Brain-Body Approaches to Reduce Dementia Risk

As our population ages, a key medical challenge facing our society is to develop treatments for age-associated brain deterioration. One of the major obstacles to making progress in this respect is the current practice that restricts the care of sick people to separate medical specialties—i.e., neurologists focus on disorders of the brain and nervous tissues, cardiologists deal with diseases of the heart, and so on.

The same narrow focus has also been widely adopted in research. Unfortunately, such an organ‐centered, blinkered perspective does not take into account the many physiological systems that operate simultaneously and in synchrony in our bodies. The brain is not separate from the body. A case in point is the well-known fact that patients suffering from heart failure have an increased risk to develop age‐associated dementia.

Now, researchers from the German Center for Neurodegenerative Diseases have found a possible cause for the increased risk of dementia in people with heart problems. In their experiments, mice afflicted with heart failure developed cognitive decline. This in turn was linked to increased cellular stress pathways and altered gene activity in neurons of the hippocampus. These pathological changes were ameliorated by the administration of a drug that promotes neuronal cell health. Based on these discoveries, it is not surprising that experts from the German Center for Neurodegenerative Diseases call for interdisciplinary approaches and novel therapeutic avenues to the treatment of neurocognitive disorders.

Among neurocognitive diseases, the most common and most dreaded by older people is Alzheimer’s. Recent estimates indicate that Alzheimer’s disease may rank third, just behind heart disease and cancer, as a cause of death for older people in the U.S. Alzheimer's patients’ brains contain many abnormal clumps (amyloid plaques) and tangled bundles of fibers (neurofibrillary, or tau, tangles). Most therapies designed to treat Alzheimer’s target these plaques, but without much success.

Pharmaceutical companies, understandably, have focused their efforts on brain pathology. In doing so, they have overlooked the fact that the brain is connected to the body by multiple two-way communication systems. Through these channels, a change in any part of the body will affect the brain and vice versa. The brain, as I have said before, does not work on its own.

Researchers from the University College Cork (UCC) have introduced a novel approach to reverse age-related cognitive decline by way of the microbes in the gut. Their studies have demonstrated that by transplanting microbes from young into old animals they could rejuvenate aspects of brain and immune function and improve learning ability and cognitive function. This research opens up possibilities in the future to promote brain health by modulating gut microbiota as a therapeutic target.

And still on microbes: A growing body of research points to a connection between gum disease—a leading cause of tooth loss—and cognitive decline. In addition, tooth loss may reflect life-long socioeconomic disadvantages that are also risk factors for cognitive decline. Senior author Bei Wu, of NYU Rory Meyers College of Nursing, conducted a meta-analysis using longitudinal studies of tooth loss and cognitive impairment. Their analysis involved a total of 34,074 adults of which 4,689 were diagnosed with diminished cognitive function. Moderate-quality evidence suggested tooth loss was independently associated with cognitive impairment and dementia; risk of diminished cognitive function correlated with the number of teeth lost.

New data explore how air pollutants might impact dementia and what reducing them might mean for long-term brain health. Xinhui Wang, Ph.D., assistant professor of research neurology at the University of Southern California, and colleagues looked at a group of older women (aged 74-92) in the U.S. who did not have dementia at the beginning of the study. Participants were followed for five years and detailed cognitive function tests were performed every year to determine whether they developed dementia.

The researchers found that, in general, air quality greatly improved over the 10 years before the study began. During a six years follow-up, cognitive functions tended to decline as women aged, as expected. However, for those living in locations with a greater reduction per 10 percent of the EPA's current standard in traffic-related pollutants, their risk of dementia decreased by 14 to 26 percent. Benefits extended across a variety of cognitive abilities, suggesting a positive impact on multiple underlying brain regions. This was similar to the lower level of risk seen in women two to three years younger.

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A very similar study by Christina Park, of the Department of Epidemiology at the University of Washington, and colleagues examined associations between exposure to air pollutant levels of fine particulate matter, larger particles and nitrogen dioxide and levels of Aβ1-40, one of the major protein components of plaques, in more than 3,000 individuals who were dementia-free at the beginning of the Ginkgo Evaluation of Memory Study. The study evaluated and averaged air pollution levels at participant residential addresses for time periods up to 20 years prior to taking blood tests to measure individuals' beta-amyloid.

People who were in the study longer than eight years showed a strong link between all three air pollutants and Aβ1-40. "Our findings suggest that air pollution may be an important factor in the development of dementia," Park said.

These studies provide new evidence that by improving air quality we may be able to significantly reduce the risk of cognitive decline and dementia. We are also discovering that the microbes in the gut as well as in the mouth affect brain health. Finally, researchers studying mice afflicted with heart failure observed that the mice’s cognitive decline was linked to increased cellular stress pathways and altered gene activity in neurons of the hippocampus. These pathological changes were ameliorated by the administration of a drug that promotes neuronal cell health.

This recent research clearly indicates that only by recognizing the many pathways that connect the brain to the rest of the body are we going to make progress in treating age-related dementia and Alzheimer's.