The research study used a transcranial random noise stimulation (TRNS) device to stimulate the dorsolateral prefrontal cortex (DLPFC), a key brain area for arithmetic skills, while subjects underwent five days of cognitive training with math calculation exercises.

The results showed that the group receiving TRNS performed significantly better on both math calculations and recall of arithmetic principles, compared to the control group. In addition, the TRNS group still showed the positive training effects six months later.

This long term training effect has some good implications for how “active” neuro devices can be combined with education principles and cognitive training to produce better classroom outcomes, along with work performance.

The Current Biology study adds to a growing list of innovative use of personal neuro devices for a variety of (future) school, work, and healthcare applications. The technology is moving at such a rapid pace that regulatory bodies are still grappling with how (or if) to apply traditional medical device guidelines to these new tools.

In the meantime, we expect active personal neuro devices to find their way into the hands of adventurous consumers who want to give them a spin. It will be interesting to see how this new market develops.

Read also: A New World of Personal Neuro Devices
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In general, Omega 3 sources like fish, beans, and green leafy vegetables are known to promote good cardiovascular and brain health, while too much Omega 6 from sources like corn oil, most fried foods, frozen processed foods, margarine, and peanuts is associated with unhealthy outcomes like diabetes, obesity, and Alzheimer’s disease.

The PLOS ONE study looked at what happens when Omega 3 supplements (fish oil pills) were added to the diets of mice who were consuming high amounts of Omega 6 fats that are common in western diets, especially from fast food outlets. It turns out that supplementing with “good” Omega 3 fats on top of high Omega 6 intake actually caused a number of mice to die from sepsis, a serious inflammatory condition brought on by severe infection. The study indicates that Omega 3 supplementation impairs Omega 6 infection-induced inflammatory responses, resulting in sepsis (at least in mice).

In other words, eating a bucket of fried chicken with a side of curly fries and potato salad with extra mayonnaise, and then trying to balance out this Omega 6 orgy with a couple of fish oil pills isn’t going to work, and may end up being harmful.

A better way is to focus on heart healthy and brain healthy foods, and limit intake of fast foods/ fried foods to a very occasional indulgence. Your brain will thank you.

See also: This is Your Brain on Fat and Sugar
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Baxter announced today that Gammagard did not provide any cognitive or functional improvement in 390 patients with mild to moderate Alzheimer’s disease. The patients who were enrolled in the Phase III trial received the drug through infusions over an 18 month period.

This outcome isn’t surprising for a number of reasons, including Baxter’s decision to proceed with an expensive Phase III trial based on modest improvement in a total of 4, count them: 4 patients in an earlier trial.

Gammagard is now added to the list of other clinical trial blowups that relied almost exclusively on the amyloid hypothesis. Turning the Alzheimer’s research community towards other avenues such as hyperphosphorylated tau may pick up speed now with amyloid clearance drugs approaching 20 clinical trial fails.

Readers can download a free report on early detection testing for Alzheimer’s disease that also includes a snapshot of other Alzheimer’s drug candidates.
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By using consumer friendly EEG recording sensors, packaged in a wireless headband linked to a smartphone, companies like Toronto based InteraXon are pioneering the development of personal neuro devices that will be used for a wide range of wellness and entertainment applications.

Other neuro device companies include Samsara Labs, developing a transcranial direct stimulation (TDCS) headband, Personal Neuro Devices, a company developing neuro games for smartphones and tablets, and Blue Marble Game Company, developing immersive games for neuro-rehabilitation and repair, after brain injuries such as stroke and severe, debilitating concussions.

We believe this emerging market will develop along two main paths:

1. A lightly regulated market for consumer wellness neuro devices and applications, with companies using the standard disclaimer along the lines of “This product has not been evaluated by the FDA, and is not intended to diagnose, treat, cure, or prevent any disease.”

2. A formally regulated market for medical devices and applications. Some companies will choose this somewhat arduous and expensive route because it establishes a higher level of credibility with the buyers, which in this case will be the health care insurance companies.

The disruptive technology and distribution models being developed by neuro device companies also bring the additional possibility of a parallel, unregulated gray-market, where enterprising free agents combine neuro devices and applications in new ways to provide a cognitive high performance edge to people willing to pay for a perceived competitive advantage (think about the sports performance doping market among pro athletes, and you can see where this could go.)

Welcome to the emerging world of personal neuro devices!

See also: Brain Training: Does it Work?
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Larry Cahill, Professor of Neurobiology and Behavior at UC Irvine, provided details on recent brain imaging research that indicate different activation levels of the amygdala in men and women, in response to the same emotional content.

The amygdala, commonly known as the “fear center” in the brain, is actually involved in processing a wide range of both negative and positive emotions. We have two amygdalae in our brains – the right amygdala handles the gist, or “big picture” content, while the left amygdala is better at the details of the same emotional content.

Dr. Cahill reviewed data from recent studies that indicate two things: that in men the right amygdala is preferentially activated in response to emotional content, while in women, the left amygdala is activated more by the same emotional content. (In one of the studies, the emotional content included a story about the death of a child, which was obviously designed to elicit feelings of sadness.)

This “gender lateralization” of emotional processing has recently been confirmed through several other brain imaging studies. The results are also a bit counterintuitive, with male brains apparently picking up the ‘big picture’ part of emotional content, while female brains preferentially process more of the ‘who/what/where/when/why’ part of the same emotional story.

These results also have some important implications for central nervous system (CNS) medications like antidepressants and anxiolytics (anti-anxiety drugs). It could be that one medication for both men and women is the wrong approach for any drug that acts on the CNS. (This is something that pharmaceutical companies probably won’t want to hear, since it means increased expense in clinical trials.)

Dr. Cahill’s work on gender differences in the human brain challenges several decades of dogma in neuroscience and related fields that except for hormone and reproductive differences (mainly with the hypothalamus), there are no credible or important differences in how men and women process emotional information. His research efforts strongly suggest the reverse is more accurate.

See also: Brain Health Primer – Four Ways to Maintain Your Brain
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Most of the brain imaging focus is on detecting the presence of amyloid beta, a type of protein that is the hallmark of Alzheimer’s disease pathology in the brain. Amyloid beta is also present in the brains of persons with Mild Cognitive Impairment (MCI), a milder disease state that may lead to full blown Alzheimer’s later on. Surprisingly, a significant percentage of cognitively healthy older adults also have amyloid deposits in their brains. There is still debate on whether amyloid presence in the brains of cognitively healthy adults has any predictive value on the chances of developing Alzheimer’s disease later in life.

(Download a copy of the state of the market report on early detection tests for Alzheimer’s disease.)

This situation brings up a series of interesting questions:

Can life insurance and long term care insurance providers demand an amyloid imaging test, and potentially deny coverage based on those test results, even for people that are cognitively normal?

Can a person with MCI, and a positive amyloid imaging result, still drive a car? (Yes, most likely they can.) Should they still drive a car? (Some US states mandate physician reporting of “impaired drivers” to the DMV.)

Are most physicians prepared to educate patients on the results and implications of amyloid imaging tests? (Probably not.)

This last question gets to the heart of one looming ethical issue with brain imaging tests: A model for physician and patient education on what an amyloid imaging test result means doesn’t exist yet. This opens the door to much potential confusion and patient harm if the test results aren’t understood in a framework that physicians and patient advocacy groups agree on.

MyBrainTest will continue keep an eye on this issue as it percolates in the health care industry.
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That’s the goal of new cognitive technology systems in development that were demonstrated at the ESCoNS 2.0 conference, which marries entertainment software with practical cognitive neuroscience.

Much of the current virtual reality (VR) research is being funded by the Dept. of Defense, which has been trying for years to help military service members who suffer from brain injuries and PTSD symptoms as a result of the wars in Iraq and Afghanistan.

Dr. Skip Rizzo from USC’s Institute for Creative Technologies demonstrated a powerful VR environment, dubbed “exposure therapy”, that places the user in a Humvee during an IED attack. In addition to the visual and auditory stimulation, the VR system includes strong low frequency waves that approximate the blast wave of an IED detonation. The hope is that allowing service members to relive these experiences in a “safe” environment, the training will tune-down the overly active stress responses many have after returning home.

VR cognitive training for emotional resilience and good coping behaviors also show some promise. Typical addiction relapse rates are very high with traditional treatments, which has created something of a revolving door (and profitable business model) with the hundreds of addiction treatment centers in the US. Lower cost VR applications could open the door to better and more sustainable outcomes for many types of addiction.
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Several population based studies have already pointed to a connection between vascular risk factors such as smoking, diabetes, and high cholesterol levels and the increased incidence of migraines.

The new Cephalalgia study looked at a link between patients who have migraine with aura and the potential risk of ischemic stroke or heart attack, and concluded that migraine with aura can elevate the risk of these serious cardiovascular events. The “how & why” of increased stroke and heart attack risk in people who report migraine with aura isn’t well understood at this point.

On a related note, the American Academy of Neurology (AAN) has released new recommendations for testing and treatment of migraines and headaches. The new AAN guideline on medications for severe headaches and migraines strongly suggest that opioids and barbiturates should be avoided – frequent use of these medications can actually increase the severity of migraine events.

The second AAN guideline suggests that electroencephalography (EEG) tests are not useful for diagnosing headaches, and are an unnecessary expense. This second recommendation is part of the “Choosing Wisely” initiative, where many professional medical associations have recommended that many tests be stopped as they add little clinical value.
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What tends to be missing from these studies is a more in depth understanding on what has changed in the life of an older adult that may make him or her more vulnerable to financial exploitation. One of the main changes can be the onset of short term memory loss associated with the early stages of Alzheimer’s disease and other types of dementia.

Memory changes in loved ones to look for include new difficulties in calculating tips and change, and forgetting to pay bills. A key point here is that a sustained negative change in handling personal finances should be a cause for concern. A free Alzheimer’s – Dementia Symptom Checklist can be completed online here, and also downloaded for later reference.
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The NIH study then followed up with participants a decade later to determine how many had received a diagnosis of depression since the original study years. It turns out that study participants who regularly consumed four or more cans of soda per day had a 30% greater chance of developing depression compared to participants who did not consume soda drinks.

A key point to highlight here is the almost quaint idea of having only a 12 ounce can of soda, which contains about 39 grams of sugar. Most fast food soda drinks now contain around 38 ounces (128 grams of sugar), and double Big Gulps contain a whopping 50 ounces (160 grams of sugar). In other words, super-sizing one soda drink is the same as drinking four regular size cans of soda. There is a direct link between high levels of sugar consumption, diabetes, and obesity. It follows that depression can be part of this spiral.

So what about drinking only diet sodas every day? The research evidence points to the possibility that using “fake” sugar like saccharin and aspartame alters the food consumption feedback loop between the body and brain. When your brain can’t tell the difference between real and fake sugar, it discounts the importance of any sweet food, which can encourage higher food consumption levels. Read more here.

As with most things, moderation is a virtue. Drinking a soda on an occasional basis is fine, drinking the equivalent of 4-5 cans of soda every day probably isn’t.

On the positive side, the NIH study indicates that drinking four cups of coffee each day may provide a modest defense against depression. Study participants who drank four cups of coffee daily had a 10% less chance of depression compared to non-coffee drinkers.

See also This is Your Brain of Fat and Sugar.
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A positive aspect of rising living standards in most of the world has been a significant improvement in worldwide average life expectancies, increasing from 52 years in 1960 to 69 years in 2009. Regional differences are even more striking — the average life expectancy for a person living in North America has risen from 70 years in 1960 to 78 years in 2009, while the life expectancy in East Asia & Pacific countries as a group has grown from 47 years to 73 years during this same period.

In tandem with improving life expectancies, the global population of people over age 65 has risen dramatically, from 150 Million in 1960 to over 500 Million in 2010. An important corollary to this trend is the accelerating rate of worldwide dementia cases, which carry significant health care, social, and public policy implications. Over 35 Million people are living with dementia worldwide today, and this number is projected to increase to 66 Million in 2030 and 115 Million by 2050.

Accelerating Dementia Care Costs

The worldwide cost of dementia care (both direct and indirect costs) is estimated to be the equivalent of 1% of global GDP, or more than US$600 Billion in 2010. Over 70% of this cost (approx. US $423 Billion) is centered in North America and Europe.

The rapid rise in global dementia cases over the next 30-40 years will present a series of challenges for governments, health care providers, and families, ranging from overburdened health care systems, to the need for public awareness of dementia and support services for caregivers. Another important part is the need for standardized dementia screening guidelines.

Early Screening and Detection of Alzheimer’s Becomes Important

In 2011, the US National Institute on Aging and Alzheimer’s Association released updated diagnostic guidelines for Alzheimer’s disease. These new guidelines include a clear delineation of Alzheimer’s disease stages:

A common theme emerging from both completed and ongoing clinical trials is the need for early detection of Alzheimer’s disease, either in the Pre-Clinical or Mild Cognitive Impairment (MCI) phase. The need for early detection stems from two primary sources:

Many Alzheimer’s drug candidates, designed to prevent the buildup of amyloid beta in the brain, will most likely only be effective before any substantial amounts of the brain protein accumulate. This will require one or more testing methods to detect the initial presence of amyloid beta deposits, and/or initial signs of cognitive impairment.

Alzheimer’s symptom management medications such as donepezil (and future adjuncts) are also significantly more effective at the beginning of the disease process, rather than starting medication after obvious signs of cognitive impairment are present. Effective symptom management for Alzheimer’s requires a proactive approach for early symptom detection.

An increased research focus on validating methods of testing for Alzheimer’s disease has yielded a number of approaches for detecting disease markers before obvious cognitive impairment symptoms appear.

To read more about early detection testing options for Alzheimer’s disease, download the full report:

Companies listed in the report include Pfizer (PFE), Merck (MRK), Eli Lilly (LLY), Johnson & Johnson (JNJ), Roche-Genentech (RHHBY), GE Healthcare (GE), Philips (PHG) Siemens (SI), Positron Corporation (POSC), NeuroTrax, CogState (CGS.AX), TauRX Pharmaceuticals, and more.
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The study followed more than 1,700 women (all over age 65) for a decade, recording detailed histories for study participants that included age at onset of menopause, and when (or if) they began hormone therapy.

It turns out that the study participants who began hormone therapy shortly after menopause (within the first 4 years) had a 30% lower incident rate of Alzheimer’s later in life compared to participants who did not choose HT after menopause. The women who began HT shortly after menopause, and then continued with the therapy for at least 10 years, showed the greatest reduction in Alzheimer’s risk — it seems that “early” HT can provide a neuroprotective booster.

However, the study data also suggests that waiting more than 5 years after menopause to begin HT may actually increase the risk of Alzheimer’s. How could this be? It seems that the type of HT (opposed vs. unopposed), if started long after menopause, can deliver a modestly increased risk of Alzheimer’s later in life — opposed HT was associated with a modestly increased AD risk in the study, when started more than 5 years after menopause.

Further research is warranted on the effect of HT on Alzheimer’s risk, but the Neurology article provides some useful information on timing and duration of HT.
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The good news is that advances in stroke treatment have improved the odds for a full recovery, especially if help is administered in the first 90 minutes after stroke signs and symptoms appear. The odds for a favorable stroke outcome decline rapidly after the first 90 minutes without effective treatment, with some modest benefit remaining if administered within 4 hours of symptom onset based on several studies.

The most current ischemic stroke treatment is intravenous recombinant tissue plasminogen activator, or rt-PA. rt-PA helps dissolve the clot, usually located in an artery in the neck or brain, that is causing the stroke.

A key point here is that the ideal 90 minute time window includes time to transport the patient into the hospital ER, conduct tests (including a CT scan in most cases), and then administer rt-PA. This is why knowing the most common signs of stroke are so important – minutes really do count.

Creating Comprehensive Stroke Centers in Each State

rt-PA treatment for ischemic stroke is still being rolled out in the US to major hospital centers in every state. Expect to see “Comprehensive Stroke Centers” in major urban centers that have passed a certification procedure. Most community and rural hospitals will need to coordinate acute care and transportation with the stroke centers. There are also some interesting pilot programs being tested with mobile stroke care units that come to the patient, rather than the other way around.
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Finding a cure for Alzheimer’s, or a method to significantly slow disease progression, continues to be a very challenging goal for stakeholders. A common theme emerging from both completed and ongoing clinical trials is the need for early detection of Alzheimer’s disease, either in the pre-clinical or Mild Cognitive Impairment (MCI) phase.

An increased research focus on validating methods of testing for Alzheimer’s disease has yielded a number of approaches for detecting disease markers before obvious cognitive impairment symptoms appear. These testing approaches can be broadly segmented into brain imaging tests, neurocognitive tests, cerebrospinal fluid tests, genetic tests, and the future possibility of blood serum tests.

>> Request a complimentary copy of this report. <<

Companies listed in the report include Pfizer (PFE), Merck (MRK), Eli Lilly (LLY), Johnson & Johnson (JNJ), Roche-Genentech (RHHBY), GE Healthcare (GE), Philips (PHG) Siemens (SI), Positron Corporation (POSC), NeuroTrax, and CogState (CGS.AX).
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We’ll give you the answer up front: It depends.

With the growing number of brain training products and cognitive training service providers in the market today, it’s important to understand the potential benefits and drawbacks of formalized, structured cognitive training.

Using analogies with physical rehabilitation and fitness training can help define the type (and potential benefits) of many of these brain training products.

Analogy 1: Cognitive Rehabilitation – Physical Rehabilitation

Serious accidents can cause serious physical injuries, and health care systems have developed a pretty well defined rehabilitation process to achieve the best possible recovery after sustaining broken bones, torn ligaments, and other unfortunate occurrences. The same goes for physical therapy after surgery for a hip or knee replacement. Generally, physical rehabilitation can last from a few weeks to several months.

Cognitive rehabilitation can be viewed as brain exercise therapy for cognitive problems associated with conditions such as ADHD, autism, and brain injuries (severe concussion, stroke, etc). Cognitive rehabilitation relies on the process of neuroplasticity, where the brain has an innate capability to rewire itself to regain skills, and workaround damaged neural connections. The techniques and timeframes for cognitive rehab aren’t as well defined as they are for physical rehab, but a few months to several years can be a typical range.

Successful rehabilitation, whether cognitive or physical, requires sticking to a schedule that challenges the body and brain to heal. For example, Cogmed provides a software based ADHD remediation program that lasts an average of 8 weeks, with 4 training sessions each week (each session is about 45 minutes). Cogmed has published some peer reviewed research that shows ADHD symptom improvement is possible (for both children and adults) *if* the rigorous training schedule is followed.

Posit Science and SuperBetter are two other companies with a cognitive rehabilitation focus. Posit Science originally began as a brain training software company, but has now moved entirely online with their new BrainHQ offering. SuperBetter was created by a game designer who suffered a severe concussion and then struggled through recovery. SuperBetter provides a path to reach brain health goals through achievable, incremental steps with help from the game and allies (friends & family) that users enlist.

Analogy 2: Brain Training – Fitness Training

Whether it’s joining a gym, signing up for yoga classes, or training for a marathon, people usually have a health goal such as shedding weight, keeping in shape, or improving flexibility and strength. Likewise with brain training, the goals tend to be along the lines of better focus and memory, improved processing speed and the ability to learn faster.

Lumosity and MindSparke Brain Fitness are two general purpose brain training sites. They both offer a variety of brain training exercises that are based on sound neuroscience principles. The exercises are structured more as games, versus “boring” cognitive tests.

A more hands-on approach to brain training, especially for school age children, comes from LearningRX, a franchise business that offers a blend of traditional tutoring and classroom brain exercises.

The science is a bit more fuzzy on the utility of general brain training for cognitively healthy individuals. It certainly won’t hurt to play with brain training programs, but current research hasn’t yet proven that general brain training transfers to improved performance at school, work, and everyday life.

Want to try your hand at some free brain exercises? Try these memory and brain speed tests.
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The study looked at brain regions associated with food reward, and noted some important differences between participants who regularly consumed several zero calorie sodas each week, and participants who didn’t drink diet soda as part of their weekly routine.

It turns out that habitual diet soda drinkers had an outsize response in their brains to any sweet taste (both artificial & natural) compared to non-diet soda drinkers. More importantly, the brains of diet soda drinkers had lost the ability to differentiate between “real” sugar and “fake” sugar, compared to the control group.

When Your Brain Can’t Tell The Difference

This result has some startling implications on how artificial sweeteners might be altering the finely tuned reward circuits that drive much of human behavior, especially when it comes to food choices.

The first implication is that artificial sweeteners (saccharin, aspartame, etc) offer up the false promise of a high calorie/high energy food source to our evolutionary ancient mammal brains, but the body ends up getting “cheated” when consumption of very sweet fake sugar doesn’t result in any calorie intake.

A second result is the possibility that if our brains lose the ability to differentiate between sucrose (high calorie/high energy content) and artificial sweeteners (no calorie/no energy content), the brain’s food reward feedback loop will begin to discount the importance and value of any sweet food.

Paradoxically, this may well mean that food intake will actually increase over time, since the brain’s food reward circuits can’t reliably signal the difference between real and artificial sugar choices.

The SDSU/UCSD study supports this possibility with the discussion that the right caudate (a brain region directly involved in feeding behaviors), showed lower activation in habitual diet soda drinkers compared the control group. Lower activation in the right caudate is typically associated with dis-inhibition and compulsive behaviors, such as mindlessly reaching for that third diet soda in the afternoon.

Food for thought, so to speak.

See also– This is Your Brain on Fat and Sugar.
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New additions include a complete Annual Wellness Visit record that every patient can take home: a personal folder with tabs for the Medicare Screening Template (My Wellness Schedule), “My Medications”, My Immunizations”, “My Health Care Team”, and more.

View the entire Annual Wellness Visit template kit here.

There are a number of new online brain health tools that launched this year at the conference, with many more on the way soon. Some of these health technology firms bill themselves as online mental health platforms, and others as “social health gaming” tools, but they really serve the same purpose: promoting and maintaining a healthy, resilient brain.

Here’s a rundown on several of these online brain health companies:

SuperBetter has a refreshingly non-clinical take on ways to recover from a health crisis, or reach personal health goals. Created by an expert game designer who suffered a severe concussion (and then struggled through recovery), SuperBetter provides a path to reach health goals through achievable, incremental steps with help from the game and allies (friends & family) that you enlist.

Kairos Labs takes social health gaming to larger multi-player groups with the goal of achieving lasting, sustainable behavior change. Called Habitual, this online health tool draws on psychology research and behavior change theory to promote behavior change on a large scale – think how this could positively affect obesity rates and food choices, as an example.

In response to an overwhelming need to treat injured military service members who have suffered brain trauma, the Veterans Administration created PTSD Coach, a mobile brain heath application available on Android and Apple devices. Kudos to the dedicated VA staff that pulled this simple but useful tool together.

AbilTo and Empower Interactive are moving the traditional cognitive behavioral therapy (CBT) approach of one-to-one psychotherapy office visits to the web — with online video sessions, user guided online therapy education modules, and virtual therapist support teams. So who will pay for these new tools? In the future, probably your employer or health plan. Possible roadblocks for consumers: how “real” will online therapy feel, and how much personal online therapy details will be made available to employers and health plan sponsors.

Next week we’ll detail some trends with wearable & home based health sensors that could have positive implications for cognitive health, especially for older adults.
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The results showed that the study participants with Type 2 diabetes scored significantly lower on cognitive performance tests compared to participants without this condition. The study concluded that “poor glycemic control may contribute” to reduced cognitive health in diabetic subjects.

The second study, published in the journal Neurology, suggests a more worrisome problem, even for people who haven’t received a diabetes diagnosis. The Neurology study looked at correlations between blood sugar levels and brain region atrophy in 250 participants over a four year period.

The Neurology study found a consistent link between deterioration in the size of the hippocampus, a brain region important for memory and learning, and fasting blood sugar levels no higher than 6.1 mmol/l, or 110 mg/dL. These levels are currently considered high-range normal.

Elevated and sustained blood glucose levels contribute to “metabolic dysfunction”, which includes increased oxidative stress and a heightened inflammatory response in the brain, which are both bad for cognitive health.

Food and drink choices create an active neurofeedback loop with our brain. These recent studies suggest a closer look at what are currently considered “normal” blood sugar levels.
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The Neurology study provided an interesting differentiation of football “speed players” (quarterbacks, running backs, halfbacks, fullbacks, wide receivers, tight ends, defensive backs, safeties and linebackers), and “non-speed players” (defensive and offensive linemen). It turns out that the speed players had a statistically higher risk of brain disease compared to the non-speed players.

This makes sense, since a combination of a high number of hits to the head + high magnitude shocks likely contribute to chronic traumatic encephalopathy (CTE) as the primary cause of Alzheimer’s and other brain diseases in retired NFL players.

As we have mentioned before, the NFL can be viewed as a multi-billion dollar entertainment franchise with mounting legal and financial risks. It will be interesting to see where this topic leads us over the next few years.
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Neurogenesis is the creation of new brain cells (neurons). Neurogenesis is a very active process in infants and small children – this is why the human brain more than triples in weight from birth to the early teens. Much of this weight increase occurs in the cortical layers, responsible for a variety of tasks like language, learning, logic, and social awareness. A very limited amount of neurogenesis can occur during adulthood, typically in the hippocampus, an area involved in memory formation and storage.

Neuroplasticity is an “always on” process that reshapes and fine tunes (both strengthening & pruning) the more than 100 trillion neural connections (synapses) that exist in the human brain. Each single neuron can receive signals from 5,000 – 10,000 other neurons through dendrite connections:

A single neuron has only one axon to transmit signals, so it tends to “listen” to input from many of its dendrite connections before sending a signal of its own. Neuroplasticity is the biological method for how the brain responds to its environment – learning the skills and adaptive behavior necessary to survive.

Over time, this pattern of learned behavior, skill acquisition, and memory is sometimes also known as experience and wisdom.
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Looking at the larger picture, I think that the communities of neuroscience research and pharmaceutical companies might need to do some serious soul searching on whether they have been racing down an amyloid blind alley.

Respected scientists, and drug company executives, are just as susceptible to cognitive dissonance as the rest of us. It’s much easier to choose one belief and stick with it (even when it might be wrong), rather than actively consider and pursue alternate ideas.

The real tragedy here is the wasted time not pursuing alternate hypotheses (such as hyperphosphorylated tau), with the same resources and vigor that have been afforded to the amyloid hypothesis over the past decade.

I believe we’ll eventually find a solution to the Alzheimer’s Dementia problem (a drug that can delay symptom onset for 10 years would be hailed as a huge success), but I think that the Alzheimer’s research community might need to issue a tacit mea culpa, and begin shifting major resources away from amyloid towards other research avenues.
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In the first study, the Journal of the American Medical Association (JAMA) looked at the average number of imaging tests ordered by doctors employed by HMOs, and found that the number of CT scans jumped 300% from 1996 to 2010. This increase is especially significant, because there is little or no financial incentive to order expensive tests in an HMO environment.

The JAMA study also reviewed the average radiation exposure per CT scan, and found that some patients received dangerously high doses. Some CT scans were conducted at between 20 and 50 millisieverts (mSv) of radiation, a level considered to be very high. For comparison, nuclear plant workers are limited to 20mSv of radiation exposure per year.

The real danger is when a patient receives multiple CT tests. A recent Lancet study on pediatric CT scans found that as little as three CT tests before the age of 15 could almost triple the risk of leukemia and brain cancer. Using a metric of 20mSv per scan, this means a child would be exposed to 60mSv or more, a very high level for children, who are more radiosensitive than adults.

This information becomes even more important when considering diagnostic tests for sports concussions. Generally, a CT scan for concussions won’t reveal any useful results, and will expose the athlete to unnecessary radiation. And most of the time, it’s the parents – not the doctors, who push for an expensive CT scan.

A note on MRI scans: MRI uses a powerful magnetic field, radio waves and a computer software to produce detailed images. MRI scans do not use ionizing radiation.
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The study, published this month in the New England Journal of Medicine, has some unusual characteristics compared to the typical research project on Alzheimer’s. First, the average age of study participants is 39 years, far younger than other studies. Second, about 70% of the 128 participants have a strong genetic predisposition to a form of dementia called Familial Alzheimer’s Disease, or FAD. FAD is also sometimes referred to as early-onset (before age 65) Alzheimer’s.

The participants who were gene carriers for the early-onset form of Alzheimer’s allowed the researchers to observe a “fast forward” view of the disease progression, and compare them to the non-carriers in the study.

What they found was that there were several tests that can reliably give a caution flag many years before Alzheimer’s symptoms appear. The tests fall into three main categories:

Cerebrospinal fluid (CSF) tests require a lumbar puncture, and measure the levels of certain brain proteins that are known to change during Alzheimer’s Disease progression. MRI and PET imaging scans can detect changes (shrinkage) and protein deposits in brain structures, and also measure glucose consumption in the brain, which declines in Alzheimer’s patients. Memory and cognitive tests measure a variety of memory, logic, and reasoning skills.

Moving Research Tools into the Doctor’s Office

This study provides some very useful information, but the gap between research tools and “routine” doctor’s office screening tests is still very large. Consider the following test features with cost:

Cerebrospinal Fluid (CSF) Tests: Invasive procedure, expensive test ( $2,000+ with diagnostic services)

Brain Imaging (MRI,PET) Tests: Non-invasive procedure, very expensive test ($3,000 – $6,000)

Memory/Cognitive Tests: Non-invasive procedure, less expensive test ($150 – $500 in office)

Given the test costs alone, it’s clear that memory screening is the best choice for a general purpose test. Episodic (short term) memory impairment is one of the clearest signs of possible Alzheimer’s. A number of paper tests do a decent job with cognitive screening, but newer computerized/tablet/online cognitive tests tend to be more sensitive and precise vs paper screening for memory impairment.

With the new Medicare Annual Wellness Visit now in its second year, this preventive health visit might be able to serve as a platform for routine cognitive health screening for older adults.
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The AAN analyzed over 280 clinical studies on the effectiveness of several different classes of medications to either alleviate or prevent migraine symptoms. The analysis confirmed the reliability of certain drugs, highlighted a particularly effective herbal preparation, and also pointed out which drugs consistently fail to treat migraines.

On the positive end, several established medications received confirmation that they are effective. The Triptan known as frovatriptan (Frova), Beta Blockers propranolol & metoprolol, and Anti-epileptics divalproex sodium (Dapakote), sodium valproate (Epilim), and topiramate (Topamax) all received a “Level A” established efficacy rating by the AAN. However, readers should also check with their doctor on possible negative side effects with these drugs.

A newcomer to the Level A list is Butterbur, a plant in the daisy family. Butterbur plants contain petasin, a natural chemical with anti-inflammatory properties.

Over the counter medications that received a Level B rating (probably effective) for migraines include Ibuprofen and Naproxen (Aleve).

On the negative end, the AAN analysis concluded that montelukast (used for asthma relief) and the anti-epileptic lamotrigine (Lamictal) failed to show any positive relief for migraine sufferers. Acebutolol (a drug for hypertension), clonazepam (Klonopin), and nabumetone (a drug for osteoarthritis) also received low marks.

See also: Migraine Signs and Symptoms.
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Apolipoproteins are proteins that transport cholesterol and fats in the blood stream. There are several types of these proteins in the human body, and researchers were able to identify that lower levels of the apolipoproteins ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratios increased the risk of cognitive decline over two years in cognitively normal individuals.

This is all still in the research phase, but it points the way to a future screening tool for Alzheimer’s that can reasonably be administered in a primary care setting, aka the doctor’s office. In addition to an independent study that will be needed to validate the Sydney findings, there is still a lot of work to be done in hammering out what “normal” reference ranges are for apolipoprotein levels.

Consider the following typical blood screening test result:

The last column lists blood component “reference ranges”, or what are considered normal levels, based on age range and gender. These blood panel reference ranges were established and validated through a 20 year medical research effort that began in the 1960s.

Reference ranges do not exist yet for apolipoprotein levels in the blood. In practical terms, this means a validated, reliable blood test for Alzheimer’s Disease is still several years away. But the basic research described in the PLoS ONE journal moves us a few steps closer.

See also… The Pros and Cons of Amyvid Scans for Alzheimer’s, and Moving Cognitive Screening into the Doctor’s Office
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Dr. Rabinovici, a recognized expert on amyloid imaging, took the unusual approach of presenting a strong case against using imaging tests for many possible Alzheimer’s scenarios. This was a useful exercise, as it helped identify the cases in which Amyvid imaging would be especially helpful.

First, the positives on Amyvid: it’s reliable, with results for sensitivity and specificity in the 83% to 90% range. And this is for both visual (human) readings and quantitative (computerized) readings of imaging results. Amyvid also has the FDA’s stamp of approval as a diagnostic agent for brain imaging of amyloid plaques in patients. “Diagnostic” is the key word here: this is an example of a neuroscience research tool moving into the (specialist) doctor’s office.

The Problems with Amyvid Imaging for Amyloid Beta

So what are the drawbacks with Amyvid? There are several:

Very high rate of potential false positives. There are millions of healthy, cognitively normal older adults (age 65+) who have significant amounts of amyloid beta in their brains. An Amyvid scan could raise a false red flag with these individuals. (Read this article on why amyloid deposits may not be the proximate cause of AD.) Physicians and staff will need extensive training on how to correctly interpret Amyvid scan results, based on each individual patient’s health history, age, and cognitive profile.

It’s diagnostically accurate only in the narrowest sense. A positive Amyvid scan means confirmation of amyloid beta deposits in the brain. So what does this mean? If the scan is for a cognitively healthy 75 year old, the result might not mean much (see first drawback). Also, the Amyvid scan won’t differentiate between Alzheimer’s pathology and, say, Dementia with Lewy bodies (DLB), another form of dementia that includes amyloid beta in the brain.

Amyvid scans are very expensive. The current cost for Amyvid is $1,600 per dose, and that doesn’t appear to include the PET scanner time and staff overhead, so $3,000 – $4,000 per scan is probably a good “all in” number. Medicare is being petitioned to approve and pay for Amyvid scans – no word yet on whether they will sign up for this. Given the 60+ Million potential Medicare beneficiaries who could start receiving advertisements for “brain health scans” and the like, the potential for abuse and cost to the US taxpayer is enormous.

Dr. Douglas Galasko, MD, Director of the Shiley-Marcos Alzheimer’s Disease Research Center at UCSD, mentioned during his talk that he worries a bit about “drive thru” imaging and biomarker commercial enterprises, that are heavy on technology but light on clinical experience and judgment. Given the costs of these new imaging techniques, this is a valid concern.

When Amyvid Scans Make Good Sense

Back to the positive. There are definitely cases when Amyvid scans can be very helpful and prescient. The general profile on when to use this technology includes the following:

Cognitive impairment in middle aged (< 65 years) patients. The prevalence rates for Alzheimer’s Disease in people who are in their 50s or early 60s is quite low – less than 1%. If noticeable cognitive problems are present in a 55 year old, then an Amyvid scan can help confirm or rule out early onset Alzheimer’s Disease.

The Amyvid scan could also potentially help point to (but not diagnose) other considerations such as corticobasal syndrome, posterior cortical atrophy, and a host of other rather esoteric neurological conditions with this middle aged patient.

In general, Amyvid is a good addition to a very thin list of diagnostic tools for Alzheimer’s Disease, if it is used selectively with patient age and symptoms in mind.

Cognitive screening tools, such as computerized cognitive assessments, can also be useful in clinical settings. Medicare instituted a new preventive health benefit known as the Annual Wellness Visit (AWV), which includes a loosely defined “detection of any cognitive impairment”. This wellness visit could act as a large platform to move (cost effective) cognitive health screening into primary care offices.
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Dr. Stern’s talk revolved around the long term consequences of repeated, consecutive knocks on the head, of the type many football and soccer players receive over the course of a single season. What’s astonishing are the total number of times these athletes get hit on the head:

• Football players, depending on position, can receive more than 1,500 hits each season
• Soccer players can receive more than 1,000 hits per year, through the act of “heading” the ball

Most of these are subconcussive blows to the head, but that doesn’t make them trivial events. Two football linemen can generate enough forward speed to run into each other at a combined speed of 20 miles per hour – this puts more than 20 g of force on all body parts, including the brain.

One of the key points for readers to consider and understand is the following:

It is an inaccurate belief that brain tissue can be “toughened up” in the same manner that muscle and bone tissue can be strengthened against physical stress and impact.

Our brain has the physical strength and consistency of refrigerated jello – think about what this means when someone is struck on the head hard enough to cause concussion symptoms. Helmets and other gear can provide a limited amount of protection, but they don’t stop the laws of physics from doing their work on brain tissue.

Focus on Long Term Consequences of Subconcussive Blows

So why all the focus on all these “regular” subconcussive hits on the head? Because we’re only beginning to understand the potential long term consequences to the brain of repeated hits that are common in some sports.

Research presented during the talk indicates that a cascade of damage starts in neuronal axons – the wires that connect brain cells together. As damage from cumulative hits grows, the axons begin breaking down, causing neuron death and a host of cognitive and emotional problems. It was confirmed that Dave Duerson was suffering from brain damage before he committed suicide last year, and it’s possible that Junior Seau also had brain trauma related to his football career.

I believe we will eventually find that personal genetics plays an important role in how people respond to “minor” brain injuries. It could be that the toughest 250lb football lineman on the field will also have the most vulnerable brain when it comes to head injuries.

Longer term, the possibility of screening for “concussion resistant” brain genome profiles in applicants and recruits. In addition to the military, I can see how school and professional sports teams would find this capability useful. However, we’re still probably many years away from having a practical screening application on this.
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The new practice guidelines have two parts that are designed to reduce the chances of concussions in children who play football:

1. Eliminate full speed head-on blocking or tackling drills in which the players line up more than 3 yards apart (this reduces forward speed before the players make contact with each other)
2. Total contact drill time is limited to 1/3 of total practice time

The new guidelines are as much a marketing and PR effort as they are a practical attempt to begin the process of changing a deeply entrenched playing culture in football. It remains to be seen if players, coaches, parents, and fans will accept these new limits.

As predicted in this January post, meaningful change in the culture of US football will happen first at the youth and high school level, before slowly percolating up to college and professional teams. Given the huge financial stakes involved at the top level, I believe this process will take decades.
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A number of high profile cases involving long term risks of concussions in contact sports has spurred sports concussion legislation in many states. State legislation will typically require mandatory concussion management policies that school administrators and athletic departments are responsible for implementing. Many schools are opting for computerized cognitive testing for all players as part of a concussion management process.

This guide is intended to provide a useful framework for schools and athletic departments to consider when implementing concussion management policies, including:

• How to establish valid baseline concussion tests
• Emerging research on concussion recovery time and process
• Concussion signs and symptoms
• Post-injury testing options

A product guide to computerized concussion testing systems, with sample baseline reports from Axon Sports, Concussion Vital Signs, HeadMinder CRI, and ImPACT Applications are included.
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