New Program Focuses on Alzheimer's Prevention

By Jamie Santa Cruz

Studies have shown that exercise, nutritional modifications, and sleep can significantly affect the AD disease process, slowing or delaying cognitive decline.

With the rapidly escalating Alzheimer's disease (AD) crisis, prevention has become a pressing concern. A new Alzheimer's Prevention Program at Cedars-Sinai Medical Center in Los Angeles seeks to address related concerns, focusing on the twin goals of early identification of at-risk patients plus launching early interventions to prevent cognitive decline and minimize the impact of the disease.

Currently, there are approximately 5 million patients with AD, but that number is expected to nearly triple to 13 or 14 million by 2050, says Dean Sherzai, MD, MAS, PhD, the program's director. Those figures do not include other types of dementias, which affect an even larger percentage of the population: Up to 10% of individuals aged 65 or older have dementia, and that percentage rises to 45% of those aged 85 or older.

"In the last 20 years we've actually had a reduction in a number of other chronic diseases such as heart disease, COPD, and stroke," says Sherzai. "Alzheimer's is one of the only chronic diseases that keeps growing exponentially."

Treatments Too Late
Although there has been extensive research on AD over the last two decades, to date it has produced little in the way of treatment options. According to Keith Black, MD, a neuroscientist and the chairman of the department of neurosurgery at Cedars-Sinai, there have been nearly 250 different clinical trials focused on treating AD patients, but all have failed. And of the approximately 50 drugs developed to treat AD, they have been almost totally unsuccessful when applied to humans, even after showing promise in animal models.

The current view among many, says Black, is that many of these trials likely failed because they were focusing on patients who were already symptomatic, which meant they were being applied too late in the disease process. "The disease actually starts about 30 years before one becomes clinically symptomatic," he says. "By the time one actually becomes symptomatic, the disease is in a very advanced stage, and patients have already lost a significant number of their brain cells and brain weight, and it's very difficult to treat at that point."

There is substantial evidence, however, that early intervention—during the pre-Alzheimer's stage of mild cognitive impairment (MCI)—can significantly affect the AD disease process, slowing or delaying cognitive decline. According to Sherzai, a variety of studies have shown that exercise, nutritional modifications, and sleep can have an impact, and there is some evidence that cognitive activity can also provide benefits. And although drug therapies have proven unsuccessful to this point, Sherzai believes that many of the failed drugs would have a significant effect if they were applied earlier.

The key focus of the new AD prevention program at Cedars-Sinai, therefore, is on identifying at-risk individuals early on. The program's first goal is to screen large numbers of individuals at the point when they have just begun to show memory problems, in order to characterize their AD risk. The second goal is to immediately put at-risk individuals in a comprehensive care program that will include both lifestyle interventions and drug therapies, with the goal of preventing or at least slowing the disease progression.

"We're not aiming to treat patients with Alzheimer's," says Black. "What we're really trying to do is develop an Alzheimer's prevention program for patients who are in the presymptomatic or early symptomatic stages."

The program's goals are in line with the general direction in which the field of AD treatment is headed. Prevention is currently "a very intense area of interest," according to Black, and he has observed other programs beginning to gravitate toward similar approaches. Currently, however, the Cedars-Sinai program, focusing on screening and comprehensive care for patients in the predisease state, is the only one of its kind. "What's new and different is focusing on patients in the early stages," he says.

Comprehensive Care Program
To screen patients, the program is making use of a novel retinal imaging technique that can reveal the development of amyloid plaque in the retina, which is an extension of the brain. This technique is key, according to Black, because previously a significant problem in AD treatment has been the lack of an effective screening method. PET scans and spinal taps can pick up early signs of the disease, but they cannot easily be applied to large numbers of patients. Cognitive tests, meanwhile, are imprecise and can detect only more advanced stages of the disease. Retinal imaging, however, can be used on a large scale, and it can detect amyloid plaque buildup while patients are still in the predisease state and before they become symptomatic. Meanwhile, the high resolution of the technique may make it easier to determine whether specific interventions are working.

After patients receive an initial evaluation and are determined to be at high risk for developing AD, they are followed at least every six months to a year, according to Sherzai. Most patients will be placed into various clinical trials, including some with drugs that are already FDA approved. For instance, says Black, a current theory is that insulin resistance in brain cells plays a role in AD, so one trial will involve a drug that has already been approved for diabetes for the purpose of reversing insulin resistance. Another trial will involve a drug that is currently used in multiple sclerosis to modulate the immune system and may increase clearance of amyloid plaques. In addition to being placed in clinical trials, a large segment of patients will also enter a specialized care program stressing optimal nutrition, physical activity, sleep, and mental activity—in other words, all the factors that have been shown to exert an effect on cognition at the MCI stage.

Unique to the Cedars-Sinai program, according to Sherzai, are interventions that will focus on a variety of disease pathways. Most other treatment programs have focused exclusively on the amyloid pathway, but the Cedars-Sinai program is targeting other pathways as well, such as inflammation and metabolic processes. According to Sherzai, studies on inflammation and metabolic processes have so far failed when applied to AD patients, but there has been significant response to both of these pathways in animal models, including in studies conducted in Cedars-Sinai's own labs. The failures in human studies, he believes, are largely a result of interventions applied too late, a problem he hopes to address by focusing on patients who are in the predisease or MCI stage.

Raising Awareness in the Medical Community
Eventually, individuals will likely begin to self-refer, but at present the program relies on area physicians to identify prospective patients. Typically, says Sherzai, general practitioners initiate no specific treatment for patients who exhibit symptoms of MCI because until now, there had been nowhere to refer patients. For the present, then, the emphasis is on raising awareness in the local medical community both about the importance of early detection and about the care program available at Cedars-Sinai.

"We are putting out a call to all the physicians in the region as well as giving talks," says Sherzai. "We're looking for patients who are having memory problems later in life that are more than you would expect. It's not the same old 'senior moment,' but it's a little more than that."

Most costs of the program are covered by insurance, since individuals enrolled will be receiving the standard of care for patients with MCI. Any costs not covered by insurance, such as retinal scanning, other specialized testing, and training, are covered by the program itself.

Eventually, according to Sherzai, the goal is to raise funds to build a full, comprehensive clinic, but the cost to do so will approach $50 million, so those plans are in the future. Meanwhile, however, Black believes the information garnered through the existing program can substantially impact the future of Alzheimer's care. "The program will feed back and help us get a better understanding of the disease," he says. "[It's going to] move our knowledge base about this problem forward."

— Jamie Santa Cruz is a freelance writer based in Englewood, Colorado.