September 06, 2015

Paradigm Shift?

The most powerful explanatory model in medicine is the germ theory of disease. It’s simple and it’s elegant: find the offending microbe, kill it, and cure the disease. This approach has led to some of the most dramatic and effective advances in medical history: identifying the leading cause of pneumonia (the pneumococcus bacillus), finding a chemical that kills the bacteria without harming people (penicillin), diagnosing disease (by some combination of physical examination, a chest x-ray, and examination of sputum under the microscope), and treating the patient with antibiotics. The result?  Pneumonia cedes its place as the leading cause of death in older people to heart disease. 

Life has turned out to be a bit more complicated than the germ theory suggests. Expose a group of people to exactly the same dose of a microbe and not all of them will get sick. Of those who do become ill, not everyone is equally sick. Other factors proved to matter, ranging from the vigor of the patient’s immune system to socioeconomic status. And pneumococci were not the only causes of pneumonia: all kinds of other bacteria can cause much the same clinical and radiographic picture, as can a whole host of viruses. Even with our enhanced understanding of the causes of disease and of how and why illness develops in different individuals, we haven’t been able to eradicate pneumonia. Together with influenza, it’s still the seventh leading cause of death in older people.

These caveats mean we’ve had to refine the model, to elaborate on it. But the germ theory of disease still stands as the gold standard for all of medicine. Doctors in areas under than infectious disease seek to find a similar master key that unlocks the diseases of their particular organ system. Cardiologists have focused on atherosclerosis as the unifying feature underlying coronary heart disease; neurologists have seized on amyloid as the basis for Alzheimer’s disease. But the reductionist view of the world seems to break down when it comes to geriatric syndromes, problems such as falls and incontinence that are responsible for so much misery in older people. What seems to explain reality more effectively is a multifactorial understanding. Maybe that’s why even though last week’s JAMA includes two reports of failed efforts to stave off Alzheimer’s disease, one with anti-oxidants taken as nutritional supplements, and one with exercise, the editorial accompanying the articles optimistically maintains that we can make a difference. We just have to eat well and exercise and play mind games.

Now there are a number of possible reasons that the JAMA studies may have been unable to find any benefit of their interventions. The anti-oxidant study was carried out in older patients with macular deterioration, a chronic eye disease. Its main hypothesis was that supplements would stave off progressive visual loss—preventing cognitive impairment was a secondary aim. Conceivably, people with macular degeneration are sufficiently different from the general population that what works, or doesn’t work, for them may not be the same as for everyone else. The trial used pills, not diet rich in anti-oxidants, and there are at least some nutritionists who maintain that the purified version of a chemical won’t work the same way as that chemical in combination with food. The exercise study used moderate intensity physical activity such as walking, it used resistance training, and it used flexibility exercises, which it compared to an educational program. It’s at least possible that other kinds of exercise, or exercise of different intensity or duration, would have been more effective. 

The commentary in JAMA, written by a psychiatrist and an internist from Ontario, Canada, mentions these possibilities. But it also seizes on a different study, one of the few encouraging ones in a field littered with negative results. And that is the FINGER trial, a multifaceted intervention involving diet, exercise, and cognitive training in Finland in people aged 60-77. After two years, there were measurable benefits to the study population as determined by psychological testing. So despite the negative findings of the two studies they are charged with reviewing, the editorialists put on their rose-colored glasses and assert that “it is still likely that lifestyle factors such as diet and physical activity have important roles in the prevention of cognitive decline, dementia, and performance of the activities of daily living.”

There is precedent for a multifactorial intervention working when no single approach succeeded. In her path-breaking work on falls, Mary Tinetti of Yale found that fall rates in community dwelling older people could be significantly decreased if they had an evaluation that focused on physical hazards (throw rugs or poor lighting), on a medication review (getting rid of drugs that cause orthostatic hypotension or confusion), and on strength training. Similarly, Sharon Inouye, now at Harvard, recognized that delirium in the hospital is difficult to prevent, but found the most effective strategy involved a multi-component intervention targeting sleep, mobility, vision, hearing, cognition, and fluid intake. 

So maybe we can make a difference in preventing dementia or delaying its onset or slowing its progression. Maybe the recent meta-analysis that was widely quoted in the media (published in the somewhat obscure Journal of Neurology, Neurosurgery, and Psychiatry) as claiming that “modifiable risk factors” are responsible for 2/3 of the risk of Alzheimer’s disease is onto something. Or maybe it’s all wishful thinking and we should redouble our efforts to look for the magic bullet, the switch that we can turn off amyloid deposition in the brain, stopping dementia before it starts. Or maybe we just have to do something. Eating vegetables, going for walks, and doing crossword puzzles won't hurt. They don't cost a lot of money. They won't jack up the cost of American health care. And in combination, they just might help.

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