Lyme does not cause Alzheimer's disease

All disease results from the interplay of genes and environment. DNA, whose mysteries are slowly being unravelled, is the blue-print of everything we are and everything we will be. Four base pairs- codons- genes- make proteins which control everything else. Infections: viruses, parasites, bacteria--in some cases Borrelia burdorferi, become environmental factors which interact within a genetically encoded milieu. The relative importance of heredity and environment vary greatly depending on the disease. For example, if you are born with the cystic fibrosis gene your fate is predetermined before you are born. On the other hand, as with many other diseases--cancers, diabetes, coronary heart disease, multiple sclerosis and others, this interplay of genes and environment is no so easy to predict.

Alzheimer's disease, multiple sclerosis, lupus, arthritis and many other diseases are not caused by Lyme disease, or at least directly, as many patients mistakenly believe. Lyme may be an environmental factor associated with many diseases.

Susceptibility to Lyme is genetically coded and so is the virulence of a particle strain of the Lyme bacteria. In general, patients with chronic Lyme disease have central nervous system (brain) involvement, more often than not. Their clinical features are all quite different.

Borrelia burdorferi, unlike most other bacteria, is able to readily cross the blood brain barrier-- taking up residence within the brain. Inside the brain the spirochetes are seen as: atypical cystic forms, granular forms, blebs, rolled forms, colonies, rings, stretched strands, spherules and others.

Associated neuro-inflamation is complex and has been well described. Inflammation occurs as Bb encounters local immune cells such as macrophages and dendritic cells. Cytokines and chemokines induce inflammatory responses. Other immune cells, killer T-cells and B cells are activated. Bb can invade local glial cells and astrocytes. OspA is upregulated which induces apoptosis (cell death). Neurotoxins are produced. Nitric oxide and quinolinic acid have neuro-toxic effects. Autoimmune reactions also occur. There are different models of autoimmunity. Perhaps both molecular mimicry and Innocent bystander mechanisms occur. Lyme spirochetes have been observed in patients with concomitant Alzheimer's disease. Lyme does not cause Alzheimer's disease.

Alzheimer's disease has been studied for many decades. Various genetic mechanisms have been clearly established. Pathologically, Alzheimer's is characterized by an accumulation of amyloid protein in the brain neurofibrillary "plaques and tangles" and tau proteins. In animal models it has been shown that Alzheimer's does not occur when the protein which regulates the degradation of amyloid precursor is up-regulated.

Alzheimer's disease is considered the most common type of dementia. Dementia is characterized by chronic, progressive, global loss of cognitive functions. Numerous forms of dementia have been described. BSE (mad cow disease) is called prion disease. It is associated with mutated proteins in the brain. Lewey body dementia is associated with Parkinson's disease.

Rare genetic disorders, such as forms of porphyria can be associated with dementia (The madness of King George). Dementia may be the result of min-strokes and many other syndromes to numerous to list here. These syndromes may appear similar in the peri-morbid state, but they have clear differences in the earlier stages of the disease.

Of course, dementia can be associated with infection. For example, HIV and chronic CNS fungal infection are established causes of dementia. The dementia which most closely resembles Lyme dementia--neuroborreliosis associated dementia, is the dementia of neuro-syphilis. Syphilitic dementia is called "general paresis" and is known to be the cause of death of many historical characters.

Thankfully, most patients with neuroborreliosis do not develop dementia. They may suffer with severe cognitive deficits but these deficits are not global in nature. Patients usually maintain the ability to perform most activities of daily living. Certain cognitive processes in most Lyme patients remain relatively unaffected. SPECT/PET scans show patchy dysfunction. In Alzheimer's disease, the scans are global--not spotty.

Make no mistake. Neuroborreliosis is a devastating disease. Its treatment remains challenging. Still, many patients experience remarkable recoveries/remissions.

Amongst many in the Lyme community there is a reductionist tendency to oversimplify and claim that everything is caused by Lyme disease. This is neither true nor helpful.

Both sides must learn to speak a common language to find areas of disagreement and agreement.

Everyone has Lyme disease

The last post was not a real patient. It was a composite of several patient. I pushed the envelope a bit--providing the appearance of mixed symptoms. Here is the problem.

Remember, when the original ELISA(EIA) test for Lyme was developed, many "normal" controls tested positive. Lyme couldn't be that prevalent--at least that is what the early investigators thought. This is why the bar was set high, hence, the confirmatory Western Blot.

It unknown how many people in an endemic area are infected with Lyme. Is it 10%? Is it 90%. We have no idea. For the sake of argument, let us say the number is 50%. We then have no clue what percent are "symptomatic". Furthermore, we do not have a clear definition of what "normal" is. There are natural physiological changes which occur with aging. I am 54 years old. If I play tennis, my brain may tell my body to do the same things it did when I was 20---not going to happen.

Asking patients to answer specific questions in inherently problematic. When a patient comes in with a long list of clear symptoms it is one thing. When positives are elicited only when a patient is queried, it may mean something entirely different. If a patient thinks long enough about any question, a positive response may be forthcoming. A lot has to do with the individual's personality.

As physicians know, testing becomes meaningful when the "pretest" clinical sense, points in that direction. Testing for Lyme is unreliable. A basic rule of thumb for me is: treat the patient, not the lab. Most patients don't want to shell out the money for a speciality Lyme WB. "Just send the test to Labcorp." And, if an Igenex is done-- the results borderline positive, what does this mean? Only a physician's clinical judgment can decide if a patient's symptoms are likely the consequences of chronic Lyme disease.

Most major scientific breakthroughs have been made by young people, under age 30. Mathematical abilities decline with age, although verbal abilities do not, and in fact may improve.
So what is there to do when a patient appears "normal" by the physician's best judgement? Again, there is no definition of normal. When queried, most over 50 year olds have some aches and pains with exercises, but recover quickly. Perhaps there are some mild cognitive changes(?normal). Nonetheless, the "patient" feels normal. He has no fatigue or functional incapacity. Testing is not done simply because other family members have chronic Lyme disease.

If I treat what am I treating? What is the goal? What is the endpoint?

This is why I recommended watchful waiting. Otherwise, if one looks hard enough--turns over every rock: everyone has Lyme disease. Patients who suffer with Lyme disease see this case through a different lens--the lens of their illness. It is just not that simple.

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Doctor: I want a Lyme disease test

A patient comes in to the office. Let's say he or she is 5o years old. Many friends and family members have Lyme disease, he wants to know if he has it too. He is generally well but complains of some aches and pains. His joints hurt occasionally, especially after exercise, but recover quickly. His energy level and sleep are good. When asked about memory and cognitive problems he pauses for a moment: Perhaps his memory is not as good as it used to be. There has been some decline over several years. Word retrieval is a problem at times. His focus is not as good as it used to be. His mathematical abilities are not as good as they once were but they are OK. There are no other neurological symptoms. He functions normally at work and at home. These mild changes in cognition have occurred gradually over a period of years but are not bothersome.His family history reveals than a parent developed Alzheimer's disease at age 86. A recent physical has been done. His exam and routine lab work were fine. Should he be tested for Lyme disease?


No. Many patients have asymptomatic infection. This could be the case; still, I would not test. Positive results would only open a Pandora's box. These symptoms are mild and likely within the range of what might be expected in a 50 year old. The normal brain is sharper at age 25-35: minimal cognitive changes--neuronal fall out, occur in normal people. Alzheimer's disease? His risk may be slightly greater than that of the general population. Perhaps general recommendations would be made: exercise brain and body--eat well--perhaps drink coffee and take extra vitamin D.

The patients would be given a list symptoms to watch for. Treatment: watchful waiting--a term frequently used by doctors.

Vitamin D: A retraction--I got it all wrong

Vitamin D is much more complex than I have indicated earlier. The only thing I can say about the reversed pattern (active D higher than inactive D) is that it appears to be a marker for Lyme disease and/or inflammation--perhaps a very good marker.

Much research has been done on vitamin D. All of it is based on measurement of the inactive form, vitamin D hydroxy 25, which correlates with stored vitamin D. Yes, vitamin D has anti-inflammatory properties, but this may not be a bad thing. It affects cytokines andT-cell activation. But contrary to previous comments, it is active vitamin D that increases production of an anti-microbial peptide: cathelicidin. (Past statements that active D tilts the immune system from Th1 to Th2--causing production of anti-microbial peptides is wrong). The binding of active D to receptors modulates the genetic expression of complex proteins. VDRs (vitamin D receptors) are found in many organs in the body, including: brain, heart, skin, gonads, prostate and breast. Vitamin D receptors are found on a variety of immune cells, including: monocytes, B-cells and activated T-cells. It also has effects on dendritic cells. Vitamin D toxicity is very rare, even in patients with very high levels of active vitamin D, the 1,25 dihydroxy form.

Anti-inflammatory effects of D may lower the risk cancers, autoimmune disease, diabetes, heart disease and others. Recent research has shown that vitamin D is required to activate the histocompatibility gene, HLA-DRB 1501. This activation is necessary for the immune system to differentiate between self and non self in a select group of patients.

A link between vitamin D and MS has been shown. Perhaps the lack of MS in tropical climes
is not related to the absence of Bb and other infectious agents, as some have postulated, but due to higher levels of D from birth on.

The main source of D is sun light. Increased melanin decreases UVB penetration through the skin needed for conversion of D. It has been shown the black skin increases the risk of prostate cancer in the US but not in Africa--perhaps evidence of D's cancer fighting effects.

The Canadian Cancer Society has recommended that all it's citizens supplement with 1000 units of D daily.

D supplements are generally in the form called D3. This is the same form obtained from sun exposure. There are many forms of D and it's metabolism is very complex. Clinically, we only measure D in its stored and active forms.


In these numerous studies, only stored vitamin D is measured. Some doctors on the "cutting edge" have suggested that vitamin D hydroxy 25 levels are optimal at 75 (normal
32 to 100). But they are not looking at lab values I see in my practice. The range for normal active vitamin has been expanded, (10 to 75).

Many of my patients typically have stored vit D levels of 12--very low-- and active vit D levels of 100-- still high even though the range has changed.

In some way, the body--the immune system ostensibly, is trying to rectify the problems related to the infection (maybe). After treatment many patients have D levels in the normal ranges. This varies: some patients have D levels which drop across the board.

It now seems to me that judicious supplementation of D may in fact be very useful. Levels need to be monitored. the use of Benicar to inhibit renal conversion of inactive to active D may be a bad idea. Our bodies are pretty smart: let them balance the levels as needed. If active levels are above 100 I am somewhat hesitant to recommend D supplements. I have no basis for this. Again, vitamin D toxicity is difficult to attain. Reported cases have only been reported in individuals taking 40,000 units daily over a period of time.

Why doesn't my doctor believe in Lyme disease?

Scientists do research. They work in labs, at Universities. They work with bugs and test tubes; develop hypotheses, and design experiments to prove or disprove their theories. Sometimes they do basic science research-- to discover the basic structure and function of things. They publish their findings in prestigious, peer reviewed journals like Science and Nature. Such scientists have discovered much about the spirochete, Borrelia burdorferi, the causative agent of Lyme disease. This data is called "in vitro." Many doctors will claim that such results may not apply to the "in vivo" processes inside the body.

Physicians do not read these journals. They operate in parallel. They also have hypotheses. They evaluate their hypotheses with controlled clinical trials. Frequently medical trials provide confusing and contradictory data. In such cases the investigators can draw varying conclusions, sometimes informed by pre-existing biases.

Physicians(practitioners) are not scientists, although some may disagree. There are a few exceptions to this rule. Physicians work within the box of their trade. In medical school they are busy learning basic rules: structure and function of the body, types of disease--causes and treatments. Much of this is complex and ever changing. Evidence based medicine has helped physicians develop protocols and algorithms. The evidence is based on an analysis of the published studies in prestigious journals such as The New England Journal of Medicine and others. At times there is no or little data to support diagnoses and therapies. In such cases a body of "experts" informs the public of physicians regarding the best diagnoses and therapies. Even where no "science" exists, these opinions are surrogates for "science" and become-- "evidence based medicine." The waters are muddied. The distinctions between fact and opinion can become blurred.

The field of medicine is vast. It is broken down into various boxes. Some of these would include disciplines such as: internal medicine, orthopedics, rheumatology, neurology and infectious disease. (Of course this is a tiny selection of medical specialties for purposes of this discussion).
Perhaps readers do not know that all infectious disease specialists start out as generalists--internist or pediatricians, followed by a 2 year fellowship in infectious disease medicine. An infectious disease doctor has done: 4 years of college, 4 years of medical school, 3 years of residency and two years of training in infectious diseases. Note: for the first 11 years, the internists or family practitioner has had basically the same training as an "ID" doctor. Infectious disease doctors see sick hospital patients. They familiarize themselves with a wide range of esoteric infections: bacterial, viral, fungal, parasitic and others. They learn by reading text books, rounding with mentors and performing consults on sick patients, generally in hospitals. They spend very little time in an office setting. They become experts. They do not treat patients with chronic, "low grade" illnesses. They do not treat patients with fibromyalgia, depression, chronic fatigue syndrome and a whole other array of syndromes which they sometimes like to diagnose (in lieu of Lyme disease). Of course, they were generalists before they became specialists.

Each specialty has its own box. It works from a list of common diagnoses. Keep in mind--if you are a hammer, everything looks like a nail.

For example, a patient has joint pain. The orthopedist considers: tendinitis, a torn cartilage, a ligament injury, a mechanical injury--or something--not in his specialty, requiring referral to another specialists. The patient may be referred to a rheumatologist who considers: rheumatoid arthritis, lupus, Reiter's syndrome, post-infectious arthritis, gout and Lyme disease and others. He may conclude it is not in his field. He may refer on to an infectious disease specialist where considerations may include: an infected joint with something like gonorrhea, viral synovitis and perhaps Lyme disease. The Lyme results are negative for Lyme by the IDSA /CDC screening test. No answer is found. The patient is referred back to his primary care doctor. Physical therapy and pain medicines are recommended. If the patient asks about Lyme disease he is told this has already been excluded.

Lyme disease--LLMD style-- is outside the normal boxes. It is rejected by practitioners of the traditional boxes. It is foreign and rejected. After all, the true experts have spoken. These new practitioners outside the box, are easily labeled quacks. Paradigms do not change easily.

And in a nutshell, that is why your doctor does not believe in Lyme disease.

Cystic forms and relapse

It happens all the time. A patient has finally done great. No symptoms. Remission at last.
Symptom free with a "maintenance" med or regimen-- Doxycycline alone or Amoxicillin and Biaxin. Meds are stopped. Lyme symptoms return almost instantly, within days or weeks.

Why?

I have given this some thought. Lyme spirochetes grow slowly. They replicate every 24 hours give or take. The Lyme "load" hasn't suddenly grown exponentially. Is it autoimmune? Antibiotics do have anti-inflammatory properties; have they been suppressing a smoldering autoimmune response lying in wait? No--autoimmune processes generally progress gradually.

This leaves only one possibility. What happens quickly? Cyst forms of Lyme quickly convert to spirochetes, within hours. Ah-ha--the ready source of spirochetes!

As a patient recently told me: "The other antibiotics just cause everything (spirochetes and L-forms) to convert to cysts. Do they?

Cysts are metabolically inactive and generally don't make us sick; the brain seems to be the exception.

In the brain, cyst forms are associated with inflammation. There is experimental evidence supporting this. Tindamax-- the magic drug - sharpens the brain - eliminates vestiges of brain fog.

With the relapse, cognitive functions frequently remain intact while other Lyme symptoms explode. If brain cysts cause more damage than spirochestes there-- I quess this makes sense.

Questions: few answers. Do cyst busters lower relapse rates? Early or late?

Are dreaded L-forms in fact more docile than cysts? Not in the brain.

Perhaps a regimen of a cell wall inhibitor-cyst buster might work better in (in patients lacking cognitive dysfunction), assuming the germs have not passed the blood brain barrier.

Just a thought.

How it is supposed to work

I tend to write about unusual cases. Here is a more typical case--a successful one.

A 68 year old female visited me in January 2009. In 2005 she was sero-positive for Lyme disease. Treating was aggressive by standards of the day. She was treated with Doxycyline for 4 months. She recalls that her chief complaints then were rash, fatigue and joint pain associated. After treatment she felt better.

Over the past year she had not felt up to snuff. Pains in the large and small joints had returned. She had neck pains and muscle pains. She had numbness and tingling of her extremities. Her energy level was lower, she had fatigue, headaches, night-sweats, shortness of breath, an unsteady gait, poor sleep and a decline in cognition. She had trouble finding words and focusing.
She had brain-fog. Her sleep was disturbed.

Her exam was abnormal (neurological findings):her Igenex was positive IgG --34, 41: her Igenx B. duncani test IgM, 1:20 was borderline: a Clongen wet mount showed motile bacteria, presumed to be a species of Bartonella. Her SPECT scan showed poor perfusion to the left anterior temporal lobe: her MRI showed multiple white matter lesions consistent with Lyme disease or MS.

After treatment with courses of: Omnicef, Biaxin, Plaquenil, Tindamax, Zithromax, Mepron, Amoxicillin, Tindamax and Rifamin (in various combinations) She feels essentially normal. The treatment to date has lasted about 11 months. She is still on antibiotics and weaning will be done gradually. I suspect she will be on maintenance medications for a long time to come.