Risk factors for Alzheimer's disease

Alzheimer's disease has joined cancer at the top of the list of feared diagnoses, and although Alzheimer's does have the potential to devastate millions of patients and families, there are reasons for hope - and possibly opportunities to reduce risk or alter the course of disease progression, according to Keith Black, MD, professor and chair of the Department of Neurosurgery at Cedars-Sinai.

"With no cure, no effective treatment and not even a reliable, practical way to diagnose it, Alzheimer's has become one of the most dreaded diseases of our time," said Black, director of Cedars-Sinai's Maxine Dunitz Neurosurgical Institute, director of the Johnnie L. Cochran, Jr. Brain Tumor Center and the Ruth and Lawrence Harvey Chair in Neuroscience.

"When we talk about new noninvasive technology aimed at providing early detection, many people say they wouldn't want to know in advance. The outlook is just too frightening and they say there's nothing they could do about it anyway. But there's a lot of misinformation about the disease, and emerging data suggest that some very simple things we can do right now might change its course, especially if we intervene early in disease progression - years before symptoms begin," Black said.

Until recently, the hallmark changes in the brain leading to a diagnosis of Alzheimer's disease could be seen only after death in brain sections treated to reveal plaques containing beta-amyloid protein and neurofibrillary tangles containing abnormal tau protein. Special imaging studies - positron emission tomography, or PET scans - and tests of cerebrospinal fluid now offer the best - though imperfect - chance to detect and diagnose the disease in living patients. But spinal taps cause discomfort and PET scans require injection of a radioactive tracer. Even if the tests were 100 percent accurate, however, they would not be convenient, practical or cost-effective as an early screening method, Black said.

"A few years ago, we discovered at Cedars-Sinai that beta-amyloid plaques occur not only in the brain but also in the retina in the back of the eye, which is literally an extension of brain tissue. We also found that the plaques can be seen in the retina even before they begin to accumulate in the brain, and we developed a device that enables us to look through the eye - just as an ophthalmologist looks through the eye to diagnose retinal disease - and see these changes," Black said, adding that the device is in patient clinical trials at several sites in the United States and as part of a major study on aging in Australia.

"Preliminary results suggest the optical imaging device may be extremely predictive, possibly providing earlier detection than other methods, yet the test is quick, far less expensive, completely noninvasive and painless," said Black, who understands the disease from scientific and personal experience; his mother lost her life to the disease.

"One of the big challenges we face with Alzheimer's is that brain cell destruction begins years or even decades before symptoms emerge. A person whose disease process starts at age 50 might have memory loss at 75, but by the time we see the signs, the patient has lost 40 to 50 percent of their brain cells. If we focus attention on the early stages and work to slow the destructive process, we may prevent many people from being affected by the disease even before we can cure it. By slowing the process by half, memory loss might begin at 100 instead of 75, and most patients with the disease would live out their natural lives without suffering its consequences," Black said, adding that Cedars-Sinai researchers are studying immune system modulation as a way to treat the disease.

"We believe Alzheimer's is a complex disease involving inflammation and the immune system. In preclinical studies, we've found that if we manipulate the inflammation in the brain we can significantly slow disease progression. I think we'll see in the next few years the emergence of treatments that can stop this process, but there also are simple things we can do now that may improve our odds. We're beginning to realize that the adoption of healthful lifestyle choices may help defend against the disease," said Black, adding that researchers have begun to link risk factors for heart disease and stroke to Alzheimer's.

"What's good for the heart appears to be good for the brain, so it may be beneficial to reduce fats, simple carbohydrates, sugars and salt in the diet while increasing fruits and vegetables. Certain nutritional supplements and herbs - curcumin, fish oil, green tea extract and others - also appear to have protective, anti-inflammatory properties. And some studies suggest that getting regular exercise - something as simple as briskly walking 30 or 40 minutes a day - may be the single most important activity we can do to improve our odds against the disease," Black said.

Konrad Talbot, PhD, a research scientist who recently joined Cedars-Sinai's Alzheimer's disease research team, adds that a proactive lifestyle can be very beneficial because it reduces insulin resistance in the body, which in turn can reduce brain insulin resistance, a complex phenomenon that he and his colleagues have found to be a common feature of Alzheimer's disease.

"The progression, at least toward mild cognitive impairment, the early stages of Alzheimer's, can be decreased by exercise and a good diet. I like to stress the value of the Mediterranean diet, with the addition of other beneficial foods," said Talbot, who studies a complex process called insulin resistance in the brain - and its potential role in Alzheimer's disease development.

"What I call an anti-AD diet includes a lot of olive oil, salmon, walnuts, blueberries and whole wheat or whole grains," Talbot said. "I think green tea is especially important, and there's an interaction between green tea and fish oils; more of the beneficial component of green tea gets into the brain if you have fish oils in your system."

Black added, "Alzheimer's is a disease process many years in the making. But it looks like the course of the disease often may be altered through basic lifestyle changes. The key may be to start early and stick with it for the long run."