facebook pixel Skip to main content
Alzheimer's & DementiaInfections & Inflammation

Alzheimer’s: A Biological Model of Prevention – Finally!

By 07/01/2019August 29th, 2021No Comments26 min read

Alzheimer’s: A Biological Model of Prevention – Finally! (Part 1)

Dr. James Greenblatt
News media are replete with alarming statistics about the current and future incidence of Alzheimer’s Disease. A recent CBS headline announced the latest data from the Centers for Disease Control predicting already troubling rates will “soar” in coming decades, with the number of cases potentially doubling by 2060 to almost 14 million Americans. With its impact going significantly beyond a personal toll to create devastating burdens on the family and the economy, Alzheimer’s Disease has become a disturbing public health phenomenon. What is most frightening is that despite billions of dollars spent annually on Alzheimer’s research, we don’t seem to be any closer to pinpointing a cause or finding a cure.

Drug Development Hits a Wall

In the last few years, many major drug companies have ceased conducting clinical trials for Alzheimer’s Disease. Just this year, dramatic articles have announced that Johnson & Johnson, Eli Lilly/AstraZeneca, and most recently Pfizer have abruptly discontinued trials, halted research funding, and laid off researchers due to embarrassing or even dangerous outcomes. From thousands of failed trials, the Food and Drug Administration has approved a total of 5 drugs, only 3 of which arrived in the last 14 years. Sadly, none of these approved prescriptions has shown long-term effectiveness. As discouraging accounts continue to pour in, fresh perspectives and optimism are critical.

The Value of Early Detection

Experts agree that early detection is the primary goal, yet physicians rarely discuss preventive measures beyond generic diet and exercise mantras. Clinicians remain slow to translate into practice mounting scientific research identifying the risk factors and objective diagnostic markers that are essential for developing more effective prevention and treatment strategies. Many lack full understanding of the disease process and thus fail to explore unconventional options, offering little hope to patients and their families. Furthermore, all currently approved prescription drugs for Alzheimer’s were developed using incomplete models of disease, exemplifying the futile efforts of pharmaceutical research.

Many have described Alzheimer’s Disease as an inevitable effect of aging, but proof is mounting that its roots begin decades before obvious symptoms manifest. Neuroscientific discoveries have given us unprecedented knowledge about the how, when, what, and where of disease in the brain, and technological progress is allowing us to distinguish structural and functional impairments in their earliest stages of development. Consensus is gaining that, discovered earlier, brain damage leading to Alzheimer’s Disease may be both treatable and preventable. Robust research indicates that specific risk factors, genetic errors of metabolism, and biochemical imbalances are identifiable in the initiation of Alzheimer’s Disease that suggest precise, achievable treatment models based on individual variations.

Modifiable Factors Potentially Involved in Alzheimer’s Risk

The neurocognitive symptoms of dementia and Alzheimer’s Disease stem from barriers to communication between neurons primarily attributed to plaques and tangles, essentially scar tissue that obstruct, isolate, and kill brain cells. Loss of connection and death occurs when neurons lack access to sufficient nutrients for energy and protection and incur cumulative insults from inflammatory activity. The significant metabolic turnover in the brain requires a substantial variety of nutrients including B-vitamins, mineral cofactors, and antioxidants that neural cells require for optimal functioning, communication, and defense against inflammation. Like the rest of the body, the brain obtains the majority of these substances from the food we eat, and its integrity is determined by the composition and quality of our diets.

While the brain’s significant energy demands are well known, it seems that most physicians overlook the fact that its nutrient needs are also elevated. Despite a bounty of evidence indicating that nutrition is just as important for the brain as it is for the body, conventional medicine stubbornly refuses to abandon reactionary models that attempt to treat nutritional deficiency symptoms with pharmaceutical drugs. The human diet provides not just fuel for cells, but the vitamins, minerals, antioxidants, and other compounds that keep the brain’s machinery running smoothly. Accurate control and response by neurons require careful concentrations and ratios of these invisible means of communication that produce thought, memory, mood, and movement. Given the brain’s profound role in human health and well-being, it is astonishing that more attention is not given to nourishing and protecting our most vital organ.

Pharmaceutical drugs fail patients because, at best, they provide interference within dysfunctional processes and slow the rate of deterioration; they do nothing to promote recovery or provide hope. Since we now know that neural dysfunction and loss ultimately leading to Alzheimer’s Disease originate decades before significant symptoms bring concern. By the time patients display notable problems with cognition and memory, it is likely that much of the damage to the brain is irreversible. In order to repair and strengthen the brain, we must provide what neurons need to revive and restore connections. By targeting specific cellular nutrient requirements, we target neural degeneration at its roots and facilitate the brain’s innate healing capabilities by correcting interrupted processes and providing the tools it needs to rebuild.

Don’t Wait Until It’s Too Late

The impacts of aging on the brain begin years before we want to think about growing old, but just like saving for retirement, we can’t afford to wait until we run out of money. It is similarly irresponsible for doctors to wait until obvious symptoms of dementia and cognitive decline appear before addressing brain health. With the growing epidemic of Alzheimer’s Disease, new perspectives and novel treatments based on advancing science are the clear path forward for preventing this devastating disease from robbing families and society of the love, wisdom, and productivity that come with age.

The only cure for Alzheimer’s Disease is prevention.

Valid and useful models for prevention are clearly outlined in the scientific literature that do not involve prescribing pharmaceuticals at end-stage dementia. Nutritional interventions have both profound public health implications and the potential to stop escalating rates of Alzheimer’s Disease. In this series of articles, I will begin to explore the science and research describing nutritional Lithium, Vitamin B12, and Folate for both treatment and prevention of Alzheimer’s Disease. Next time we will take a closer look at Lithium, an unassuming mineral that holds astounding implications for preventing and treating Alzheimer’s Disease. Supplied primarily from tap water, this essential nutrient has been shown in randomized clinical trials to be at least as effective as currently-approved drugs for inhibiting cognitive decline and dementia in Alzheimer’s patients.

ZRT Laboratory offers a simple to collect, non-invasive way to asses lithium levels in dried urine. The urine lithium test allows for assessment of dietary intake or lithium supplementation.

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

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.

Alzheimer’s: A Biological Model of Prevention – Finally! (Part 3)

The Silent Flame

Theories abound on the origins of most major diseases, and many share one factor in common: inflammation. The biological consequences of inflammation are at the root of virtually every human malady from the common cold to cancer, allergies to arthritis, and headaches to heart disease. Yet inflammation is a natural, self-protective response of the body with the best of intentions. Inflammatory chemicals rush to the scene of injury or infection, and safeguards rein in the potent reaction before its benefits are outweighed by potential harm. When these defenses are compromised, immune responses lead to chronic inflammation, the root of major diseases.

Inflammation and the Brain

Just as the cells that make up our organs and tissues can be damaged by incessant inflammation, so too the cells that construct our brain experience its impact. Accelerated activity in the brain renders neurons even more vulnerable to inflammatory injury. Networks of neurons shape the nature and stability of our thoughts, moods, and behaviors; physical injury to these neurons has far greater implications for our health and well-being. In addition to neurological disorders such as Parkinson’s and Multiple Sclerosis and mental health conditions including depression and schizophrenia, Alzheimer’s Disease is one of several brain abnormalities highly associated with inflammation.

As we remarked in the last article in this series, the hallmark features of Alzheimer’s Disease—often called plaques and tangles—are accumulations of malformed protein fragments resulting from aberrant metabolic processes in the brain. Overactive enzymes, inefficient cellular waste removal, and biochemical imbalances caused by nutritional insufficiency and stress represent several research-supported mechanisms that underly the progressive neurodegeneration characterizing Alzheimer’s. In each of these models, inflammatory responses to injury play a major role in initiating and exacerbating the damage that kills neurons and severs the communication required for us to think, remember, and act. Thus, inflammatory status serves as a primary risk factor and measurable biomarker of short and long-term brain health.

A Major Modifiable Risk Factor – Homocysteine

Predictably, high homocysteine is one of the most striking predictors of dementia and Alzheimer’s Disease, and one that is easily measured with a blood test.

Though not initially designed to survey neurological outcomes, the multi-generational Framingham heart study, ongoing since 1946, published population data that revealed highly significant long-term correlations between blood levels of homocysteine, cognitive decline, and eventual Alzheimer’s Disease. Participants with homocysteine levels above normal doubled their chance of being diagnosed, with risk increasing by 40% at each incremental level. Remarkably, these associations were found several years before an official diagnosis and held independent of any other cardiovascular risk factors. A plethora of incontrovertible evidence has added to the Framingham report, leading researchers to formulate the “homocysteine hypothesis” as a leading theory to explain Alzheimer’s Disease. The statement endorsed by an international committee of experts reads “We conclude that elevated plasma total homocysteine is a modifiable risk factor for the development of cognitive decline, dementia, and Alzheimer’s disease in older persons.”Inflammatory status is routinely measured by medical practitioners to assess overall health and risk for chronic disease. Homocysteine levels in the blood are often assessed as sensitive measures of inflammation for screening of cardiovascular disease, as elevations are highly associated with heart attack and stroke. An intermediate amino acid derived from methionine, homocysteine holds a pivotal spot in the methylation cycle, a critical biological process that drives protein synthesis. Importantly, efficient operation of this cycle relies heavily upon Folate, Vitamin B-12, and Vitamin B-6. Elevated homocysteine is a beneficial indicator of deficiencies in these dietary essentials. The most severe symptoms of insufficient Folate, B-12, and B-6 are neurological in nature, and can produce debilitating motor and cognitive issues with potentially permanent consequences. Predictably, high homocysteine is one of the most striking predictors of dementia and Alzheimer’s Disease, and one that is easily measured with a blood test.

The theoretical basis behind the “homocysteine hypothesis” of Alzheimer’s suggests a similarity in the mechanisms tying homocysteine with cardiovascular disease: excessive inflammation as a result of oxidative stress. As chronically high homocysteine triggers an incessant immune response, brain cells are overstimulated to exhaustion and inundated with toxic levels of inflammatory chemicals causing injury and death. The consortium behind the “homocysteine hypothesis” also added greater beta-amyloid production and phosphorylation of tau, processes that encourage the growth and buildup of plaques and tangles. Synthesis of observational and laboratory data from men and women in middle age substantiates the striking relationship between this simple blood marker and progressive memory loss, cognitive decline, dementia, and Alzheimer’s Disease.

Bs for the Brain

With the recognition of such a strong predictor of neuroinflammation and risk for Alzheimer’s Disease, early detection and arrest of brain deterioration appears straightforward. Although high homocysteine was deemed a “modifiable risk factor”, ample intake of Folate, Vitamin B-12, and B-6 from food is often not a reliable gauge. The concept of biochemical individuality, a central tenet of integrative psychiatry, comes strongly into play. Inherent genetic variations in enzymes involved in the methylation cycle are particularly influential in determining B-vitamin needs, which can differ significantly from USDA recommendations and between individuals.

Without adequate Folate and B-12 to sustain protein methylation in the brain, repair and regeneration of neurons is impaired.

Fortunately, at-risk individuals with and without genetic influences driving B-vitamin status can manipulate homocysteine with specific supplemental forms of Folate, Vitamin B-12, and Vitamin B-6 and adequately protect the brain from neurodegenerative disease. Patients with MTHFR variants respond remarkably well to L-methylfolate, the activated form of Folate that is highly bioavailable to the body and brain, or to 5-methyltetrahydrofolate, which bypasses the MTHFR impediment. Low B-12 responds most quickly and effectively to intravenous or sublingual delivery as either hydroxycobalamin or methylcobalamin. For individuals with a CBS gene mutation, Vitamin B-6 supplements in the bioactive form Pyridoxal-5-Phosphate (P5P or PLP) can kickstart the conversion of homocysteine and prevent its buildup.One of the most familiar and common classes of gene variants occurs in Methylene Tetrahydrofolate Reductase (MTHFR), a critical enzyme driving the metabolism of Folate which also requires Vitamin B-12 to function properly. MTHFR defects limit the activation of Folate to a form that can cross the blood-brain barrier.  Furthermore, disruptions in the methylation process allow homocysteine levels to build up, triggering its detrimental effects on delicate neurons. Without adequate Folate and B-12 to sustain protein methylation in the brain, repair and regeneration of neurons is impaired. Vitamin B-6 is required to neutralize homocysteine by converting it to the amino acid cysteine, an important factor in protein synthesis and detoxification. Individuals with defects in the Cystathionine-β-synthase (CBS) enzyme do not adequately use Vitamin B-6, leading to poor recycling of homocysteine.

Even healthy individuals who supplement with B-vitamins show improved measures of cognition that typically decline with age as well as superior integrity and maintenance of grey matter volume. In addition to showing a direct relationship to homocysteine levels, multiple research studies supply data showing an inverse relationship between B-vitamin status and cognitive decline, dementia, and Alzheimer’s Disease. Consistently, individuals with greater intakes of Folate, Vitamin B-12, and Vitamin B-6 have less brain atrophy and better neurological function over time. Beyond the methylation cycle, B-vitamins are key factors for the synthesis of red blood cells and maintenance of neurological processes throughout the body. Adequate B-vitamin intake from well-rounded diets and high-quality supplements is recommended for optimal health regardless of age or health status.

New Hope is Here

The most effective and unfailing treatment strategies are founded upon knowledge and understanding of the key biological processes involved and what is missing, out of balance, or not functioning correctly. At the same time, the answers to these questions should be reliably measured, precisely targeted, and easily monitored.  Homocysteine levels therefore represent a clear marker for early detection, prevention, and treatment of Alzheimer’s Disease, and B-vitamins offer a straightforward, safe, and effective solution for eliminating this substantial risk factor. With readily accessible genetic testing methods, we can even address the “unmodifiable” risk associated with poor B-vitamin metabolism in some patients, providing Folate and Vitamins B-6 and B-12 in ready-to-go forms that enable normal turnover of homocysteine. By providing ample supplies of easily recognizable, naturally present nutrients, cells can withstand the pressures of normal wear-and-tear and are more robustly equipped to combat oxidative stress and inflammation.

We don’t have to look far to sense the pessimism and loss of hope within the medical community as headlines stack up announcing another failed pharmaceutical drug trial in the search for an Alzheimer’s cure. Time ticks on as new diagnoses are charted by the seconds. With despair threatening Alzheimer’s patients and their loved ones, there is an urgent need for fresh news. The big business of conventional medicine ignores any non-lucrative treatment, yet billions are funneled into clinical trials doomed to fail. But wasted money is far from the greatest loss to society from Alzheimer’s; we are losing our parents, grandparents, and mentors far too early. And the cost of elderly care for Alzheimer’s patients is staggering.

After years of studying and practicing integrative psychiatry and following evolving research efforts, my perspective remains grounded in biological models of disease that arise from nutritional and genetic imbalances. Scientific evidence continues to deliver unmistakable confirmation that our diets, environments, and lifestyles have profound roles in determining our physical and mental health, and unseen consequences begin years before disease symptoms begin. This article series gives only a brief glimpse into the biochemical underpinnings of Alzheimer’s disease, but even a cursory glance supplies abundant pathways for prevention and treatment. We have the responsibility to use what we know, and we are privileged with unprecedented tools at our disposal. The future of successful Alzheimer’s treatment is now. As the truth about early detection and measurable risk unfolds and expands, we can reverse the prevailing cynicism and doubt and establish a new paradigm of triumph over this ruthless foe.

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 Therapies for Alzheimer’s disease, 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.

References

  1. Welsh A. (2018). Number of Americans with Alzheimer’s expected to soar in coming decades. CBS News. https://www.cbsnews.com/news/number-of-americans-with-alzheimers-dementias-expected-to-double-by-2060/?ftag=CNM-00-10aac3a. Accessed 09/22/18.
  2. Alzheimer’s Research Impact. (2018). Fiscal Year 2019 Alzheimer’s Research Funding Fact Sheet. http://act.alz.org/site/DocServer/2015_Appropriations_Fact_Sheet__FY16_.pdf?docID=3641. Accessed 09/22/18.
  3. Shurkin J. (2018). Alzheimer’s Drug Trials Keep Failing — It May Be Because We Don’t Understand the Disease. Inside Science. https://www.insidescience.org/news/Alzheimer%27s-Drug-Trials-Keep-Failing. Accessed 09/29/18.
  4. Matsunaga S. (2015). Lithium as a Treatment for Alzheimer’s Disease: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 48(2):403-10.
  5. Alzheimer’s Association. (2018). What is Alzheimer’s – Risk Factors. Alzheimer’s Association website. https://www.alz.org/alzheimers-dementia/what-is-alzheimers/risk-factors. Accessed October 6, 2018.
  6. Forlenza, O.V., et al. (2011). Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomized controlled trial. British Journal of Psychiatry 198:351-365.
  7. Greenblatt JM. (2018). Integrative Medicine for Alzheimer’s.
  8. Greenblatt, JD. (2018). New Hope for Alzheimer’s Disease: Nutritional Lithium as the Foundation for Prevention Part 1. Townsend Letter. October 2018.
  9. Hamilton, A., Zamponi, G.W., Ferguson, S.G. (2015). Glutamate receptors function as scaffolds for the regulation of beta-amyloid and cellular prion protein signaling complexes. Molecular Brain, 8, 18.
  10. Hooper, C., Killick, R., Loveston, S. (2008). The GSK3 hypothesis of Alzheimer’s disease. Journal of Neurochemistry, 104(6), 1433.
  11. Kessing, L. V., Gerds, T. A., Knudsen, N. N., Jørgensen, L. F., Kristiansen, S. M., Voutchkova, D., … & Ersbøll, A. K. (2017). Association of lithium in drinking water with the incidence of dementia. JAMA psychiatry, 74(10), 1005-1010.
  12. Matsunaga, S., Kishi, T., Annas, P., Basun, H., Hampel, H., Iwata, N. Lithium as a treatment for Alzheimer’s disease: A systematic review and meta-analysis. Journal of Alzheimer’s Disease,48(2), 403-410.
  13. Mauer, S., Vergne, D., & Ghaemi, S. N. (2014). Standard and trace-dose lithium: a systematic review of dementia prevention and other behavioral benefits. Australian & New Zealand Journal of Psychiatry, 48(9), 809-818.
  14. Moore, A.H., O’Banion, M. (2002). Neuroinflammation and anti-inflammatory therapy for Alzheimer’s disease. Advanced Drug Delivery Reviews, 54 (12), 1627-1656.
  15. Moore, G. J., Bebchuk, J. M., Wilds, I. B., Chen, G., & Menji, H. K. (2000). Lithium-induced increase in human brain grey matter. The Lancet, 356(9237), 1241-1242.
  16. Nunes, M.A., Viel, T.A, Buck, H.S. (2013). Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer’s disease. Current Alzheimer Research, 10(1), 104-107.
  17. Purse, M. (2018). Lithium: The First Mood Stabilizer. Very Well Mind website. https://www.verywellmind.com/lithium-the-first-mood-stabilizer-p3-380277. Accessed October 7, 2018.
  18. Sarkar, S., Ravikumar, B., Floto, R. A., & Rubinsztein, D. C. (2009). Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies. Cell death and differentiation, 16(1), 46.
  19. Alzheimer’s Association. (2018). What is Alzheimer’s – Risk Factors. Alzheimer’s Association website. https://www.alz.org/alzheimers-dementia/what-is-alzheimers/risk-factors. Accessed October 6, 2018.
  20. Cummings, J. L., Morstorf, T., & Zhong, K. (2014). Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimer’s research & therapy, 6(4), 37.
  21. Durga, J., van Boxtel, M. P., Schouten, E. G., Kok, F. J., Jolles, J., Katan, M. B., & Verhoef, P. (2007). Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. The Lancet, 369(9557), 208-216.
  22. Forlenza, O.V., et al. (2011). Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomized controlled trial. British Journal of Psychiatry 198:351-365.
  23. Greenblatt JM. (2018). Integrative Medicine for Alzheimer’s.
  24. Greenblatt, JD. (2018). New Hope for Alzheimer’s Disease: Nutritional Lithium as the Foundation for Prevention Part 1. Townsend Letter. October 2018.
  25. Hamilton, A., Zamponi, G.W., Ferguson, S.G. (2015). Glutamate receptors function as scaffolds for the regulation of beta-amyloid and cellular prion protein signaling complexes. Molecular Brain, 8, 18.
  26. Hooper, C., Killick, R., Loveston, S. (2008). The GSK3 hypothesis of Alzheimer’s disease. Journal of Neurochemistry, 104(6), 1433.
  27. Kessing, L. V., Gerds, T. A., Knudsen, N. N., Jørgensen, L. F., Kristiansen, S. M., Voutchkova, D., … & Ersbøll, A. K. (2017). Association of lithium in drinking water with the incidence of dementia. JAMA psychiatry, 74(10), 1005-1010.
  28. Leszek, J., E Barreto, G., Gasiorowski, K., Koutsouraki, E., & Aliev, G. (2016). Inflammatory mechanisms and oxidative stress as key factors responsible for progression of neurodegeneration: role of brain innate immune system. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders), 15(3), 329-336.
  29. Matsunaga, S., Kishi, T., Annas, P., Basun, H., Hampel, H., Iwata, N. Lithium as a treatment for Alzheimer’s disease: A systematic review and meta-analysis. Journal of Alzheimer’s Disease,48(2), 403-410.
  30. Mauer, S., Vergne, D., & Ghaemi, S. N. (2014). Standard and trace-dose lithium: a systematic review of dementia prevention and other behavioral benefits. Australian & New Zealand Journal of Psychiatry, 48(9), 809-818.
  31. Moore, A.H., O’Banion, M. (2002). Neuroinflammation and anti-inflammatory therapy for Alzheimer’s disease. Advanced Drug Delivery Reviews, 54 (12), 1627-1656.
  32. Moore, G. J., Bebchuk, J. M., Wilds, I. B., Chen, G., & Menji, H. K. (2000). Lithium-induced increase in human brain grey matter. The Lancet, 356(9237), 1241-1242.
  33. Nunes, M.A., Viel, T.A, Buck, H.S. (2013). Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer’s disease. Current Alzheimer Research, 10(1), 104-107.
  34. Purse, M. (2018). Lithium: The First Mood Stabilizer. Very Well Mind website. https://www.verywellmind.com/lithium-the-first-mood-stabilizer-p3-380277. Accessed October 7, 2018.
  35. Sarkar, S., Ravikumar, B., Floto, R. A., & Rubinsztein, D. C. (2009). Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies. Cell death and differentiation, 16(1), 46.
  36. Seshadri, S., Beiser, A., Selhub, J., Jacques, P.F., Rosenberg, I.H., D’Agostino, R.B., Wolf, P.A. (2002). Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. The New England Journal of Medicine, 346(7), 476.
  37. Zylberstein, D.E., Lissner, L., Bjorkelund, C., Mehlig, K, Thelle, D.S., Gustafson, D, Skoog, I. (2011). Midlife homocysteine and late-life dementia in women. A prospective population study. Neurobiology of Aging, 32(3), 380-386.