Tulane researcher asks, “Could chronic Lyme contribute to Alzheimer’s dementia?”

In 2019, the late-great-science-writer Sharon Begley wrote an insightful article, “The maddening saga of how an Alzheimer’s ‘cabal’ thwarted progress toward a cure for decades.”

Begley’s reporting described how a powerful group of researchers became fixated on one theory of Alzheimer’s causation at the expense of all others. Their hypothesis: that Alzheimer’s cognitive decline was caused by neuron-killing, beta-amyloid protein clumps in the brain, and that if you dissolved the clumps, the disease process would stop.

As this theory hit a brick wall, Begley showed how the actions of the cabal harmed patients: “…for decades, believers in the dominant hypothesis suppressed research on alternative ideas: They influenced what studies got published in top journals, which scientists got funded, who got tenure, and who got speaking slots at reputation-buffing scientific conferences.”

Decades later, with no cure or effective drugs for Alzheimer’s dementia, some researchers are gathering evidence on a different causation theory — that dementia could be triggered by any number of chronic infectious diseases, and that amyloid plaques are a byproduct of an active infection, not the cause.

One of these researchers is Monica Embers, PhD, an associate professor of microbiology and immunology at the Tulane National Primate Research Center. She’s also the leading expert in identifying treatments that can eradicate Lyme bacteria infections in nonhuman primates, our closest mammalian relatives. In her new continuing medical education course, “Chronic Infection and the Etiology of Dementia,” she lays out the evidence that the Lyme bacteria could be one possible cause of dementia.

Her theory is this: When pathogens like the Lyme bacteria sneak past the blood-brain barrier, the immune system doesn’t allow protective killer cells from the entering the inflexible brain cavity, because resulting brain inflammation and swelling could lead to death. Instead, it encapsulates invading microbes with protein clumps, called beta-amyloid plaques or Lewy bodies, to stop the infection. As a person ages, the bodily processes that clean up this “brain gunk” slows, resulting in protein accumulation that impedes brain signaling and kills neurons.

In her 31-minute course, Dr. Embers describes the clinical symptoms of Alzheimer’s and Lewy body dementia, the impact on public health, genetic risks, and the list of infections associated with dementia-like symptoms.

The course also reviews a well-documented case study about a 54-year-old woman who was treated for the Lyme bacteria (Borrelia burgdorferi), developed dementia, then died 15 years after the initial infection. After death, B. burgdorferi was identified by PCR (DNA detection) in her brain and central nervous system (CNS) tissues, and by immunofluorescent staining of the bacteria in the spinal cord. (For more, read this peer-reviewed study.)

Dr. Embers and her study’s co-authors conclude, “These studies offer proof of the principle that persistent infection with the Lyme disease spirochete may have lingering consequences on the CNS. Published in postmortem brain autopsy images and extensive pathology tests are a compelling reason to pursue this line of scientific inquiry.”

You can watch this free CME here

To help us launch our CME curriculum in hospitals and medical schools, donate here.

Invisible International’s Education Platform for Tick-borne Illness is funded by the Montecalvo Family Foundation. This platform currently offers 24 free, online Continuing Medical Education (CME) courses on the diagnostics, epidemiology, immunology, symptoms, and treatment of Lyme disease, Bartonellosis, and other vector-borne diseases. 

A historic case study on chronic Lyme disease

In this free medical education course, Kenneth Liegner, MD, a New York-based internist who has been treating tick-borne disease patients since 1988, discusses one of the earliest documented cases of chronic Lyme disease.

In 1987, Vicki Logan, a 39-year-old pediatric intensive-care-unit nurse from Goldens Bridge, New York, began suffering from headaches, fevers, fatigue, progressive paralysis, cognitive difficulties, and memory loss. Her doctors couldn’t figure out what was wrong, so she was left to cope with this debilitating chronic illness on her own.

Two years later, Dr. Kenneth Liegner of Pawling, NY, decided to take on Logan as a patient, in what may be one of the earliest and most scientifically validated case of chronic Lyme disease on record.

First, he tested Logan for Lyme disease, and all the tests came back negative. She had no history of tick bite or rash, but he knew that Logan lived in a hot spot for Lyme disease, so he decided to presumptively treat her with intravenous antibiotics. After three weeks of IV cefotaxime and four months of oral minocycline, he saw no improvement in her condition.

This started a long diagnostic process to figure out what was wrong with Logan. Along the way, Dr. Liegner consulted with experts in rheumatology, immunology, and neurology. Repeatedly he sent her cerebral spinal fluid (CSF) to pathologists, all of whom observed no bacterial infections. Finally, he sent a spinal fluid sample to the Centers for Disease Control (CDC), and, when the fluid was placed in a special BSK-II growth medium, spirochetes began multiplying. On Jan. 14, 1994, the CDC experts verified that this was the first “gold standard” proof that the Lyme bacterium, Borrelia burgdorferi, can survive in a patient after months of IV and oral antibiotic treatments.

Because Logan’s Lyme disease case was so well documented, her post-mortem tissues have been used in numerous research studies. These studies have shown that the Lyme bacteria had invaded her heart, liver, and brain. A more recent study suggests that Borrelia burgdorferi is able to withstand the administration of antibiotics by forming biofilm structures, protective clusters of microbes, polysaccharides, proteins, lipids, and DNA, around itself.

You can watch a first-hand account of this fascinating medical mystery story here.

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This course is part of Invisible International’s Education Platform for Tick-borne Illness, funded by the Montecalvo Family Foundation. It currently offers more than 22 free, online Continuing Medical Education (CME) courses on the diagnostics, epidemiology, immunology, symptoms, and treatment of Lyme disease, Bartonellosis, and other tick-borne diseases.

Invisible International, a 501(c)(3) nonprofit organization, is committed to alleviating the suffering caused by invisible illnesses, through education, research, and community empowerment.

You can sign up to receive news and updates at https://invisible.international/mission

Other related courses: Borrelia persistence “Bench to Bedside” E-Colloquium, Antibiotic efficacy for treatment of Lyme disease, The impact of immune responses on diagnosis and treatment of Lyme disease

Tulane researcher discusses the evidence for persistent Lyme and promising new treatment strategies

Monica Embers, PhD, director of the vector-borne disease research center at Tulane University School of Medicine, summarizes evidence that suggests that Lyme bacteria can survive long after standard treatment protocols in a new online medical education course. She also discusses promising new treatment strategies for eradicating these bacteria.

Emerging evidence from animal studies suggest that the Lyme disease bacterium, Borrelia burgdorferi, is a clever trickster that uses multiple strategies to evade the immune system and survive long after an onslaught of the recommended course of antibiotics. This begs the question—Are our current Lyme treatment protocols all wrong?

In the accredited continuing medical education course, “Antibiotic efficacy for treatment of Lyme disease,” Monica Embers, associate professor of microbiology and immunology and a leading expert in investigating B. burgdorferi infections in a nonhuman primate model, summarizes current Lyme treatment protocols, key studies on antibiotic efficacy, and new strategies aimed at curing the infection.

“It’s clear from the cumulative evidence that persistent Lyme disease is a common occurrence and that we urgently need to explore more effective treatment strategies,” said Embers.

This new 32-minute course, part of Invisible’s Montecalvo Platform for Tick-Borne Illness Education, has been approved for 0.5 CME credit by the American Academy of Family Physicians. Each CME course includes a list of studies cited in the lecture.

One of the more surprising revelations in the lecture is that doxycycline, the drug of choice for treating adults with Lyme disease, doesn’t clear all of the causative bacteria. It only slows their proliferation, disrupting cell-wall creation as each forms a copy of itself by splitting into two. When the Lyme bacteria sense doxycycline, they shapeshift into spherical, dormant forms called persister cells, so they can wait out the chemical storm.

Dr. Embers backs up these claims with a series of thoughtfully designed experiments on nonhuman primates, our closest mammalian relatives. In one study, she treated five rhesus macaques with a 28-day course of doxycycline and five without. A year after the trial began, nine out of the 10 macaques, both treated and untreated, showed signs of ongoing illness and live Lyme spirochetes were isolated. In addition, those that received doxycycline had more bacteria in the brain.

The study’s conclusion: “We observed evidence of persistent, intact, metabolically-active B. burgdorferi after antibiotic treatment of disseminated infection and showed that persistence may not be reflected by maintenance of specific antibody production by the host.”

Simply put, treating with doxycycline didn’t seem to be a cure, and the Lyme bacteria appear to have ways of suppressing antibody production so that it can fly under the radar of the immune system.

Given this evidence, why does the medical establishment still recommend doxycycline as a front-line Lyme treatment? One reason is that doxycycline appears to be effective at most early infections, along with Rocky Mountain Spotted Fever and anaplasmosis, other serious tick-borne diseases that are often mistaken for Lyme disease in the early stages.

Embers also says that treatment study results may be skewed by the overuse of mice as test subjects. Mice are cheap, but they’re lousy stand-ins for humans. They’ve evolved alongside ticks to serve as a living holding tanks for the Lyme bacteria, so they don’t get as sick as humans when infected.

Lyme disease is the fastest vector-borne illness in the United States, with an estimated 476,000 new cases a year, according to the Centers for Disease Control. Approximately 10 to 20% of those treated with antibiotics go on to experience disabling long-haul symptoms, such as severe fatigue, joint/muscle pain, brain fog, and neurologic symptoms. There have been no human treatment studies published in over 20 years, and only 0.30% of the National Institutes of Health Lyme research budget has been focused on human treatment studies in the last five years (2015-2019).

At the end of lecture, Dr. Embers cited several lab studies (bacteria-in-a-dish) and animal studies showing that a cocktail of three antibiotics are highly effective in eradicating the Lyme bacteria. (This study from Johns Hopkins found that a combination of daptomycin, cefoperazone and doxycycline was effective in eradicating persister cells.) But of course, clinical trials are needed to validate these findings.

One of the ways Invisible International is working to accelerate the movement of treatment evidence to patient care is by launching Tick Bytes, a centralized clinical data repository that provides quality de-identified tick-borne illness patient data to researchers nationwide. Researchers can mine this data using advanced biostatistical methods to discover symptom profiles for mixed infections and treatment regimens that work. With this precision medicine approach, more quality evidence will reach physicians, insurers, and the government. This in turn will improve diagnostics and treatment options, leading to better outcomes, insurance coverage, and more sophisticated understanding of tick-borne diseases. Invisible is currently looking for funding for 10 data collection sites.

Dr. Embers’ CME course was funded by the Montecalvo Platform for Tick-Borne Illness Education, through Invisible International, a 501(c)(3) nonprofit foundation dedicated to reducing the suffering associated with invisible illnesses and social marginalization through innovation, education, and data-driven change projects. You can sign up to receive news and updates on our website.

Invisible International is a 501c3 that aims to solve challenges related to tick-borne illness through research and physician education. Its core team includes health care providers and scientists specializing in Infectious Disease, Internal Medicine, Family Medicine, Pathology, Pharmacy, Psychology, and Physical Medicine and Rehabilitation, as well as innovation and healthcare leaders.

Other related courses: The impact of immune responses on diagnosis and treatment of Lyme diseaseBorrelia persistence “Bench to Bedside” E-ColloquiumPersistent Lyme disease

Image credit: Hailshadow at iStock

Harvard study identifies symptom clusters in Lyme patients with persistent symptoms after treatment

retrospective study of 270 post-treatment Lyme patients identified the most debilitating neurological symptoms, paving the way for future studies on root causes of disease and better treatments.

The largest study to-date characterizing ongoing symptoms [1] of Lyme patients after antibiotic treatment has been published by a group of investigators at Harvard-affiliated hospitals and Invisible International, a non-profit organization. They also examined the relationship between symptom severity and perceived disability, identifying five of the most debilitating symptom categories — fatigue, cognitive deficits, neuropathy (nerve numbness or weakness in the extremities), migraine headaches, and mood disorders.

The study lays a scientific foundation for future research that will help the growing ranks of post-treatment Lyme patients suffering from lingering symptoms. Lyme disease is the fastest vector-borne illness in the United States, with an estimated 476,000 new cases a year, according to the Centers for Disease Control. Approximately 10 to 36% [2] of those treated with antibiotics go on to experience disabling long-haul symptoms, such as severe fatigue, joint/muscle pain, cognitive problems, and neurologic symptoms.

Patient impairment was assessed through medical chart reviews of 270 individuals who had been treated for Lyme borreliosis through the Dean Center for Tick-Borne Illness at Spaulding Rehabilitation Hospital Boston, a Harvard affiliate, between 2015 and 2018. Symptom and disability data was also collected through scientifically validated questionnaires. Symptom clusters were defined as two or more symptoms occurring together, indicating that they might share the same triggering mechanism. This approach, used in other chronic conditions, such as cancer and inflammatory bowel disease, helps guide researchers in identifying root causes and better treatment strategies.

“This study is an important first step in figuring out why these patients aren’t getting better,” said Dr. Nevena Zubcevik, DO, the first author on the study and the former co-director of the Dean Center for Tick Borne Illness. “Going forward, we’re taking what we’ve learned to set up a multi-institutional clinical data repository that will provide high quality, de-identified tick-borne illness patient data to any interested researcher.”

To expedite the discovery of clinical treatments for patients suffering with chronic tick-borne illness, Dr. Zubcevik is now leading the Tick Bytes Clinical Data Research Platform through Invisible International, in her role as Chief Medical Officer. The resulting open-source data would enable researchers to access prospectively acquired clinical and laboratory data, as well as possible biorepository specimens, on a large group of well-defined pediatric and adult patients with complex Lyme disease. This repository would also collect data on mixed infections and/or environmental/toxic exposures, influences that often worsen the outcomes of these patients. Using this precision-medicine approach, more quality evidence will reach physicians, insurers, and government. This, in turn, will improve diagnostics and treatment options, leading to better outcomes, insurance coverage, and government funding. Invisible is currently raising funds to launch 10 data collection sites at research institutions, community clinics, and hospitals across the nation.

Invisible International, a 501(c)(3) nonprofit organization, is dedicated to reducing the suffering and social marginalization associated with invisible illnesses through innovation, education, and data-driven change projects. Invisible’s core team includes board-certified health-care providers in Infectious Disease, Internal Medicine, Family Medicine, Psychiatry, Pharmacy, Pathology, and Physical Medicine and Rehabilitation, many trained at or are affiliated with top-tier universities such as Harvard, Stanford, MIT, Brown, UC Berkeley, UC San Francisco, the US Air Force Academy, University of Virginia, and University of Pittsburgh.

This study and Invisible International’s Change Platform for Tick-borne Illness were funded by generous donations from Mark and Eileen Lovell. The organization is currently seeking additional support to expand its TickBytes data collection sites. To learn more about how you can help, go to: https://invisible.international/give

You can sign up to receive news and updates at https://invisible.international/mission

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Other related courses: Persistent Lyme diseaseNeurologic complications of Lyme diseaseBorrelia persistence “Bench to Bedside” E-Colloquium

Photo credit: francescoch/iStock

End Notes

[1]

Marques A. Chronic Lyme disease: a review. Infect Dis Clin North Am. 2008;22(2):341-viii. doi:10.1016/j.idc.2007.12.011

Asch ES, Bujak DI, Weiss M, Peterson MG, Weinstein A. Lyme disease: an infectious and postinfectious syndrome. J Rheumatol. 1994 Mar;21(3):454-61. PMID: 8006888. [Retrospective evaluation of 215 Lyme patients who were diagnosed and treated > 1 year prior.  Found/described persistent symptoms in 114 (53%).]

Clarissou J, Song A, Bernede C, et al. Efficacy of a long-term antibiotic treatment in patients with a chronic Tick Associated Poly-organic Syndrome (TAPOS). Med Mal Infect. 2009;39(2):108-115. doi:10.1016/j.medmal.2008.11.012. [Open-label prospective study of 100 patients after treatment for chronic TAPOS (Tick Associated Poly-Organic Syndrome), evaluating their evolution on prolonged antibiotics.]

Horowitz RI, Freeman PR. Precision Medicine: The Role of the MSIDS Model in Defining, Diagnosing, and Treating Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome and Other Chronic Illness: Part 2. Healthcare. 2018; 6(4):129. https://doi.org/10.3390/healthcare6040129. [Patient symptom survey and retrospective chart review of 200 patients with chronic Lyme/PTLDS.]

[2]

Strle, F., Cimperman, J., Maraspin, V. et al. Azithromycin versus doxycycline for treatment of erythema migrans: Clinical and microbiological findings. Infection 21, 83–88 (1993). https://doi.org/10.1007/BF01710737. [“Minor” symptoms in 15/52 (29%) who received doxycycline and 10/55 (18%) who received azithromycin.]

Dattwyler, R.J.; Luft, B.J.; Kunkel, M.J.; Finkel, M.F.; Wormser, G.P.; Rush, T.J.; Grunwaldt, E.; Agger, W.A.; Franklin, M.; Oswald, D.; et al. Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease. N. Engl. J. Med. 1997, 337, 289–294. [Persistent symptoms at last follow-up visit in 18/68 (26%) Ceftriaxone vs 10/72 (13.9%) doxycycline.]

Aucott JN, Rebman AW, Crowder LA, Kortte KB. Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here?. Qual Life Res. 2013;22(1):75-84. doi:10.1007/s11136-012-0126-6. [Prospective cohort study of 63 patients with EM rash and systemic symptoms treated with doxycycline reported a 36% rate of PTLDS.]

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