Antioxidants & Dementia Risk – A New Study in Neurology

May A. Beydoun, PhD, MPH of the National Institute on Aging of the NIH in Bethesda, Maryland and associates published a study on blood antioxidant levels, food consumed and the risk of developing dementia as you aged. The study hoped to determine which foods were best to eat to limit your chances of developing cognitive impairment in later years. The researchers discovered that those individuals with the highest serum levels of lutein+ zeaxanthin and beta-cryptoxanthin at baseline were less likely to develop dementia decades later than their peers with lower levels of these protective antioxidants.

Lutein and zeaxanthin are found in green leafy vegetables such as kale, spinach, broccoli, and peas. Beta -cryptoxanthin is found in fruits such as oranges, papaya, tangerines, and persimmons. “Antioxidants may help protect the brain form oxidative stress, which can cause cell damage,” said lead author Dr. Beydoun.

The study, published in the journal Neurology analyzed 7,283 participants in the 3rd National Health and Nutrition Examination Survey who were at least 45 years old at the start of the study and were then followed for 16-17 years. The data showed the higher the serum levels of beta-cryptoxanthin at baseline the lower the risk of developing dementia. No such protection was found for lycopene, alpha-carotene, beta carotene or Vitamins A, C, or E.

This was an observational study looking at data already collected. In critiquing the study, Dr B. Hooshmand, MD, PhD and Milia Kiviipelto, MD, PhD of the Karolinska Institute, Stockholm, Sweden commented on the research noting that this was an observational study and previous studies supplementing individuals with antioxidants were disappointing and did not prevent development of cognitive dysfunction. They believe there is a more complex relationship between the foods we eat, antioxidants, socioeconomic status and lifestyle which all contribute to the development of dementia.

While there is work to be done in this field, this study certainly supported my love for a fresh orange or tangerine to start off the day. The accompanying editorial made it clear that consuming my antioxidants and vitamins in fresh fruit and produce seems to be healthier than depending on store purchased supplements.

Constipation Treatment with a Vibrating Pill

Constipation is a major quality of life problem. When confronted with it, physicians advise more hydration, more exercise and activity and more fiber in your diet. If that doesn’t work, we try medications.  We start with medications to increase the bulk and fiber in your gut and to soften the stools. Next, we move to different strength laxatives. The problem with laxatives is that often the timing and consistency of the next bowel movement are unpredictable. Getting phone calls about new onset of diarrhea in patients taking a laxative for constipation is common. Chronic use of laxatives can adversely impact the muscles of the colon rendering them less, or completely, ineffective.

Satish Rao, MD, PhD, professor of Medicine at the Medical College of Georgia, presented a paper at the Digestive Disease Week meeting and reported by Medscape about a vibrating pill that reduced constipation. The pill is swallowed at 9:00 p.m. and then is activated remotely to vibrate for three seconds and then rest for 16 seconds. This process continues for two hours twice a day. There were virtually no side effects although some participants said they felt the vibrations. Spontaneous bowel movements per week increased in the treated group. Less straining was required to have a bowel movement and stool consistency was considered improved. Quality of life was felt to be improved. The timing of the vibration cycles enabled participants to have bowel movements at the time of the day they were accustomed  to having bowel movements.

The vibrating pill is now being reviewed by the FDA for approval sometime in 2022.

FDA Approved LabCorp Test for COVID-19, Influenza & RSV

The FDA has approved an at-home testing kit that can differentiate between symptoms of an upper respiratory virus being caused by COVID-19, Influenza A/B or Respiratory Synctial Virus (RSV) . It is called the Pixel by LabCorp COVID-19+Flus+ RSV Test Home Collection Kit. You obtain a nasal swab and send it directly to LabCorp for testing. The results will be sent by an app that can be downloaded to a smartphone or tablet.

Since children returned to school after a prolonged isolation due to the COVID -19 pandemic, we are seeing a large number of viral upper respiratory tract infections in this group, their parents, and caregivers. “Is it COVID-19?” is always the first concern, “but if its not COVID what is it”?  This testing will  allow patients to swab themselves and obtain a diagnosis without having to first go to the doctor for a visit.

I suspect your doctor will still wish to see you or your child prior to prescribing anti-viral therapy once the diagnosis is reported,  but this is the first at-home testing approved for all three virus types. The test can be purchased online at the LabCorp website or at pharmacies.  The retail price has not yet been disclosed.

New Life Expectancy Prediction Model Available

Elizabeth C. Chase, PhD, of the University of Michigan, and colleagues, developed a new model for the prediction of life expectancy that was studied and published in BJU International. Traditionally, life expectancy predictions relied on Social Security Administration (SSA) data.

Dr. Chase’s model used “Other Cause Comorbidity Adjusted Mortality( OCCAM) which includes age, education, marital status, diabetes, hypertension, stroke, body mass index and smoking history to predict life expectancy. To develop their predictive model, they examined the data on 2,420 participants in the National Health and Nutrition Examination Survey. They then validated their predictive model using 8,220 men in the Prostate, Lung, Colon and Ovarian Cancer Screening Trial (PLCO).

The new model suggests that the SSA data is too optimistic for young men with prostate cancer and didn’t anticipate the comorbid conditions they would develop with age and, was too pessimistic for older adults. This becomes especially important because guidelines for treating various cancers use the SSA predictions to guide cancer treatment. For example , National Comprehensive Cancer Network (NCCN) guidelines for the treatment of prostate cancer call for less aggressive treatment in patients with a life expectancy less than 10 years. Using the new model, the recommendations on aggressiveness of treatment would have been different for nearly 15% of the men in PLCOS trial.

At this point, I suspect survival and quality of life data will need to be developed looking at the choice of treatment based on life expectancy predictions in the new model versus the SSA model. Patients and referring physicians may have to ask their treating oncologist which life expectancy model was used in deciding which course of treatment they are recommending.

FDA Approves New Diagnostic Test for Early Alzheimer’s Disease

The Lumipulse G Beta Amyloid Ratio test, made by Fujirebio Diagnostics, detects amyloid plaques found in Alzheimer’s disease in adults 55 and older under investigation for cognitive disorders. Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health said, ”The availability of an invitro diagnostic test that can potentially eliminate the need for time-consuming and expensive PET scans is great news for individuals and families concerned with the possibility of an Alzheimer’s disease diagnosis. With the Lumipuls test, there is a new option that can typically be completed the same day and can give doctors the same information regarding amyloid status, without the radiation risk, to help determine if a patient’s cognitive impairment is due to Alzheimer’s disease.”

Currently the PET scan is used to visualize amyloid plaques to diagnose Alzheimer’s disease. The FDA says this test may eliminate the need for a PET scan, “…. a potentially costly and cumbersome option.”

As a physician, I appreciate the innovation and technical expertise required to develop a test that compares the ratio of Beta amyloid 1-42 and Beta amyloid 1-40. To do this, you first must perform a lumbar puncture or spinal tap to access cerebrospinal fluid which is the specimen used in the test.  This requires injecting an anesthetic into one’s back and spine and then inserting a needle to enter the spinal canal and drain the fluid. The needle is then removed, and the patient is required to stay immobile on their back for several hours to prevent a post spinal tap headache. Putting a needle into someone’s spine raises the risk of bleeding, post procedure leak and infection being introduced. Then, add in the cost of the procedure room and the post procedure observation costs and, suddenly, the non-invasive expensive PET scan seems reasonable.

I look forward to the day when a simple blood test based on drawing blood from your arm will be able to provide the information required to support a diagnosis of Alzheimer’s disease. I applaud the scientists and researchers who developed this product but the enthusiasm of the FDA in their statement is probably not shared by anyone who has had to undergo a spinal tap.

New Insomnia Drug Available

Quviviq (Daridorexant) has been approved and is now available on the market for the treatment of insomnia in adults who have problems with sleep onset and or sleep maintenance. Its use was studied in two Phase-3 studies which were “double blinded” and compared the safety and effectiveness of the drug to placebo in 1,854 patients 18 years of age or older with at least three months of insomnia.

The drug showed meaningful improvement in sleep onset, sleep maintenance and patient-reported total sleep time. Patients kept a validated sleep diary and it revealed a significant reduction in daytime sleepiness.

Despite its efficacy, Daridorexant was not associated with “next morning residual effects, rebound insomnia or withdrawal symptoms upon discontinuation”. The drug is considered to be in the “hypnotic” class and there is a risk of C NS depression, worsening of existing depression or suicidal ideation, sleep paralysis, hallucinations and other sleep related issues. The drug is not designed for and is contraindicated in narcolepsy. It has not been approved for, or studied in, patients with obstructive sleep apnea requiring CPAP or patients with advanced COPD.

Like many new drugs, Quviviq is metabolized by the CYP3A4 system and drug interactions. Changing of dosages will be necessary for patients already taking medications using this metabolic pathway. The drug comes in a 25mg and 50mg dosage per MPR, the online journal which covered this medication release. It should be taken 30-minutes before sleep and is designed for patients who have seven full hours to stay in bed. Daytime impairment or sleep walking can occur in those who take it with less than seven hours to stay in bed (a full night’s sleep). It should be taken on an empty stomach to prevent delay of onset of its action. A new sleep medicine that does not cause withdrawal symptoms on discontinuation is always a valuable new tool. Like most new medications entering the market in drug classes that have proven options, I will wait six months to a year to observe the real-world effects of this new medication before comfortably prescribing it. It will be listed as a scheduled Class IV drug and its current cost to patients is not yet available.

Vaccine for Prevention of Alzheimer’s Disease in Development

Vaxxinity has been testing an immunotherapeutic vaccine candidate that targets aggregated amyloid beta in the brain considered to be toxic and contribute to the progression of Alzheimer’s Disease. The topic was discussed in the online journal MPR early in May. The vaccine , known as UB-311 has been in human clinical trials for three years now. Volunteers have received repeated doses of the vaccine with adverse effects no worse than in the placebo group in the trial. The manufacturer in the main study ClinicalTrials.gov Identifier: NCT025518009 showed that a “ robust and durable anti-amyloid beta antibody response was elicited in their patients while no amyloid related imaging abnormalities or edema were reported in the mild to moderate Alzheimer’s patients observed. In view of the early success shown the FDA has granted this drug Fast Track designation to speed its development and production .

The development of a medication that slows down and or prevents the development of this fatal progressive neurological disorder would be a major step forward in the battle against this relentless illness.

A Dose of Reality. Rejoining the World

My wife and I flew to Chicago this past weekend to attend a wedding of a dear niece. The pandemic resulted in three previous postponements of this wedding. It was postponed for so long that there is now a family addition of a lovely eight month-old daughter.

The trip involved leaving the state of Florida for the first time in three years due to COVID and flying commercially to a busy airport and then taking a taxi to a busy downtown hotel. If that wasn’t scary enough for a couple living in isolation for two years, the wedding included 175 guests meeting inside for a Friday night reception and then a Saturday service and reception. All rules, recommendations, and suggestions for preventing the transmission of, or acquiring, COVID were basically ignored by the parents (all four professionals with post doctorate degrees), the maid of honor (graduate of an Ivy League public health program and director of an internationally recognized COVID response program) and the bride and groom (both practicing physicians).

My wife and I planned to wear our masks on our flights to and from Chicago which was easily accomplished. We planned to eat outdoors only which could not happen due to two days of pelting rains, gale force winds and temperatures in the low forties. Downtown Chicago was young, maskless and completely oblivious to the fact that a COVID pandemic was ongoing. All these young adults were talking about is how they were still working remotely due to COVID, but they were populating bars, clubs, restaurants, theaters, sports venues maskless with not a care in the world about this contagious and fickle disease. To say it was different and a bit overwhelming would be an understatement.

The Friday night reception for attendees in an overcrowded undersized private room of a large Chicago blues club resulted in us saying hello, having a drink and quickly leaving. The wedding was less crowded and cramped but there was no pre-function COVID testing. Several of the guests on the bride’s side had refused vaccination. I saw one masked guest at the wedding, a young female pregnant physician. Every precaution we had taken for the last three years was ignored – throwing caution to the wind.

All my adult daughters and their guys flew in for the festivities and it was just wonderful to be with family. The parental hosts for the wedding were warm and loving and they knew how to throw a great party. I was concerned about the consequences of being with large groups of people inside despite being vaccinated against COVID and receiving two booster shots. We flew home Sunday night getting into our residence around midnight.

I tested for COVID daily for several days. No one in my immediate family contracted COVID. We know of only one guest who turned positive the day after the wedding, and she was one of the non-vaccinated attendees. The weekend of the wedding the COVID positivity percentage in Chicago was less than 2%.

I have no idea if we were just lucky or if the vaccines and boosters work well. With the positivity rate in Broward County now 21.7%, I suspect we will soon find out

Pfizer Pill “Paxlovid” & Post-Treatment Relapses

The introduction of the Pfizer antiviral pill Paxlovid to treat COVID-19 infected patients, within five days of contracting the disease, was supposed to be a “gamechanger.”  Reviewers compared it to Tamiflu, the antiviral pill used against influenza and taken twice a day for five days.

The rollout and distribution of Paxlovid have been a problem from day one. Pharmacies objected to their reimbursement for distributing the product and doing the labor-intensive paperwork required because it is an Emergency Utilization Authorization (EUA) product – not yet FDA approved. In addition, it interacted with so many commonly taken medications that use the CYP3A4 pathway, including common antihypertensive and antidepressant drugs. The result is that very few pharmacies agreed to stock it and distribute it. The Federal government established an online locator of pharmacies that distribute it but often the pharmacies listed do not have it in stock when you call them to prescribe it.

This week a new wrinkle and complication appears to have been discovered. Patients treated with Paxlovid within the first five days, and completing the twice a day course, are now relapsing on days 9 and 10 post-infection. Quick at home antigen tests are turning positive in some. Viral loads are being detected and mild symptoms are returning. These relapsed patients still may be able to spread the infection.  

Pfizer representatives are suggesting we treat these patients with a second five-day regimen. The FDA has not yet advised treating for a second round. At this time the issue of post Paxlovid relapses needs to be studied. Those projects are now under way.

For this reason, until more is known about Paxlovid treated COVID relapse, our first line treatment for high risk COVID infected patients will be referral to the Baptist Health Boca Raton Regional Hospital Monoclonal Antibody program. Their use of bebtelovimab within seven days of infection continues to prevent the disease from progressing to the serious form.

My patients with any questions about this, should call the office at 561.368.0191.

Cocoa Flavonoids & Avocados May Protect Against Cardiovascular Death

The COSMOS study, sponsored by Pfizer and Mars Candies, looked at the effect of Cocoa flavonoids on cardiovascular events such as a heart attack, cardiovascular deaths and consumption of cocoa flavonoids and green tea. There were 21,442 U.S. adults in the study followed for 3.6 years.

The experimental group received cocoa and green tea. While there were just as many cardiovascular events in the study group as in the control group, the number of deaths dropped by 27%. The study was published in the American Journal of Clinical Nutrition and was commented on by David Rakel, MD, FAAFP in the online medical journal Primary Care.

Flavonoids are found in dark colored grapes and berries, apples, pears, green tea and dark chocolate. If you eat 1/4 of a dark chocolate bar you are getting the same dosage the experimental group was given in this study.

Dr. Rakel suggested that Flavonoids maintain the flexibility of the blood vessels as we age. Recent related studies indicate a handful of blueberries or cranberries daily have similar effects. A glass of red wine with a square of dark chocolate and some dark berries suddenly sounds like a healthy snack!

Avocados apparently convey cardiovascular protection as well. In a study published in the March 30, 2022 Journal of the American Heart Association researchers followed 110,00 adults for 30 plus years and found that those who consumed two or more servings of avocado a week had a much lower risk of developing cardiovascular disease then non consumers.