Brain Health: Today is Almost Tomorrow

by Blake Ebersole

This article was first published in Natural Products Insider Digital Magazine, in 2014

The brain is a fantastically complex organ, and we are still trying to understand how it works. As people live longer, diseases of the brain are becoming a predominant issue for our health care system. For example, Alzheimer’s disease is the sixth leading cause of death in the United States, and the only disease in the top 10 that continues to grow.

One in eight Americans older than 65 years, and 50 percent older than 85 years have Alzheimer’s disease or dementia. Families affected by Alzheimer’s know the toll it takes on caregivers. In 2010, 149 million family caregivers gave 17 billion hours in unpaid care. In 2011, the national cost of Alzheimer’s care was USD $183 billion, and by 2050, it is estimated to be $11 trillion. And these are just statistics for the United States.

Today, we still don’t have good answers to some important consumer questions: How can I know whether I’m at risk, and what can I do now to prevent or prolong the inevitable downward slope of cognitive decline?

Amyloid-beta and tau are the primary culprits responsible for Alzheimer’s disease. Plaques and tangles begin to accumulate many years before noticeable cognitive issues arise, in some cases starting in the teenage years. Unfortunately, by the time we notice we are starting to forget things, it may be too late. But now that we have identified the early markers accumulating while we are healthy, researchers are working to develop ways to stop or slow their progressions.

Diagnostic tools are rapidly emerging to help us detect issues early on, and in the near future, they are expected

to offer greater understanding of how dietary compounds can protect the brain. Key markers for brain health are becoming better defined: a combination of oxidation, inflammation, genetic expression and the resulting downstream elements, such as protein aggregation, all occur increasingly as we age. However, many of these markers, when measured in blood, are not reliable predictors of brain health. And while cerebrospinal fluid is more reflective of what is happening in the brain, getting it is too painful to be practical.

Emerging technologies that use non-invasive imaging of the brain (and retina as an extension of the brain) are thought by many experts to provide avenues for early detection within the next couple of years. The hope is that these technologies will become more affordable and available to the pre-disease public, where they can be used in tandem with long-term nutritional interventions and preventive medicine. Together, diagnostics and nutrition are considered by many to represent the future of healthy brain aging.

Some researchers believe one of the reasons we have not been able to put a dent in Alzheimer’s rates thus far is that we are isolating amyloid and tau protein aggregates as the only cause of Alzheimer’s. The conventional wisdom is changing as single-mechanism amyloid-clearing drugs like monoclonal antibodies fail, and our understanding of the causes of aging increases. Now, we understand that Alzheimer’s is not just about amyloid, but also about neuroinflammation, oxidation, neurotransmitter regulation, as well as glucose and fat metabolism in the brain.

The ideal intervention may be one that can address many or all of these markers in a positive way. Currently, options that fulfill this promise are few and far between. Likewise, new research on compounds with multiple activities, such as docosahexaenoic acid (DHA), curcumin and phospholipids, make them prime targets for research. Like research in other therapeutic areas, combinations of multiple compounds or entities are increasingly being found effective compared to single ones. This is mirrored in the preclinical research, which has indicated overall that most single-entity interventions do not impact all of the key pathways required for an overall benefit.

As we are able to narrow down the functions of the different entities, we are better able to intelligently combine them. Over time, this knowledge gain should allow us to focus and find interventions bearing better results. For example, by adding the neurotransmitter benefits of herbs such as Bacopa monnieri or Chinese club moss, to the anti-amyloid, anti-tau and anti-inflammatory effects of curcumin and the plural benefits of DHA, we have a combination of entities known to work on different levels and pathways. It is not unrealistic to think our work can reveal a winning combination offering effects that no single chemical entity or herb could match.

Mechanistically, antioxidants that target different segments of pathways can be combined together to form a likely synergistic effect. For example, fruit and berry polyphenols from blueberries and pomegranates are thought to impact signal transduction pathways, which include p53, p38 MAPK and JNK mediators—regulators of oxidative stress levels and ultimately the formation of amyloid plaques. Antioxidants that have dual benefits on glucose regulation, such as cinnamon, have also improved cognitive function in preclinical work.

The multiple action effect extends to other critical brain pathways as well. DHA acts as an anti-inflammatory by competing with arachidonic acid, reducing its availability for COX2 and lipoxygenase enzymes. Combined with curcumin, which possesses anti-inflammatory activity at other points related to the NF-kB and COX2 pathways, a synergistic effect on cognitive function will likely be observed in humans like it previously has in animals.

The brain is not simple, and neither are any answers. Early risk detection and a combination of interventions are the focus of today’s research by thousands of scientists and physicians who are likely to bear fruit in the near future. We are constantly growing closer to fulfilling the promise of today to impact the fastest growing health issue of our time.