Alzheimer’s: A Biological Model of Prevention – Finally! (Part 2)

Dr. James Greenblatt
The Alzheimer’s Association states that “the greatest known risk factor for Alzheimer’s is increasing age”, leading many to presume that a diagnosis is inescapable. Sadly, it is not only the uninformed expressing this cynicism; even highly-educated medical professionals have slumped in defeat. Of the leading causes of death in America, Alzheimer’s Disease stands alone as the only malady largely unaffected by pharmaceutical interventions and continues to confound researchers vigorously seeking a cure. Despite decades of earnest effort, medical science seems no closer to clear answers for treating, much less preventing this cruel disease. At the current trajectory, chances are climbing that you or someone you know will face Alzheimer’s Disease.

Why We Need an Integrative Approach to Early Diagnosis and Prevention

In our previous article, we detailed the ongoing waste and failures associated with pharmaceutical research into Alzheimer’s Disease treatments.  Billions of dollars, dashed hopes, dear relationships, and precious lives are the unintentional casualties of bureaucracy, ignorance, and greed in Big Pharma. While intentions may be sincere, stubborn adherence to narrow, reductionist theories and methods have resulted in diagnoses at late stages of the disease and treatment applied when brain tissue loss is profound, and most damage is irreversible. We pointed to evidence that brain damage related to Alzheimer’s begins decades before obvious symptoms manifest, and we explained why the focus must shift to early prevention by recognizing modifiable risk factors and defining objective diagnostic markers that can be detected early in the disease process. Science supports an integrative perspective to neurological disease wherein nutritional components play critical roles in the whole human organism, including the brain.

Is Nutrition the Key?

At this point, most physicians recognize the integral relationship between nutrition and overall health. Even without knowing or understanding the specifics, medical practitioners generally agree that well-rounded, nutritious diets and active lifestyle behaviors foster the best environment for disease prevention and longevity. Unfortunately, generic “healthy diet” mantras have done little to demonstrate the powerful and convincing effect that minute components of the human diet have on normal physical and mental function. As a matter of fact, even the drinking water we take for granted contributes to our health beyond hydration. Trace minerals carried in groundwater and that permeate the soil in which our food is grown are absolutely essential to many of the body’s biological processes, and it turns out that our exposure to these elements can vary widely by location, water source, and what we eat.

The Mighty Micro Mineral – Lithium

Lithium is recognized as one of the primordial elements at the foundation of our universe and the planet we call home. Most associate the diminutive metal with the batteries in our phones, electronic gadgets, and most recently, our cars. In fact, battery production demands approximately 75% of the lithium collected from the Earth around the world. Yet while modern society has benefited greatly from the discovery of lithium in terms of technology, this remarkable mineral holds even greater potential for serving humanity. Relatively unrecognized in medicine until the 1940s, early mental health pioneers realized that lithium possesses an amazing influence on brain function, initially revealed by its powerful effects to stabilize moods in psychiatric patients. In fact, 7-Up soda pop began as a lithiated elixir promoted for its ability to lift the spirits, and lithium hot springs became popular tourist attractions in the mid-20th century. Doctors enthusiastically prescribed lithium for bipolar disorder, then called manic depression, which had the unfortunate consequence of obscuring lithium’s benefits with a negative stigma associated with mental illness and concerns over its toxicity at high doses.

The link between lithium and mental health and mood has been powerfully demonstrated through observational data collected over the last 50 years. Rates of suicide, violence, and dementia have all been studied in relation to drinking water concentrations of lithium, consistently reporting that an opposing relationship exists between lithium intake and aberrant behavior. In a 2014 systematic review, Mauer, et al., revealed significant correlations between these factors in 9 out of 11 epidemiological studies comprising millions of individuals from across America and Europe. Importantly, these data also establish that the high doses used for psychiatric patients are unnecessary to deliver lithium’s mood stabilizing benefits.

While observational health data are often dismissed by medical researchers, gold-standard randomized and controlled trials (RCTs) have unanimously confirmed lithium’s role in neurological health. Remarkably, lithium’s multi-factorial biological effects were not well-defined until recent decades, but with blazing advances in scientific medicine, research has illuminated the numerous pathways through which lithium protects and regenerates neurons. Not only has lithium demonstrated its ability to prevent further destruction of brain tissue caused by Alzheimer’s pathology, it is capable of restoring grey matter volume by stimulating the growth of new brain cells and enhancing their connectivity. Long-term RCTs in high-risk patients indicate not only cognitive improvements at least as effective as FDA-approved pharmaceuticals, but measurable decreases in the accumulation of tau protein, one of the familiar markers of Alzheimer’s Disease status.

Brain-derived neurotrophic factor (BDNF) and Neurotrophin-3 (NT-3) are two notable signaling molecules whose poor status has been linked to Alzheimer’s Disease.

Lithium is involved along the entire life cycle of neurons. When adequate amounts are present, lithium counteracts multiple opportunities for nerve degeneration and brain tissue loss. Like other body cells, the birth, differentiation, and maturation of neurons require specific growth factors to instruct them in what to do and how to do it. Brain-derived neurotrophic factor (BDNF) and Neurotrophin-3 (NT-3) are two notable signaling molecules whose poor status has been linked to Alzheimer’s Disease. They direct and maintain cognition and memory by enhancing the strength and integrity of neural connections. Moreover, as brain cells incur injury caused by the detrimental effects of internal and external stress, growth factors support resilience and repair. Lithium is an integral component in the synthesis of both BDNF and NT-3, and it amplifies the sensitivity of neural receptors to recognize and receive the signals triggered by these molecules.

Lithium: The Vigilant Vanguard of the Brain

A second important action of lithium in thwarting the development and progression of Alzheimer’s Disease involves the powerful enzyme Glycogen Synthase Kinase 3 (GSK-3). Normal activity of GSK-3 includes appropriate coordination of the protein synthesis involved in neural growth and development. In Alzheimer’s Disease, the formation of plaques and tangles occurs as the overactivity of GSK-3 increases the rate that beta-amyloid and tau protein fragments accumulate, creating physical barriers to the signals that are key to neural function and survival. Eventually, excessive buildup in certain areas of the brain interfere with the process of memory formation.

The role of GSK-3 in Alzheimer’s Disease is so well-established that it is a primary target for pharmaceutical researchers. Incidentally, lithium is one of the most potent GSK-3 inhibitors, effectively moderating its activity and facilitating cellular processes that eliminate waste products such as beta-amyloid and tau fragments. Furthermore, in addition to promoting cellular waste removal by regulating GSK-3, lithium also influences the genetic expression of chemicals that control cell death. By balancing the concentration of these molecules, lithium optimizes neural life cycles and prevents impediments to communication in support of healthy brain tissue.

Where Do Neurotransmitters Come In?

The brain is a carefully-controlled environment involving precise amounts and ratios of numerous chemicals that largely govern our mood, behavior, and response to stressors by activating and inactivating neural signals. Imbalances resulting from nutritional inadequacy, excess or deficiencies in hormones and neurotransmitters, inflammation, and disease can disrupt normal stimulation of the cellular responses with a multitude of downstream effects. Glutamate is often considered the most important neurotransmitter for its dominant role in allowing neurons to communicate. Yet while strong neural communication is desirable, too much glutamate exhausts neurons and accelerates the production of damaging free radicals that hasten cell death. As it turns out, Alzheimer’s patients often have high levels of glutamate in brain tissue. Overexcitation by glutamate contributes to an environment of heightened oxidative stress that is toxic to delicate neurons, accelerating the loss of brain tissue needed for high-level cognition and learning.

Once again, lithium proves its worth by protecting neurons from potential assault by excessive glutamate. Lithium prevents the damaging effects of overexcitation by reining in the uptake of glutamate by cells. In fact, lithium directly attaches to glutamate receptors on neurons, successfully blocking its unnecessary uptake. Other consequences of heightened inflammation in the brain also benefit from lithium’s utility. Cell studies indicate that lithium dampens the activity of chemicals that promote the inflammatory response; conversely, lithium actually increases the level of anti-inflammatory substances by influencing the metabolism of fatty acids that are required for their synthesis. New data have also shown that lithium encourages learning and memory formation even at the genetic scale by facilitating the expression of related genes.

Validated studies and clinical practice both corroborate the conclusion that early and consistent use of lithium in low doses, matching levels naturally present in some foods and groundwater, prevents cognitive decline and even improves cognitive performance in Alzheimer’s patients.

Amazingly, we have only scratched the surface of lithium’s multifunctional involvement in the brain. Fortunately, even a brief look at the scientific rationale and research data provides plenty of evidence to endorse the use of lithium for treating dementia and Alzheimer’s Disease. Validated studies and clinical practice both corroborate the conclusion that early and consistent use of lithium in low doses, matching levels naturally present in some foods and groundwater, prevents cognitive decline and even improves cognitive performance in Alzheimer’s patients. Like many essential dietary nutrients, individual access and intake of lithium varies considerably, suggesting that supplemental sources should be a consideration for anyone concerned about boosting brain health.Lithium Is Key for Alzheimer’s Prevention

Inspired by overwhelming support for this miracle mineral that has existed for decades, I have safely used lithium in my own clinical psychiatric practice for over 30 years in a wide range of doses with no adverse effects. Based on what we have learned of lithium’s impact on the brain at even trace levels in the general population and its direct functionality in targeting markers of Alzheimer’s Disease, I advocate that all clinicians should include lithium as a fundamental component of their Alzheimer’s treatment model. As objective biological markers of disease come to light, early detection of risk reveals a critical window for reinforcing the brain’s own capacity to function and heal with nutrient-based interventions that prevent and arrest deterioration. Alzheimer’s, dementia, and cognitive decline are not inevitable; prevention is possible.

We have just learned about the potential of a lesser-known nutrient for protecting and restoring the brain. In our final installment in this series, we will explore the roles that much more familiar B-vitamins play in the features of Alzheimer’s Disease and why despite their ubiquity in the human diet, some individuals may still not receive adequate amounts. At the same time, Vitamin B-12 and Folate are integral in the body’s control of homocysteine levels, a prominent marker of inflammation and a modifiable risk factor for Alzheimer’s.

James M. Greenblatt, MD

Dr. James M. Greenblatt is chief medical officer and vice president of medical services at Walden. He provides medical management, leadership and oversight of Walden’s eating disorder and psychiatric programs in Massachusetts and Connecticut. Dr. Greenblatt is board-certified in child and adult psychiatry.

He received his medical degree and completed his adult psychiatry residency at George Washington University in Washington, D.C. He completed a fellowship in child and adolescent psychiatry at Johns Hopkins Medical School. In addition, Dr. Greenblatt is a clinical faculty member in the psychiatry department at Tufts Medical School as well as the Geisel School of Medicine at Dartmouth College in New Hampshire.

He lectures extensively throughout the United States and Canada on integrative therapies for mental health. Dr. Greenblatt is the author of six books including one textbook and books on depression, eating disorders and ADHD. His latest book is on Integrative Medicine for Alzheimer’s, exploring the research on nutritional lithium. Dr. Greenblatt is the founder of Psychiatry Redefined, a healthcare education training program for integrative psychiatry.

He can be reached at: Walden Behavioral Care, 9 Hope Avenue, Suite 500, Waltham, Massachusetts, 02453; (781) 647-2901. For more information on Dr. Greenblatt please visit www.jamesgreenblattmd.com.

Related Resources

References

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