Flu Vaccination May Guard Against Alzheimer’s Dementia

While it is early summer here in North America, most primary care practices have already ordered their influenza vaccine for the fall of 2022. Our practice will be using the “senior” high dose quadrivalent vaccine for patients 65 years of age and older as recommended by the ACIP (American College of Immunization Practices), a division of the CDC.

While experts debate when to administer the vaccine, we prefer to do it between Halloween and Thanksgiving based on when influenza arrives in South Florida and the limited length of protection seniors get from the vaccine. Flu shots can protect against serious infection and hospitalization in most cases.

Avram Bukhbinder, MD, of the University of Texas Medical Center in Houston believes the vaccine also protects seniors against Alzheimer’s disease. His work was published in the Journal of Alzheimer’s Disease recently.

His group looked at almost one million influenza vaccinated adults and compared them over time with a similar sized unvaccinated group of senior citizens 65 years of age or older. The median age was 73.7 years and 57% were women. All were free of dementia over the six year “look back period”.

They followed these groups for 46 months and found the risk of developing Alzheimer’s Disease was 40% lower in the vaccinated group. The paper did not determine why the flu vaccine lowered the risk of developing Alzheimer’s dementia. Dr. Bukhbinder hypothesized that the vaccine may have prevented severe inflammation seen with infection reducing the development of amyloid plaques and neurofibrillary tangles. An official with the Alzheimer’s Association was quick to point out that possibly those who took flu shots were more health conscious leading to less development of Alzheimer’s Disease.

Further research is warranted but this study provides an additional incentive to obtain your flu shot this fall.

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.

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.

An Extra Tablespoon of Olive Oil Per Day May Keep Death Away

Dr. Marta Guash-Ferre’ and team at Harvard T. H. Chan School of Public Health evaluated whether substituting a teaspoon of olive oil daily to replace margarine, butter, mayonnaise and dairy fat led to a drop in the likelihood of death from cardiovascular disease, cancer, dementia and respiratory diseases.

Her team looked at 92,00 participants who were free of cancer and cardiovascular disease in 1990. Every four years, for the next 28 years of follow-up, the researchers assessed each person’s diet through a detailed questionnaire. Olive oil consumption was determined from olive oil used on salads, cooking, or used on breads and foods.

Their long-term calculations showed that olive oil consumption increased in the study participants during the test period while consumption of margarine decreased, and other fats stayed the same. Participants with higher olive oil consumption were more likely to be physically active, less likely to smoke, consumed more fruits and vegetables than lower olive oil consumers. When the researchers compared those with little olive oil consumption to those with the highest consumption, the high consumers had a 19% lower risk of death from cardiovascular disease, a 17%lower risk of cancer death, a 29% lower risk of death from dementia and an 18% lower risk of respiratory disease death. The study also concluded that substituting ten grams of olive oil per day (a bit less than one tablespoon) for other fats such as butter, margarine, mayonnaise, and dairy fat their death risk dropped by 8-34% from all causes.

In reviewing the data, its seems that their study group represented an extremely well-educated health-conscious group of individuals. Substituting olive oil for other fats is certainly a worthy goal based on these numbers and I will certainly aim to try it.

Dementia – Multiple Trials & Interventions to Delay Cognitive Decline

There have been multiple studies presented at scientific meetings recently that look at what influences the development of dementia and what may delay it. We have known for years that anything that interferes with sensory input to the brain can lead to increased risk of dementia. Improving hearing with hearing aids was found long ago to improve your chances to avoid dementia as you age.

A recent study published by Cecelia Lee, MD MS in JAMA Internal Medicine revealed that individuals undergoing improvement of vision with cataract surgery reduced their risk of dementia significantly. The study looked at over three thousand patients undergoing cataract surgery and or glaucoma treatment between the years 1994 and September 2018. Patients were evaluated every two years during the study with Cognitive Abilities Screening Instrument (CASI) and those with scores indicating a cognitive decline were referred for more detailed testing. Although having cataract surgery reduced your risk of dementia treating glaucoma, it did not provide the same risk reduction for dementia. There were numerous theories on why cataract repair helped based on the type and quality of light reaching the retina and brain, but it was an improvement to normal in another of our senses.

Another study looked at the effect of taking a daily multivitamin on the risk of developing dementia. This study funded in part by Centrum Silver and called the COSMOS trial looked at 2262 men and women all older than sixty-five with a mean age of seventy-three. They were evaluated before entry into the study with cognitive tests and again every year for three years. Those taking a multivitamin exhibited a “slowing of cognitive aging by 60%”. Taking a multivitamin seems like an easy inexpensive intervention to preserve cognitive function and hopefully these results will be confirmed and reproduced in future studies.

Recent studies looked at the benefits in maintaining brain volume and cognitive function when drinking coffee and tea containing caffeine. The studies showed that coffee drinkers benefitted more than tea drinkers but they both benefitted in reducing the risk of cognitive decline. A recent publication took the research a step further by having test subjects drink several cups of coffee and several cups of tea per day. The benefits of drinking both beverages on the same day were far greater than drinking individually.

    Last but not least , a study executed by the Cleveland Clinic Genomic Medicine Institute under the direction of F. Cheng, PhD, looked at insurance data to determine if taking Viagra (Sildenafil) modified your risk of developing Alzheimer’s disease (one form of dementia)  The study over a 6-year period suggested that Viagra users were 69% less likely to develop Alzheimer’s disease than non-Sildenafil users. This study, which was announced and covered extensively on television news and the print media, resulted in more phone calls to my office than the other studies. This was an observational type of study and further research is needed before prescribing this medication for this preventive reason.

Of interest to me was the fact that most of the men who called asking for Viagra after reading this article were on other medications for other medical illnesses that prevented them from safely using Sildenafil products.

FDA Approves New Non-Verbal Computerized Test for Cognitive Impairment

Many of you are used to the Mini Mental Status Test or Montreal Cognitive Assessment Test during which an examiner asks you verbal questions and there are some pictures to interpret. This week the FDA approved a new test taken on an iPad or tablet using images of animals. The test asks you to classify the pictures as either an animal or nonanimal. The advantage of using the nonverbal picture test is it eliminates bias based on level of education and culture. In addition, it eliminates a successful score on subsequent tests due to a “learning the test” effect.

The test results can be incorporated into a patient’s electronic health medical record and become a part of the patient’s permanent chart. The test was given to 230 volunteers. There were eighty individuals with mild cognitive impairment, 55 with mild Alzheimer’s Disease and 95 healthy individuals. The results revealed the test was as sensitive as current verbal tests currently used to detect early dementia.

CognICA is the name of this new test and will be available for purchase in the next few months

Blood Test Biomarkers for Alzheimer’s Disease

Adam Boxer, MD, PhD of the University of California San Francisco and associates published in Lancet Neurology a study which discussed their identifying two chemical biomarkers that distinguish normal patients from those with Alzheimer’s disease or other types of dementia. The two blood markers, phosphorylated tau 217 (p-tau217) and phosphorylated tau 181(p-tau181) showed “exquisite sensitivity and specificity” for discriminating Alzheimer disease from normal and other entities.

These biomarkers are currently only being used for research purposes and are not available to be used by doctors and patients through commercial labs yet. The researchers believe a commercially available lab test will be developed within the next few years

Walking Helps Stave Off Dementia

A paper presented at the Alzheimer’s Association 2021 International Conference by Natan Feter, PhD of Pelotas, Brazil suggested that even low levels of exercise as you age reduces your chances of developing Alzheimer’s type dementia. Their study looked at the English Longitudinal Study of Aging that included 8,270 individuals 50 years or older between the years 2002-2019. Fifty-six percent were female with a mean age of participants of 64 years. Over the 17-year course of the study, 8% of the participants developed dementia. T

They found the risk of dementia increased by 7.8% for each year increase in age. The risk of developing dementia was reduced by individuals who were physically active – more so for moderate to vigorous exercisers than for low level exercisers. Eighty-year old’s who were vigorous exercisers turned out to have a lower risk of dementia than inactive 50 -69-year-olds.

The message from the study was simple if you exercise even one time a week you reduce your risk of developing dementia. Walking certainly counts favorably. A reviewer simply said that regular walking is good for the heart and what is good for the heart is good for the head.

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.

Sleep Apnea and Cognitive Impairment

Convincing a patient to undergo a sleep analysis for obstructive sleep apnea is a difficult task. During our history taking session, we ask about excessive snoring, periods of not breathing while asleep, daytime sleepiness and we look at the patient’s body habitus, weight and height. Often, the patient’s spouse or partner has complained about their snoring keeping them up. Most of the time, when I ask about this the response is, “Why go for an evaluation if I am not going to wear that mask anyway?  I have a friend who has a CPAP mask and I am just not going to do that.”

Obstructive sleep apnea and periods of apnea (not breathing) results in the lung blood vessel blood pressure rising.  We call it pulmonary hypertension.  It is different from systemic arterial essential hypertension in that traditional blood pressure medicines do not lower the pulmonary pressures.

If you examine our heart and lung anatomy you realize that the very non-muscular right side of the heart, primarily the right ventricle, pumps blood a short distance to the lungs to exchange gases and removing wasteful gases in exchange for oxygen. That oxygen rich blood returns to the left side of the heart where the very muscular left ventricle pumps it out to the body.

When the body’s systemic blood pressure rises the left side of the heart has to work harder. The muscular left ventricle is much more suited for that task than the right ventricle is suited to pump against pulmonary vessel hypertension.  The result is the right heart fails much sooner than the left side and the treatment options and medications are far less successful.  This explanation to patients is often received, digested and dismissed as hypothetical and down the road.

This week the American Academy of Neurology received a presentation by a group at the Mayo Clinic in Rochester that showed that patients with untreated sleep apnea produced an increased amount of tau protein deposition in the brain. Tau protein deposition is associated with Alzheimer’s disease.  The researchers, led by Diego Z. Carvalho, MD, are not sure if more Tau protein accumulates in brains of people with untreated sleep apnea or if Tau protein accumulation actually leads to sleep apnea?  That research is ongoing.

The lesson is that sleep apnea is something that needs to be diagnosed and treated. I am a fan of referring patients’ to sleep evaluation centers where that is the primary disease state reviewed.

While sleep apnea is one of the abnormalities evaluated, there are many other disorders of sleep that can be recognized and treated to improve patient sleep. At home sleep monitors are available as well but may be limited in diagnosing sleep apnea alone.

If you are determined to have obstructive sleep apnea then treatment choices include weight loss, laser treatment of the uvula, dental appliances to open up your airways, adjustments to your sleep position and many types of facial and nasal CPAP devices.

Most of my patients who try a CPAP mask require 8-12 weeks to adjust to it. Once adjusted to it, their quality of sleep is so good that I rarely have to convince them to keep using it.