in tissue culture (like growing bacteria in a Petrie dish), this observation was confirmed in two separate ways -- by directly adding insulin to nerve cells, and by adding a drug that improves insulin sensitivity (meaning when the insulin that was normally present binds to its receptor of the nerve cells, the response is enhanced). Both interventions improved insulin signaling and decreased inflammation and loss of synapses.

While these studies were done in tissue culture, there are other ways to enhance brain insulin signaling, which include calorie and carbohydrate restriction. These interventions were studied in mice who were placed on low calorie/low carb diets. The lead author in this study was Dr. Giulio Maria Pasinetti. Based on his findings, he noted, "Both clinical and epidemiological evidence suggest that modification of lifestyle factors such as nutrition may prove crucial to Alzheimer's disease management. This research, however, is the first to show a connection between nutrition and Alzheimer's disease neuropathy by defining mechanistic pathways in the brain and scrutinizing biochemical functions."

When we are young and are eating a healthy diet, there are minimal fluctuations in the level of blood glucose. This is not very exciting because blood glucose doesn't get too high or too low. But that's exactly how things should work. However, as we get older the body is not as efficient at regulating and controlling blood glucose. As a result, the swings get bigger -- too high at some times and too low at others. What we eat can have the same effect. A sugary meal or snack can send blood glucose sky rocketing minutes after the meal ... and then plummeting down below normal an hour later. As a matter of fact, this is a fairly common occurrence today and is easily observed at work. Look around at your coworkers an hour or so after lunch. What do you see? Most of them are ready for a nap. They are sluggish and inefficient. This is what happens when glucose levels fall. Why? Because the brain burns glucose and when it's main fuel supply is not available, it suffers. Mental brownouts occur, energy levels fall and mental torpor is the result. Clearly, these dramatic glucose fluctuations are not good for the brain. This is what I call the Roller Coaster Effect.

Most of us think immediately about diabetes when a doctor mentions blood sugar problems. Now it appears that memory loss and Alzheimer disease might  be just around the corner. This is due to the Roller Coaster Effect. We have just discussed why so many of us feel sleepy and just not very sharp after lunch. Let's look at a more extreme example of the same thing. We all know people who were diagnosed with childhood diabetes (Type 1 diabetes, or "insulin-dependent" diabetes) because they are always checking their glucose level and injecting themselves with insulin shots throughout the day. One of the major complications this group of individuals experience is low blood glucose -- or hypoglycemia. When this occurs they can feel jittery, light-headed or even sleepy. If the condition goes uncorrected, and the blood sugar becomes quite low, they think more slowly and may even become comatose. This is related to low blood glucose and the resultant lack of an energy supply for the brain. It causes power outages and loss of mental function. These periods of low glucose represent the dips in the roller coaster ride.

Brain researchers have recently discovered a link between brain health and high blood glucose levels. At first, this may seem counterintuitive because with high glucose levels one would think that the brain would be happy. However, such appears not to be the case. Over the past couple of years, researchers have starting connecting the link between elevated blood sugar and and elevated risk for Alzheimer disease. That is now a well-known fact. More recently, a study presented by Swedish scientists showed that simply experiencing higher than normal blood sugar levels may be enough to potentially lead to Alzheimer disease.

The number of individuals this affects is not trivial. More than 40 million Americans fall into this category. They are in the "pre-diabetic" group. It is well known that obesity is a risk factor for memory loss and more serious conditions. Now we can add to this the Roller Coaster Effect -- that is, poor control of blood sugar.

What concerns many public health officials about these recent findings is that Alzheimer disease is expected to increase fourfold in the next four decades as baby boomers live longer. Now, in addition to living longer, we have a huge pool of aging Americans with increasingly more abnormal blood glucose control, another potent risk factor for these afflictions. It now appears that aging and poor glucose control are going to dramatically magnify the numbers of Americans developing Alzheimer disease. As a result, many researchers are worried that Alzheimer's will swamp health care systems worldwide.

More recently, investigators at Columbia University found that even modest swings in blood sugar levels can lead to memory loss severe enough to affect everyday function. These sugar fluctuations can be subtle enough not to even be considered a disease state!

One of the major processing regions for memory function is called the hippocampus. Subjects with abnormal blood glucose levels were found to have decreased hippocampal volumes compared to subjects with normal blood glucose levels.

To make matters worse, other researchers have noted an association with poor blood glucose control and the buildup in the brain of sticky clumps of protein that lead to the development of senile plaques -- the hallmarks of Alzheimer disease.

How can blood sugar be controlled? Eating properly and  exercising! The same recommendations that insure a healthy body. So get started now and avoid the Roller Coaster Effect!