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!

The term "neurodevelopmental disorders" encompasses a large group of neurological disorders that become evident during periods of brain maturation. They frequently share complex neurological features including various learning disabilities and complex behavioral features. These disorders become evident in early childhood and tend to persist into the adult lifespan. Included in this constellation of disabilities are autism, ADD (attention deficit disorder) and pervasive developmental disorder. It is believed they are caused by genetic mutations and environmental factors.

Alterations in the configuration, wiring and connectivity of the developing brain are key contributors. There are specific periods during brain formation where certain influences can produce significant functional alterations that might be insignificant if they first occurred in adults.

Fetal and perinatal programming experiments in animals have documented persistent abnormalities in glucocorticoid receptors and signaling in offspring related to variations in maternal care that engender the perception of stress in the offspring. This alters stress responsivity -- changes that persist into adulthood. Many of the mutations that cause developmental disorders disrupt genes that are also expressed in the adult brain. This insight is significant because in addition to the developmental affects they cause in the brains of young children, it is possible that altered function of these genes may produce additional effects in adulthood (additive to those changes in brain wiring produced during the formative years).

This very possibility has been investigated in animal models of human neurodevelopmental disorders. Results suggest that persistent expression of the genes that caused the disorder to manifest initially during childhood may contribute to cognitive or behavioral problems in adults. These studies support the concept that treating the disrupted molecular mechanisms in adults might result in functional improvement. It has even been speculated that biochemical improvement of the underlying genetic defects may produce metabolic changes that allow adult neuroplasticity mechanisms to compensate for certain of the characteristic developmental problems.

The animal studies have investigated models of neurofibromatosis, a disorder in which neurological symptoms including attentional issues, deficits in executive function and learning disabilities are produced. One of the effects of the NF (neurofibromatosis) gene is to interfere with specific cellular signaling pathways. This results in the activation of Ras-signaling pathways.

There are pharmacological interventions that can reduce the isoprenylation of Ras, thereby tending to normalize this vital signaling pathway. HMG-CoA reductase inhibition with the drug lovastatin (a cholesterol-lowering drug) is one such intervention. Notably, short pharmaceutical treatment of animals with NF using lovastatin reduces the cognitive impairments in these animals while having no effects on control animals. When tested in humans, a 12 week treatment with simvastatin improved performance on a neuropsychological test. Moreover, the treatment protocol had the most robust beneficial effect on patients with the worst baseline status.

Similar benefits using this molecular approach have been observed in animal models of other neurodevelopmental disorders including Down's syndrome, Rubenstein-Taybi syndrome (another genetic disorder that is characterized by intellectual disorders, and specific physical features such as broad thumbs and and toes), Tuberous sclerosis, Fragile X syndrome (associated with learning disabilities, autism, ADD (attention deficit disorder) and epilepsy) and Rett syndrome.

The obvious conceptual epiphany in this approach is the ability to improve functional indicators in adults with neurodevelopmental disorders long after the brain has matured. Many of these disorders are common and disabling. They also have limited treatment options.

In BACE-ball and your brain I discussed how energy shortages in the brain tend to increase the activity of an enzyme (BACE1) that speeds up the activation of APP (amyloid precursor protein). This increases the formation of A-beta (for beta amyloid), which is associated with the development of Alzheimer disease. Thus, energy brownouts are to be avoided at all costs. Dr. Robert Vassar, the lead author of this insightful article, linked deficits in energy generation in the brain with the development of narrowing of the arteries to the brain.  Oxygen and nutrients such as the major brain fuel glucose are delivered to nerve cells via the circulatory system. When blood flow is restricted, these vital compounds don't get where they need to go and brain cells suffer. One result is impaired energy generation and activation of BACE1.

Another interesting paper that relates to this very issue was recently published in the medical journal Brain Research (1226 (2008): 209-219). It further investigates the connection between power brown outs in the brain and A-beta formation. The investigations were performed in very old dogs who spontaneously produce A-beta in their brains.

The authors noted that localized declines in cerebral glucose metabolism are an early and progressive feature of Alzheimer disease. They state that such declines occur long before symptoms develop and, as such, offer a window of time for medical intervention. Medium chain triglycerides (MCTs) are rapidly turned into ketone bodies in the liver and ketones are used efficiently in the brain as an optional fuel source. Noting this, they provided a nutritional product (MCT oil) that can generate this alternative fuel (ketones) for the brain when glucose is in short supply or is not being used efficiently. In their study, dogs were supplemented with MCT oil for several months and brain metabolism was subsequently investigated.

They documented that aged dogs receiving the MCT therapy showed markedly improved mitochondrial (mitochondria are the small intra-cellular inclusions that generate energy) function. The effect was most prominent in the parietal lobe region. This is where early decreases in glucose use tends to occur in patients with Alzheimer disease. APP levels also decreased. There was also a trend towards a decrease in total A-beta in the parietal lobes of the treated dogs.

What this tells us is that energy generation was improved and with it APP and A-beta levels fell. These results are consistent with the hypothesis that brain cell energy failure (an inciting cause of Alzheimer disease) can trigger the buildup of A-beta, which ultimately leads to neurodegeneration. Furthermore, they suggest that by supplying another fuel source for the neurons to use, the process can be reversed with beneficial results. The take home message might be that for anyone at risk for such diseases, that chronic supplementation with MCT oil might be a prudent preventative intervention.

Alzheimer Disease (AD) and a host of other so-called neurodegenerative diseases such as Parkinson Disease and Lou Gehrig Disease (also called ALS -- for Amyotrophic Lateral Sclerosis -- a wasting disease that tends to affect motor nerves and secondarily muscle function in the arms and legs as well as the swallowing and breathing muscles) have been refractory to treatment largely because the exact cause of each of these devastating disorders is unknown. They have been the subject of intense research to no avail -- that is until recently. A remarkable paper was recently published in the medical journal Neuron. The lead author was Dr. Robert Vassar from Northwestern.

The purportedly toxic compound that builds up in the brains of persons afflicted with AD is called beta-amyloid (A-beta for short). It is produced by the cleavage of amyloid-beta precursor protein (APP) by the action of beta-site APP cleaving enzyme 1 (BACE1). This accelerates the buildup of A-beta. The level and activity of BACE1 are increased in the brains of AD patients. This led to the idea that the chronic increase in BACE1 in the brain may contribute to the development of AD.

This is not of much help to those persons at risk for this devastating disease unless something can be done about it. From a pharmaceutical perspective, such hope is on a distant horizon. However, an interesting observation might provide a clue as to what leads these sticky amyloid fibrils to form and aggregate. This insight was identified by the application of several metabolic manipulations that each decreased energy generation in neurons. One involved impairing the electron chain, which is the main conveyor belt that turns food into energy. Another was a potent inhibitor of an enzyme in the glucose metabolic pathway, while yet another manipulation involved administering an overdose of insulin to the lab animal. This latter model of energy impairment caused cerebral brownouts by causing blood glucose levels to fall to markedly subnormal levels. This prevented the neurons from accessing their primary fuel -- glucose.

The common thread in each of these models was an increase in BACE1 and the accumulation of A-beta.

The researchers suggested that physiologic changes that increased blood flow to the brain, which would deliver more oxygen and more glucose, would enhance energy production and lessen A-beta via a beneficial effect on BACE1. What they omitted to mention is that many neuroscientists are starting to refer to AD as Type 3 diabetes because of the presence of a similar inability of the brain to take up and metabolize glucose as that which exits in the tissues of the body in Type 2 diabetes (the type generally associated with obesity). This is significant because diabetes is a metabolic disorder that responds to various lifestyle factors that stabilize blood sugar swings and enhance insulin sensitivity. These same interventions would be expected to enhance cerebral glucose metabolism and act to alleviate energy shortages, BACE1 activation and accumulation of A-beta, the alleged culprit behind the initiation of AD.

These findings are consistent with a reversible etiology of one of the primary modern day medical scourges. One that we may ameliorate by making appropriate lifestyle choices that are easily within our control.

By David Derbyshire

Two months ago Clem Fennell was fading fast.

The victim of an aggressive type of dementia, the 57-year-old businessmen was unable to answer the phone, order a meal or string more than a couple of words together.

In desperation, his family agreed to try a revolutionary new treatment - a bizarre-looking, experimental helmet devised by a British GP that bathes the brain in infra-red light twice a day.

To their astonishment, Mr Fennel began to make an astonishing recovery in just three weeks.

Dr Gordon Dougal, a GP from County Durham, treated dementia patient Clem Fennell with his infra-red device

"My husband, Clem, was fading away. It is as if he is back" said his wife Vickey Fennell, 55. "His personality has started to show again. We are  absolutely thrilled."

While the helmet has yet to be proven in clinical trials, the family say the effects of the 10 minute sessions are incredible. Mr Fennell can now hold conversations and go shopping unaccompanied.

The treatment is the brainchild of Dr Gordon Dougal, a County Durham GP. He believes the device could eventually help thousands of dementia patients.

"Potentially, this is hugely significant," said Dr Dougal, who is based in  Easington, County Durham and is a director of Virulite, a medical research company.

Developed with Sunderland University, the helmet has 700 LED lights that  penetrate the skull. They are thought to be the right wavelength to stimulate the growth of brain cells, slowing down the decline in memory and brain function and reversing symptoms of dementia.

Clem Fennell - the head of a family engineering firm in Cincinnati, Ohio - travelled to the UK after neurologists told him nothing could stop the decline of his dementia. The family's friends had seen  a report about the helmet on CBS.

"Honestly I can tell you that within ten days, the deterioration was stopped,  then we started to see improvements," said Mrs Fennell,  from North Kentucky. "He started to respond to people more quickly when they talked to him." 

Three weeks later, the father of two is still making gradual improvements.

His daughter, 22-year-old Maggie said: "When we go to the restaurant  we usually have to order his meals for him, now he can order for himself." 

"Now we are okay about letting him go to the bank or the  post office but he would not have been able to do that three weeks ago.

Mr Fennell could hardly string two words together. But since using the infra-red helmet, he can hold a conversation.

"Dr Dougal has been a godsend to our family. There was nothing anyone could do  to help Clem until now." 

It is too soon to say whether Dr Dougal's invention could help other sufferers. The symptoms of Alzheimer's disease and dementia can vary from day to day - and relapses are not unusual. And not all patients may benefit from the treatment.

Dr Dougal stressed that a full, clinically controlled trial would be needed  before his anti-dementia helmet could be licensed for public use. A trial of 100 patients is expected to start later this year.

"I made it clear to the Fennells that I didn't know for a fact  whether it would work or not, but the results are good," said Dr Dougal.

"He was monosyllabic when I first saw him, but if I ring up now he will answer  the phone. He didn't have the verbal skills to do that three weeks ago." 

The Fennells have been told they can take the prototype helmet back to the US  with them so they can continue the treatment at home.

Commercial versions of the helmet will include 700 LEDs and cost around £10,000.

The Alzheimer’s Society said: "’A treatment that reverses the effects of dementia rather than just temporarily halting its symptoms could change the lives of the hundreds of thousands of people who live with this devastating condition.

‘Non-thermal near infra-red treatment for people with dementia is a potentially interesting technique. We look forward to further research to determine whether it could help improve cognition in humans. Only then can we begin to investigate whether near infra-red could benefit people with dementia.’

One in three people will end their lives with a form of dementia. Around 700,000 suffer from dementia - with more than half having Alzheimer's disease.

Proteins are the compounds that are responsible for balancing and regulating all of the intricate chemical reactions that coordinate the biochemistry that goes on non-stop in each cell of the body. They are long strings, like links in a chain, of building blocks called amino acids hooked end to end. To become activated they must first be wrapped into a precise three dimensional structure. This brings together the functional components of the long protein molecule that bind specific compounds, place them together in an appropriate configuration, and manipulate chemical reactions. As cells age, these proteins lose their distinctive configurations. When this happens, other proteins unwind and then rewind around, or recycle, each of the functional proteins.

As part of the cellular repair and maintenance process, these repair proteins work like the recycling arm of the waste management company. They wrap around the misfolded proteins and enable them to be reconfigured in a functional fashion. The effective action of this system keeps cells young. When it goes awry, parameters of aging are accelerated.

Researchers at the University of Pennsylvania School of Medicine investigated this unfolding protein response (UPR) in sleep-deprived young and old mice. When nerve cells in the cerebral cortex were evaluated after a period of sleep deprivation, the UPR was appropriately active in the younger group but it failed to do its job in the older group. As a result, misfolded proteins built up within the cells. In addition, protein synthesis, rather than being down regulated, continued unabated thus complicating the situation. In addition, old sleep-deprived mice had more "cell death" proteins accumulate as well.

Thus, several protective neuronal mechanisms were found to be upset by sleep deprivation in the old mice. The first author of the paper that appeared in the June, 2008 issue of the Journal of Neuroscience, Nirinjini Naidoo, speculated that sleep disturbances in older humans might place an additional burden on an already stressed protein folding and degradation system. He suggested that future studies should examine whether interventions that augment key protective proteins will delay the effects of aging and reduce sleep disturbances.

Cognitive Training Studies for ADHD Yield Promising Findings

-- By Dr. David Rabiner

Although medication treatment is effective for many children with ADHD, there remains an important need to explore and develop interventions that can complement or even substitute for medication. This is true for a variety of reasons including:

1) Not all individuals with ADHD benefit from medication.
2) Among those who benefit, many have residual difficulties that need to be addressed via other means.
3) Some individuals experience adverse effects that prevent them from remaining on medication.
4) Medication treatment does not result in benefits that extend beyond when medication is being taken.

Except for #3 above, the same limitations hold for behavior therapy, which is the other intervention for ADHD that is widely considered to have a strong evidence base at this time.

Because of these limitations, some researchers have pursued cognitive training as an alternative method of treatment. The basic idea behind cognitive training is that important cognitive skills such as attention and working memory can - like any other skill - be strengthened and enhanced with intensive and focused practice. Furthermore, when an individual builds these skills the benefits may endure beyond the time when the actual training is provided.

Although this is a logical and compelling idea, the research base as it applies to individuals with ADHD is rather limited and the idea that attention is a skill that could be strengthened by focused training has not been carefully studied. In fact, when I was preparing a grant application several years ago for an attention training study, I was surprised to locate fewer than 5 studies of this issue. Furthermore, these were generally small preliminary studies that would be considered pilot investigations.

In recent years, however, researchers in the ADHD field have devoted greater attention to examining the potential benefits of cognitive training for ADHD. Below, I review 2 recent studies that highlight the potential value of training oriented approaches.

- Study 1: Computerized Progressive Attentional Training for Children with ADHD -

This study was conducted with 36 6-13-year-old children in Israel who were diagnosed with ADHD. Results from this study were published last year in Child Neurospsychology [Shalev, Tsal, & Mevorach (2007). Computerized progressive attentional training: Effective direct intervention for children with ADHD. Child Neuropsychology, 13, 382-388.]

Participants were randomly assigned to receive 8 weeks of computerized attention training (one hour sessions two times per week) or to a control group. The basic premise of computerized attention training is simple: the program requires children to attend to a variety of computer exercises and to make different responses depending on the stimuli presented. For example, a particularly simple task would require the child to press the space bar each time the number 2 was flashed but to refrain from responding when any other number is flashed. To perform well, the child must sustain their attention and refrain from responding impulsively.

Although other tasks may be far more complicated, and place demands on both problem solving skills and working memory, all tasks require sustained attention to do well. They also become more difficult and longer as the child moves through the training program. Thus, the child receives repeated practice in sustaining attention to increasingly challenging tasks that last for longer time periods. Ideally, the difficulty level adjusts to match the child's ongoing performance so that the child is constantly challenged to perform at their best possible level - not too easy but not too hard.

By succeeding in the program, the child is demonstrating an increasing ability to sustain their attention to challenging cognitive activities. Although children may get better at attending to the actual computer exercises, however, the important question is whether this generalizes to the classroom and other settings where focused attention is critical for success. If not, become better at attending to the attention training exercises would be of little value.

The attention training program tested in this study was designed to train 4 different aspects of attention: sustained attention (the ability to maintain attention and persist on task until completion), selective attention (the ability to maintain a specific cognitive set in the face of competing distractions), orienting attention (directing one's attention to critical stimuli), and executive attention (allocating attentional resources between competing demands and choosing what to attend to). During each session children were trained on these different types of attention and the tasks become more difficult as children's performance improved.

Children in the control group played computer games - rather then receiving attention training - for the same amount of time. These games also required children to sustain their attention to succeed and became more difficult as children progressed. Thus, the amount of time children spent under adult supervision working on computer activities that became more difficult as they progressed was the same for each group. Unlike children randomly assigned to the attention training group, however, children in the video game control condition were not exposed to activities that focused on training specific components of attention.

Before and immediately following training, parents rated their child's ADHD symptoms using a standardized behavior rating scale (the authors report that parents were blind to which group their child was in). In addition, academic performance was tested pre- and post-training using math problems, reading comprehension problems, and passage copying problems taken directly from children's school books. Standard achievement tests were not used because such tests are not available in Hebrew. Information about whether any children were on medication during the training or during testing was not provided.

- Results -

Encouraging results were obtained. Parents of children in the attention training group reported a significant decline in their child's inattentive symptoms compared to parents of children in the control group. The change in hyperactive-impulsive symptoms was in the same direction but was not significant.

After controlling for academic performance before training, children who received attention training did significantly better than controls in reading comprehension and in their speed of copying passages. Math performance was in the same direction but was not significant.

- Summary and Implications -

The authors conclude that their attention training program produced significant improvements in parents' ratings of inattentive symptoms and on academic tests. This is the first demonstration I am aware of that suggests attention training may improve academic performance.

The authors note several important limitations to their study. First, the sample is relatively small. Second, no behavioral data was obtained from children's teachers. Third, there was no extended follow-up so the duration of the benefits observed at post-test is unknown. To these concerns I would add that the academic results would be stronger if a standardized achievement measure had been used. Finally, I wonder if parents truly remained blind to whether their child was receiving attention training or was in the video game control group.

These limitations not withstanding, these are promising results that highlight the potential of attention training procedures for children with ADHD. A larger controlled trial that addresses the limitations of the current work is certainly warranted.

Note - To my knowledge, this attention training program is not currently available outside of Israel.

- Study 2: The impact of different types of working memory training for children with ADHD -

Working memory is a key cognitive function that allows individuals to hold information in mind for brief periods of time. This ability plays an important role in countless daily tasks including following directions, accurately tracking conversations, reading comprehension, solving complex math problems, and staying focused on a project. Current theories of ADHD that emphasize the critical role of executive functions highlight working memory deficits as an important aspect of the disorder; in fact, research has shown that many individuals with ADHD have poor working memory compared to same age peers without the disorder.

A study published several years ago reported evidence that working memory is a skill that can be improved with intensive training. In a randomized controlled trial conducted with 53 children diagnosed with ADHD, working memory training was found to yield significant gains in non-trained working memory tasks and a reduction in ADHD symptoms as reported by parents (you can find a review of this study Here). Additional controlled studies of working memory training have reported positive results in other groups including younger and older adults without ADHD, typically developing preschoolers, and stroke victims. Until recently, however, additional controlled studies documenting positive effects in children with ADHD have not been reported.

At the May 2008 recent meeting of the American Psychiatric Association, Dr. Christopher Lucas and his colleagues at NYU Medical School presented new data on the use of working memory training in children diagnosed with ADHD. Their study reported on the results of 2 different types of working memory training - auditory training or visual-spatial training - conducted with 46 children aged 7-12 who were participating in an intensive summer treatment program for ADHD.

Participants were randomly assigned to received either auditory or visual spatial working memory training using the computerized training program developed by Cogmed. The idea behind assigning children to these different types of training was to see whether one was more effective then the other; the researchers had hypothesized that children who received visual-spatial training would achieve better results.

A typical auditory training exercise would involve the computer presenting the child with a string of digits, and the child had to subsequently indicate the correct order - either forward or backward - via the keyboard. In a typical visual spatial working memory training task, the child would be required to recall the location of different objects that lit up on the screen. You can view actual examples of the working memory training tasks Here.

Training took place for 30-35 minutes per day, 4 days per week, over a 6-week period so that a target of 25 training days could be provided. Both auditory and visual-spatial training protocols automatically increased the difficulty level of the working memory tasks depending on how well the child is performing, becoming more difficult when the child is successful and easier when the child is struggling. These adjustments are made on nearly a trial by trial basis by increasing or decreasing the number of items to recall. As a result, the child is consistently challenged to work at their maximum performance level without the task becoming so difficult that they become frustrated and give up.

The researchers were interested in 2 basic questions. First, did children who received visual-spatial training show greater gains in working memory performance on non-trained tasks than children who received the auditory working memory training? This was assessed by having children complete a comprehensive working memory assessment before and after training using tasks that differed from what they were actually trained with. It is important to evaluate training using tasks that differ from training activities to see whether training improvements extend to non-trained activities.

The second question was whether visual-spatial working memory training was also associated with behavioral improvements. To answer this question, the researchers examined the number of positive behavior points, i.e., points awarded for behaving appropriately and following camp rules, that children in both groups received from camp counselors between weeks 4 and 6 of the training. The counselors who awarded points were not aware of which training condition children had been assigned to.

This represents a stringent test of working memory training on behavior for several reasons. First, the ratings were being made by blind observers. Second, most children were being treated with medication, and their behavior would already have improved because of this. Third, all children were involved in an intensive behavioral therapy program designed to promote positive behavior. Thus, any improvement from working memory training would be above and beyond gains achieved from treatments that were already in place.

- Results -

Before and after the training, children were tested on several non-trained measures of working memory. Consistent with the researchers' prediction, children who received visual-spatial training performed significantly better on several of these tasks than children who received auditory working memory training.

Of particular interest is that children who received visual-spatial working memory training earned significantly more positive behavior points from the camp counselors. Thus, these children were rated as doing a better job of consistently following camp rules and behaving appropriately.

- Summary and Implications -

Results from this study support the benefits of working memory training for children with ADHD and indicate that training of visual-spatial working memory is especially important. The fact that this training was associated with an increase in positive behavior above and beyond medication and behavior treatments already in place is a very encouraging result.

As with Study 1, this study has several limitations to consider. Although the behavior improvements noted by camp counselors is important, it would also be important to document that such behavioral gains were also observed by parents and teachers. This, however, was not examined in the study. As with Study 1, there was no extended follow-up so the duration of training benefits can not be determined.

- Overall Summary -

Results from these two cognitive training studies highlight that cognitive training interventions may provide an important complement to traditional medication treatment and behavior therapy. Both studies included appropriate control groups, employed random assignment, and had outcome measures provided by individuals who were "blind" to which condition children were assigned to. They are thus well-designed studies from which scientifically sound conclusions can be drawn. They add to the growing research base that intensive practice and training focused of key cognitive skills can have positive effects that extend beyond the training situation itself.

As noted above, however, each study has limitations that should be addressed in subsequent work. It is encouraging to see the momentum for such work building and I look forward to reviewing other studies in this important area as they become available.

Can We Play?

-- By Dr. David Elkind

Play is rapidly disappearing from our homes, our schools, and our neighborhoods. Over the last two decades alone, children have lost eight hours of free, unstructured, and spontaneous play a week. More than 30,000 schools in the United States have eliminated recess to make more time for academics. From 1997 to 2003, children's time spent outdoors fell 50 percent, according to a study by Sandra Hofferth at the University of Maryland. Hofferth has also found that the amount of time children spend in organized sports has doubled, and the number of minutes children devote each week to passive leisure, not including watching television, has increased from 30 minutes to more than three hours. It is no surprise, then, that childhood obesity is now considered an epidemic.

But the problem goes well beyond obesity. Decades of research has shown that play is crucial to physical, intellectual, and social-emotional development at all ages. This is especially true of the purest form of play: the unstructured, self-motivated, imaginative, independent kind, where children initiate their own games and even invent their own rules.

In infancy and early childhood, play is the activity through which children learn to recognize colors and shapes, tastes and sounds—the very building blocks of reality. Play also provides pathways to love and social connection. Elementary school children use play to learn mutual respect, friendship, cooperation, and competition. For adolescents, play is a means of exploring possible identities, as well as a way to blow off steam and stay fit. Even adults have the potential to unite play, love, and work, attaining the dynamic, joyful state that psychologist Mihaly Csikszentmihalyi calls "flow."

With play on the decline, we risk losing these and many other benefits. For too long, we have treated play as a luxury that kids, as well as adults, could do without. But the time has come for us to recognize why play is worth defending: It is essential to leading a happy and healthy life.

Play and development

Years of research has confirmed the value of play. In early childhood, play helps children develop skills they can not get in any other way. Babbling, for example, is a self-initiated form of play through which infants create the sounds they need to learn the language of their parents. Likewise, children teach themselves to crawl, stand, and walk through repetitious practice play. At the preschool level, children engage in dramatic play and learn who is a leader, who is a follower, who is outgoing, who is shy. They also learn to negotiate their own conflicts.

A 2007 report from the American Academy of Pediatrics documents that play promotes not only behavioral development but brain growth as well. The University of North Carolina's Abecedarian Early Child Intervention program found that children who received an enriched, play-oriented parenting and early childhood program had significantly higher IQ's at age five than did a comparable group of children who were not in the program (105 vs. 85 points).

A large body of research evidence also supports the value and importance of particular types of play. For example, Israeli psychologist Sara Smilansky's classic studies of sociodramatic play, where two or more children participate in shared make believe, demonstrate the value of this play for academic, social, and emotional learning. "Sociodramatic play activates resources that stimulate social and intellectual growth in the child, which in turn affects the child's success in school," concludes Smilansky in a 1990 study that compared American and Israeli children. "For example, problem solving in most school subjects requires a great deal of make believe, visualizing how the Eskimos live, reading stories, imagining a story and writing it down, solving arithmetic problems, and determining what will come next."

Other research illustrates the importance of physical play for children's learning and development. Some of these studies have highlighted the importance of recess. Psychologist Anthony Pellegrini and his colleagues have found that elementary school children become increasingly inattentive in class when recess is delayed. Similarly, studies conducted in French and Canadian elementary schools over a period of four years found that regular physical activity had positive effects on academic performance. Spending one third of the school day in physical education, art, and music improved not only physical fitness, but attitudes toward learning and test scores. These findings echo those from one analysis of 200 studies on the effects of exercise on cognitive functioning, which also suggests that physical activity promotes learning.

In recent years, and most especially since the 2002 passage of the No Child Left Behind Act, we've seen educators, policy makers, and many parents embrace the idea that early academics leads to greater success in life. Yet several studies by Kathy Hirsch-Pasek and colleagues have compared the performance of children attending academic preschools with those attending play-oriented preschools. The results showed no advantage in reading and math achievement for children attending the academic preschools. But there was evidence that those children had higher levels of test anxiety, were less creative, and had more negative attitudes toward school than did the children attending the play preschools.

So if play is that important, why is it disappearing?

The perfect storm

The decline of children's free, self-initiated play is the result of a perfect storm of technological innovation, rapid social change, and economic globalization.

Technological innovations have led to the all-pervasiveness of television and computer screens in our society in general, and in our homes in particular. An unintended consequence of this invasion is that childhood has moved indoors. Children who might once have enjoyed a pick-up game of baseball in an empty lot now watch the game on TV, sitting on their couch.

Meanwhile, single and working parents now outnumber the once-predominant nuclear family, in which a stay-at-home mother could provide the kind of loose oversight that facilitates free play. Instead, busy working parents outsource at least some of their former responsibilities to coaches, tutors, trainers, martial arts teachers, and other professionals. As a result, middle-income children spend more of their free time in adult-led and -organized activities than any earlier generation. (Low-income youth sometimes have the opposite problem: Their parents may not have the means to put them in high-quality programs that provide alternatives to playing in unsafe neighborhoods.)

Finally, a global economy has increased parental fears about their children's prospects in an increasingly high-tech marketplace. Many middle-class parents have bought into the idea that education is a race, and that the earlier you start your child in academics, the better. Preschool tutoring in math and programs such as the Kumon System, which emphasizes daily drills in math and reading, are becoming increasingly popular. And all too many kindergartens, once dedicated to learning through play, have become full-day academic institutions that require testing and homework. In such a world, play has come to be seen as a waste of precious time. A 1999 survey found that nearly a third of kindergarten classes did not have a recess period.

As adults have increasingly thwarted self-initiated play and games, we have lost important markers of the stages in a child's development. In the absence of such markers, it is difficult to determine what is appropriate and not appropriate for children. We run the risk of pushing them into certain activities before they are ready, or stunting the development of important intellectual, social, or emotional skills.

For example, it is only after the age of six or seven that children will spontaneously participate in games with rules, because it is only at that age that they are fully able to understand and follow rules. Those kinds of developmental markers fall by the wayside when we slot very young kids into activities such as Little League. When Little League was founded in 1939, the adult organizers looked to children themselves in setting the starting age, which ended up being about age nine or older. But the success of Little League was not lost on parents eager to find supervised activities for young children. Before long, team soccer was promoted for younger children because it was an easier and less complex game for the six- to nine-year-old age group. The rapid growth of soccer leagues challenged the popularity of Little League. This led to the introduction of Tee Ball, a simplified version of baseball for children as young as four.

By pushing young children into team sports for which they are not developmentally ready, we rule out forms of play that once encouraged them to learn skills of independence and creativity. Instead of learning on their own in backyards, fields, and on sidewalks, children are only learning to do what adults tell them to do. Moreover, one study found that many children who start playing soccer at age four are burned out on that sport by the time they reach adolescence, just the age when they might truly enjoy and excel at it.

Bring back play

Play is motivated by pleasure. It is instinctive and part of the maturational process. We cannot prevent children from self-initiated play; they will engage in it whenever they can. The problem is that we have curtailed the time and opportunities for such play. Obviously we cannot turn the clock back and reverse the technological, social, and economic changes that have helped silence children's play. Television, computers, new family models, and globalization are here to stay.

What is important is balance. If a child spends an hour on the computer or watching TV, equal time should be given to playing with peers or engaging in individual activities like reading or crafts. It is important to involve the child in making these decisions and setting the parameters for how they spend their time. If we give children some ownership of the rules, they are usually more willing to follow them than when they are simply imposed from above. It is also important to appreciate individual differences. You will not be able to keep some children from playing sports, while others prefer more sedentary activities.

Another way we can help bring play back into children's lives is to have schools restore recess for at least half an hour. As research demonstrates, academics are unlikely to suffer from this change; if anything, they'll benefit. Schools also argue that they cannot afford recess because of high insurance costs and parents' greater appetite for litigation. But when I speak with insurance officers about this issue, they claim that argument is overblown. Either way, children could still be taken outside, or to the gym, for calisthenics to exercise their bodies.

We must also address the more general problem of test-driven curricula in today's schools. When teachers are forced to teach to the test, they become less innovative in their teaching methods, with less room for games and imagination. More creative teaching methods build upon children's interests and attitudes—their playful disposition—and this encourages them to enjoy their teachers, which in turn enhances their interest in the subject matter. Though computers are one of the forces limiting play, they can be creatively used in the service of playful learning. As more young teachers who are proficient in technology enter the schools, we will have the first true educational reform in decades, if not centuries.

But you don't have to be a teacher to help bring back play. Many neighborhoods badly need more playgrounds. This was also the case in the 1930s; in response, we saw the "playground movement," when local communities set up their own playgrounds. A new playground movement is long overdue, especially for our inner city neighborhoods, where safe play spaces are often in short supply. A playground should be required of any new large-scale housing development.

We could go further. In Scandinavian countries, there are play areas in even the best restaurants, as well as in airports and train stations. These countries appreciate the importance of play for healthy development, and we could well follow their example.

Finally children do as we do, not as we say. That gives us incentive to bring play back into our adult lives. We can shut off the TVs and take our children with us on outdoor adventures. We should get less exercise in the gym and more on hiking trails and basketball courts. We can also make work more playful: Businesses that do this are among the most successful. Seattle's Pike Fish Market is a case in point. Workers throw fish to one another, engage the customers in repartee, and appear to have a grand time. Some companies, such as Google, have made play an important part of their corporate culture. Study after study has shown that when workers enjoy what they do and are well-rewarded and recognized for their contributions, they like and respect their employers and produce higher quality work. For example, when the Rohm and Hass Chemical company in Kentucky reorganized its workplace into self-regulating and self-rewarding teams, one study found that worker grievances and turnover declined, while plant safety and productivity improved.

When we adults unite play, love, and work in our lives, we set an example that our children can follow. That just might be the best way to bring play back into the lives of our children—and build a more playful culture.