The rush for research
More than 5 million Americans live with Alzheimer’s disease, a figure that’s expected to triple by 2050. It’s the sixth-leading cause of death in the United States; of the top 10 causes of death, Alzheimer’s is the only one that cannot be cured, slowed, or prevented.
Medical experts are hoping to change those statistics. About 100 drugs are now in U.S. clinical trials for Alzheimer’s. “We desperately need an answer,” says Heather Snyder, PhD, director of medical and scientific operations at the Alzheimer’s Association. “Every idea should be explored to get us to have a way to stop and slow the progression of the disease.” There are currently five FDA-approved Alzheimer’s drugs, which temporarily boost performance of brain chemicals in about half of the people who take them. They don’t treat the underlying decline and death of brain cells.
Scientists are hopeful one of the following areas of research may lead to a solution that will.
Breakthrough: Importance of lifestyle changes
Though scientists have traditionally studied how to treat later stages of Alzheimer’s, they are now also studying whether we can prevent disease, particularly through lifestyle changes. “Scientists are looking at the difference between people who have a specific [lifestyle] ‘recipe’—such as nutritional guidance, physical activity, cognitive intervention, and management of cardiovascular risk factors—and those who don’t, to see if people who have that intervention have less of a chance of developing Alzheimer’s,” says Snyder.
A 2014 Finnish study of 1,260 volunteers, ages 60 to 77, found that people who exercised, changed their diet, socialized, and did memory training performed significantly better on memory tests two years later than those who did not. Though the study doesn’t prove these changes prevent Alzheimer’s, it suggests that engaging in physically and mentally stimulating activities help protect the brain.
Breakthrough: Identifying beta-amyloid sooner
Beta-amyloid is protein that clumps together to build plaques in the brain, which can block cell-to-cell communication and activate immune system cells that trigger inflammation. Many anti-amyloid therapies are currently being tested in human trials, but of particular concern to scientists is whether finding beta-amyloid in patients early (before memory changes appear) and then treating with medication might be especially effective. “Scientists are taking pictures of participants’ brains, checking to see if they have amyloid, and then testing an anti-amyloid therapy to see if they can change or slow the cognitive changes in those individuals,” says Snyder. The Alzheimer’s Disease Neuroimaging Initiative, for example, is an ongoing study that has been investigating how to detect Alzheimer’s disease at the earliest stage possible through brain-imaging techniques since 2005. The study will conclude in 2016.
Breakthrough: Exploring insulin treatments
Irregularities in insulin, a hormone that helps regulate blood sugar, may play a part in brain changes associated with Alzheimer’s. Insulin allows glucose to enter the brain's neurons, which helps them function. For this reason, scientists are studying how to deliver insulin to the brain without disrupting blood sugar levels elsewhere in the body. Researchers are currently exploring insulin nasal spray that reaches the brain within minutes. A 2015 Wake Forest Baptist Medical Center study tested 60 adults diagnosed with mild cognitive impairment or mild to moderate Alzheimer’s, administering nasal spray to certain participants for 21 days. Those who received the highest doses showed significant improvement in processing and retaining information compared with those who received a moderate dose or no dose. Though previous trials had shown promise for insulin spray, this is the first study to use insulin detemir, a long-lasting type of insulin often used to treat diabetes. Further studies will test the safety and effectiveness of the treatment for Alzheimer’s patients.
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Breakthrough: Repurposing other medications
It's possible that drugs already approved to treat other conditions may also help with Alzheimer's disease. One example: Yale University School of Medicine researchers found that a cancer drug, saracatinib, restored memory loss and reversed brain problems in mice. They are now testing its effectiveness in humans. “They are investigating a pathway that results in the activation of a protein called Fyn kinase,” says Snyder. The cancer drug targets the Fyn kinase protein, which plays a major role in how clusters of beta-amyloid damage brain cells. The research team has been able to expedite trials (because the drug is already used to treat cancer) and is currently enrolling more participants for a large trial to assess its safety for treating Alzheimer’s. A total of 152 participants will receive either saracatinib or a placebo for one year. Researchers expect results within two years.
Breakthrough: Understanding tau tangles
Tau is a protein in the brain that can twist into microscopic fibers called tangles. When this happens, the brain’s transport systems can no longer stay straight and eventually disintegrate. Cells die because nutrients can no longer move through them. “Tau tangles are not unique to Alzheimer’s disease,” says Snyder. “Tau clumps in other brain diseases, like Parkinson’s disease dementia, so it’s being researched in other communities as well.”
In a 2015 Mayo Clinic study, researchers examined more than 3,600 postmortem brains and found that the progression of dysfunctional tau protein is a major driver in memory loss and cognitive decline observed in Alzheimer’s patients. A Harvard study is currently using new PET scan imaging to track tangled tau buildup in up to 500 people with beta amyloid buildups who are at risk for memory loss. In the study, expected to be completed in 2020, patients will be given anti-amyloid treatments, which researchers hope will also help control tau.
Breakthrough: Investigating the role of heart health
Brain health may be intricately tied to heart health. In a 2014 study published in JAMA Neurology, researchers examined brain images and artery stiffness of dementia-free elderly adults. At the beginning of the study, 48 percent of patients had plaque in their brain; after two years, that figure grew to 75 percent. Plaque development was associated with increased artery stiffness.
In a Vanderbilt University Medical Center study released earlier this year, researchers recorded participants’ cardiac index (a measure of how much blood the heart pumps), and found that those with decreased heart function were two to three times more likely to develop significant memory loss over a follow-up period of up to 11 years. “For the average adult, the brain accounts for 2 percent of overall body weight but receives as much as 15 percent of blood leaving the heart,” Angela Jefferson, PhD, principal investigator of the study, said in a press release. “But as we age, our vessels tend to be less healthy. They become less adaptable to blood flow changes, and those changes may affect brain health and function.”
Breakthrough: Early detection
Though much research about Alzheimer’s disease has been focused on its later stages, in which people have significant memory changes that affect their daily life and independence, a new research trend is clear: early detection. There may be a window of time to identify underlying biological changes and intervene to slow or stop the progression of the disease. “We have new technologies and tools at our disposal to identify people at the earliest stages of the disease," says Snyder. Though there is not yet definitive evidence about what can prevent Alzheimer’s, the National Institute on Aging recommends making choices for better overall health—such as exercising regularly, engaging in social and intellectually stimulating activities, eating a healthy diet, and getting treatment for depression—as research continues to pinpoint a possible solution.
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