Climate Change, Alzheimer’s Disease and the Conundrum of Scientific Authority

There is perhaps no greater source of authority in modern society than science.  As a result, scientific claims are nearly ubiquitous, and often controversial. How do we decide when to trust and when to doubt ostensibly authoritative science?

This question was brought home to me in a couple of exchanges I’ve been part of this year concerning climate change and Alzheimer’s disease. When Peter Whitehouse recently wrote a post on the Myth of Alzheimer’s blog asserting that extreme weather events associated with climate change pose a significant threat to elders, particularly those with cognitive impairment, a climate change denier thanked him for exposing the myth of Alzheimer’s but took him to task for falling for the myth of global warming.

Going in the opposite direction, back in March someone took great offense at a talk I gave questioning the ostensibly authoritative claims of Alzheimer’s researchers and accused me of engaging in the equivalent of climate denial: making specious arguments that are dismissive of the very real problem Alzheimer’s disease presents to individuals and society, and thus reducing the global commitment needed to recognize and respond to it. (This exchange happened to take place as I was preparing for a four day bicycle trip with my 12-year-old daughter from central PA to Washington DC to raise awareness about the need for climate action, so it did get under my skin.)

It’s tempting to dismiss these criticisms as simple ignorance. After all, as I pointed out in reply to the same climate denier’s 30-link torrent  in response to a subsequent post by Whitehouse on climate change, a very strong scientific consensus on anthropogenic climate change is in the realm of objective fact: A survey of nearly 12,000 relevant peer-reviewed scientific articles published from 1991-2011 show that 97% of them support the basic consensus on climate change, and virtually every prestigious scientific society in the United States and around the world has issued or signed on to statements supporting the consensus that climate change is being driven by emissions from the burning of fossil fuels and poses a serious threat to human society. And my criticism of the emphasis over the past thirty years in the Alzheimer’s field on cure and prevention rather than support for creative, stable caregiving hardly amounts to a denial that dementia is real, and causes real suffering and loss to society.

But a legitimate question remains. It seems that on the one hand, I am pleased to accept the claims of a majority of climate scientists as authoritative. On the other, I seem equally pleased to criticize the claims of a majority of scientists and practitioners in the Alzheimer’s field. How can I justify this apparent inconsistency? Perhaps I have enough direct familiarity with the content of the relevant branches of science in both of these broad fields to make an informed judgment? Absurd. I’m very knowledgeable about Alzheimer’s for a non-scientist, and probably better read than the average person on climate science.  But the volume and degree of specialization in modern scientific research makes it a challenge for scientists to keep up with research even in their own narrow fields. Directly assessing the volume of work in broad fields like dementia or climate research is simple impossible. At some point, no matter how broad or thorough your scientific education and competency may be, you will need to trust (or not) the claims of others about science. But how to decide who and what to trust?

Here I think the academic fields that have formed me as a scholar – the history of medicine and STS (Science, Technology and Society) – have much to offer. The implicit idea of these fields is that understanding some of the science itself is necessary but far from sufficient. To understand science deeply enough to reach sound judgments about when to trust and when to question scientific claims, one must learn and think more about science and the way it is actually practiced in the world. One must understand the social and cultural contexts that shape scientific interest and help determine what kind of scientific questions are pursued. One must consider the social, economic and political factors that inevitably influence scientists. One must be able to recognize the way that social and cultural values are embedded in seemingly mundane questions of scientific method and analysis. The point of these sorts of questions is not to dismiss or diminish science, but to understand its real power, and in so doing reach better judgments about how it should be used to better serve human flourishing.

It’s the consideration of these sorts of questions that lead to my different stances toward climate science and Alzheimer’s research. As I mentioned above, in simple numerical terms the consensus on climate change is very strong. But in socio-historical terms, the breadth and resilience of the consensus is even more impressive. As shown by physicist and historian of science Spencer Weart’s comprehensive research, the consensus around the theory of anthropogenic climate change is not supported by evidence generated from the work of a single scientific field, but emerged with the convergence of many lines of research from a broad range of scientific fields ranging from geology, chemistry, atmospheric physics, meteorology, oceanography, computer modeling and many more. Practitioners in these fields use different methods and approaches to what counts as evidence, so that the theory has been challenged and tested from multiple directions. Scientists in different fields also get research funding from different sources within the federal government and the private sector, so the potential funding bias is less than when funding comes from a more narrow range of sources. Moreover, since the theory of anthropogenic climate change implicates the energy industry, it is profoundly threatening to some of the most powerful political interests, who have responded by spending vast sums to discredit it. Historians Naomi Oreskes and Eric Conway have shown that this involve funding the activities of a handful of scientists with an anti-regulatory bent who have attacked not only the climate change consensus, but had also been involved in earlier attacks on scientific research showing the harmful effects of DDT, CFCs, and tobacco. Journalists have also begun to trace the donations of hundreds of millions of dollars from conservative billionaires with fossil fuel industry ties to public relations and lobbying campaigns aimed at attacking the climate change consensus in the media and on Capitol Hill.  That a strong consensus supporting the theory of anthropogenic climate change remains despite decades of well-funded, systematic attack enhances its credibility.

While I in no way intend to dismiss research in the Alzheimer’s field over the past several decades that has produced much important knowledge about some of the likely pathological mechanism that lead to dementia, a consideration of socio-historical factors raises questions that are not often enough asked, especially in media coverage. First, while there is no credible denial that age-associated progressive dementia exists as a significant individual and social problem, there are many different  theories regarding what causes it among respected researchers in the field, and debate within the field about whether it can truly be disentangled from usually more benign processes of systemic brain aging. Second, while researchers from diverse fields certainly conduct Alzheimer’s research, the dominant approach emphasizing the drive to pharmacological treatment and prevention is the product mostly of psychiatrists and neurologists, and this group is largely supported by a narrow funding stream from the pharmaceutical industry. Critics like David HealyCarl ElliottJohn Abramson  and others have documented the distorting effects of pharma money on medical research in general, and several authors in a book on dementia treatment I co-edited show that this happens in the Alzheimer’s field as well. Finally, unlike climate change, the dominant approach to Alzheimer’s disease is in sync with the interests of the pharmaceutical industry, which has accordingly spent vast sums to persuade the public and lawmakers of its importance to society so that there has been relatively little public debate about it. None of this amounts to a reason to dismiss mainstream Alzheimer’s research outright, but it does suggest there is a need to ask some critical questions.

Both climate change and Alzheimer’s disease are complicated problems, and much will no doubt continue to change in the scientific understandings of both of them. But the persistence of such a strong scientific consensus around the fundamental of climate change despite factors that we would normally except to weaken that consensus, especially the strong resistance of powerful economic interests, helps convince me that it is time to take strong steps as a society to lower carbon emissions. While we must also continue to take the challenge of Alzheimer’s disease very seriously, I see a need for a broader debate about whether the emphasis on developing a pharmaceutical solution – which has been promoted by powerful economic interests – has led us to pay too little attention to other ways of effectively responding.

And beyond both of these issues, we need to move beyond ubiquitous claims of scientific authority and superficial controversy to a more thoughtful public discourse about science and its place in society.

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Skewering the Emerging “Brain Fitness” Industry

Capture brain fitnessPerhaps I should look into joining The New Yorker as a staff writer now that major articles on dementia seem to have become a regular feature of the magazine. In this week’s issue, humorist Patricia Marx skewers the emerging “brain fitness “ industry.  Her tone is breezy and light compared to the gravity of the two articles I reviewed in my previous post, going for laughs by probing the tension between mid-life anxiety about cognitive decline and the range of improbably diverse claims for the cognitive benefit of various activities:

It’s a pretty regular occurrence for me to leave my reading glasses God knows were or lose my train of thought or have trouble recalling the word `phlogiston’ – and, egads, what happened to all that stuff I used to know about Charlemagne’s in-laws? In my darkest moments, I imagine that my friends are humoring me when they insist that their amnesiac lapses are no less alarming than mine. (“Have you ever squeezed toothpaste onto your contact lenses?” a friend asked triumphantly.) Am I, like so many of my gang, just another one of the `worried well?’(A 2011 survey found that baby boomers were more afraid of losing their memory than of death.) Should I get out a crossword? Learn to play bridge? Chew gum? Take a nap? Drink more coffee? Eat blueberries? Give up tofu? There are studies that tout the benefits that each of these undertakings has on the brain. What to do?”

Readers who themselves are struggling with significant cognitive loss, or caring for people with dementia, may be put off by the tone of the article. But Marx is making an important point about how the purveyors of brain training software and other “neurobic exercise” programs are forging a billion dollar industry on anxiety about dementia and scientific sounding claims about various techniques for re-invigorating the brain.

Marx is not, however, completely dismissive of recent findings about neuroplasticity and the potential for diet, exercise and stress management to prevent cognitive decline. The work of Kenneth Kosik, a neuroscientists at the University of California at Santa Barbara and founder of a non-profit brain fitness center, comes off as reasonable, legitimate, and firmly grounded in real science. Citing the well-known nun study and other recent research, Kosik explains the scientific basis for believing that social, physical and intellectual enrichment that promotes good brain health across the lifespan can increase the resilience of the brain and help prevent dementia. Kosik, who is also involved in more mainstream biomedical research, is careful to keep claims about brain fitness modest, arguing that they should be part of an overall health lifestyle. Of his brain fitness center , Kosik says that “I’m sure some of my colleagues in Boston would look at this as a fringe operation, a storefront with walnuts and incense. On the other hand, we can wait for science to come up with a cure or we can jump in and try to create an atmosphere that is conducive to good brain health.”

Though Kosik is clearly right that this holistic approach to brain health as a factor in dementia is at odds with the reductionist drive in biomedicine to find the key to curing or preventing dementia in specific pathological mechanisms, he is quite wrong about how the brain fitness industry looks. The companies Marx spends most of the article quite justifiably mocking are careful not to look like smoky dens of new age mysticism. Rather, they relentlessly deploy neuroscience lingo and wildly extrapolate from limited research evidence to make absurdly inflated claims for the efficacy of their products.

After a crash course of several weeks Marx concludes:

Judging from the series of questionnaires I’d filled out during the course of my training, my mood brightened, my sleep was more restful and I felt more confident. I may also have become a bigger liar on questionnaires but that was not evaluated. As for the exercises, my scores were higher across the board. In an email summing up my progress, Merzenich [neuroscientist and co-founder of BrainHQ] wrote `Your advances on these exercises comes from brain remodeling. If we had recorded from/imaged your brain before and after training, we could have easily shown that you now have a `better’ (stronger, faster, more reliable, more accurate) brain.’ (Wouldn’t they make dandy wallet photos?) Compared with my poky old brain, my souped-up brain, according to Merzenich, has more synapses, better wiring, stronger connections, and more forceful activity. (Doesn’t that sound like an ad for a five-thousand-dollar stereo?)

I’m not sure I noticed my newfound cognitive abilities in everyday life. It’s hard to be both scientists and lab rat. On the positive side, I am slightly less troubled about the size of my hippocampus. On the negative side, why did I sprinkle NutraSweet on my broiled salmon last night?”

The New Yorker on Dementia: Crisis in Scientific Research and Progress in Caregiving

The peer-reviewed article may be the coin of the realm in academic science, but the high profile magazine article is the bellwether of popular attitudes toward health, medicine and disease. Thus it’s notable that The New Yorker, one of the few remaining popular periodicals aimed at well-educated general readers, recently published two major articles about the search for new approaches to Alzheimer’s and dementia. One focuses on the lack of progress in scientific research, and the other on encouraging developments in nursing home care.

Jerome Groopman’s “Before Night Falls,” which appeared in the June 24 issue, aims to describe the current state of research on Alzheimer’s disease and the search for new directions.  Groopman holds a prestigious medical research chair at Harvard Med, but is more widely known as the author of a number of bestselling books that explore the experience of illness, the often tangled relationship between doctors and physicians, and the inherent difficulties of the diagnostic process.  Groopman’s popularity is well-deserved.  He is an excellent writer, and here he provides a compelling description of the struggle of leading Alzheimer’s researchers to find a viable direction following “three decades of Alzheimer’s research [that] has done little to change the course of the disease.” But Groopman’s qualities as a writer and critical observer of medicine make the limitations of this article all the more disappointing.

Groopman depicts the Alzheimer’s field as essentially split between two camps – the majority of researchers who continue to believe that the key to the disease is the excess accumulation of the protein beta-amyloid that ultimately forms plaques in the brain, and the smaller group of dissenting researchers who call instead for a focus on the tau protein involved in the formation of neurofibrillary tangles or some other putative cause, or who suggest that the disease is simply too complex and scientific understanding too limited to warrant focus on a single target.

The article strikes a fair enough balance between these two camps. It focuses on the work of champions of the amyloid orthodoxy like Dennis Selkoe and Reisa Sperling, and especially on the emerging emphasis on early diagnosis and prevention in the wake of the failure of anti-amyloid drugs to improve the cognitive functioning of people who have been diagnosed with dementia. But it also gives ample space to the views of prominent critics like George Perry and Peter Davies to explain their doubts.

Indeed, the article is far from the sort of naïve expression of fervent belief in the inevitability of medical progress that is all too typical of medical journalism today. It does not gloss over the uncertainties, risks and costs involved in the new emphasis on early diagnosis and treatment targeting amyloid accumulation. Moreover, the personal and societal consequences of Alzheimer’s are depicted as so grave that, as the title suggests, the overall tone of the piece is more gloomy than triumphant. The final section of the article reiterates the apocalyptic demography that characterizes so much Alzheimer’s advocacy: the looming economic burden of the disease, reckoned to be more than a trillion dollars a year by 2050, makes spending billions of dollars on research, whatever the uncertainties, seem like the only rational course of action – even to budget hawks like Republicans Eric Cantor and Newt Gingrich. Groopman gives researcher Reisa Sperling the final, almost desperate word:

I think it’s a war – a war against Alzheimer’s disease, and we are losing, so I’m going to use military terms,” she said. She argues that those who are concerned about an ill-conceived rush to preventive trials lack the appropriate sense of urgency. “The idea of waiting another ten years, just to study the natural history of Alzheimer’s disease, is not tenable,” she said. “These are the dilemmas. How do we make the best possible decision right now, in the absences of all the data we need?” She paused for a long moment, then said, “My biggest fear is that we are just doing too little too late, and that even if we move sooner, we are not lowering amyloid sufficiently. So we will get to the end of the trial and say, `Well, here we are, and we have the same conundrum. We just did not do enough.’”

There are two glaring omissions in Groopman’s article. First, there is virtually no discussion of big pharma’s role in the development and continued dominance of the amyloid approach. Critics like David Healy, Carl Elliott, John Abramson  and others have documented the distorting effects of pharma money on medical research, and several authors in a book on dementia treatment I co-edited show that this happens in the Alzheimer’s field as well. While reasonable people may disagree about the effect of the pharmaceutical industry on medical research, it is inexcusable to simply ignore the issue in a story of this length and prominence. Second, there is absolutely no mention of the many studies suggesting that non-pharma approaches to overall brain health like diet, exercise, and social engagement can effectively lower the risk of dementia, most recently two studies showing that dementia rates in Denmark and the United Kingdom may actually be falling even as the population ages.  Such approaches, which anecdotally at least appear at least as promising as any drug, have the advantage of being safe and cheap – and something we should want to do for other compelling reasons anyway. It is surely worth asking why Alzheimer’s researchers working to establish a new regime of early diagnosis and prevention would not want to rigorously explore how non-pharma approaches could be part of that strategy.

As an antidote to the feeling of gloom and desperation in Groopman’s depiction of the search for an effective medical treatment for Alzheimer’s, one should turn to exciting developments in the field of nursing home care that are promising to dramatically improve the lives of people with dementia and their families today. These developments are described in great depth by Rebecca Mead in an article called “The Sense of an Ending” that appeared in the May 20th issue.

Mead focuses on the work in dementia care at the Beatitudes Campus in Phoenix, AZ, and the NYC chapter of the Alzheimer’s Association that is exploring ways to incorporate its approach in nursing homes there. Beatitudes is part of a culture change movement in nursing home care that encourages moving away from a medical model of care focused on treatment and efficient service delivery, to a more holistic, person centered approach to dementia care that aims to create environments that minimize distress and value the enjoyment and meaning inherent in the non-cognitive human capacity for sensory pleasures and intimacy.  “Without any immediate prospect for a cure,” Mead writes “advocacy groups have begun promoting ways to offer people with dementia a comfortable decline instead of imposing on them a medical model of care, which seeks to defer death”

But the culture change movement is about more than making people with dementia comfortable as they await the release of death. It is based on a profound re-valuing of the person with dementia, focusing not just on the cognition that is lost, but the physical and emotional capacities that remain, capacities that might even be enhanced in dementia. Mead writes that Tena Alonzo, director of education and research at Beatitudes, views people with dementia as “closer to the higher being. This is who they are: real, honest, and sometimes raw. There is no ability to reason, or to cover up who you really are. And so, for much of the time, you see the loveliness of the soul – it is bare  for everyone to acknowledge.”

Seen from this perspective, the aim of caregiver is no longer to change or manage the person with dementia, but to overcome the anxieties and defenses that prevent caregivers from developing real, life-giving relationship with who the person with dementia has become.  Mead acknowledges the difficulty of this, especially for children or partners who cannot help but grieve the abilities that the people with dementia they love have lost. Nonetheless, one can see in her rich description of the world of care at Beatitudes what caregivers can gain from these relationships. Mead describes a woman who spent most of every day walking up and down the corridors. In a typical nursing home, this behavior might be seen as pathological and worrisome, a risky problem behavior to be managed and perhaps suppressed. But the staff learned that she had worked in retail for decades, and determined that she was not going to stop walking just because she was in a dementia unit, so they sought merely to minimize her discomfort by considering additional pain killers when her feet appeared to be painfully tired. Mead describes her feelings when she interacted with her:

I spent some time on day walking along the corridor with this woman, into the sunroom and out of it again. Her face brightened at the company, and she was eager to talk, even when her side of the conversation devolved into singsong nonsense. Sometimes she stopped to shimmy for a moment, and I could imagine what a figure she must have cut at a dance. Being in her company triggered memories of being a child alongside my grandmother, now long dead. I recalled the at-a-loss-for-words feeling that I used to experience with her, even as she made me feel held within a sphere of affection. This woman’s powers of cognition were limited, but her capacity to experience emotion seemed unimpaired, and she demanded engagement the way a small child does: it made no more sense to resist her impulse toward intimacy than it would to withhold a smile from a baby. When she grasped my hands and told me I was perfect, I told her that she was perfect too.”

What will strike many people as most remarkable about Beatitudes is that is cost-effective. Mead notes that despite the innovations that make Beatitudes a much more gracious place to live than the typical nursing home, the average cost of care is roughly the same. Not least among the ways that a person-centered approach to dementia care can save money is by reducing the use of expensive anti-psychotic drugs, which can cost hundreds of dollars per month for every patient on them. Mead quotes Alice Bonner, director of the Center for Medicare and Medicaid Services: “People are starting to realize that, with some creativity and curiosity, we can figure out other ways of taking care of people with dementia.”

Taken together, these two articles suggest a change in emphasis. The future of the dementia field may lie less with developing high-tech medical interventions aimed at curing or preventing dementia, and more at developing and practicing innovative models of care. Perhaps we can learn to see dementia as less of a personal and collective apocalypse than a great human challenge that can bring out the best in us.

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.

History and the Will to Power in the Alzheimer’s Field

It is a strange time to be a historian interested in Alzheimer’s disease.

On the one hand, since the putative one hundredth anniversary of Alzheimer’s disease, which was confusingly celebrated in both 2006 and 2010, the Alzheimer’s field seems completely enamored with its storied past. Virtually every major book, conference or news articles on contemporary Alzheimer’s research contains at least a brief account of the origins and development of the basic concepts of the Alzheimer’s disease field. On the other hand, as history, these accounts are typically superficial at best, and are often distorted and misleading. The Alzheimer’s field remains so distressingly unaware and uninterested in its actual past that one could wonder about whether it is afflicted with some sort of memory disorder—except that this alienation from a meaningful engagement with history is  quite typical of  contemporary society.

My quarrel with the way the Alzheimer’s field represents its history is grounded in what I see as the core value of historical scholarship. If being a historian means anything, it is a commitment to the complexity of the past. Our interest in history comes from questions and concerns we have in the present and the patterns we see in the past are inevitably shaped by this. But we must remember that the people of the past,  whose experiences we would try to understand and learn from, had lives fully as complex as our own, and did not necessarily know and share the concerns we have in the present. When we attend to the complexity of the past it can serve as a source of rich human experience to interrogate and learn from. But if we impose the concerns of the present too strongly, we silence the individual and collective voices we could learn from and produce a self-serving narrative that can only reinforce our own biases. Historians cannot accept facile, reductive accounts of the individual and collective lives of people in the past in order to serve our purposes in the present.

A recent infographic on the history of Alzheimer’s disease research has begun circulating that distills the field’s warped history of itself into a viral nugget. It’s a nice design that pulls together information on the prevalence and financial burden of Alzheimer’s, the growth in funding for biomedical research, a list of drugs that have been approved for treating Alzheimer’s, and a timeline of “breakthroughs in research” drawn from standard sources: the websites of the Alzheimer’s Association and other major organizations in the Alzheimer’s field and mainstream media sources like CNN and Consumer Reports. As a whole, the infographic makes it clear that this is, or soon will be, a history of  medical triumph:

It has been called incurable, and its diagnosis comes as a death sentence. But as research accelerates, new breakthroughs become the norm, and donations come pouring in, sufferers of Alzheimer’s and their families are finding new hope in the possibility of future research and treatment options. See the history behind Alzheimer’s disease, the milestones in its research, and the global push for a cure.”

Shorn of any clarifying or qualifying context, all of the information in the graphic is grossly oversimplified. But  the distortion of history is simply outrageous. The timeline begins with the early twentieth century work of Alois Alzheimer’s associating plaques and tangles in the brain with dementia, and Emil Kraepelin’s creation of the term “Alzheimer’s disease” in 1910. This is all true, but ignores the fact that their concept of dementia was quite different, reserving the term Alzheimer’s  to distinguish the rare cases of early onset dementia from the much more common form of senile dementia, which they seemed content to view as an extreme form of normal aging. Moreover, Alzheimer and Kraepelin did not view dementia  as a major public health issue, and they showed no interest in developing therapeutic interventions; rather, their interest in dementia was aimed at advancing the intellectual power and social authority of psychiatry.

Remarkably, the only “breakthrough” mentioned between 1910 and the 1980s is the  invention of the electron microscope that allows  “deeper study of the brain.” Inclusion of this in a timeline on Alzheimer’s research is inexplicable since its inventors had no interest in Alzheimer’s disease, and Alzheimer’s researchers would not use the electron microscope in their work until the 1960s.

But to anyone who has systematically studied the history of Alzheimer’s disease , even more inexplicable is that a major body of research on the dementias is ignored. From the 1930s through the 1950s, American psychiatrists wrote extensively about age associated cognitive deterioration from a psychodynamic perspective. While this work goes against the grain of more recent research on brain pathology, as I showed in my first book, it was highly influential at the time, challenging  the therapeutic nihilism that had characterized medical approaches to senility and contributing to a broader transformation in social expectations for old age without which the emergence of Alzheimer’s as a  major public issue would be impossible.

The creation of the National Institute on Aging n 1974 and the Alzheimer’s Association in 1980 are noted, but there is no explanation indication of  the  political machinations behind them. They are, it seems, the straightforward and inevitable  institutional forms that emerge to deal with a dread disease. These have indeed been important organizations, but suffice it to say the reality is a good deal more complex than this.

The remainder of the timeline is devoted to breakthroughs in drug treatment or that contribute directly to dominant trends in current research, such  as the identification of the beta amyloid and tau proteins, the discovery of gene associations, or  the development of the transgenic mouse model of Alzheimer’s disease. Each of the drugs that have been licensed in the United States for treatment of Alzheimer’s is noted, but the now out-of-date  “cholinergic hypothesis” on which they were based is ignored, as is the controversy that surrounded tacrine and the fact that all of these drugs have proven to provide little if any benefit to patients. The 1999 success of an Alzheimer’s vaccine in transgenic mice is noted, though not the fact that initial human trials proved a disastrous failure when it caused fatal swelling of the brain. The timeline culminates with the  use of a cancer drug to reverse Alzheimer’s in mice earlier this year.

Those not  afflicted with the sensibilities of the professional historian might wonder why this is so bad. Is oversimplification of the past really so bad if it encourages public support for research and provides hope for people who are struggling with Alzheimer’s disease?

My response is that an oversimplification of history encourages naive thinking about our present situation. This is a winner’s history, in which scientific developments in the past are included only if they contributed directly to the  research agenda that is dominant in the present. It is a history that serves the interest of the leaders in the Alzheimer’s field today, suppressing contingency, complexity, and uncertainty so that the discovery of a prevention or cure seems inevitable if only we will make the necessary investment  in their work. On this account,  a crude version of Nietzsche’s will to power not Alzheimer’s research on plaques and tangles in the brain, seems to be the real foundation of the Alzheimer’s field.

Such history inevitably leads to an inflated sense of the efficacy and importance of dominant social institutions like medicine, and ignores or marginalizes the importance of other social and cultural resources like art or spirituality that can and should be part of our understanding of the problem and part of our response. In the case of Alzheimer’s, this distorted history helps to rivet  attention on faulty molecules in the brain and to foster a desperate hope in the power of biomedicine to produce a cure.

We need to create richer, more profoundly optimistic understandings of dementia and how we might respond to it. Attending to the complexities of the history of Alzheimer’s research is a good place to begin.
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NOTES:

Confusingly celebrated in both 2006 and 2010. Alzheimer described the case of Auguste Deter at a small, regional conference of German psychiatrists in Tübingen in 1906, and Kraepelin created the eponym Alzheimer’s disease based largely on this case in the eight edition of his influential textbook Psychiatrie, published in 1910. 

Nietzsche’s will to power. The nuanced version of the will to power, which can be found in Nietzsche’s original work, did not condone a simplification of history  to fit the wishes of those seeking to exert power and remains an important concept in history and theory. 

Medical Journalism in the War on Alzheimer’s

They say that truth is the first casualty of war. So how is the truth doing in news coverage of medical research on dementia now that we have finally declared War on Alzheimer’s?

ImageThe question is prompted by the recent major article on the genetics of early onset Alzheimer’s disease by New York Times science reporter Gina Kolata in last week’s NYT Magazine. The article immediately generated a lot of positive buzz in the Alzheimer’s research and caregiver communities. It’s the kind of piece that usually garners awards, not opprobrium. So let me begin by saying what Kolata does right before making the case that she gets the most important things very, very wrong.

Kolata’s writing is a beautiful, and she tells a compelling story of the members of a family struggling to live with the burden of knowing that they may have a gene for early onset Alzheimer’s, and their sometimes enthusiastic and sometimes ambivalent involvement in medical research that can tell them for sure. She also describes some complicated genetic science with commendable clarity.

The problem is that Kolata uncritically accepts the perspective of Alzheimer’s researchers in a way that violates the fundamental value of systematic skeptical inquiry that ought to be at the heart of both journalism and science. There is nothing new or exceptional in this, of course. Frankly, Kolata’s many articles in the Times hyping the latest Alzheimer’s research, like so much of medical reporting in general, reminds me of the sort of journalistic failure, most egregiously by Judith Miller of the Times, that led so many to accept the Bush administration’s claims about weapons of mass destruction in Iraq. Just as uncritical reporting of the Bush administration’s false claims about the presence of WMDs, and its rosy assessment of how American troops would be received by the Iraqi people after dislodging Saddam, influenced the public and congress to support a war in Iraq, uncritical reporting of the sorts of claims made in the article about the imminence of therapeutic breakthroughs will influence the public and congress to continue supporting the war on Alzheimer’s and the growth of the biomedical industrial complex behind it.

Now I am not saying that the motivations of medical researchers in Alzheimer’s or other fields are the same as warmongers in the Bush administration On the whole, I am a fan of Alzheimer’s and other medical researchers and the work they do. But good journalists, whether they are covering the war on terrorism or the war on disease, should be skeptical of sources that have an obvious self-interest. And medical researchers have an obvious self-interest in presenting their research in the most favorable light possible. Thus it should be no surprise, even to people familiar with the daunting complexities of understanding, treating and preventing dementia, that the researchers profiled in the article “say that within a decade there could be a drug that staves off brain destruction and death.” But Kolata should have raised questions about this claim, and talked to experts not directly involved in the research who are far less optimistic about its potential to so quickly lead to effective treatments.

Kolata’s article uncritically reiterates two other important aspects of the perspective of many Alzheimer’s researchers: a warped view of history, and an oversimplification of the disease.

Fairytale History

Regarding history, Kolata spends about 800 words connecting German psychiatrist Alois Alzheimer’s first encounter in 1901 with a patient with what we would today call early-onset Alzheimer’s to contemporary research. Alzheimer brilliantly described the pathological features of the disease, but lacked the scientific tools needed to understand what caused it let alone how to do anything to stop it. “There matters stood until the latter part of the 20th century,” when contemporary researchers heroically enter the stage with powerful new technologies to penetrate the mysteries of the brain and will soon, we are assured, be able to set things right.

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Alois Alzheimer (1864-1915)

While it is attractively simple and flattering for researchers to think of themselves as part of a unified, continuous research enterprise stretching back more than a century in which they finally are able make progress on the medical mystery Alois Alzheimer unearthed in the brain of his patient more than a century ago, the truth is a good deal more complicated than that. Scientific and clinical research on dementia has never been a unified enterprise. The goals and approaches of researchers and clinicians are strongly shaped by the historical contexts in which they practice, and given the dramatically different context in which Alzheimer practiced, it is highly unlikely that he shared our concerns about age-associated cognitive decline. Though no one has done a serious historical study focusing on Alzheimer and his lab, I have looked at the available evidence enough to conclude that Alzheimer and his contemporaries simply did not view the disease that was named for him as terribly interesting or important. When he died in 1915, none of the admiring colleagues who eulogized him – not even Emil Kraepelin who named the disease for him in 1910 – listed the discovery of Alzheimer’s disease as one of his major accomplishments.

Moreover, the claim that nothing of significance happened regarding the medical understanding of Alzheimer’s disease and senile dementia between Alzheimer’ and the latter twentieth century ignores a major historical development. In the middle decades of the twentieth century, a group of American psychiatrists developed a psychodynamic framework for understanding and managing dementia and made sweeping claims about how it finally removed some of the mystery shrouding the condition and would soon lead to efficacious means of preventing cognitive deterioration in old age. It is perhaps understandable that contemporary researchers, trained in biological psychiatry and neuroscience and focused on pathology in the brain, have forgotten this chapter in the history of Alzheimer’s research. It is unfortunate though, if only because considering the now largely forgotten work of researchers who thought themselves on the cusp of being able to prevent dementia just might lead today’s researchers to consider the virtues of humility and circumspection in making claims about imminent progress.

While it might be presumptuous of me to suggest that Kolata should have known all this by making herself familiar with my work, she need not perpetuate a history of the field that is so obviously driven by the biases of contemporary researchers. It should not take a historian to recognize a self-serving fairy tale.

Simplifying Alzheimer’s

Regarding the oversimplification of the disease, there are a couple of points to make. First, the many scholars, clinical professionals and caregivers who have been working to lessen the stigma and despair associated with dementia – whom I am proud to count myself among – might take issue with the unremitting grimness with which Kolata represents having dementia. Without denying or diminishing the very real losses and challenges imposed by dementia, we have been working in different ways to show that a life cannot be reduced to a disease, even a disease that brings profound cognitive deterioration. Possibilities for human flourishing remain. Kolata’s story, like so much reporting on Alzheimer’s, represents people with dementia as pure victims – unable to comprehend or resist in any way a disorder that takes everything from them.

But I am willing to cut Kolata some slack here. While we need more stories about living well with dementia, that is not the story Kolata set out to write, and the one she did is important. Her story is about the dread associated with early-onset, familial Alzheimer’s disease, the very rare form of dementia that is associated with several autosomal-dominant gene mutations. Frankly, early-onset familial Alzheimer’s does seem more dreadful to me than the much more common variant that occurs at much older ages. Some may regard this as ageism, but developing a profound cognitive disability in your fifties or even forties does seem much worse than developing it in your seventies, eighties or nineties. And living with the sharp either/or risk of a Mendelian gene for dementia in one’s family seems much more dreadful to me than the gradually increasing risk for dementia associated with the normal vicissitudes growing older.

The problem is that Kolata’s story tends to conflate this very rare form of early-onset dementia, which is estimated to account for only one to five percent of all cases of Alzheimer’s, with the category as a whole. The story acknowledges this explicitly at only one point, nearly 700 words into a 5,400 word story, when it describes the rationale of the Dominantly Inherited Alzheimer Network (DIAN) project:

Though as much as 99 percent of all Alzheimer’s cases are not a result of a known genetic mutation, researchers have determined that the best place to find a treatment or cure for the disease is to study those who possess a mutation that causes it. It’s a method that has worked for other diseases. Statins, the drugs that are broadly prescribed to block the body’s cholesterol synthesis, were first found effective in studies of people who inherited a rare gene that led to severe and early heart disease.

Alzheimer’s is the sixth leading cause of death in this country, and is the only disease among the 10 deadliest that cannot be prevented, slowed or cured. But DIAN investigators say that within a decade there could be a drug that staves off brain destruction and death.”

Throughout the rest of the story, Kolata drops the qualifiers “early onset,” “familial” and most importantly, “rare” and simply uses the term “Alzheimer’s disease.” In the online version of the story, the first reference to Alzheimer’s disease is even linked to the NYT Health Guides general entry for Alzheimer’s disease. The elision of this important distinction has undoubtedly fueled the needless fear many people often have of being at greatly increased risk for dementia because a relative developed cognitive problems in their seventies or eighties, which can be seen in some of the many comments from readers to the online version of the article  It also reinforces the central dogma of the contemporary Alzheimer’s field – that it is a single disease, distinct from aging, caused by some unified patho-physiological mechanism that can be isolated and addressed with a linear therapeutic intervention.

As Kolata must surely be aware, many if not most researchers in the Alzheimer’s field will acknowledge privately though not so often in public that this central dogma is shaky.  In this case, some closer attention to the real history of Alzheimer’s research would be helpful. The term Alzheimer’s disease was originally created to describe cases of dementia – such as the 51-year-old woman Alzheimer encountered in 1901 – where the clinical and pathological features of senility appeared at a relatively early age. Though Alzheimer and his contemporaries had no inkling of the genetic basis, they thought that early onset was sufficient grounds for a separate disease category. In the late 1970s, a group of American researchers, government officials within NIH and activist caregivers lobbied successfully to drop the distinction. Their goal was to generate awareness and funding for biomedical research into dementia, and they were very savvy about the political ramifications of disease categorization. Since there was no meaningful clinical or pathological distinction between Alzheimer’s and senile dementia, they argued that the two should be considered a single entity – and that entity, crucially, should be called Alzheimer’s. By combining the two categories, they could claim that the condition was a major health problem afflicting millions of people; by calling it Alzheimer’s rather than senile dementia, they could claim it was not aging, but a dread disease worthy of a massive, publicly funded research initiative to understand its cause and discover a means of effective treatment or prevention.

Ironically, among the most important research findings generated by the torrent of funding that was unleashed by the political power of the re-conceptualization of Alzheimer’s was the discovery of the genes associated exclusively with the early onset form – which would logically seem to support a return to the original distinction made by Alzheimer and his contemporaries. But the concept of Alzheimer’s as a single, unified disease distinct from aging remains too powerful to abandon. So at the level of policy advocacy and popular news accounts at least, most researchers continue to talk as though Alzheimer’s disease were quite a clear-cut thing, when the reality is much more complicated.

Researchers in the DIAN project and others described in the article are exploring the distinction between presenile and senile dementia, and hoping that the ability to identify and follow subjects from families with early onset genes to test the use of drugs at much earlier stages in the development of Alzheimer’s will be quick route to a drug that can effectively prevent the disease.

I hope this strategy pays off, and that in a few years we will see more big stories of successful drug trials from the DIAN project – though even then I hope they will be stories that more accurately represent the complexities of medical research on Alzheimer’s. But given the complexity of dementia and the difficulty of identifying efficacious patho-physiological targets for drugs in a disorder with multiple, inter-related causal mechanisms, I think it much more likely that the drugs tested in these trials will be of limited value. In that case, if we read about it in publications like the NYT at all, it will likely be a much smaller item buried in the back pages. Meanwhile reporters like Kolata will be on to writing splashy front page articles about the next imminent breakthrough.

That’s how we roll in the War on Alzheimer’s.