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An Integrative, Ecologic Approach to Alzheimer's Disease

By Ted Schettler It’s no surprise that fear and a profound sense of hopelessness are frequently the response to the diagnosis of Alzheimer’s disease. It almost seems to promise an unalterable decline in much of what makes us human, while basic biologic functions keeping us alive flicker out more slowly. Population-wide trends in memory loss, cognitive decline, and Alzheimer’s disease have generally increased in lock step with an aging population. Many people think not much can be done—that it’s inevitable with increasing life expectancy and growing old. But it’s more complicated.

About ten years ago, three colleagues and I set out to write Environmental Threats to Healthy Aging (see One of our principal goals was to identify environmental connections to the risk of dementia. Because we thought that a multi-disciplinary perspective was essential, we reviewed books and papers from clinical medicine, epidemiology, toxicology, nutrition, agriculture, exercise and stress physiology, sociology, public health, government regulations, and city planning.

Advancing age doesn’t completely explain Alzheimer’s disease. Our health as we grow older is strongly influenced by interactions among diverse aspects of our daily lives—creating, in a sense, an ecology of relationships among cells, tissues, organs, individual people, families, communities, and society—beginning decades before, even in the womb.

Epidemiologic studies show increasingly clear causal connections between cognitive decline and diet, nutrition, activity levels, socioeconomic status, social networks, environmental chemicals, and pollution. Each of these has substantially changed in recent decades as a result of choices we have made individually and collectively—and those changes are not always in a healthy direction. Coincident increases in obesity, diabetes, heart disease, some kinds of cancer, asthma, and autoimmune diseases are not unrelated. They, too, are influenced by interactions among many of the same features of our daily lives. Even more basically, interrelated biologic mechanisms such as chronic inflammation, excessive oxidative stress, insulin resistance, and others are common to many of these complex diseases. This suggests that interventions addressing these aberrant pathways could improve health in various ways.

Mainstream clinical medicine favors a pharmaceutical approach to treating most of these disorders, with surgery when indicated, sometimes supplemented with general advice about diet, exercise, and other behavioral changes. But cognitive impairment, including Alzheimer’s disease, has been stubbornly resistant to drug interventions, despite numerous trials. Nothing yet tested seems to work very well or for very long, and clinical medicine has had little to offer.

Most drug trials have focused on attempts to reduce amyloid plaques and protein tangles in the brain that many scientists think are primarily responsible for Alzheimer’s disease, despite conflicting evidence. And, when those trials fail to arrest progression of symptoms, investigators then wonder if the results might have been different if drug treatment had started earlier—perhaps by targeting plaques or tangles in their earliest stages, even before symptoms appear.

Meanwhile, observational and a few interventional studies show that regular exercise and certain dietary changes can help slow progression of age-related cognitive decline and early Alzheimer’s disease—as well as cardiovascular disease and diabetes. In fact, dietary changes and exercise can actually prevent the onset of diabetes in adults at risk, more effectively than pharmaceuticals. Combinations of diet, exercise, stress reduction, and social support can prevent and in some cases even reverse cardiovascular disease.

Medical publications increasingly call for “prescribing” exercise to improve quality of life and slow or prevent memory loss in older people. Prospective studies find that a Mediterranean or other versions of heart-healthy diets are associated with slower cognitive decline among older people with follow up over a number of years. Some show that lower dietary intake of folic acid, vitamins B-12 and B-6 are associated with more rapid memory loss, suggesting that optimal dietary levels may help preserve cognitive function.

Few studies, however, have looked at these and other relevant variables in combination, and none has combined them in a randomized controlled trial similar to the design of drug trials. Now, a recently published pilot study from UCLA and the Buck Institute for Research on Aging begins to address this increasingly urgent need with extremely promising, preliminary results. (The study is available here

Ten people with memory loss and a diagnosis of Alzheimer’s disease or disabling cognitive impairment of aging participated. A systems approach using multiple interventions was uniquely designed for each person. After three to six months significant improvement in cognition was observed in nine of the ten. In fact, six of the ten participants whose cognitive decline had already substantially interfered with their ability to work were able to return to work or continue without difficulty. No pharmaceutical intervention has come close to having these remarkable results.

The complex therapeutic program involved changes in diet, exercise, optimization of sleep, specific pharmaceuticals and vitamins, and other measures that affect brain chemistry—personalized for each participant after detailed evaluation. Typical dietary interventions included increased fruits and vegetables, meat reduction, and elimination of refined carbohydrates and processed food, with fasts for a minimum of 12 hours between dinner and breakfast. Sleep improved with nighttime melatonin. Choices of vitamins, minerals, and dietary supplements were based on blood test results. Some participants used probiotics. All engaged in regular exercise and efforts at stress reduction. The goal was to optimize the physiologic and metabolic milieu as an integrated network—not just for brain function but for the entire person. Not only did their cognitive function improve but participants were generally healthier after beginning the program.

The idea being tested in this small study is that multiple interventions that collectively shift system conditions—by reducing inflammation, excessive oxidative stress, stress hormones, and autoimmune reactions while improving insulin sensitivity and other measures of metabolic health—will be beneficial to people whose memories were already significantly impaired. The authors concluded that memory loss in people with cognitive impairment and at least the early stages of Alzheimer’s disease may not be only slowed but actually reversed with sustained improvement. But with the small number of participants, they claim no more than anecdotal status for these findings and encourage larger trials.

This small pilot project adds to the growing support for an integrated, systems approach to common complex diseases—intervening where possible to address disease ecology by shifting system conditions toward resilience and restoration, using readily available, often-inexpensive modalities. This approach holds great promise for improving health and preventing disease. In important ways it can be a framework for re-connecting medical care with public environmental health where we know that strategically-chosen, integrated multi-level interventions can maintain or restore the health of communities, populations, and ecosystems.

In Environmental Threats to Healthy Aging we used this ecologic framework to help identify opportunities to improve health in an aging population—beginning with the earliest stages of child development. In The Ecology of Breast Cancer, I used this model to help understand the origins of breast cancer, identify ways to reduce the risk of the disease, and improve outcomes after diagnosis and treatment. (see ) [1]. Growing evidence supports the value of this framework, and the recent pilot study reporting reversal of memory loss adds to it.

Pharmaceuticals obviously play a critically important role in medical practice, but sometimes they are not enough, may be ineffective, can cause dangerous side effects, or be unnecessary. Various drug trials for Alzheimer’s disease prevention and treatment are underway but so far have not produced much of value. They feature single interventions aimed at single targets while cognitive impairment of aging and Alzheimer’s disease, like other common complex disorders, are better thought of as multi-factorial, ecologic, systems problems. We are likely to have more success in preventing and treating them if we address them in that way.

Of course affected individuals and their families urgently need fresh approaches that may help them. But there’s a public health imperative, too. Large-scale cardiovascular disease prevention projects show that strategically-designed community- and societal-level interventions can have population-wide benefits that far exceed those gained by focusing only on individuals at risk. They help to ensure that more people encounter healthier environments throughout their lives

We know enough from existing studies to design dementia prevention and treatment strategies into community institutions and policies more generally. Encouraging and making available and affordable diets with ample fruits and vegetables, omega-3 rich oils, nuts, and fish, with limited refined carbohydrates and red meat consumption, will almost certainly decrease the risk of dementia and Alzheimer’s disease. Adding increased physical activity and safe opportunities for regular exercise will likely reduce risk even more and have the added benefit of lowering the risk of cardiovascular and metabolic disorders, as well as some kinds of cancer. By re-shaping system conditions, these measures and others will benefit people of all ages—not just those at risk of cognitive decline and dementia.

[1] Also available in hard copy through Amazon ( )