Brief Cognitive Tests and Alzheimer's Diagnoses

Contributed by: Dennis Fortier, President, Medical Care Corporation

Over the weekend, the Chicago Tribune ran an important article about Alzheimer's Disease and how brief cognitive tests might enable much earlier intervention. There are several points in the article that I want to discuss here.

First, the general theme about the importance of early detection is well supported by scientific evidence. However, the assertion that early detection of "dementia" is important obscures the point that we really need to detect medical problems before they progress all the way to dementia. In fact, once a person is demented, tests and technology become all but unnecessary for "detection" because the physician and the family will surely recognize the presence of a problem.

Second, brief cognitive tests are now harnessing the power of computers to distill patterns of cognitive performance and to compare those patterns to large data banks of well studied patients. These tests are highly accurate and are increasingly embraced by primary care physicians to distinguish the worried well from those with an early stage medical problem that deserves further evaluation. In this way, such brief tests are already enabling earlier intervention and improving clinical outcomes.

Finally, the article discusses the notion that some patients may not wish to know about a problem (such as Alzheimer's) if there is no cure. That attitude is also changing rapidly as the masses gain knowledge about the many causes of memory loss. Many can be completely resolved and most others can be improved with proper treatment. Even Alzheimer's disease can be slowed to maintain a higher quality which is a worthy and obtainable goal. In addition, the FDA pipeline for better treatments looks very promising and may yield improved treatments within the next five years.

Long-Term Memories Formed During Sleep?

Contributed by: Dennis Fortier, President, Medical Care Corporation

One theme of this blog is the ongoing scientific quest to better understand the brain as a means of optimizing our efforts to keep it healthy. An interesting study published this week in Neuron has perhaps opened another door on the still murky realm of memory formation.

Researchers at MIT have published a study showing that a key neural process for encoding long-term memories appears to happen during sleep. Their research, on both mice and humans, makes a compelling case about the underlying mechanisms in the brain.

In mice, it was shown that the same neural circuits that fired while the mice were learning a maze, continued to fire during their sleep shortly after, providing evidence that the solution was being encoded for longer term storage. Humans who were allowed to nap shortly after learning some word pairs were then shown to out perform other humans who had not napped after the learning exercise.

Taken together, these experiments suggest an important connection between sleep and long-term memory formation. This may have important benefits in the ongoing campaign to understand the brain. It is also interesting from an evolutionary biology point of view as it may be an explanation for the purpose of sleep.

Effective Alzheimer's Treatment Hampered by the Blood/Brain Barrier

Contributed by: Dennis Fortier, President, Medical Care Corporation

As we know, scientists are hard at work to understand the underlying pathology of Alzheimer's disease. Doing so will clarify treatment strategies and inform development of new drugs to delay or cure its progression. However, the disease is complex and, as of today, poorly understood.

While the progress of the past decade is encouraging and we can now identify Alzheimer's earlier, diagnose it with more certainty, and slow its progression meaningfully in many patients (especially those diagnosed in an early stage), we still face some challenges. For example, delivering new treatments to the brain is a major obstacle.

The Boston Globe recently summarized this topic with great insights from many researchers in this field. The article provides an interesting overview and describes some of the approaches in development for getting treatments across the blood/brain barrier.

The Costs of Alzheimer's Disease

Contributed by: Dennis Fortier, President, Medical Care Corporation

With the intensity of current discussions on Healthcare reform, I am re-posting this earlier comment (from March 23) on the costs of AD and Dementia. The figures may surprise you.

March 23, 2009 - This week has seen extensive media coverage of a report from the National Alzheimer's Association stating that the annual costs of care for an Alzheimer's patient are triple the cost of an elderly person without Alzheimer's Disease. These figures are very consistent with a bevy of other studies indicating a similar cost differential but can viewed with more clarity from another perspective.

First, it is useful to compare the demented elderly vs. the non-demented elderly as opposed to Alzheimer's patients vs. non-Alzheimer's patients. This adds clarity because the driver of the cost increase is the presence of dementia, regardless of its cause (Alzheimer's is the cause of about 65%, vascular disease 20%, Parkinsons/Lewy Body and all others 15%).

Second, since these diseases cross all socio-economic strata, some of the afflicted pay for their own institutional care while others rely on public support programs. As such, aggregating figures that include the costs of institutionalization muddies the view.

Here are the figures comparing the costs of medical services (physician appointments, hospital stays, procedures, and medications) for demented vs. non-demented people aged 65-74:

Average Annual Cost of Non-Demented: $3,851
Average Annual Cost of Demented: $15,998

The demented are more costly by a factor of 4.2. However, it is very rare for an elder, demented person to be completely free of other chronic conditions. Chronic conditions require management via thorough and consistent self-care which is often difficult when coupled with dementia. As such, it is the combination of dementia and other chronic diseases that drives costs most impressively.

Consider these figures showing prevalence of four common chronic medical problems in the aged 65-74 population:

29% Coronary Heart Disease (CHD)
28% Congestive Heart Failure (CHF)
23% Diabetes
17% Chronic Obstructive Pulmonary Disease (COPD)

Now look at the costs associated with these medical problems when combined with dementia compared to the costs associated with those problems in cognitively vital elders:

Dementia +CHD - $27,237 ($10,894 no dementia)
Dementia + CHF - $34,304 ($17,993 no dementia)
Dementia + Diabetes - $24,392 ($7,469 no dementia)
Dementia + COPD - $28,463 ($12,059 no dementia)

It is clear that dementia drives higher utilization of medical services, especially when combined with other common medical problems. Of course, figures associated with the cost of institutionalized care (and informal care giving) make the picture all the more bleak but this view is perhaps the most clear.

Can Alzheimer's be Prevented?

Contributed by: Dennis Fortier, President, Medical Care Corporation

Yesterday I highlighted an article published in Scientific American that succinctly summarized the current state of treatment and our march toward a cure for Alzheimer's disease.

For those of you who would appreciate a slightly more comprehensive overview of our current knowledge about AD, I recommend this recently updated report from the National Institute on Aging. It concisely describes the scientific landscape in terms of the pathology of AD, risk factors (including how to manage them), and treatment strategies (both current and in the pipeline).

The title of the report is Can Alzheimer's be Prevented? There is growing evidence for the case that, for may of us, it can probably be delayed until we are likely to die from some other malady. We call this concept "Prevention through Delay".

One day we will have a cure but for now, prevention through delay offers a realistic approach to reducing the tragic impact of this poorly understood disease.

Straight Talk About AD Prevention and Cure

Contributed by: Dennis Fortier, President, Medical Care Corporation

Published online today by Scientific American is a fantastic interview with P. Murali Doraiswamy, a leading researcher in the Alzheimer's field and an occasional contributor to this blog.

In the interview, Doraiswamy succinctly summarized some misconceptions about AD treatment and described the need for earlier intervention against this disease. He also commented on some promising research in both the diagnostic and treatment fields.

I especially appreciated, and want to emphasize, his careful distinction between "curable" and "treatable" as these terms pertain to AD. His comment is captured here:
The larger point is that while Alzheimer’s is still incurable it’s not untreatable. There are four FDA-approved medications available for treating Alzheimer symptoms and many others in clinical trials. Strategies to enhance general brain and mental wellbeing can also help people with Alzheimer’s. That’s why early detection is so important.
As the age structure of the population continues its march upward, it is imperative that we raise general awareness about the benefits of earlier detection. Articles like this can be very useful in accomplishing that goal and I encourage all of you to read it and to share it with others.

Care Givers Guide Published by NIA

Contributed by: Dennis Fortier, President, Medical Care Corporation

We know from a strong canon of research that well educated care givers (that is, well educated in the art and science of caring for an Alzheimer's patient) have less stress than their poorly educated counterparts. We also know that education drives a measurable health benefit to the patient which is most clearly observable in the length of time that nursing home placement can be delayed.

The National Institute of Aging has compiled a fantastic resource for care givers to help them with may aspects of this challenge. It can be downloaded at their website for free.

I encourage any of you who are directly caring for an Alzheimer's patient or supporting someone other primary care giver, to take a few moments to get this resource and review its contents. It will be good for you and good for the person for whom you care.

Detection vs. Diagnosis

Contributed by: Dennis Fortier, President, Medical Care Corporation

These are two terms that are similar but distinct in their meaning and, unfortunately, often used interchangeably by the press when writing about health care and clinical practices. The primary purpose of this post is to sensitize readers that news stories can be misleading when writers are careless in choosing between them.

In clinical practice, to "detect" a problem is to objectively observe symptoms caused by the problem or to hear a subjective but credible complaint from the patient about a symptom that is not visible (i.e. back pain). To "diagnose" a problem is to ascertain the specific medical condition that is causing the problem.

Here is an example from the field we follow. A physician would "detect" memory loss by objectively establishing that a patient's recall ability is not in the normal range for the patient's age and educational peer group. The physician need not know the cause of the problem to detect it.

Once detected, the memory loss would then be "diagnosed" as (for example) a thyroid disorder, or as Alzheimer's disease, or as any number of other memory impairing medical conditions. The diagnosis informs the forthcoming decisions about treatment.

In general, much of the news about neuro-psychological tests being developed is news about improving our ability to detect problems. Much of the news about bio-markers is news about improving our ability to diagnose problems. In the realm where I see the most common misuse of these terms, much of the news about imaging techniques crosses between the two.

Alzheimer's Detected Too Late

Contributed by: Dennis Fortier, President, Medical Care Corporation

The Atlanta Constitution Journal has a nice piece today about the poor state of Alzheimer's detection. While we refer to this reality quite frequently in this blog, it is worth reading the article because they do a good job describing the magnitude of the problem and they frame a possible solution.

The focus of the article is on the lack of screening in physician offices. While I agree that a general screening approach to the aging population could be a factor in solving this problem, I don't think it is necessarily the only approach and probably not the most efficient approach. I would suggest a "case-finding" mentality where physicians are well-educated about what questions to ask and which signs to watch and where they have viable assessment tools to help them further evaluate patients likely to have an emerging problem.

The article describes several reasons that such screening is not more common including lack of physician education, lack of screening standards, and lack of time for screening in an office visit. On slow news days going forward (if there are any), I will revisit this post and give my thoughts on each of those barriers.

Many Theories about the Causes of Dementia

Contributed by: Dennis Fortier, President, Medical Care Corporation

For regular readers of this blog, it is my hope that certain lines of thought emerge clearly and consistently.

For example, we think that early detection of memory loss combined with an accurate diagnosis and timely treatment yields great benefits to the patient, particularly when the underlying problem is a degenerative brain disorder such as Alzheimer's disease.

We also believe that, although a cure for Alzheimer's disease is badly needed, current medications are significantly more efficacious than widely believed. The truth is, we intervene too late in most cases to objectively evaluate the efficacy of a regimen that includes a balanced diet, physical/mental exercise, and drug therapy. Earlier detection and intervention could greatly improve treatment with today's approved medications.

One other theme that should be clear is that, despite a diligent and ongoing effort among some of the world's preeminent scientists, the cause(s) of Alzheimer's disease and it's ultimate dementing effects are poorly understood at many levels. A thorough read of the current literature, partially summarized in these posts, makes it clear that no single theory has emerged as the most likely explanation.

Because it is novel and interesting, but also to make the point that scientists are still casting a fairly wide net in their attempt to understand Alzheimer's disease, I am sharing this story about a theory from a scientist in Russia. As reported in New Scientist, Yuri Moskalenko has introduced the idea that dementia from many conditions and disorders (including Alzheimer's disease) is at least partially caused by intracranial pressure, a problem that can be relieved by drilling a hole in the skull.

Measuring Brain Volume to Predict Cognitive Decline

Contributed by: Dennis Fortier, President, Medical Care Corporation

Researchers at the University of California, San Diego have published interesting findings in the journal Alzheimer's Disease and Associated Disorders suggesting that volume measurements computed from MRI images of the brain might be useful for predicting cognitive decline due to Alzheimer's disease (AD).

Their study followed 269 patients with MCI over a six-month period. They analyzed the relationship between tissue volume in three regions of the brain and the patients' scores on neuro-psychological tests. While the relationship between atrophy in one portion of the brain (the hippocampus) and cognitive decline has been suggested for some time, this study demonstrated that useful clinical information can also be drawn from measures of the amygdala and the temporal horn. Taken together, these volumetric measures constitute a useful bio-marker for clinical and research applications in cognitive health.

Using automated, software-driven measures of brain volume, this research suggests that physicians may now have an early clue as to whether or not a particular MCI patient will decline further with Alzheimer's disease. Such knowledge could enable more timely intervention and more effective treatment for AD in the near term.

Inflammation and AD

Contributed by: Michael Rafii, M.D., Ph.D - Director of the Memory Disorders Clinic at the University of California, San Diego. _______________________________

For many years, it’s been believed that brain inflammation contributes to the development of Alzheimer’s disease, and based on that claim, numerous clinical trials with anti-inflammatory drugs have been conducted. However, they have all been unsuccessful in slowing the disease.

Now, researchers with the University of Florida, in collaboration with scientists at the University of Frankfurt, Germany, have discovered a possible explanation for the lack of efficacy seen witih anti-inflammatory drugs in AD: inflammation of microglia — an abundant cell type that plays an important supporting role in the brain — does not appear to be associated with dementia in Alzheimer’s disease.

Glial cells, including microgia, outnumber neurons 10-to-1. Inflammation theories of AD suggest that microglia become “activated” and mount an immune response to beta-amyloid, and instead of being helpful, actually cause damage to neurons, worsening the disease effects.

However, the researchers used high-resolution imaging techniques to look at microglial activation in AD brains and their observations did not find evidence that Abeta activates, or inflames, human microglia cells. Nor did they find evidence that inflammation is to blame for neuronal death.

Thus, it may be that beta amyloid is causing all of the damage, and that microglial cells are simply witnesses to the incident, and not active participants.

More News on the Relationship Between Alzheimer's and Depression

Contributed by: Dennis Fortier, President, Medical Care Corporation

A study published in the June 16 issue of Neurology, the journal of the National Academy of Neurology, suggests that people with memory loss who are also depressed have a greater likelihood of getting Alzheimer's disease (AD).

In a three year study of 756 subjects aged 55 to 91, those diagnosed with depression and memory loss developed AD at a higher rate than those with memory loss and no depression.

The study also had some good news about Aricept, a cholinesterase inhibitor commonly used to treat AD. Among a group of subjects with both memory loss and depression, 11% of those given Aricept developed AD during the study while 25% of those not given Aricept developed AD.

This finding suggests that Aricept may have slowed the progression of Alzheimer's pathology and prolonged high quality of life. This bodes well for our ongoing ability to treat AD in a more effective manner.

Limited Availability of AD Drugs in the UK

Contributed by: Dennis Fortier, President, Medical Care Corporation

The National Institute for Health and Clinical Excellence (NICE) in the UK has ruled again that paying for cholinesterase inhibitors (drugs including Aricept, Exelon, and Razadyne) is not a cost-effective use of NHS funds. As such, these drugs are essentially unavailable to patients with mild Alzheimer's disease in the UK.

In 2005, NICE made the initial ruling that denied reimbursement for these drugs for mild and moderate stage Alzheimer's patients. After public outcry, the ruling was amended to allow treatment for moderate but not mild stage disease. With a rightly unsatisfied public, the manufacturers of these drugs pushed for a judicial review which has yielded this latest news of NICE standing firm on its past decision.

It is speculated that, with the judicial process complete, NICE will begin a new review of its policy incorporating latest clinical data that may lead to a more aggressive treatment policy going forward.

Dimebon Study Fully Enrolled

Contributed by: Dennis Fortier, President, Medical Care Corporation

Medivation, Inc. has announced that the phase III FDA trial for Dimebon is now fully enrolled.

This is encouraging because the full enrollment was achieved briskly at a time when many trials are competing for the same patients. Overall, it indicates rising interest and increasing optimism about treatment options for Alzheimer's disease.

Dimebon, which we described in earlier posts, is manufactured by Medivation and, if approved, will be jointly marketed with Pfizer.

Curry and Alzheimer's Disease

Contributed by: Michael Rafii, M.D., Ph.D - Director of the Memory Disorders Clinic at the University of California, San Diego.

Preparations of the plant Curcuma longa Linn have been used to treat various ailments for centuries in Ayurvedic medicine, a traditional Indian system of healing. This plant, also known as turmeric, is a member of the ginger family. Within Ayurveda, turmeric preparations are taken orally to treat dyspepsia, flatulence, liver disease, urinary tract disease and as a “blood purifier.” Now, curcumin appears to have primary effects on beta-amyloid aggregation in addition to its known antioxidant, anti-inflammatory, and platelet aggregation inhibiting properties

Several other studies have found curcumin, an antioxidant, is beneficial in Alzheimer's disease and a trial is now under way to test the theory in humans with the disease. Interestingly, Indian communities that regularly eat curcumin have a surprisingly low incidence of Alzheimer's disease but we don't yet know why.

Other studies on curry and Alzheimer's include:
•A laboratory study by researchers at UCLA in 2006 showed that curcumin could help clear the human brain of toxic protein deposits thought to cause the memory loss and confusion of Alzheimer's.
•A study of more than 1,000 older men in Singapore last year found that those who ate lots of curry-spiced food did better on memory tests than those who rarely ate the spice.

There is substantial laboratory data indicating that curcumin has antioxidant, anti-inflammatory, and now anti-amyloid activity. In addition, studies in animal models of AD indicate a direct effect of curcumin in decreasing the amyloid pathology of AD. Curcumin is becoming a promising agent in the treatment of AD.

New Test Detects Dementia

Contributed by: Dennis Fortier, President, Medical Care Corporation

This headline, or a version of it, is widely published today and refers to the Test Your Memory (TYM) test.

The ensuing story gives hope to the idea that we will now begin to intervene earlier (and more effectively) to treat patients with Alzheimer's disease. We all want that to be true but we probably still have a ways to go.

I have read about a dozen stories on this news and here are a couple of comments to help you digest what you may be reading:

First, many of these articles are improperly interchanging the terms "Dementia" and "Alzheimer's". As we have described in earlier posts (here and here), Alzheimer's is one cause of dementia but about 40% of the demented population have another cause. These terms are not interchangeable and it is negligent for journalists to perpetrate the confusion with such careless writing.

Second, dementia is a well defined clinical term referring to a pretty severe cognitive impairment. When a person is demented, a trained physician or even a close family member with no medical training will detect the problem through conversation and observation. In other words, if the decline is severe enough to meet the definition of "dementia", no test is needed. While a test to detect early Alzheimer's disease (prior to the dementing stages) would be fantastic, a test to detect dementia is really not that useful.

Finally, the TYM test makes no claim of being diagnostic in terms of identifying the cause of cognitive impairment (be it Alzheimer's disease, stroke, head trauma, etc.), but the press has conferred on it the ability to do so. This process unintentionally sets high expectations for a new technology and may result in unfair criticism later.

Let's all be careful to understand that the researchers who developed this test have made some cautious claims that I believe they can support entirely. Let's not be disappointed if the test can't meet all the claims the press wants to make in their sensational headlines.

Looking optimistically forward, I am hopeful that the TYM test may, upon further evaluation, prove to be sensitive to earlier stages of decline and perhaps even have diagnostic value. As I have written in this blog, the biggest and most immediate step forward we could make in treating Alzheimer's disease is to find it earlier and treat it before it progresses. Tests like the TYM may make that possible in the near term.

MCI Correlated with Higher Mortality

Contributed by: Dennis Fortier, President, Medical Care Corporation

A study recently published in Archives of Neurology shows that individuals with MCI have much greater risk of mortality compared to cognitively healthy individuals.

Robert S. Wilson, PhD, Rush University Medical Center, Chicago, Illinois, and colleagues studied 1,715 older adults, assessed their cognitive status, and measured mortality rates during an ensuing 10-year follow-up period.

"Compared with people without cognitive impairment, risk of death was increased by about 50% among those with mild cognitive impairment and was nearly 3-fold greater among those with Alzheimer's disease", said Wilson

While these results are not surprising, this study is one of the first to show such a clear link between life expectancy and cognitive health.

Is Alzheimer's Contagious?

Contributed by: Dennis Fortier, President, Medical Care Corporation

No. Alzheimer's disease is not contagious.I am posting this as a preemptive answer to forthcoming headlines that might suggest otherwise.

A study published in Nature Cell Biology showed that scientists were able to replicate the spread of Tau tangles in healthy mice by injecting them with brain tissue from mice known to have such a defect.

This research may shed helpful light on how tangles spread within the brain and improve our understanding of Alzheimer's disease pathology. It does not, as the authors clearly noted, suggest that Alzheimer's disease is contagious.

Brain Today on Twitter

Contributed by: Dennis Fortier, President, Medical Care Corporation

Some days, there is more news and important content distributed than my colleagues and I can write about meaningfully in this space. We try to read it all and consider its importance when deciding what to post in the blog.

There is little doubt, however, that among the readership there are those who would like to see more, smaller stories covered and those who would perhaps like to see a tighter focus on only the most important stories. For the former group, I direct you to the scrolling Tweets in the right margin of this blog. There you will see our running reference to online content that we think worthy of promotion.

At the bottom of the scroll is an option to "follow me on Twitter". If you would like more comprehensive notification of relevant news and developments, I encourage you to do so.

AD Treatment Perspective #1

Contributed by: Dennis Fortier, President, Medical Care Corporation

Current treatments do not cure AD but they can slow disease progression. This is an important difference. If you are expecting treatment to help the patient regain their former cognitive abilities, you will almost surely be disappointed. If you are expecting some stabilization or slowing of their decline, you may well be satisfied.

Remember: Slowing the advance of the disease can add precious months or even years to a patient’s independence and should not be marginalized as meaningless simply because a cure would be better.

Solanezumab: Information on the Clinical Trial

Contributed by: Dennis Fortier, President, Medical Care Corporation

The phase III clinical trial (EXPEDITION2) for Solanezumab is now open and enrolling patients.

Participants must be over the age of 55, be diagnosed with mild to moderate AD, and have an MMSE score of 16 through 26 in addition to a few other criteria (here) related to other health conditions and medications.

This is the third of three interesting drugs in phase III right now (Dimebon and Bapineuzumab) that could take us much closer to effective treatment for Alzheimer's disease.

Alzheimer's Disease and Stem Cells

Contributed by: Dennis Fortier, President, Medical Care Corporation

The scientific process can be long and slow. In fact, the very nature of science is to be deliberate, comprehensive, and redundant as a means of objectively elevating hypotheses into facts.

You may have seen headlines this week about a potentially important discovery from the Garvan Institute of Medical Research in Sydney, Australia. The researcher's (Bryce Vissel and Andrea Abdipranoto) findings published in the journal Stem Cells suggest that excessive inflammation can prevent the brain from repairing itself properly. They also have hypothesized that a certain brain chemical, activin A, can suppress inflammation and allow the brain's stem cells to stimulate repair.

This is early stage research performed in mice and, as noted, the scientific process is generally long and arduous. But this is a new finding that may shed some important light on the disease process in Alzheimer's and Parkinson's. I suspect we will be hearing more about this.

Alzheimer's Disease: Of Course You Want to Know

Contributed by: Dennis Fortier, President, Medical Care Corporation

In the 90's, it became popular to avoid confronting an unpleasant diagnosis by adopting the mindset that "there is nothing to be done about Alzheimer's disease so I would rather not know". This thinking is dangerously out of date and needs to be brought forward.

I see headlines posing the "would you want to know" question quite regularly. For example, this one on CBS news last week had high exposure.

Journalists perpetrate old thinking merely by asking the question. What we really need is definitive headlines clarifying the importance of early detection.

I was pleased that the resounding answer to the question in the CBS story was "YES". I will say that the argument put forth supporting the answer could have been much stronger based on the full compendium of current research.

The best reason for getting a timely diagnosis of Alzheimer's is that current treatments can delay the progression of the disease and afford the patient a longer period of high quality living.

Solanezumab – Another monoclonal antibody reaches Phase III

Contributed by: David Geldmacher, M.D., Medical Director of the Memory Disorders Clinic at the University of Virginia.

On May 21, Eli Lilly and Co. announced that a Phase III Trial of their agent solanezumab, also known as LY2062430, would begin enrollment.

In Lilly’s Phase III program, a total of 2000 patients with mild to moderate AD are expected to receive either a 400 mg infusion of solanezumab or a placebo once every four weeks. Each research volunteer will participate over about 19 months. The overall trial is anticipated to be completed in mid 2012.

On first pass, this agent would appear to be similar to bapineuzumab which is already in Phase III trials being carried out by Elan and Wyeth. There are molecular differences between the two monoclonal antibody lines, which suggest that solanezumab acts primarily outside the brain to sequester soluble amyloid beta peptide in the peripheral circulation. If true, this would predict a lower risk for toxic events in the brain, like the vasogenic edema (brain swelling) reported in Elan’s Phase II trials.

On the other hand, a site of action outside the central nervous system might mean lower overall potency. Given the small absolute effects seen with bapineuzumab in its Phase II trial, lower potency would not bode well for solanezumab’s effectiveness. Of course, all anti-amyloid immnunotherapies depend a great deal on the validity of the amyloid hypothesis.

At a practical level, participants in the solanezumab trial will receive infusions every four weeks instead of the quarterly regimen for bapineuzumab. This will triple the risk for infusion related complications, and places a higher burden on patients. If approved under their current regimens, costs of drug administration would also likely favor the agent requiring the fewest number of infusions. However, a dramatically greater effectiveness would go a long way to off-setting increased treatment costs.