Top Researchers Believe Prevention is the Future of Alzheimer’s Research

Top Researchers Believe Prevention is the Future of Alzheimer’s Research

The Alzheimer’s disease scientific community is changing its research focus from treatment to prevention, according to researchers from the University of Alabama at Birmingham (UAB).

The shift has been driven by increased insights into the mechanisms of the disease, as well as better tools to study Alzheimer’s-associated brain changes in living people.

“In my experience, Alzheimer’s disease is the most feared disease in people over 65,” said David Geldmacher, MD, the director of the Division of Memory Disorders in the Department of Neurology at the UAB. Geldmacher’s remarks were made to Bob Shepard of UAB News in an article about the University’s research efforts.

“And while it’s true that efforts to find a cure for AD [Alzheimer’s disease] have not yet proved successful, much of that fear may be misplaced, since we have learned so much about the disease in the last several decades,” he said.

According to Geldmacher, these insights suggest that prevention is a more likely scenario than a cure.

One of the developments that has changed Alzheimer’s research is the development of a tool for detection of amyloid-beta buildup in the brain of living humans. Only a decade ago, the only way to diagnose Alzheimer’s disease was by an autopsy after the patient died.

Meanwhile, research suggested that amyloid-beta starts aggregating in the brain decades before a person starts developing cognitive symptoms. Now, a brain-imaging method called positron emission tomography (PET) has been adapted to the discovery of amyloid plaques while a person is still alive.

“We can now use PET imaging to look at the brain of a person without any symptoms of memory loss or dementia, and see if a buildup of amyloid is already occurring,” Geldmacher said.

“This doesn’t tell us when symptoms of dementia might start, but does indicate an increased risk for Alzheimer’s at some point in the future. More importantly, it gives us a target for aggressive efforts to reduce the amount of amyloid and hopefully reduce the risk,” Geldmacher said.

Importantly, the researchers point out that prevention in the form of drugs is only one way to approach the disease. In addition to his other obligations, Geldmacher directs the UAB Alzheimer’s Risk Assessment and Intervention Clinic — the first U.S. clinic to offer risk assessments and help in managing modifiable risk factors.

Focus on what can be controlled

Despite what many might believe, Alzheimer’s is not an inevitable fate for those at risk; even when someone has plenty of amyloid plaque in his brain, other factors determine if he will develop Alzheimer’s.

“We focus on the reversible risk factors,” Geldmacher said. “So many people facing dementia focus on the irreversible risk factors, such as ‘I’m getting older’ or ‘My dad or mom had dementia.’ We can’t change those things, but we can change things like levels of physical activity and cholesterol counts and blood-pressure numbers.”

Numerous studies show that those factors are large contributors to Alzheimer’s development. Reducing these risk factors can have a major effect in preventing disease, according to Geldmacher.

UAB also is involved in several clinical trials that aim to prevent Alzheimer’s disease. The A4 study recruits people with a normal memory and cognitive capacity that have amyloid-beta buildup in the brain.

The participants receive solanezumab, an antibody-based drug that aims to reduce brain amyloid-beta, which recently failed to improve mild Alzheimer’s dementia. Despite the failure, researchers speculate the drug may be effective in preventing dementia in people who have amyloid-beta aggregates in the brain.

Another study, called EARLY (NCT02569398), intends to achieve the same goal using another type of molecule.

UAB also participates in the DIAN-TU study (NCT01760005) — exploring genetically inherited Alzheimer’s disease — and EMERGE (NCT02484547), which tests the antibody aducanumab in people with mild cognitive impairment.

“Now that we can use PET imaging to predict the likelihood of Alzheimer’s, we’ve changed how we characterize the disease,” said Erik Roberson, MD, PhD. Roberson is the Patsy W. and Charles A. Collar professor of neuroscience, and primary investigator at UAB for the DIAN-TU trial.

“We used to consider mild cognitive impairment to be a precursor of Alzheimer’s. Now we look upon it as part of the disease, simply an early stage. For prevention strategies to work, we have to consider the first sign of amyloid buildup — before symptoms emerge — as the starting point of Alzheimer’s disease,” he added.

Still look for treatments

Despite the strong focus on prevention, both researchers underscore that it also is crucial to develop better treatments for those already affected by Alzheimer’s. Such efforts should include better support to caregivers and families of patients, they say.

“We can’t reverse dementia once it has begun, and we can’t induce the body to make more neurons after brain cells are lost,” Roberson said. “We have to find ways to ease symptoms and provide a better quality of life.”

Attempts to use a person’s genetic makeup to predict which treatments might work best to reduce symptoms, are ongoing. Other efforts include phone-based support to caregivers.

“I am more optimistic that we will find ways to prevent and treat Alzheimer’s disease now than when I started in the field,” Geldmacher said.

“The Risk Clinic, pre-symptomatic diagnosis, imaging gains — all of these advances have given us new targets for investigation. During my career, we have sequenced the amyloid peptide, and we have discovered the genes that might modify and regulate it. Most importantly, we have developed an understanding of the factors under our control that we can use now to modify the risk for developing Alzheimer’s disease,” he said.


  1. Lance Packer says:

    The essence of the message here is that most researchers still can’t drop the Amyloid hypothesis for Alzheimer’s. They refuse to give up on 20+ years of trying to prove it is the key to all Alzheimer’s causation, in spite of 100% clinical trial failures, increasing evidence of multiple disease pathways, new avenues of treatment (especially repurposing existing drugs), and the simple fact that about half of all people having concentrations of amyloid plaque do not express Alzheimer’s symptoms. I get suspicious of motivation for such blind adherence at many levels of the research process given these stark facts.

    Yes, prevention is important, but so is my wife and millions of other Alzheimer’s sufferers. Are they to be so cavalierly discarded to the wayside of symptom management because they don’t benefit from the past myopic infatuation with amyloid? This is immoral and scientifically illogical. There are lots of alternatives being discovered which must be examined and developed; they must brought into the mainstream of major research centers and funded just like those in the history of amyloid failures.

  2. Marcus Wood says:

    “Alzheimer’s Disease” unfortunately is a catch-all term, like “cancer.” My wife is third generation suffering a distinct pattern that is genetic based with noticeable on-set in early 60s. Until the various forms of dementia that even researchers call AD are differentiated we will continue with flawed research results.

  3. Considering the nature of this disease, it makes sense to focus on prevention. The question is, focus on what? The most promising approach, i.e. immune therapy, despite of the support provided by aducanumab, is practically death. A casualty of an endless series of ill fated clinical studies; yet, those failures were the result of using the wrong strategies to develop effective products. But, the recent successful clinical studies from AXON Neurosciences with a tau vaccine have shown promising results; an outcome that should reinvigorate R&D in active immune therapy or vaccination to prevent AD. Hence, the new R&D efforts should recognize that the past activities were due to incomplete information defective, and start new studies taking into consideration the available body of new information, rather than ignoring it. Indeed, both aducanumab and AXON clinical studies provide strong support to active immune therapy of AD as a preventive approach. Hence, those efforts should end in success, assuming that the experimental designs are well thought and correct. Otherwise, we would see another 20 years of chasing unachievable AD drugs.

  4. While rather new to this (my wife 64, is 2 years into AD), I have been following this and of course, I like others, would rather the weight of research be towards treatment sooner, I can’t dismiss preventive research altogether. When electricity was first developed there were 2 different delivery methods, AC or DC. It didn’t take long for the U.S. to choose which was better. 20+ years into Amyloid brushes on excessive waste. I think a re-focusing is needed.

  5. Robert Lovell says:

    My wife is in stage 7 of this awful affliction. I don’t like the term “disease” – she is not infected. Throughout her life she has been fit, agile and an accomplished skier. She watched her weight, never used much alcohol, had low blood pressure and a great sense of humour. She drank more than three cups of tea per day and was superb at crossword puzzles and general knowledge quizzes.

    All that is gone now, and she has just turned 60. She is now in permanent high care in a hospital for the treatment of mental health.

    Her mother died from AD four years after diagnosis. Five years later, my partner of 25 years presented with the condition. Too young, far too young.

    I would like to think that early diagnosis might lead to better treatment regimes, but I see no evidence that any intervention either ameliorates or slows the advance. So why would you want to know that this affliction is going to rob you of your faculties by. It’s inexorable advance? Why put yourself through the horror and mental agony of the years of knowing your fate? I see no benefit in early diagnosis.

    This is a geneticically inherited condition, and I suspect that only through gene therapy will any solution be found to halt it. I hope for all sufferers that a solution is found soon. For us, it will all be too late.

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