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.

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.

Marginalizing the Psychiatric in Dementia Treatment

I recently came across an interesting  post written by Allen Power that raised the question of whether dementia is better thought of as a psychiatric or a neurological problem. Power argues that dementia is increasingly viewed as a psychiatric illness, with symptoms of distress and analogous to mental illness. Psychiatrists are brought in as “expert pill jockeys” to control behavioral problems with antipsychotic drugs. Power thinks this approach is wrong:

Dementia is not a psychiatric illness. It is a change in one’s experience of their surroundings and how they process information, based on structural neurologic changes. It is as much a psychiatric illness as would be a stroke. And people’s interpretations of the world around them may seem confused to us, but they are nothing like the symptoms of an organized psychosis.”

According to Power, the tendency to psychiatrize dementia leads us to overlook non-pharmacological interventions, which he argues have been shown to be the safest, most efficacious and most enduring ways to manage the behavioral problems associated with dementia. He concludes that it would be much better to view dementia as “a neurological disability with secondary psychological challenges,” and that psychiatry’s role should not be simply prescribing pills to control behavior  but helping with the broader psychosocial challenges that dementia entails.

I follow and admire Power’s work as a geriatrician and one of the leading critics of the dominant drug-based approach to treating dementia. But I think that there is an important historical issue that structures the problem he raises. Without understanding and explicitly confronting this issue, efforts to change the dominant approach are not likely to have much traction.

In arguing that that dementia is a neurological rather than a psychiatric condition, Power follows the dominant modern medical approach to dementia in placing cognitive symptoms, attributed to “structural neurological changes,” at the center and relegating emotional and psychological changes  to the periphery — mere epiphenomenal reactions to the primary cognitive damage. This is somewhat arbitrary since, for patients and family members at least, the emotional and psychological symptoms are often as prominent and disturbing as the cognitive ones. But it follows a deep historical tendency in modern medicine to view psychiatric symptoms and mental disorders as less legitimate because they are not clearly attributable to pathological structures in the body.

This bias emerged clearly, in the United States at least, in the late nineteenth century as the development of germ theory and microbiology created a more scientific approach to medicine. Acute, infectious diseases which could be attributed to a particular pathological agent and effectively treated with a specific drug increasingly became the paradigm of modern medicine, especially as antibiotics emerged in the twentieth century. Chronic illnesses, especially psychiatric ones, seemed less legitimate, and the medical specialties that focused on them lost prestige in the era of “the magic bullet.”

Psychiatry was further marginalized during this period by its overlap with the other medical specialty claiming expertise over the brain and mental phenomena, neurology. Though the distinction between the psychiatric and the neurological has perhaps always been somewhat arbitrary, neurologists during this period, especially in the United States,  were generally successful in associating their specialty with cutting edge science while psychiatrists struggled under the stigma of their historic association with asylums and chronic, incurable madness.

The history of psychiatry since the late-nineteenth century can be interpreted as trying to compensate for this marginalization. Leading psychiatrists of the period, especially in Germany, sought to put their field on a scientific basis commensurate with the advance of medicine as a whole by showing that mental illness could be linked to specific brain pathologies. When this approach failed, Emil Kraepelin turned toward a quantitative assessment of clinical symptoms as a more scientific means of defining psychiatric disorders. Freud and his followers meanwhile sought to provide a scientific basis for psychiatry by turning away from the intractable problem of psychosis and developing a unified, expansive theoretical framework to explain and treat the mind. In recent decades, armed with new insights into genetics and neurochemistry and new technologies for exploring the brain, psychiatry has returned to the dream of anchoring psychiatric symptoms and disorders firmly in the brain. But apparent progress in understanding the brain only perpetuates the marginalization of psychopathology that cannot be clearly associated with something specific that is wrong with the brain. Psychiatric symptoms and clinical disorders continue to have an ambiguous status unless they are clearly associated with specific pathological processes in the brain.

While Power provides a strong critique of psychiatry’s reductionist approach to managing the “problem behaviors” of dementia with antipsychotic drugs, in this post at least he ironically appears to endorse much of the mainstream medical concept of dementia that historically produced such reductionism. So long as a reductionist model of dementia as simply a brain disorder retains a near exclusive grip in medicine, so long as pathology is considered more real than psychiatric symptoms, let alone social and cultural factors, medical practitioners of all kinds are much more likely to respond with a prescription pad than with the agenda for  social and cultural change that Power calls for.