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.
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