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Alzheimer’s

Alzheimer’s disease is marked by protein deposits and twisted fibers that build up in the brain and, scientists believe, destroy nerve cells. This causes dementia, which starts as mild memory loss and eventually leads to death. It’s the sixth leading cause of death in the United States, and the only one in the top 10 that can’t be prevented, cured or slowed. Not surprising, it’s also the most feared disease, after cancer. Although the facts are scary, promising research offers hope for the future.

the genetic link
Although the greatest risk factor for Alzheimer’s is advanced age, there’s a genetic component to both early-onset and late-onset types of the disease. Scientists don’t yet know what causes Alzheimer’s, but they do know which genes are involved, and they’re hopeful that information can lead to a cure.

early-onset
There’s no definitive genetic cause for most Alzheimer’s diagnoses. A notable exception is the early-onset form of the disease, which accounts for just 1 percent of all cases. There are three genes that, if inherited, guarantee a person will experience Alzheimer’s symptoms, typically before age 65 and sometimes as early as 30. “The only scenario where it’s invariable, the most tragic scenario, is someone with early-onset disease,” says SLUCare geriatric psychiatrist Dr. George Grossberg.

Testing is available for the APP, PS-1 and PS-2 genes that cause early-onset Alzheimer’s, but doctors warn against it. The results could affect insurance eligibility and have emotional ramifications. “Research has shown that once people become aware of their risk of any disease, they worry so much that their quality of life deteriorates,” Grossberg says. “We don’t have a way to treat Alzheimer’s, so the risks outweigh any potential benefits of knowing.”

Doctors are hopeful more will be understood soon about this powerful genetic link, thanks to research with a St. Louis connection. Washington University is part of an international partnership of leading scientists examining early-onset Alzheimer’s. The multi-year Dominantly Inherited Alzheimer Network (DIAN) study hopes to uncover clues that could lead to treatments for all forms of dementia.

late-onset
Scientists haven’t found a direct genetic link for the most common form of Alzheimer’s, which is called late-onset or sporadic. In these cases, certain genes can increase the risk, but don’t guarantee it will happen, says Dr. David Carr, an Alzheimer’s specialist at Washington University. The gene with the strongest influence is APOE-e4, which might be a factor in 20 to 25 percent of Alzheimer’s cases.

Advancing age is the greatest known risk factor for Alzheimer’s, and like genetics, it is beyond control. “Family history is important, but it’s far from an absolute in the most common type of Alzheimer’s,” Carr says. People who have a close relative with Alzheimer’s tend to overestimate their own risk for getting the disease, which Grossberg says is an exercise in needless worry. “If you compare your risk to a family where Alzheimer’s disease has never been found, you are at a greater risk, but it’s still relatively small, he notes. “The only strong genetic finding that’s predictive is in the very small group of early-onset familial cases.”

important research
So far, genetic breakthroughs in Alzheimer’s research have been useful only in diagnosis, Grossberg says. Scientists hope, however, that their work will eventually lead to a cure. The first step toward that goal is to uncover what causes an affected person’s brain cells to die. “That’s the Nobel Prize question,” Grossberg says. “It’s a huge issue and a major limitation in developing a vaccine or something that can stop the disease in its tracks.”

There are at least 225 clinical trials being conducted across the country, according to the Alzheimer’s Association, and some continue to investigate how genetics may cause or accelerate the disease. “If you can hone in on a genetic variation or mutation that is impacting the function of an enzyme or protein, you may be able to design a drug that hopefully will block the negative effects or enhance the positive effects,” Carr says.

treatment options
Currently, there’s no way to cure Alzheimer’s or stop it from progressing. For now, patients rely on a mix of medications and non-drug treatments to mitigate symptoms such as memory loss and confusion.

early detection
Before seeking treatment, get an accurate diagnosis. While there’s no tool that can definitively test for the disease, doctors can make an educated guess after first ruling out other possibilities. Alzheimer’s disease accounts for 60 to 80 percent of all dementia cases, but hundreds of other issues cause similar symptoms. Hypothyroidism, sleep apnea, depression, vitamin B12 deficiency and even wax in the ears can cause memory problems.

“Not everything is Alzheimer’s. There are treatable issues that, if you catch them early, can make a big difference,” says Dr. John Morley, an endocrinologist and geriatrician who sees patients in Des Peres Hospital’s Senior Care Clinic. “I had a lawyer with clear dementia on the screening test. I discovered he had sleep apnea, and after he was treated, his memory returned to normal.”

Anyone concerned about Alzheimer’s should talk to their physician. Morley recently helped develop a rapid screening test that assesses memory problems in less than 3 minutes. “If doctors only ask you a few questions about what happened during the week, that’s not enough screening,” he says. After testing, a patient may be referred for a brain scan to look for plaque, but often simply ruling out other disorders and diagnosing cognitive impairments is enough to confirm suspicions, Morley says.

current therapies
Early, precise diagnosis is important, SLUCare’s Grossberg says, because evidence suggests current FDA -approved drug therapies are most effective when they begin early and continue over the course of the disease. “Even though we don’t have a cure, treatment is available for all stages of Alzheimer’s disease, from mild and moderate to more advanced,” he says.

The Alzheimer’s Association awarded its first research grants in 1982. That work led to one of the four medications currently approved to treat Alzheimer’s. “They can’t halt the disease or revive dead brain cells, but they may help the individual maintain their functioning for a longer period of time,” Grossberg says. “That approach is better than not doing anything at all, but we’re not happy about where we’re at with treatment now.”

on the horizon
Alzheimer’s drugs currently available only mask symptoms. Researchers are hoping they can uncover a breakthrough drug that will delay or stop cell damage. “There are close to 300 different treatment approaches in the pipeline,” Grossberg says. “They’re in different stages of development, most of them very early.”

Scientists are exploring everything from vaccines to immunity-enhancing agents, Morley explains, but nothing of a preventive nature is close to approval. He warns patients not to get their hopes up when they hear reports of promising new drugs. “They look very exciting, but I think most of the results are overblown because we are testing on animals now. Going from mice to men is a very big leap.”

An Alzheimer’s researcher himself, Morley says new drugs are likely 10 to 15 years from hitting the market. “It’s all very exciting, but the problem is, it’s years away from getting to patients.” Anyone can help advance this important research, he says, by using the Alzheimer’s Association’s TrialMatch service to sign up for a clinical study. Scientists need both individuals with Alzheimer’s and healthy volunteers to participate in their research.

prevention possibilities
More research is needed to prove definitively whether Alzheimer’s can be prevented, and which strategies are most effective. Until then, however, doctors say a handful of lifestyle changes that promote good overall health should be embraced.

heart-head connection
“There’s no proven way to prevent, treat or slow Alzheimer’s, but there are ways to reduce the risk of cognitive decline,” says Stacy Tew-Lovasz, president of the St. Louis chapter of the Alzheimer’s Association. Mitigating risk, she says, begins by remembering that what’s good for the heart is also good for the head.

Autopsy studies have shown that as many as 80 percent of individuals with Alzheimer’s also have cardiovascular disease, according to the Alzheimer’s Association. That suggests that reducing risk for conditions linked to cardiovascular problems, such as diabetes or high cholesterol, also can reduce the risk of developing Alzheimer’s.

Physical exercise and diet top the list of risk-prevention strategies, Tew-Lovasz says. “There are very clear benefits to exercising on a regular basis, three to five times a week, versus having a sedentary lifestyle,” she notes. In addition to a mix of cardio, strength and stretching, she says a Mediterranean diet of lean meats and fish, fresh fruits and vegetables, and healthy oils may be beneficial for protecting the heart and brain.

pillars of prevention
“There are things you can do right now to have an impact on this disease,” Tew-Lovasz says. Studies suggest that getting plenty of sleep, about eight hours a night, boosts brain health. Stress-management techniques, such as meditation or tai chi, also are beneficial.

Many studies show a link between staying mentally active and reducing the risk of cognitive decline. Doing crossword or sudoku puzzles isn’t enough, Tew-Lovasz says. “The greatest benefits come from continuous, lifelong learning, which is very different than doing a puzzle.” She suggests learning a new language, studying a musical instrument or taking up a new hobby. “Challenge yourself with something that will stimulate the brain in different ways,” she says.

It’s also important to stay socially engaged. “There are some who think 60 or 70 percent of healthy aging is about maintaining social connections,” Tew-Lovasz says. Whether volunteering at church, playing bridge with friends, or taking a group fitness class, community involvement may protect against dementia. There also are proactive steps people can take to reduce the feelings of desperation often associated with the disease, says Chandelle Martel, manager of Bethesda’s Geriatric Care Program. “You can be in control for your entire life, if you plan it right.” As a social worker and care manager, Martel assists people dealing with Alzheimer’s. One practice she believes in is gathering all stakeholders in the person’s life, including family and friends, and allowing the patient to communicate his or her wishes for treatment and end-of-life issues. Those conversations, along with preparing documents like a health care directive and a living will, ease fear and worry, she says. “The senior can still be in charge,” she advises. “It also helps alleviate guilt for caregivers.”

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