Recent Trends in Alzheimer’s Research

By Dr. Michael Plopper
Medical Director, Sharp Clinical Research Center

We are on the verge of breakthroughs in the treatment of Alzheimer’s disease (AD), and we need volunteers to help us get there! The search for a cure is accelerating and recent developments, including results from clinical trials, have been encouraging. For the first time, a treatment designed to change the course of AD, aducanumab, is being reviewed by the FDA for approval.*

We now have a better understanding of the pathology of AD, and therefore can create interventions aimed at specific molecular targets. For example, Eisai Pharmaceuticals has created an antibody, BAN2401, which specifically targets an early form of the toxic protein beta amyloid, which deposits in the brain in AD. It is anticipated treatments are more likely to be successful early in the course of the disease, before extensive amyloid plaque formation.

We also have a better idea of the time course of AD, and that pathologic changes in the brain occur many years earlier than the onset of symptoms. This has led to an increased focus on enrolling people very early in the course of AD into clinical trials to allow our interventions to truly alter the course of the disease.

RELATED | Dementia research in San Diego County

We also now have better methods to confirm that a person has Alzheimer’s, versus another form of dementia. Through greater use of biomarkers, for example presence of amyloid on a brain PET scan (sophisticated brain scan), we can better predict that a person has the necessary brain pathology to respond to the treatment. Other biomarkers are in development, especially looking at less expensive ways of identifying the disease, including blood tests, which are markers of changes in the brain. A recent example of this is the development of NFL, or neurofilament light chain, which is associated with the breakdown of neurons and is measurable by a single blood test.

While we are developing new treatments and new ways to identify those who are likely to develop the disease, we remain completely dependent on volunteers to participate in clinical trials for AD. Through Alzheimer’s San Diego, we at Sharp HealthCare are reaching out to the community to encourage those concerned about memory issues to participate. Through joining a clinical trial, you are able to undergo sophisticated diagnostic testing which is not available to the general population. You receive close attention and follow-up, sometimes over a matter of years, for a disorder which often is not well attended to by medical professionals. You have available to you the possibility for an effective treatment. Most importantly, you are contributing to our ability to find a cure for this most devastating disease.

Click here to learn more about Sharp Mesa Vista Alzheimer’s clinical trials >>

At Sharp Mesa Vista Hospital Clinical Research Center, we are currently conducting several clinical trials including the aforementioned BAN2401, and encourage you to contact us. We conduct free memory screenings on site, and are happy to provide that for you and discuss our available trials if you have an interest. For more information about local research, or to schedule a free memory screen, call us at 858-836-8350.

*Editor’s note, 11/6/2020: An FDA panel declined to endorse aducanumab, saying the study failed to provide “strong evidence” it effectively treated Alzheimer’s. However, the FDA could still approve the drug, as the review continues. It is expected to make a decision by March 2021.

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Other Research Updates

By Alzheimer’s San Diego Staff

It can seem like there’s a new Alzheimer’s “breakthrough” almost every day. We sift through the headlines and pull together the relevant, reputable research updates for you. Here are 8 things you should know about Alzheimer’s and dementia research from the last month.

1. Molecule in blood linked to cognitive decline and heart disease
A new study has found a molecule that could serve as a biomarker to identify those at greater risk of developing dementia in later life: asymmetric dimethylarginine (ADMA). ADMA reduces the amount of nitric oxide which reduces the amount of blood flow in blood vessels.

• Researchers at the University of Aberdeen and the University of Oxford in the United Kingdom, and Flinders University in Melbourne, Australia, analyzed data from 63-year-olds, who had all taken the same mental ability test at Scottish schools in 1947 when they were 11 years of age, as part of the 1936 Aberdeen Birth Cohort.
• Blood samples were taken in 2000, and the participants underwent a series of cognitive tests at regular intervals over the next 4 years.
• After adjusting for their childhood intelligence test scores, the authors of the new study found a link between raised ADMA concentrations in their blood and a decline in cognitive performance four years later.

Low levels of nitric oxide are associated with Alzheimer’s, as well as plaque in the blood vessels and heart disease. So this could potentially mean that ADMA could serve as a biomarker for detecting Alzheimer’s risk earlier in life, or existing treatments for modulating ADMA could be implicated in Alzheimer’s treatment. Researchers warn that this is a small cohort of around 90 people – a larger study would be needed to replicate findings.

Read more at Medical News Today, Medical Express. Read the study at the International Journal of Geriatric Psychiatry

2. Detecting TAU in the bloodstream
Scientists have been able to find a TAU protein, identified as phosphorylated tau 217, present in the bloodstream as a predictor for the presence of beta-amyloid protein. This could eventually become an easier, cheaper alternative to PET scans.

• The authors of the study analyzed the brain scans and blood samples from 34 people and found if a person had amyloid in their brain, they were approximately two or three times more likely to have tau protein in their blood.
• The authors then repeated their test with a new group of 90 participants and still found the same strong correlation.

Read more at Medical News Today, Alzheimer’s News Today. Read the study here.

3. Baby Boomers may face greater cognitive decline than previous generations
Baby Boomers are showing greater cognitive decline than older generations, which is a reversal of previous findings. The change could be due to lifestyle factors, economic factors, and social connection.

• A study from the University of Michigan’s Health and Retirement Survey analyzed data between 1996 and 2014 and found that on average Boomers achieve lower scores in cognitive tests than previous generations.
• The decline is seen in all groups: men and women, across all races and ethnicities, and across all education, income, and wealth levels. Many things may explain this generational difference: conditions in childhood, health conditions like obesity, or aspects of modern life, such as the increase in economic inequality and feeling less connected to friends.
• However, this seems to conflict with a previously published study of reduction in the prevalence of dementia. This trend might reverse as Baby Boomers continue to age.

Read more at Medical News Today, Science Daily, Pharmacy Times. Read the study at The Journals of Gerontology.

4. FDA panel votes against Biogen’s new Alzheimer’s drug

On November 6, 2020, an FDA panel declined to endorse aducanumab, saying the study failed to provide “strong evidence” it effectively treated Alzheimer’s. However, the FDA could still approve the drug, as the review process continues. It is expected to make a decision by March 2021.

Data from Aducanumab’s clinical trials were initially disheartening, but revisiting the data showed that higher doses of the drugs showed promise according to Biogen. One trial was a deemed a success, as patients with early Alzheimer’s who were given high doses of aducanumab experienced significantly less decline on a cognitive test than patients given the placebo. Results from another other trial showed the opposite effect, with patients on placebo doing better than those on the high-dose drug.

However, upon re-reviewing at the results of the second trial, Biogen claims a high dose of the drug was helpful in clearing beta-amyloid. The finding has been controversial: analysts aren’t sure what these findings mean for long term use of the drug, and there have been some notable side effects, like brain swelling.

Read more at NBC News, BioPharmaDive, MedCityNews, Neurology Live

5. Authorizing PET scans through Medicare not associated with cost savings

Many argue that if Medicare covered PET scans, which are normally very expensive, overall medical costs would be reduced by providing families with more accurate, earlier diagnoses. However, a study has found that this is not the case.

• A recent study found that a positive diagnosis for Alzheimer’s with PET scanning failed to reduce hospitalizations by 10% a year after scans took place. However, there were fewer hospitalizations of those scanned and diagnosed with Alzheimer’s compared to those who were scanned and not diagnosed with the disease. The authors of the study scanned 12,684 patients with either dementia or mild cognitive impairment. The findings were compared to those of Medicare recipients who were similar in age, sex, and other factors but did not undergo scanning. What they did notice are suggestions that scans more accurately diagnosed Alzheimer’s disease, which led to altering care methods in up to 60% of cases.

Read more at Dot Med, Associated Press. Read the study here.

6. Keto diet and dementia
A Mediterranean diet has been recommended as good for the heart, and good for the brain. Researchers found that an adapted version of the keto diet, that incorporates aspects of the Mediterranean diet, showed changes in gut bacteria. A new study finds that a modified “Mediterranean Keto diet” may have health benefits that include improved cognitive function and reduced risk for Alzheimer’s.

• The study found that the secret may be in the gut fungi: they initially found a unique fungi co-living with bacteria in the gut of patients with MCI at risk for developing AD.
• The study found some differences in the gut microbiome in the two groups, and the two diets changed the gut microbiome in distinct ways.

Read the original study here. Read more at Medical News Daily, New-Medical.

7. Flu & pneumonia vaccinations tied to lower risk of Alzheimer’s and dementia
Two different studies show unexpected health benefits of getting flu and pneumonia vaccines when it comes to Alzheimer’s risk.

• Study 1: Flu Vaccine
  • People who received at least one flu vaccination were 17% less likely to get Alzheimer’s disease over the course of a lifetime
  • Led by Albert Amran at University of Texas Health, he used machine learning to analyze more than 310,000 health records to study the relationship between flu vaccination and Alzheimer’s disease.
  • Amran and the research team also found that more frequent flu vaccination and receiving a vaccination at younger ages were associated with even greater decreases in risk.
  • Learn more here.
• Study 2: Pneumonia Vaccine and Genetics – up to 40% reduced risk of developing Dementia Later in Life
  • Svetlana Ukraintseva, Ph.D., Associate Research Professor in the Biodemography of Aging Research Unit (BARU) at Duke University Social Science Research Institute, and team, investigated associations between pneumococcal vaccination and the risk of Alzheimer’s disease among 5,146 participants age 65+ from the Cardiovascular Health Study.
  • The researchers found that pneumococcal vaccination between ages 65-75 reduced risk of developing Alzheimer’s by 25-30% after adjusting for sex, race, birth cohort, education, smoking, and the number of G alleles.
  • The largest reduction in the risk of Alzheimer’s (up to 40%) was observed among people vaccinated against pneumonia who were non-carriers of the risk gene.
  • Total number of vaccinations against pneumonia and the flu between ages 65 and 75 was also associated with a lower risk of Alzheimer’s; however, the effect was not evident for the flu shot alone.
  • Vaccination against pneumonia between ages 65 and 75 reduced Alzheimer’s risk by up to 40% depending on individual genes.
  • Read more here

8. Actively speaking two languages protects against cognitive impairment
While bilingualism has been shown to be a protective factor in developing cognitive impairment, actively speaking more than one language shows even more benefit. In a recent paper, researchers conclude that speaking two languages on a regular basis enhances cognitive reserve and delays the appearance of symptoms associated with cognitive decline and dementia. Previous work had already found that the lifelong use of two or more languages could be a key factor in increasing cognitive reserve and delaying the onset of dementia, as well as offering advantages for memory and executive functions.

Read more at StudyFinds, UOC, Ladders. Read the study here.

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To participate in clinical trials here are some links to nationwide registries: