Intriguing New Insight into Cause of Alzheimer's

Contributed by: Dennis Fortier, President, Medical Care Corporation

As the experts in the field readily acknowledge, they really don't understand Alzheimer's disease very well.  A new hypothesis, based on a recent publication in the Journal of Neuroscience, suggests that previous views and treatment approaches might be aiming at the wrong target.

The dominant theory (the amyloid hypothesis) is that excess accumulation of beta-amyloid, a naturally occurring protein in the brain, aggregates into toxic plaques that disrupt cell function and leads to cognitive decline.  Based on the new research, it is plausible that beta-amyloid is in fact the main culprit, but that it does its damage inside the brain cells, prior to breaking free and accumulating into plaques.

Some of the general press on these findings have described the science as a complete contradiction of the amyloid-hypothesis.  In reality however, it is fairly consistent with one important difference.

The new insight is that beta-amyloid might be causing harm earlier in the biological process than previously believed.  This study suggests that once the beta-amyloid has been dispensed from brain cells and clumps together into a plaque, the damage has already been done. Previously, it has been theorized that the formation of the plaque is the beginning of a toxic biological process.

The implications for treatment are that we should be looking to reduce the presence of beta-amyloid inside the cells, as opposed to clearing it away later, once it has aggregated into a plaque. Fortunately, two of the most promising agents in the FDA pipeline, Bapineuzumab and Solanezumab, are both antibodies that bind to beta-amyloid and clear it away through the natural immune function. It is hoped that one or both of these agents might function at the early, biological stage suggested by this new insight.

Deep Brain Stimulation for Parkinson's Disease

Contributed by: Dennis Fortier, President, Medical Care Corporation

A great overview article on deep brain stimulation (DBS) for the treatment of symptoms caused by Parkinson's disease was posted today at WebMD.

DBS is accomplished by implanting electrodes directly into the brain and a transmitting device below the collarbone.  The transmitter stimulates regular electrical impulses from the electrodes, which effectively "turn off" parts of the brain where many Parkinson's symptoms originate.  Among those symptoms most commonly improved by DBS are tremors, slow movement, rigidity, and problems with walking and balance.

This is an FDA approved procedure but is commonly reviewed with caution because scientists cannot convincingly explain how or why it works.  However, the data collected in carefully designed trials on real patients is very clear and very positive.

There are many considerations in the decision to undergo DBS as part of a treatment regimen.  After all, it requires surgery that includes incisions through the skull and into the chest, so it is not a minor procedure.  However, compared to alternative approaches that intentionally destroy brain tissue, this might be considered a less invasive approach.

The cited WebMD article is fairly comprehensive and touches on a wider summary of advantages and disadvantages.  I encourage you to click through and read more about it.

Memory Lapses at a Young Age are Unlikely to be Alzheimer's Disease

Contributed by: Dennis Fortier, President, Medical Care Corporation

I hope this is the beginning of a new trend.  A recent article in the Washington Post took a very sensible, scientifically prudent, and optimistic approach to a story about Alzheimer's disease.  Essentially, the article develops the important point conveyed in the headline; that baby-boomers who sometimes misplace keys of struggle to recall a name, probably have no pernicious brain disease to worry about.

There is a fine line between dismissing concerns that are associated with normal aging, and ignoring clear signs of a real a memory problem, but this summary of evidence and quotes from experts did a nice job in achieving a proper balance.

I hesitate to criticize this story given the clear progress it represents in terms of highlighting science over sensationalism, but I do wish the headline had been more carefully written.  The actual headline in the Washington Post is "Forgetfulness at an Early Age is Rarely a Sign of Early Dementia".  It doesn't reference Alzheimer's disease although the story is written as though it does.  This disconnect suggests that dementia is actually Alzheimer's disease and begins with mild symptoms in early stages.

As readers of this blog know, "dementia" describes a state of very impaired thinking, and can be caused by many different medical conditions and diseases; Alzheimer's is the most common.  Once a person is demented, their impaired thinking abilities are severe enough to affect their daily life.  I think the headline inappropriately suggests that minor forgetfulness might be the beginning of a disease called dementia -- which is a common mis-understanding that the Brain Today blog works hard to clarify.

Lewy Body Dementia Awareness

Contributed by: Dennis Fortier, President, Medical Care Corporation

As per this press release from the NYU Langone Medical Center, October is Lewy Body Dementia (LBD) Awareness Month.

Like Alzheimer's disease and Parkinson's disease, LBD is characterized by impaired thinking and behavioral disruptions.  Because of these similarities, it is often misdiagnosed and improperly treated.

Three out of 4 LBD patients are initially misdiagnosed and the majority of patients see more than 3 doctors for more than 10 visits over 18 months before a diagnosis is established.

The obvious solution to the problem of delayed diagnosis is education, for both the public and for their doctors.

Here are a few facts about LBD to start you on the process of building higher education and awareness:
  • LBD core symptoms include: memory and thinking problems, movement problems, hallucinations, sleep disturbances and fluctuations in attention and concentration
  • LBD patients have more prominent problems with visual-spatial skills (such as depth perception, bumping into objects, not seeing things in front of them)
  • LBD patients experience a more rapid functional decline than Alzheimer’s disease patients with shorter intervals to nursing home placement and death
  • LBD patients have personality changes such as loss of interest, become more passive, quiet or withdrawn, and have trouble paying attention
  • The combination of cognitive, motor and behavioral symptoms place severe burden and stress on caregivers who often find themselves socially isolated
  • LBD patients are more likely to suffer from depression

Family History and Alzheimer's Risk

Contributed by: Dennis Fortier, President, Medical Care Corporation
This is not a simple topic.  The relationship between a family history of Alzheimer's and one's own risk for the disease, is probably more complex than previously expected.

While the evidence is fairly clear that the APOe4 gene plays a role in risk for Alzheimer's, affecting both the likelihood of getting the disease as well as the age of onset of symptoms, accumulating evidence suggests that many genes play a role, as do environmental factors.

A recent study, conducted at Washington University in St. Louis and published in Archives of Neurology, looked at changes in biomarkers in the brains and spinal fluid of 269 research subjects, 160 of whom had a family history of the disease and 119 of whom did not.  Among those with a family history of AD, only a portion had inherited the APOe4.

Interestingly, the biomarkers in the "family history" group,  regardless of APOe4 status, showed similar changes compared to the "no family history" group.  Specifically, a family history was associated with accumulation of beta-amyloid in the brain and a reduction of beta-amyloid in the spinal fluid.   This suggests that, while APOe4 genes are certainly important, there are other factors that play contributing roles in this complex process.  

Drug Prospect for Treating Early Alzheimer's

Contributed by: Dennis Fortier, President, Medical Care Corporation
We like to help keep news about potential new Alzheimer's treatments in proper perspective.  This week, there have been many news stories about an agent in the FDA pipeline that looks promising, but is in a very, very early stage of the process to becoming an approved drug.

The new agent, called Gantenerumab, is being developed by Roche Holding AG.  Like other antibody approaches in the FDA pipeline, it binds to amyloid plaques in the brain.  When the the body's natural defense system flushes the antibody from the brain, it takes the plaques along as well.  In theory, this is a direct attack on the plaques that many believe to be the cause of Alzheimer's disease.

Two agents with similar mechanisms are well ahead of this one in the FDA pipeline: Bapineuzumab (being developed by Pfizer and J&J) and Solanezumab (being developed by Eli Lilly).  Each of these are in Phase III (the final phase) of the FDA process whereas Gantererumab is in Phase I.

This is promising news and worthy of cautious optimism.  But don't think this portends of a new treatment in the near term, it will take a lot of ongoing science and many years before this agent could be established as an effective treatment and approved for sale.

Horrible Alzheimer's Advice from AARP

Contributed by: Dennis Fortier, President, Medical Care Corporation
We clarify the news about brain health.  When someone gets the story wrong, we feel it is important to provide a more balanced perspective.  The AARP got it horribly wrong in this article about early diagnosis of Alzheimer's.

While laudable for its intent to protect the public from invalid claims about Alzheimer's diagnostic tests and treatments, this article is remarkably misleading. I would expect much better from such a trusted source as AARP.

The sensationalistic statement opening the third paragraph (falsely propagating the notion that there is no diagnostic test and no effective treatment for AD) is about as harmful a message as anyone could direct at this audience.  True, there is no single medical test to diagnose AD, but as the author eventually admits, primary care physicians can diagnose it with high accuracy through a series of routine diagnostic steps.  The medical literature shows that better than 90% accuracy is easily achievable when published guidelines are followed.

As for treatment, the willingness of writers to substitute the terms "drugs" and "treatment" for one another is deplorable.  I think most experts agree that the cholinesterase inhibitors provide only moderate, symptomatic relief for Alzheimer's patients who are already demented.  However, robust treatment that includes early intervention (prior to the dementia stage), physical activity, a proper diet, strict control of diabetes and hypertension, ongoing social/intellectual stimulation, and a combination of a cholinesterase inhibitor with Nameda, has shown a much more optimistic treatment result than a single drug shows when isolated from all other aspects of treatment.

Trusted sources like AARP are invaluable as consumer advocates and they play a key role in sorting bogus claims from real science.  But in this instance, they could have done a much better job in characterizing the truth.  Suggesting that people with a memory concern should "ignore it" is alarmingly irresponsible.

Smokers Have Twice the Risk for Stroke

Contributed by: Dennis Fortier, President, Medical Care Corporation
We all know that smoking is bad for health.  The questions that require ongoing study and clarification are "how bad" and "bad for what, specifically".

In research presented last week to the Canadian Stroke Congress, scientists from the University of Ottawa Heart Institute provided some answers.  They concluded that smokers are twice as likely to suffer an ischemic stroke (caused by a blocked blood vessel) as non-smokers,  and four times more likely to suffer a hemorrhagic stroke (caused by a ruptured blood vessel) than non-smokers.

These findings were accompanied by more bad news.  The researchers found that, among smokers who had strokes, the strokes occurred about a decade earlier (on average) than strokes among non-smokers.  They also found that continuing to smoke following a minor stroke, greatly increased the likelihood of a major stroke later on.

Smoking is a preventable risk; a life-style choice with serious consequences. In addition to the well-publicized damage that smoking can cause your heart and lungs, I am hopeful that sharper insights into how it might damage your brain, will help more people make wiser choices about smoking.

Alzheimer's Diagnostic Test, Misleading the Reader?

Contributed by: Dennis Fortier, President, Medical Care Corporation
The popular press carries more stories like this in a given week than we could possibly highlight in this blog.

I am referring to this article describing a diagnostic test for Alzheimer's disease.  The test measures proteins in the spinal fluid and, according to the company with hopes of one day commercializing the test, it can diagnose Alzheimer's disease with 90% accuracy.  I believe that is a scientifically plausible claim and I suspect that careful measures of various biomarkers will achieve such accuracy in the very near future.

The potentially misleading element of this story comes from the following quote:
"Right now, diagnostic accuracy for Alzheimer's disease can be as low as 70 percent, meaning three out of 10 people who are diagnosed with this disease might not actually have Alzheimer's disease, but rather some other kind of dementia".
It is true that diagnostic accuracy for AD "can be" as low as 70 percent, if a physician does not follow published guidelines for working up a memory complaint.  However, when published guidelines are followed, then diagnostic accuracy is already better than the 90% target for which this new test is striving.

I think this test, and others, may pan out, but let's not mischaracterize the problem.  We need to help physicians update their knowledge to keep pace with the constant advances in medicine.  A new test, with inferior accuracy to the already achievable standard, is not a breakthrough, and the word "promising" probably does not belong in the story's headline.

6 Ways to Prevent Memory Loss

Contributed by: Dennis Fortier, President, Medical Care Corporation
This summary, published online today at Fox News, cites evidence supporting 6 lifestyle choices you can make to reduce the likelihood of cognitive decline.

Of course, there are no guarantees and bad genes combined with age can overwhelm even the best life-style.  Nonetheless, it is worthwhile to know the steps that might help, and to pursue as many of them as possible.

I suggest you click through and read the short story, but here is the list:
  1. Stay Physically Active
  2. Eat Fruits and Veggies
  3. Reduce Risk Factors for Heart Disease
  4. Embrace Cultural Activities
  5. Care for Your Teeth
  6. Challenge your Intellect
Remember, there is no certain method to eliminate all risk of cognitive decline, but doing what you can to stack the odds in your own favor seems like an attractive course of action.

Is AD contagious? Beta-amyloid and Prion Proteins

Contributed by: Michael Rafii, M.D., Ph.D - Director of the Memory Disorders Clinic at the University of California, San Diego. ______________________________________
A prion is an infectious agent composed of protein in a misfolded form. The word prion was coined in 1982 by Dr. Stanley B. Prusiner, and is derived from the words protein and infection.

Normal prion proteins are produced naturally in the brain, but can cause disease when they come into contact with an infectious form of the protein that folds into an unusual conformation. These infectious prions convert innocuous prion proteins into the infectious form, which forms clumps and leads to neurodegenerative diseases, such as variant Creutzfeldt-Jakob disease, the human form of mad cow disease. Prions slowly destroy the brain tissue of infected people by causing a cascade of misshapen proteins. They're known to spread via consumption of contaminated food, by getting a transfusion of blood or tissue transplant from someone who is infected.

In 2009, researchers led by Dr. Stephen Strittmatter at Yale, showed that prion proteins produced naturally in the brain interact with the amyloid-ß peptides that are hallmarks of Alzheimer's disease. Blocking this interaction in preparations made from mouse brains halted some neurological defects caused by the accumulation of amyloid-ß peptide.

Now, researchers led by Dr. Caludio Soto at the University of Texas Health Science Center, have shown that, in fact, Alzheimer's disease itself, may be a prion-like disease. His team injected the brain tissue of a confirmed Alzheimer’s patient into mice and compared the results to those from injected tissue of a control without the disease. None of the mice injected with the control showed signs of Alzheimer’s, whereas all of those injected with Alzheimer’s brain extracts developed plaques and other brain alterations typical of the disease.

These findings suggest that in an experimental setting, misfolded beta-amyloid can behave in a similar way as infectious prions. It remains to be proven whether at least a proportion of human AD cases could be due to a transmissible prion-like mechanism. It must be kept in mind, that prions are not contagious via normal human contact.

A Blood Test Predicting Rate of AD Progression

Contributed by: Dennis Fortier, President, Medical Care Corporation
This study out of Johns Hopkins, showing that a blood test might be useful in predicting the rate of cognitive decline in Alzheimer's disease,  is being widely covered in the press.  Here are some thoughts on the new science and what it might mean.

First, as the authors admit, this is very early stage work that has not yet been properly validated.  Second, if the research is eventually validated, that would be only the starting point for the long product development process prior to the day when a physicians might have a test they could use in practice.  Third, predicting the rate of progression may have some benefits, but if those benefits cannot be cost justified, then such a test might never be developed by any commercial interest.

I generally write optimistically in this space about new technologies and scientific advances that portend better care in the Alzheimer's arena.  In this case, I am surprised at the amount of mainstream coverage that has been afforded such an early stage study with (in my opinion) dubious clinical value.

On that note, I think there is a very interesting aspect to this research.  Given the massive recent investments in clinical trials to test agents for treating Alzheimer's disease, having a better understanding of each subject's propensity for cognitive decline could be highly valuable.

In a typical clinical trial, we apply a treatment to one group and a placebo to another group, then we look for differences in pre-determined outcomes.  In the future, if we could segment the research subjets into groups based on their expected rate of cognitive decline (slow, medium, and fast), as this new blood tests suggests is possible, then we might more clearly detect a treatment effect by comparing expected decline with actual decline.

In this regard, I think a blood test for predicting the rate of cognitive decline in Alzheimer's patients, if validated and commercialized, could play an important role in the effort to develop new solutions to the looming Alzheimer's epidemic.