Alzheimer's Risks and Treatment

Testing for Alzheimer’s disease can be a long, costly, and tiresome process for patients, but researchers from Brigham and Women’s Hospital have been working to make the testing process easier on patients.

The group has developed a blood test that would evaluate the level of tau -- the leading protein in the brain associated with Alzheimer’s -- before a patient is even showing signs or symptoms of the disease.

“A blood test for Alzheimer’s disease could be administered easily and repeatedly, with patients going to their primary care office rather than having to go into a hospital,” said Dr. Dominic Walsh. “Ultimately, a blood-based test could replace cerebrospinal fluid testing and/or brain imaging. Our new test has the potential to do just that.”

Though the test is currently in the testing stages, Dr. Walsh is calling it a “transformative breakthrough” based on the early results.

How it works  

Tau is a protein in the brain that is most typically associated with Alzheimer’s. Though tau can develop through a number of different related molecules, the researchers were able to create a model that differentiates between the individual types of tau to ensure that the blood test comes up with the most accurate result.

The researchers have conducted two trials so far with participants from Harvard’s Aging Brain Study and the Institute of Neurology in London. The first group consisted of 65 participants and the second group had 86.

Everyone involved in the study donated samples of plasma and cerebrospinal fluid, which helped the researchers look at the breakdown of the tau protein and see exactly what was linked to Alzheimer’s.

In both tests, the researchers found one strand of tau -- NT1 -- that was effective in predicting and identifying cases of Alzheimer’s.

The next step for the researchers is to open the test up to larger groups of participants to further test its effectiveness on a wider sample. However, these early results proved to Dr. Walsh and his team that they could be on the right track.

“We’ve made our data and the tools needed to perform our test widely available because we want other research groups to put this to the test,” he said. “It’s important for others to validate our findings so that we can be certain this test will work across different populations.”

Fighting Alzheimer’s

While this blood test could potentially change the way doctors go about diagnosing Alzheimer’s, fellow researchers have made strides this year in an effort to better diagnose and treat the disease.

In late September, researchers from the Clinical Memory Research Unit at Lund University in Sweden developed a new brain imaging technique that would help doctors make the most accurate Alzheimer’s diagnoses.

The researchers used a PET scan to evaluate the level of tau in the brain by administering a marker for the protein before the test. The researchers found this new test to be more successful than traditional Alzheimer’s screening methods.

“If the patient has tau in certain parts of the brain, the marker will detect it,” said researcher Oskar Hansson. “The result -- whether Alzheimer tau is present or not -- is very clearly visible on the PET images.”

On the treatment front, researchers found success with a clinical trial for a drug being developed to treat Alzheimer’s.

Amyloid is another protein often found in the brain with Alzheimer’s, and researchers from Biogen and Eisai worked to develop BAN2401 -- an anti-amyloid drug. Though unsuccessful in initial tests, this new and improved version of the drug was found to slow the progression of Alzheimer’s in the study’s clinical trial.

The symptoms and risks associated with Alzheimer’s disease (AD) and dementia have been well-documented, and with over 5.5 million adults across the United States currently suffering, the medical community continues to look for ways to alleviate discomfort and make advancements.

A new study was recently published in the journal American Geriatrics Society that explores the effect exercise has on reducing the risk of falls among Alzheimer’s and dementia patients. The researchers note that over 60 percent of people with AD/dementia fall every year, and they are twice as likely to fall compared with people who don’t have AD/dementia.

More movement

The researchers’ primary goal was to see if AD/dementia patients with neuropsychiatric symptoms -- such as depression, anxiety, irritability, apathy, aggression, hallucinations, etc. -- had a reduced risk of falling when exercise was a regular part of their routines.

The researchers tested this by evaluating the FINALEX trial -- a study that includes a wide demographic of people with AD/dementia and neuropsychiatric symptoms. The study compared participants who had community care -- which didn’t include exercise -- with those who participated in group or home exercise.

The two groups were monitored by physiotherapists for one year and engaged in physical activity for one hour two times per week. The participants were evaluated based on endurance, strength, multitask training, and balance.

One of the biggest takeaways from the study was that the participants who had severe neuropsychiatric symptoms -- such as depression or anxiety -- were at a greater risk for falls, though the exercise proved to be a beneficial method. Additionally, those who had less severe symptoms -- but also didn’t exercise -- still had a high risk of falling.

Those in the exercise groups were found to be at less of a risk for falls, while the opposite was true for those who weren’t in the exercise groups.  

The researchers believe that incorporating exercise into a routine of AD/dementia patients will likely reduce the risk of falls, though more research will need to be done in this area to confirm the results.

Consistent findings

The findings from this study prove to be consistent with a study from earlier this year which found that exercise was linked to improved brain function and can even help prevent memory loss, cognitive function, and diseases like Alzheimer’s and dementia.

Conducted by researchers from UT Southwestern, the study found that keeping active caused nerve fibers in the brain to deteriorate at a much slower rate than for those who didn’t exercise as frequently.

“Evidence suggests that what is bad for your heart is bad for your brain,” said Dr. Rong Zhang of UT Southwestern. “We need studies like this to find out how the two are intertwined and hopefully find the right formula to help prevent Alzheimer’s disease.”

While researchers continue to look for the cause of Alzheimer’s disease, a new study published in Frontiers in Aging Neuroscience explores the connection between the development of the condition and the herpes virus.

Researcher Ruth Itzhaki has spent over two decades studying the relationship between herpes and Alzheimer’s, and in this most recent study she studied the effects that herpes flare ups have on neurons in the brain.

Exploring the connection  

Herpes never goes away entirely, with the condition often flaring up during times of stress or illness. The most severe form of herpes is Herpes Simplex Virus 1 (HSV1), and according to Itzhaki, this strand of the infection could account for “50 percent or more of Alzheimer’s disease cases.”

A key component of Itzhaki’s theory was testing an antiviral drug that could alleviate the risk of senile dementia in people that had herpes.

To get an accurate population sampling to test this theory, Itzhaki utilized data taken from Taiwan’s National Health Insurance Research Database, which documents information on disease and infections.

As nearly all of Taiwan’s population is enrolled in the Database, Itzhaki was able to evaluate three studies published between 2017 and 2018 that described the ways patients with HSV1 were treated by healthcare professionals; the data showed the evolution of those with senile dementia.

Itzhaki found that the antiviral drug was an effective course of treatment for those who were infected with HSV1 and then developed dementia. She also found that those who already have HSV1 areat a much greater risk of later developing senile dementia.

Itzhaki noted that this study focuses on those with the most severe cases of the infection, and future research would have to focus on dementia rates in those with more mild forms of herpes.

Despite this, Itzhaki was confident in the study’s results.

“Considering that over 150 publications strongly support an HSV1 role in Alzheimer’s, these Taiwan findings greatly justify usage of anti-herpes antivirals -- which are safe and well tolerated -- to treat Alzheimer’s disease,” said Itzhaki. “They also incentivize development of an HSV1 vaccine, which would likely be the most effective treatment.”

Recent Alzheimer’s breakthroughs

Alzheimer’s research continues to be a point of emphasis for the medical community, and researchers have made considerable contributions to the field in recent months.

Back in July, a major drug company reported positive results from a clinical trial for a new Alzheimer’s drug. The study involved nearly 900 participants in the early stages of Alzheimer’s, and after 18 months, the drug was found to be successful in slowing the progress of the disease.

Later in the summer, researchers at the University of Adelaide found a link between iron in our cells and a rare genetic mutation that causes Alzheimer’s.

Most recently, researchers from the Clinical Memory Research Unit at Lund University found a new brain imaging technique that would help doctors diagnose Alzheimer’s more accurately. The PET scan involved in the study proved to be more successful than traditional treatments that are currently used to diagnose Alzheimer’s, and the researchers are confident the method will gain popularity worldwide.

Researchers from the Clinical Memory Research Unit at Lund University in Sweden recently published an article detailing a new brain imaging technique that would help doctors diagnose Alzheimer’s more accurately.

In the study, the researchers focused on the spread of two Alzheimer’s-linked proteins throughout the brain -- beta-amyloid and tau. While beta-amyloid can start spreading years before the patient starts showing symptoms of Alzheimer’s, the presence of tau on a brain scan is an indicator that the disease is much further along.

“It is when tau begins to spread that the neurons start dying and the patient experiences the first problems with the disease,” senior researcher Rik Ossenkoppele said in a press release. “If we scan a patient with memory difficulties and he or she proves to have a lot of tau in the brain, we know with a high degree of certainty that it is a case of Alzheimer’s.”

The study shows significant promise for the future of Alzheimer’s research. With the right diagnosis, patients can be put on the right track regarding a medication and diet regimen -- two things that have been linked to improved cognitive function for those living with Alzheimer’s.

The study

The researchers conducted an international study with over 700 participants, and found their method to be successful in correctly diagnosing Alzheimer’s in 90-95 percent of all cases.

“The method works very well,” researcher Oskar Hansson said in the press release. “I believe it will be applied clinically all over the world in only a few years.”

Using a PET scan to determine the level of tau in each patient, the researchers were able to get the most clear and precise image. According to Hansson, the patients received an IV of the tau marker and the PET scan did the rest.

“If the patient has tau in certain parts of the brain, the marker will detect it,” Hansson said. “The result -- whether Alzheimer tau is present or not -- is very clearly visible on the PET images.”

The new test proved to be more successful than traditional treatments that are currently used to diagnose Alzheimer’s. Because of the overlap between Alzheimer’s symptoms and those of other conditions, getting an accurate diagnosis can be difficult. The researchers’ tau test showed its effectiveness -- beating out the often used beta-amyloid-PET scan and MRI scans.

The full study has been published in Journal of the American Medical Association (JAMA).

After a series of disappointments, a major drug company has reported promising clinical trial results from its drug to treat Alzheimer's disease.

Massachusetts-based Biogen and its Japanese partner Eisai jointly announced positive topline results from the Phase II study with BAN2401, an anti-amyloid drug. The buildup of amyloid plaques in the brain is thought to be a key contributor to Alzheimer's.

The study was a large one, involving 856 patients in the early stages of Alzheimer's disease. The study achieved “statistical significance” in its effectiveness at 18 months, slowing the progression of the disease.

Researchers were encouraged because BAN2401 is the same drug that produced disappointing results back in December. The difference, they say, is the drug was only monitored for 12 months. In the second trial, the extra six months produced an improvement.

Mild to moderate side effects

This time, the researchers said BAN2401 showed an acceptable tolerability profile through 18 months of treatment. There were some side effects, but they were characterized as mild to moderate in severity.

All in all, researchers in the field of Alzheimer's disease treatment and study expressed new hope at the results.

“The 18-month results of the BAN2401 trial are impressive and provide important support for the amyloid hypothesis,” said Jeff Cummings, M.D., founding director, Cleveland Clinic Lou Ruvo Center for Brain Health. “I look forward to seeing the full data set shared with the broader Alzheimer’s community as we advance against this devastating disease.”

Alzheimer's is a type of dementia that causes problems with memory, thinking, and behavior. Symptoms usually develop slowly and get worse over time, becoming severe enough to interfere with daily tasks. Eventually, the disease is fatal.

Not a normal part of aging

Aging is a major risk factor, but the Alzheimer's Association points out that the disease is not a normal part of aging. Currently, an estimated 5.5 million people who are 65 or older have been diagnosed with Alzheimer's disease. About 200,000 people under age 65 have what is called younger-onset Alzheimer's.

“The prospect of being able to offer meaningful disease-modifying therapies to individuals suffering from this terrible disease is both exciting and humbling,” said Dr. Alfred Sandrock, executive vice president and chief medical officer at Biogen. “These BAN2401 18-month data offer important insights in the investigation of potential treatment options for patients with Alzheimer’s disease and underscores that neurodegenerative diseases may not be as intractable as they once seemed.”

In an interview with CNBC, Biogen chairman Stelios Papadopoulos called the results an encouraging first step, but he believes further progress is possible. He said a best case estimate for when BAN 2401 could be available to treat patients would be in two to three years.

Recently, researchers began developing a potential therapy for concussions, using an FDA-approved drug that helps reduce the harmful effects of swelling. Specifically, they found that the expression of a certain membrane protein called aquaporin-4 increased dramatically after a head injury and caused damage.

While work on that project continues, other experts believe that aquaporin-4 may be a prime target for Alzheimer’s research. A study conducted by researchers from Oregon Health & Science University has revealed a connection between the protein and possible prevention of the brain disease. While it may not materialize into a lasting cure, the researchers believe that their work could contribute to future therapies and prevention strategies.

"It suggests that aquaporin-4 might be a useful target in preventing and treating Alzheimer's disease," said Dr. Jeffrey Iliff, senior author of the study. "However, we aren't under any illusion that if we could just fix this one thing, then we'd be able to cure Alzheimer's Disease."

System breakdown

In a broad sense, Alzheimer’s isn’t a disease that happens all at once – it takes time and is much more progressive. There is currently no cure for it, but several therapies have been developed that may be effective in slowing it down; the researchers believe that aquaporin-4 could provide another.

Aquaporin-4’s functions as part of the brain's glymphatic system. Under certain conditions, it is the protein that allows cerebral-spinal fluid to enter the brain and wash away other proteins like amyloid and tau – the build up of which are main drivers of Alzheimer’s.

The researchers believe that when the system regulating aquaporin-4 breaks down, amyloid and tau are allowed to build up unchecked, leading to nerve damage. They tested this theory by analyzing three groups of 79 donated brains – people younger than 60 with a history of Alzheimer’s, people younger than 60 without a history of any neurological disease, and people over 60 without Alzheimer’s.

They found that aquaporin-4 levels were well organized and ordered in the brains of people without Alzheimer’s or a history of neurological disease, but older brains with Alzheimer’s had very disorganized aquaporin-4 levels. The researchers posit that Alzheimer’s may have developed in these brains due to decreased function to clear away harmful proteins.

Last year, the researchers were given a $1.4 million grant from the Paul G. Allen Family Foundation to continue their research and develop new imaging techniques that could capture brain processes as they happened. The team’s full study has been published in JAMA Neurology. 

There have been many promising breakthroughs in the field of Alzheimer's disease research, giving hope to millions at risk of the devastating disease.

The flip side of that, of course, is when these hopeful promises just don't pan out. So it was with great disappointment that pharmaceutical giant Eli Lilly announced that its promising new drug solanezumab “did not meet the primary endpoint” in it's final, phase 3 testing. The company said it would not seek Food and Drug Administration (FDA) approval of the drug.

Lilly said patients in the trial who were treated with solanezumab did not experience a statistically significant slowing in cognitive decline compared to patients treated with placebo. It dashed the hope raised by previous research.

Solanezumab is a mono-clonal antibody targeting excess amyloid in the brain. It was designed for patients considered to be at risk of Alzheimer's but who had not displayed symptoms of the disease.

Slowing memory loss by 10 years

Researchers were hopeful that doctors might eventually use positron emission tomography (PET scans) to locate beta amyloid as it begins to form plaques in the brains of people with Alzheimer’s disease 10 to 20 years before they show any symptoms of the disease.

The drug would then be administered, removing the harmful protein from the brain before it could begin to build up. Researchers were hopeful it might slow memory loss by at least 10 years.

"The results of the solanezumab EXPEDITION3 trial were not what we had hoped for and we are disappointed for the millions of people waiting for a potential disease-modifying treatment for Alzheimer's disease," said John C. Lechleiter, Ph.D., chairman, president and CEO of Eli Lilly, in a written statement. "We will evaluate the impact of these results on the development plans for solanezumab and our other Alzheimer's pipeline assets."

Lechleiter also issued a statement to the Alzheimer's community in the video below, vowing his company would continue pursuing effective treatments.

Lilly said it would present further findings from the study at the Clinical Trials on Alzheimer's Disease meeting in early December.