Alzheimer’s Disease – More Insight

The August 1, 2019 issue of the journal Neurology carried a report of a team of researchers who have developed a blood test that can detect the presence of amyloid in the brain with 94% accuracy.  Amyloid is one of the chemical constituents found to be tangling up the neuron nerve communication pathways in humans with Alzheimer’s disease.

The article emphasizes this is currently a strict research tool. It is not a laboratory test that your physician or clinic can order or use to detect this form of dementia early. The results of the blood test correlate well with imaging studies currently in use. It is one small step in the investigation of the causes of this progressive, and fatal, heartbreaking disease and hopefully will allow us to evaluate Alzheimer’s at its earliest stages.

In a journal specifically dedicated to this disease entitled Alzheimer’s and Dementia, researchers at the University of California, San Francisco discussed the increased tendency of patients with Alzheimer’s disease to nap and sleep inappropriately and ineffectively. Previously it was felt that this inappropriate sleep pattern when observed was in fact a risk factor and marker for the development of the disease.

Lea Grinberg, MD and her co-authors feel it is a symptom of the disease instead. They believe that the disease process has already destroyed or inhibited those neurons (brain nerve cells) responsible for wakefulness and alertness. In the absence of this stimulation, patients nap and sleep ineffectively and inappropriately.

Imaging of these areas is difficult to obtain because of their location in the skull and brain but, on detailed studies, more tau protein deposition in these wakefulness areas is visualized.   This concept now allows researchers to zero in on other brain chemicals associated with wakefulness, alertness and sleep as a potential form of treatment of Alzheimer’s disease in addition to those chemicals in the cholinergic system that most medications attack.

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Collusion or Conspiracy?

A 67 year-old woman with a high stress job had a vigorous disagreement with her neighbors last week. She developed severe substernal chest pain and called 911 fearing a heart attack. She is thin, has never smoked, has normal blood pressure and normal cholesterol. She is not a diabetic and runs on a treadmill for two hours at five miles per hour with an elevation for two hours four times a week. She has few risks for developing heart disease.

The ER staff was quick and efficient. An EKG revealed changes consistent with a multivessel involved heart attack. Her cardiac isoenzymes were elevated and abnormal confirming muscle injury. The ER doctor called her PCP and the cardiologist on call. This experienced interventional heart specialists on call, has worked with and cared for many of the PCPs patients. He came right over, explained the options to the patient and, with her agreement and the PCPs blessing, took her to the heart catheterization lab to perform an angiogram to find the blockages and restore blood flow to the heart muscles.

To his surprise her arteries were perfectly normal with no blockages. The heart muscle was pumping weakly exhibiting the appearance of an octopus swimming through the sea proclaiming the unusual heartbreak stress syndrome known as Takotsubos cardiomyopathy. With rest, time and reduction of stress; she was projected to recover fully in days to weeks.

She was monitored overnight and observed until her heart enzymes were normalizing, her heart rhythm was normal, and; she could walk around the room easily. She was medicated with a low dose aspirin, a low dose of a beta blocker to blunt the stress induced surge of chemicals that caused the heart damage and mild antianxiety medicines. She was advised to cancel her work schedule for two weeks, cancel a cruise scheduled for the upcoming weekend and see a psychologist for stress reduction.

She opposed each of these suggestions and demanded that I call her relative’s cardiologist for a second opinion. The very type A characteristics that led to her stress, anxiety and illness was creating the request for a second opinion. The diagnosis and treatment were straight forward.

I called her cardiologist to explain the request never expecting the reaction I received. He is successful and experienced but when I brought it up he became anxious, angry and defensive. Why? He said he was leaving the case! I begged him not to and called the cardiologist she requested for a second opinion.

“We do not do in-hospital second opinions because we wish to maintain collegiality. Let her call my office when she is home and we will see her as an outpatient.” She called that office for an appointment and was told the next appointment is in six months. I called three other groups and received the same answer of no second opinions on inpatients to maintain collegiality.

As a primary care, physician my decisions are questioned and second guessed daily. Dr Google, Dr Cousin in NY or Boston, retired neighbor doctor offer opinions on my care regularly. It comes with the territory.

An anxious fit senior citizen suffering a frightening and unexpected heart malady should be able to obtain a second opinion without threatening the egos or collegiality of professionals. I called the medical staff office and hospital administration for help and was told to work it out with my colleagues.

As we examine our dysfunctional health system, we are quick to blame insurers, big pharmacy and government interference. Medical doctors are not without blame.

Is TMAO the New LDL CHOLESTEROL?

Prevention of heart disease has centered on smoking cessation, controlling blood pressure, achieving an appropriate weight, regular exercise, control of blood sugar and control of your cholesterol.  Despite addressing and controlling these items individuals still have heart attacks and strokes and vascular events. Researchers are now directing their attention to a dietary metabolite of red meat called trimethlamine N-oxide or TMAO.

Recent peer reviewed and published studies have shown an association between high blood levels of TMAO and increased risk of all-cause mortality and cardiovascular disease.  A 2017 study published in the Journal of the American Heart Association found a 60% increased risk of a major cardiovascular event and death from all causes in individuals with elevated TMAO.  Other research has linked high TMAO levels to heart failure and chronic kidney disease.

Our bodies make TMAO when choline and L-carnitine are metabolized by our gut bacteria in the microbiome. Red meat is particularly high in L-carnitine.  A study group at the Cleveland Clinic found that red meat raised the TMAO levels more than white meats or non-meat protein. They also discovered that red meat allowed more bacteria in the gut microbiome to be switched to producing TMAO. Of interest was the fact that the amount of fat in the food, particularly saturated fat, made no difference on the TMAO levels obtained.   Stanley Hazen, M.D. PhD, section head of preventive cardiology at the Cleveland Clinic, feels the TMAO pathway is “independent of the saturated fat story.”  The important issue to Dr Hazen is the presence of the gut bacteria to produce the TMAO from foods eaten.

Not all scientists buy into the TMAO theory of cardiovascular disease because of the relatively high level of TMAO found in many fish.  Some experts believe the beneficial effects of omega 3 fatty acids in fish offset the negative effects of TMAO. The leading researcher on TMAO says it is an evolving study and he is supported by experts who believe TMAO is “atherogenic, prothrombotic and inflammatory” per Kim Williams, M.D., chief of cardiology at Rush University Medical Center in Chicago.

There is even a blood test to measure TMAO levels developed by the Cleveland Clinic and available through Quest Labs.  Do not get too excited about asking your physician to order it on your blood because it requires eliminating meat, poultry and fish plus other food items for several days in advance of the test.

For many years researchers at the Cleveland Clinic and Emory University recognized that 50% or more of heart attacks occurred in men who followed all the risk reduction guidelines including stopping smoking, controlling blood pressure and lipids, losing weight and getting active. Perhaps the answer as to why will be in the TMAO research and the solution will be changing the gut bacteria or their ability to convert L-carnitine to TMAO.

Sunscreen Ingredients are Absorbed says FDA

For years public health officials, dermatologists and primary care physicians have been encouraging people to apply sunscreen before going out into the outdoors to reduce the risk of sunburn and skin cancers.  We are taught to apply it in advance of exposure by about 30 minutes and to reapply it every few hours especially if we are sweating and swimming.   Living in South Florida, sun exposure is a constant problem so we tend to wear long sleeve clothing with tight woven fabrics to reduce sun exposure.  My 15-month old grandson, visiting last weekend was smeared with sunscreen by his well-meaning parents before we went out to the children’s playground nearby.

These precautions seemed reasonable and sensible until an article appeared in JAMA Dermatology recently.  An article authored by M. Mata, PhD. evaluated the absorption of the chemical constituents of sunscreen after applying it as directed four times per day.  The article was accompanied by a supporting editorial from Robert M. Cliff M.D., a former commissioner in the FDA and now with Duke University School of Medicine and K. Shanika, M.D., PhD.

The study applied sunscreen four times a day to 24 subjects. Blood levels were drawn to assess absorption of the sunscreen products avobenzene, oxybenzone and octocrylene.  The results of the blood testing showed that the levels of these chemicals far exceeded the recommended dosages by multiples. The problem is that no one has evaluated these chemicals to see if at those doses it is safe or toxic causing illness?

The editorial accompanying the findings encourages the public to keep using sunscreen but cautions that the FDA and researchers must quickly find out if exposure to these levels is safe for us?  We do know that the chemical oxybenzone causes permanent bleaching and damage to coral reefs in the ocean from small amounts deposited by swimmers coated with sunscreen. The state of Hawaii has actually banned sunscreens containing oxybenzone to protect their coral reefs.

The fact that these chemicals have been approved and are strongly absorbed with no idea of the consequences is solely the result of elected officials wanting “small government” and reducing funding to the oversight organizations responsible for making sure what we use is not toxic.  It is a classic example of greed and profit over public safety.  The research on the safety of these chemicals must be funded and addressed soon. The American Academy of Pediatrics and Dermatology need to advise parents of youngsters whose minds and bodies are in the development and growth stages what is best to do for their children – sooner rather than later.

Lung Cancer Screening is Underutilized

Dr. Jinai Huo of the University of Florida (Go Gators!) presented data to Reuters Health that primary care physicians are under-utilizing the technology available to screen for lung cancer. This is a particularly sore topic to me because my associate and I always screened smokers and heavy past smokers for lung cancer with an annual chest x-ray until the United States Preventive Task Force issued guidelines that it didn’t save lives and was not cost effective.  They said, it cost $200,000 in normal x-rays to find one cancer early and it was deemed not worth it.

We actually sold our chest x-ray unit, let go our certified radiology technician and cancelled a contract with radiologists to read our films because insurers stopped paying for chest x-rays after the USPTF ruling.  Twenty years later that same group said “woops” an error was made. The statistical analysis on that study was done incorrectly and actually screening does save lives and is cost effective.

Today we have the fast low dose CT scanner to screen for lung cancer and screening does save lives according to the data.  Who should be screened?

Current smokers or those who have quit smoking within the last 15 years who are 55 to 77 years old and have a smoking history of 30 packs or more per year (one pack per day for 30 years or 2 packs a day for fifteen years).  Screening should be done on individuals in good health so if a lesion is found they are considered well enough to undergo diagnostic tests and treatment.

Screening is also recommended in those individuals over 50 years old with a twenty (20) pack year smoking history and a family history of lung cancer or lung disease or occupational exposure to items associated with causing cancer such as radon.

I inquire about smoking at each visit and have been fortunate in that few of our patients still smoke so we spend less time on counseling for smoking cessation.  If you fall into one of the screening groups mentioned in this article, and have not been screened, please notify us so we can arrange for the testing which will be a low dose chest CT scan.

American College of Physicians Breast Cancer Screening Guidance

The American College of Physicians released four guidance statements on detection of breast cancer in women with average risk and no symptoms of breast cancer.

  1. Doctors should discuss with their patients the pros and cons of screening with mammography for breast cancer in asymptomatic women with a modest risk of disease between ages 40- 49 years. The potential risks of screening are felt to outweigh the benefits.
  2. Clinicians should screen average risk women aged 50-74 years for breast cancer with mammography every other year.
  3. Clinicians should discontinue breast cancer screening in women aged 75 years or greater with an average risk of breast cancer and a life expectancy of 10 years or less.
  4. Clinical breast examinations SHOULD NOT be used to screen for breast cancer of average risk women of all ages.

These guidance statements DO NOT APPLY to women with a higher risk of breast cancers including those with abnormal screening results in the past, a personal history of breast cancer or a mutation in the BRCA1 or BRCA2 gene.

At the same meeting, data was presented discussing the problems with supplemental whole breast ultrasound in women with dense breasts.  The concern is that all this testing leads to invasive biopsies, over diagnosis and treatment of breast cancer in 1 in 5 patients and complications and increased cost to patients and insurers.  Like most recommendations on breast cancer, and prostate cancer in men, the results and conclusions from following these guidelines will not be apparent until 10 to 15 years from now.

Today’s adult women will either benefit from these suggestions, which have even included no longer teaching adult women how to perform breast self-exam, or they will be the unsuspecting research victims of cost containment. I question the competence of physicians in examining problematic breast disease if they are not being trained how to evaluate a breast and following that with clinical exams. In surgery we usually do not feel a clinician is competent and fully aware of the pitfalls of a procedure until the surgeon has done 200 or more. We additionally know that doing the procedure frequently results in better results than performing a procedure infrequently.

How will that apply if young physicians no longer examine breasts routinely?  How many, and how often, will they need to do an adequate exam to be able to perform when there is a real issue?  Do we actually wish to create a narrow panel of breast experts only at Centers of Excellence who actually know how to examine a breast and use the available imaging modalities safely and effectively?  It seems these ACP recommendations move in that direction.

For several years now I have been a supporter and champion of our community’s Women’s’ Center associated with Boca Raton Regional Hospital. Run by astute future thinking clinicians and researchers, and stocked with state of the art imaging equipment, it provides an option to meet with a counselor, assess your breast cancer risk and enter a screening pathway most individually suited to your personalized needs.  I will continue to support that choice.

Keep Moving for Cardiovascular Benefits

We keep extolling the benefits and virtues of regular exercise and fitness. Some research studies have documented the intensity and duration of exercise programs with cardiovascular events and mortality. Those who do more and are fitter apparently do much better which surprises few of us.

It comes down to the “which came first the chicken or egg “question?  Are people genetically able to exercise at a high level living longer and healthier because they exercise at a high intensity and duration or vice versa?

It is quite comforting to read the recent study in JAMA by Andrea LaCroix, PhD, MPH and colleagues from the University of California, San Diego that shows the benefits of even modest movement and exercise.  The study was conducted under the umbrella of the Women’s Health Initiative and put pedometers and accelerometers on women to measure activity during waking hours.  Light physical activity was defined as less than 3 metabolic equivalents (Walking one mile in about 22 minutes expends about 3 Metabolic Equivalents of Activity).  They noted that for each hour per day increment in light activity there was a 14% lower risk of Coronary Heart Disease and 8% lower risk of cardiovascular disease.

The researchers evaluated 5,861 women with a mean age of 78.5 years. Average follow-up spanned 3.5 years with study members having 570 cardiovascular disease events and 143 coronary heart disease events. The study group was diverse with there being 48.8% Caucasian women, 33.5 % Black women and 17.6% Hispanic women.

The study’s results and message was clear. Keep moving. Even modest exercise is beneficial in reducing heart attack and stroke risk.