Book Review – Richard Noll, American Madness: The Rise and Fall of Dementia Praecox (Harvard 2011)

Reviewed for the h-madness blog. 

As indicated by the controversies swirling around the proposed revisions of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders due to be published next year, psychiatry is probably more concerned with the categorization of diseases under its purview than any other medical specialty. Yet solid knowledge of the causes and precise pathological mechanisms that might define mental illness remains more elusive than with any other sort of human affliction. In this richly detailed book, Richard Noll explores the historical predicament of psychiatry through the efforts of America’s early twentieth century psychiatric elite to integrate their field with the main currents of an emergent scientific medicine by creating a scientific classification of mental illness.

Read full review on h-madness. 

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Scrutinizing Alzheimer’s Science

A couple of weeks back, I wrote a post that offered some constructive criticism to Allen Power.  As I said then, I have great respect for Power as a leader in the efforts to change the culture of dementia care.  Today I want to applaud him for an insightful post on the need for critical scrutiny of science claims in the Alzheimer’s  field, which was picked up in post by by Howard Gleckman at Forbes.

Power asserts that in the magnitude of funding and the frenzied media hunger for reporting the big breakthrough in Alzheimer’s research has led too many scientists to ignore  some of the basic principles of good science. To his credit, Power does not just bash  pharma studies of drug treatments which he has criticized in his  highly regarded book. He starts instead by criticizing an inflated science claim by Dutch researchers and trumpeted in an email bulletin sent out by WebMD that the incidence of dementia has been falling as a result of  increased cardiovascular health—a theory of non-medical prevention that Power strongly endorses. But the findings in the study were not statistically significant; in other words, by the standard of sound science, it proved nothing.

Power then goes on to argue that a combination of  dodgy scientific claims  and groupthink have been the basis for much of the wide acceptance  in the Alzheimer’s field that anti-psychotics and cholinesterase inhibitors are safe and effective, and that amyloid clearance is the only rational route to pursue in treatment and prevention.

Gleckman’s piece in Forbes went even further, making an argument that many critics of the Alzheimer’s field agree with:

One consequence is that precious dollars are pumped into research aimed at a cure or prevention while almost no resources are available to help learn how to better care for people who already have dementia or for training or other assistance for their caregivers.

This battle over dollars has been going on for a long time. Drug companies, academics, and high profile advocacy groups such as the Alzheimer’s Association focus almost entirely on increasing research dollars for cure and treatment.”

Gleckman acknowledges the value of biomedical research on Alzheimer’s, but argues that it should not longer be virtually the only thing that the federal government will spend money on to address dementia:

So far, research is teaching us that these diseases are very complicated and progress towards cures or treatments is very slow. That’s why we should be working a lot harder to learn how best to care for people with these diseases.”

 

Will Failure of Plaque Clearing Drugs Bring Change in the AD Field?

With the news that Pfizer and Johnson & Johnson are scrapping further study of the drug bapineuzumab (bapi) after its second failure in a major clinical trial, and expectations no better for solanezumab, a similar drug under development by Eli Lilly, it now appears conclusive that the amyloid vaccine approach fails to provide any significant benefit for patients who have dementia.

The amyloid cascade hypothesis has been the dominant (though hardly exclusive) theory of the pathogenesis of Alzheimer’s for twenty years,and the idea of a vaccine targeting amyloid in the brain has been highly hyped for a decade.  It’s worth recalling the sort of enthusiasm surrounding bapi in a typical news story when clinical trials were just getting started in 2009:

It’s not yet clear what such a high profile failure will mean for the AD field. Not surprisingly, pharma leaders continue to defend the amyloid vaccine approach that they have bet so heavily on. The New York Times story on the bapi failure quotes a scientific spokesman from Johnson & Johnson reiterating the company’s belief “that targeting and clearing beta amyloid remains a promising path to potential clinical benefits for people suffering from this disease.”

Meanwhile, other academic and industry leaders are spinning out modification of the amyloid hypothesis that refine the drug target. In 2010, as prospects for drugs like bapi that target amyloid plaques began to look increasingly poor, some researchers began to argue that the problem was free floating amyloid, and that the formation of plaques might be the body’s attempt to limit the damage by sequestering amyloid.

Many others have argued that the problem is not that the drugs are ineffective, but that treatment must begin much earlier in the disease, perhaps even before patients show any clinical signs of dementia. To investigate this, the National Institute on Aging has funded the Dominantly Inherited Alzheimer Network project, which will try to capitalize on the fact that the very rare early onset form of Alzheimer’s is caused by a known gene mutation, which will allow researchers to identify and test drugs on people who will develop dementia before any symptoms have appeared. But even if positive results are found in trials with early onset cases, it is not clear that these will be relevant to the much more common late-onset form of dementia since a different set of genetic factors are involved. More importantly, nothing is known about the potential risks of long-term treatment with anti-amyloid drugs. In the best case scenario, an Alzheimer’s drug would work less like a magic bullet, and more like the anti-cholesterol drugs — with all of the costs and controversies included.

Given these costs and barriers, and the fact that it clearly established by repeated studies that maintaining good overall health through exercise, mental stimulation and social engagement can significantly lower the risk of dementia as we age, I am inclined to join Peter Whitehouse in hoping that the failure of the anti-amyloid drugs will result in a fundamental re-orientation of our approach to Alzheimer’s that emphasizes more positive and realistic attitudes about aging and focuses on maintaining a rich life world.

But, to paraphrase Winston Churchill’s famous aphorism, given the great economic, intellectual and cultural investment that has been made in finding a medical solution to dementia, we are not likely to pursue such a simple, sensible course until we have exhausted all other possibilities.

For now, the amyloid hypothesis and the broader pharmacological approach to dementia may seem to many people like one more thing in our society that is just too big to fail.

The Neuroscientific Turn: Transdisciplinarity in the Age of the Brain

Book Announcement

Cover Image for The Neuroscientific Turn

Neuroethics, neuroeconomics, neurohistory, neuroliterature, neuromarketing, neurophilosophy, neuropolitics. We are well beyond the decade of the brain, and deep into the era of the neurologism. Is there any field of human knowledge  or endeavor which has not sought enhancement by adding the prefix neuro?

Melissa Littlefield and Jenell Johnson  have put together what looks like an intriguing and important tour of  the  emerging cultural neuroterrain: fourteen essays by a diverse array of scholar from the humanities, social and the neurosciences.

Full description and table of contents from the University of Michigan Press.

Pe-order from Amazon.com