World Alzheimer's Report 2011

Contributed by: Dennis Fortier, President, Medical Care Corporation

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Alzheimer's Disease International is the federation of national "Alzheimer's associations" around the world.  Each year, they compile a world report summarizing the state of scientific knowledge in the field of Alzheimer's disease.

This year's version, World Alzheimer's Report 2011, was released last week.  You can use these links to download the Executive Summary or download the Full Report.

The highlight of this year's report is encompassed in its subtitle: The Benefits of Early Diagnosis and Intervention.  This is an important message that is undermined daily by the mantra of the popular press, where messages about the futility of treatment are persistent. In this summary of scientific evidence, vetted by some of the world's greatest experts in this field, it is clear that detecting AD at an early stage and adhering to a robust regimen of treatment, can have tremendous health and economic benefits.

I am happy to see this report's strong and optimistic emphasis on such a positive side of the story.  I hope you will join me in sharing this report as broadly as possible by passing it along to your online networks.

Larry King: Alzheimer's Special

Contributed by: Dennis Fortier, President, Medical Care Corporation

Many of you may have seen Larry King's CNN special last night on Alzheimer's disease.  It was a one-hour special report on the urgency of the challenge this disease poses for our aging population, for our health care system, and for our society.

Overall, I thought there was a fair amount of good information presented.  The expert testimonies from Dr. Ron Petersen at the Mayo Clinic and Dr. Jeffrey Cummings from the Cleveland Clinic were excellent and clearly characterized the nature and the magnitude of this epidemic.  Heartfelt stories from care givers brought a very personal face to the disease and provided an in depth look at the way this disease can affect an entire family.

Having said that, I also thought the show performed one major disservice to the public.  There was much dramatic emphasis on the fact that Larry King and Ron Reagan visited the Cleveland Clinic to be evaluated for early signs of Alzheimer's and Ron Reagan chose to forgo an evaluation based on his preference to remain "blissfully ignorant".

To be clear, everyone has the right to make such a decision and I don't begrudge Reagan his right to do so.  However, he couched his decision against the backdrop that "there is no cure" and implied that it is therefore better "not to know" about the early presence of disease process.  This is a myth we need to stop perpetrating and Larry King missed the opportunity to set the record straight.

While there is no cure for Alzheimer's disease, there is certainly treatment.  Importantly, some people respond remarkably well to treatment, adding years of independence to their lives.  Broadcasting the message that it is "better not to know", as King did last night,  may prevent some people from gathering the facts and making a more informed decision,based on the knowledge that early intervention and appropriate treatment could be significantly beneficial.

Alzheimer's Treatment May Be More Effective Than You Think

Contributed by: Dennis Fortier, President, Medical Care Corporation
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The message in this post may be one of the most important that the Brain Today blog regularly supports.  Alzheimer's treatment is more effective than the typical news story reports.

This is evident by the news from the UK today, where their governing health authority, the National Institute of Health and Clinical Excellence (NICE), extended coverage of approved drugs for Alzheimer's patients in earlier stages of the disease.  Authorities cited "better evidence" about treatment efficacy as the key motivator for the decision.

In general, the misconception about treatment effectiveness is based on three misleading frames of thought:

Drugs don't treat the disease, they only lessen the symptoms
Many well done studies support the claim that approved drugs offer no disease delaying effects.  The problem with this frame of thought is that all of the studies have been conducted on patients who are demented due to Alzheimer's.  Based on the long disease course, this means they are in a very advanced state of disease progression, and have already accumulated massive damage in the brain.  As such, it is not surprising that drugs cannot delay disease progression when treatment is initiated at such a late stage.  It stands to reason, and most experts agree, that the earlier stages of the disease are much more treatable.

The beneficial effects of drugs on symptoms last only a year or less
Again, there are many well done studies that support this notion.  However, the studies isolate "drug treatment" in order to measure its effects, whereas in the real world, Alzheimer's treatment involves more than a drug.  A robust treatment regimen includes proper diet, physical exercise, proper management of hypertension and diabetes, intellectual stimulation, social engagement, and an educated caregiver.  Many patients derive meaningful, long-term benefits from such an approach, especially if the intervention is begun at an early stage of the disease.  A drug alone may not be an effective treatment, but effective treatment does not consist of a drug alone.

There is no cure
This is absolutely true.  But the public has a tendency to interpret that statement to mean "there is no treatment".  For perspective, there is no cure for hypertension or for diabetes, but we commonly treat them, and the public generally acknowledges the benefits of such treatment.  For sure, the efficacy of our Alzheimer's treatments pale in comparison to the efficacy of our hypertension/diabetes treatments, but we need a healthy appreciation for the difference between treatment and cure for Alzheimer's disease.

I hope this high level decision by the health authority in the UK will foster a growing optimism and a more clear perspective on treatment efficacy for Alzheimer's disease.  I concur that we need better treatments than those available today, but we also need the public and the medical community to embrace a more constructive view of what can be done now.

Alzheimer's Drugs Deemed Effective by Overseas Authorities

Contributed by: Dennis Fortier, President, Medical Care Corporation
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 Efficacy of treatment for Alzheimer's disease is a topic of frequent debate and disagreement.  While the data are relatively clear, the source of the disagreement is often "expectations".

For example, if a person with memory loss and behavioral disturbances due to Alzheimer's disease takes a cholinesterase inhibitor, it would be unrealistic to expect an immediate decline of all symptoms and a full return of cognitive function.  Current drugs simply cannot repair damaged brain cells and restore function.  More likely, the treatments would mitigate the symptoms and perhaps slow their rate of progression.

So the question is, do these drugs help?  If you are expecting them to render a cure, then the answer is "no".  But if you are objectively measuring their effect on the quality of the person's life, which incorporates control of symptoms and disease progression, then the answer is "yes".

The National Health Service in the UK has formerly not payed for its citizens with early stage Alzheimer's disease to be treated with cholinesterase inhibitors.  That decision may have been based, in part, on unrealistic expectations.  However, after collecting several years of additional data and weighing the overall benefits of treatment, they have now reversed that decision.

This is another powerful example that early intervention can make a meaningful difference in the quality of life for a person with Alzheimer's disease.   Be vigilant in monitoring your cognitive health and voice any emerging concerns to your physician.

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Blood Test for Diagnosing Alzheimer's: A Major Leap Forward?

Contributed by: Dennis Fortier, President, Medical Care Corporation

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With so many of the news stories I summarize here, I include caveats about the long and arduous path that basic science must travel before a clinically beneficial advance becomes available to the public. The same caveat applies to the heavy coverage of a new, blood-based diagnostic test recently developed by the Scripps Research Institute and published in the January 7 issue of Cell.

Having said that, this scientific approach strikes me as one worthy of the frothy press it has already spawned.

The approach is exciting in its novelty. Rather than identifying the specific antigens that cause an immune response (production of antibodies) at early stages of a particular disease, and then screening the blood for the presence of those antibodies, the Scripps researchers took another path. They skipped the step at which conventional science is currently focused. That is, they did not bother with the daunting challenge of identifying which specific antigens might stimulate an immune response to fight in early stage Alzheimer's disease.

Rather, in their study, they loaded the blood with thousands of synthetic molecules designed to bind to antibodies of all sorts. By then analyzing the results from patients with Alzheimer's compared to those with Parkinson's and those deemed "healthy", they detected clear evidence that Alzheimer's patients had a much higher concentration of two particular antibodies in their blood. The conclusion, which must be validated with more data, is that these two antibodies are bio-markers for early-stage Alzheimer's disease.

This may prove to be extremely valuable in detecting early stage disease presence, but may pay other dividends as well. If these antibodies do indeed indicate a response to Alzheimer's pathology, then this study may also shed important, new light on the actual disease process which, in turn, could accelerate research on new treatments

Obviously, there is much science to conduct before the world can benefit from this research. But the prospect of leap-frogging one nagging problem in the process, the identification of specific antigens that indicate Alzheimer's, is an exciting proposition.

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Top 3 AD Research Trends

Contributed by: Dennis Fortier, President, Medical Care Corporation
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One site I follow for news in this field is the Alzheimer's Research Forum. The postings there can be quite technical as they target medical researchers as an audience. Nonetheless, the content they cover is often the same content as that which gets translated into lay terms (accurately or otherwise) by journalists in the general press.

They recently summarized their opinion of the top research trends in the AD field and I found it to be an excellent summary with a rich set of links to ongoing research stories. From a public impact perspective, I have selected the three from their list that I think are most likely to make a real-world difference, or at least be worthy news stories, in the coming year.

1. Revised Diagnostic Criteria
We posted this news followed by our perspective on this change when it was first discussed last summer. I think the new criteria, which define AD based on pathological evidence as opposed to severity of symptoms, provide a great step forward and will enable earlier intervention in a clinical setting.

2. Biomarkers
The ongoing effort to better understand AD pathology brings bio-markers to the forefront of importance. This year will likely see the first FDA approval for an agent that binds to amyloid in the brain and enables visibility on a PET scan. This along with ongoing research on proteins in the blood and spinal fluid, brain volumes, cognitive measures, and a host of other bio-markers portends a year of advance for the field.

3. The Amyloid Hypothesis (or hypotheses)
As described by the editors at Alzheimer's Forum, last year saw advances in understanding of amyloid's "...production, aggregation, function, and toxicity". All of this new knowledge must be assimilated into the evolving hypotheses about the role of beta-amyloid in Alzheimer's disease.

While there is much work underway in this field and many facets to the complex problems caused by Alzheimer's disease, the three noted trends above will certainly be central themes in the news during the coming year. Follow along with our posts at this blog to stay abreast of all developments and to understand the likely effects of each.

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Combining a Brain Scan with a Spinal Fluid Test

Contributed by: Dennis Fortier, President, Medical Care Corporation
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According to a study published in the latest issue of Archives of Neurology, researchers at University College London's Institute of Neurology have collected evidence of a correlation between two interesting brain pathologies. The research looked at low levels of beta-amyloid in the spinal fluid and, based on an MRI brain scan twelve months later, the rate of brain atrophy (or shrinkage).

The interest in this study stems from prior research showing that a low level of amyloid in the cerebral spinal fluid (CSF) is a common (but not certain) precursor to Alzheimer's disease. Furthermore, typical Alzheimer's pathology includes the death of brain cells leading to brain shrinkage. Therefore, noting that these two indicators seem to move in unfavorable directions, even before symptoms are present, might lead to methods for earlier detection and intervention.

In general, the expert research community supports the notion of combining indicators to detect early trends that should be carefully monitored. While this study is certainly noteworthy, coverage in the media, that has portrayed these findings as a method for detecting early stage Alzheimer's disease, is probably over-stated at this early point.
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Misplaced Moral Argument about Predicting Alzheimer's

Contributed by: Dennis Fortier, President, Medical Care Corporation
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When following the press in the brain health space, it is very common to find well-written opinion letters and perspective pieces about the moral dilemma of predicting Alzheimer's disease in healthy adults. Common headlines vary around the "would you want to know" or "would you take the test" theme. The crux of the argument is that, with no cure, we should not bother predicting the disease and revealing such a tragic fate.

In a nutshell, these are the usual defenses:

• Predictions allow vigilant monitoring and timely intervention when symptoms appear which leads to better treatment.
• Predictions allow for financial, legal, and spiritual preparation for end of life.
• Predictions identify important research subjects who can greatly improve scientific efforts to develop new treatments by volunteering for trials.

There are other arguments but those are the most common and most compelling justifications.

The purpose of this post is neither to condemn nor condone the notion of predicting Alzheimer's disease but to point out how often the moral debate is misplaced. For predictive approaches, like genetic tests, I say let the debate rage. However, for identifying approaches, those that indicate with certainty if a person has Alzheimer's pathology that has not yet progressed to a stage producing obvious symptoms, then the whole notion of "prediction" is misplaced.

But the moral debaters do not respect this important difference between predicting the disease and identifying the disease. People who have it, have it. And when they present to a physician and complain of cognitive difficulties, they are asking their physician to figure out the cause of the problem and treat it as best as possible. No moral dilemma; these people want to know.

Remember, everyone has the right to not visit their doctor and not investigate emerging cognitive problems. Those who want to actively manage their health should be allowed and those who wish to remain ignorant have rights as well.

Soon, we will have the ability to identify Alzheimer's pathology with a PET scan which will enable earlier and more accurate diagnoses. In the not too distant future, we will likely have a spinal fluid test (followed by a blood test) that will accurately diagnose Alzheimer's disease at even early stages through more cost effective means. These are great steps forward and there is no moral or ethical downside to gaining these important clinical abilities.

Predicting Alzheimer's disease is a topic worthy of moral debate; identifying the disease is a categorically constructive step in the right direction.

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A better understanding and more awareness of Alzheimer's related issues can impact personal health decisions and generate significant impact across a population of aging individuals. Please use the share button below to spread this educational message as widely as possible.

Revised Definition of Alzheimer's Disease

Contributed by: Dennis Fortier, President, Medical Care Corporation
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With a publication slated for the November issue of Lancet Neurology, the International Working Group for New Research for the Diagnosis of AD has updated their position paper from 2007. In the new publication, they suggest that AD should be defined as impaired episodic memory plus one bio-marker (either MRI, PET, or spinal fluid) indicating known disease pathology.

Importantly, the presence of dementia would no longer be required as part of the new definition of Alzheimer's disease. This will allow physicians to diagnose the disease and intervene with therapy at an earlier stage of symptoms.

As we have discussed here often, the current practice of late diagnosis, which is driven in many ways by the old definition requiring dementia, is a major obstacle to effective treatment.

This recommendation is in line with similar proposals from US expert panels and bodes well for future advances in this field.

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How to Best Detect Early Alzheimer's Disease

Contributed by: Dennis Fortier, President, Medical Care Corporation
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Sometimes, a lot of press coverage is devoted to an interesting misinterpretation of a fact that, once correctly understood, is not nearly as interesting. This is one of those times.

Over the past week, I have seen intense coverage of a story about how friends and family are better at spotting early signs of Alzheimer's dementia compared to traditional tests that a doctor might use. This sounds great until you unpack the headline and understand the facts.

Even Mild Dementia is a Severe State of Health
The problem, as we point out often in this space, is the definition of "dementia". Even mild dementia, which sounds like a subtle condition, is actually a severely impaired state of mental health. To meet the definition of dementia, even mild dementia, a patient must be so impaired that their loss of function interferes with their occupational or social life. Demented people, even mildly demented people, cannot completely care for themselves.

Detecting Dementia does not Require a Test
With this is mind, many experts make the case (and I agree with them), that a test for dementia is not necessary. Dementia is a readily apparent condition that a friend or family member should easily recognize. The fact that doctors still use tests that cannot accurately distinguish between a demented person and a non-demented person is indicative of ineffective clinical practices.

For the record, there are newer, more accurate tests, such as the MCI Screen, that detect dementia with almost perfect accuracy. More importantly, they also identify much earlier and subtler stages of decline known as mild cognitive impairment. However, this current finding from Washington University and published in Brain, compared the ability of friends and family at spotting spot Alzheimer's dementia with the accuracy of "traditional" tests. This is a clear and damming comment about the poor accuracy and minimal utility of the "traditional" test they used for comparison, the Mini-Mental State Exam (MMSE).

In this study, input was collected with an instrument called the AD8, an eight item questionnaire that is completed, on behalf of the patient, by an informant (friend of family member). It was shown to be better at identifying demented patients than the MMSE. That is great news and the AD8 is a non-invasive tool that would be a pragmatic improvement over the MMSE in a primary care setting.

The Bottom Line
I think the most important message, buried in this recent spate of press, is that the traditional tests are not as good as the AD8 at detecting dementia, but detecting dementia doesn't really require a test. To intervene early against Alzheimer's disease, and to reassure healthy patients that their perceived memory decline is not caused by underlying disease, physicians need instruments that accurately detect mild cognitive impairment.

Advances in detecting dementia are not interesting stories, regardless of how much press they get.

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The Most Immediate and Practical Use for an Alzheimer's Diagnostic Test

Contributed by: Dennis Fortier, President, Medical Care Corporation

Sometimes, a debate is framed in such a way that important perspectives are under-emphasized if not completely overlooked. I think this is the case in the spirited debate about if and when we should use biomarkers to help diagnose Alzheimer's disease.

I can understand that many young, healthy people would prefer not to know that Alzheimer's lurks with certainty in their future. That whole discussion is important but perhaps off-point. Here is what we should not overlook.

An increasing number of people are expressing memory complaints to physicians on a daily basis. Some are depressed, some have early stage AD, some have had a small stroke, some have a thyroid disorder, and among the others, many are perfectly healthy but correctly perceiving changes associated with their advancing age. It is the physician's job to accurately diagnose any underlying medical conditions and to treat them. In these cases, an accurate test for Alzheimer's disease has great value.

The published research in this area is clear. A great many AD patients go undiagnosed and untreated for many, destructive years as their doctors grapple with an uncertain diagnosis. Others are treated for Alzheimer's disease based on an educated guess, when in fact their true condition could have been more effectively (and perhaps less expensively) treated had the diagnosis been correct.

I do not suggest that we run out and test people with no symptoms of cognitive decline. I do suggest that a great many patients and their doctors will benefit enormously when a commercially viable diagnostic test for AD is available.
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A better understanding and more awareness of Alzheimer's related issues can impact personal health decisions and generate significant impact across a population of aging individuals. Please use the share buttons below to spread this educational message as widely as possible.

Alzheimer's Drug Fails Phase III Trial

Contributed by: Dennis Fortier, President, Medical Care Corporation
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One of Eli Lilly's late-stage Alzheimer's drugs, the gamma-secretase inhibitor Semagacestat, has failed its Phase III FDA trial and the company has halted its development. This announcement today was somewhat expected by the research community as other gamma-secretase inhibitors, namely Flurizan (Myriad Genetics), had also been deemed ineffective in a large trial.

While this is disappointing news, the overall trend of scientific progress in the field of Alzheimer's is clearly positive. New guidelines have been proposed that will facilitate earlier intervention and better treatment results. New diagnostic tests are showing greater accuracy and bode well for more certainty in clinical practice. And perhaps most importantly, the pipeline of treatments under development is full of promising agents.

An updated summary of the current FDA pipeline for Alzheimer's treatments will be posted here later in the week.

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A better understanding and more awareness of Alzheimer's related issues can impact personal health decisions and generate significant impact across a population of aging individuals. Please use the share button below to spread this educational message as widely as possible.

Predicting Alzheimer's Disease with Spinal Fluid

Contributed by: Dennis Fortier, President, Medical Care Corporation

For some years now, the research community has been intensively investigating bio-markers to help diagnose Alzheimer's disease at an early stage while the symptoms are still subtle and minimal brain damage has occurred. It is hoped that bio-markers progressing in advance of symptom progression will also be useful in understanding the disease and in unlocking the secrets of effective treatment.

There is massive press this week (NYTimes, CNN, WebMD, LATimes) on a new study published in the Archives of Neurology. The study shows that protein levels in the spinal fluid are useful in diagnosing Alzheimer's disease, even in subjects with mild memory deficits that would not meet today's criteria for a diagnosis of Alzheimer's disease. This is good news and bodes well for ongoing efforts to understand and treat this debilitating disease.

Interestingly, this finding also adds importance to another debate that has been recently prominent in the press. The debate concerns the utility of new proposed guidelines that would define Alzheimer's disease based on the presence of mild symptoms plus pathology as opposed to the current guidelines which require severe symptoms (dementia) before making the diagnosis. What began as a hypothetical (if we had a good bio-marker, would we consider subtle memory loss plus a positive indication from the bio-marker as a conclusive indication of AD?) has now become a more concrete and more urgent question.

Personally, I side with the growing consensus of experts who believe that memory loss, when coupled with a bio-marker known to be associated with AD (hippocampal atrophy, amyloid plaques, or now, signature proteins in the spinal fluid), should be diagnosed as Alzheimer's disease and treated accordingly if other common causes of memory loss (depression, thyroid, vitamin deficiency, etc.) have been ruled out.
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A better understanding and more awareness of Alzheimer's related issues can impact personal health decisions and generate significant impact across a population of aging individuals. Please use the share buttons below to spread this educational message as widely as possible.

Support for the Amyloid Hypothesis

Contributed by: Dennis Fortier, President, Medical Care Corporation
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A prevalent theory explaining the cause of Alzheimer's disease is that amyloid deposits accumulate in the brain and disrupt cell function.

While this hypothesis has driven the majority of drug development efforts over the past three years, the theory has some apparent weaknesses that must be explained. Specifically, researchers have not been able to explain why some adults with extensive amyloid deposits do not have Alzheimer's disease.

A study out of UCSF and published in Behavioral Neurology lends some support to the amyloid hypothesis. The authors reviewed over 100 published studies that involved PET scans and the PIB compound and found that there is a strong correlation between amyloid load in the brain and cognitive decline due to Alzheimer's disease. Importantly, they have documented support for the notion that there is a time lag between amyloid build-up and cognitive decline.

"Amyloid deposits appear to reach a plateau early in the disease course, when patients experience very mild symptoms or no symptoms at all," says Rabinovici, a recipient of new investigator awards from the Alzheimer's Association and the National Institute on Aging. "By the time patients have developed the symptoms of Alzheimer's disease, clinical decline and brain changes are occurring independently of further amyloid accumulation. This suggests that we have been starting treatment too late, and that amyloid-based therapies are most likely to work very early in the disease process."

Gaining a deeper understanding of the progressive pathology of Alzheimer's disease will be critical in developing effective treatment. In the meantime, the body of evidence supporting earlier intervention continues to grow.