Alzheimer’s Disease

Reisa A. Sperling, M.D., M.MSc., Director, Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital, Professor of Neurology, Harvard Medical School (Photo: Photo courtesy Brigham and Women’s Hospital)

Time’s impact on the body is pretty obvious. The hair thins and turns white. Lines and wrinkles invade the skin. We can even lose an inch or two in height.

There are some changes, however, we cannot see. The brain is aging as well. The memory gets a little fuzzy. You walk into a room and can’t for the life of you figure out why. These are mild changes, however, and cause little harm — just annoyance.

Yet, something more sinister can lurk undetected — all due to errant proteins. Tangles of a protein called tau (rhymes with “wow”) accumulate in nerve cells in the brain that are called neurons. Clumps of another protein, called amyloid plaques, build up between nerve cells and interrupt communication.

These are not good changes. The tangles strangle the cells causing their eventual demise, while plaque prevents communication between the neurons. Unfortunately, it’s that communication that allows memory, reasoning, emotion, movement and even breathing. Scientists now believe that the amyloid plaque is the major culprit here and drives the production of the tangles in the cells.

“It is normal for neurons to produce these proteins,” said Dr. Reisa Sperling, the director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital. “But it is not normal for them to accumulate.” Few are spared. “Almost everyone over the age of 65 has some tau in the hippocampus (the part of the brain that controls memory and learning),” she explained. “Roughly 30 percent have the amyloid plaque in the cortex.” The cortex controls complex functions like problem solving, emotions and comprehension.

This buildup of proteins begins earlier in life, but may go undetected for decades. Some people experience these changes to some extent with no side effects. However, in Alzheimer’s disease, the most common form of dementia, these proteins take over and wreak havoc. And their impact is very noticeable.

AD is a progressive, degenerative disease that robs victims of memory, reasoning, thinking and communication and eventually their life. It is the sixth leading cause of death in this country.

It is estimated that 5.4 million people have AD. In a recent study published in the journal Neurology, however, researchers concluded that the number is considerably higher. That’s because while the immediate causes of death are often attributed to pneumonia or other conditions, the fatalities are precipitated by AD.

Undoubtedly, the number will continue to climb. By 2030 — just 15 years away — one-fifth of the U.S. population will be 65 years or older, according to the U.S. Census Bureau. And age is the largest risk factor for AD.

The impact of AD on the economy is staggering. According to the National Institutes of Health, in 2010 the cost to treat AD was roughly $215 billion. As a point of comparison, in that same year the cost to treat cancer was $77 billion, noted the NIH.

The cause of AD is not exactly known. It is likely due to a combination of genetic, environmental and life-style factors. A gene, familiarly known as APOE — APOE-4, to be exact — is thought to play a role in the development of AD. Sperling is quick to point out that the inheritance of APOE-4 merely increases the risk, and is not a definitive cause of AD. In addition, some people lacking that form of the gene can still develop AD.

For reasons unknown, the APOE-4 gene has a higher prevalence in African Americans. In addition, cardiovascular diseases, such as hypertension and diabetes, are more prevalent in blacks, and may contribute to the disease. Cardiologists believe there is a connection between heart health and brain health.

Risk factors

AD occurs more frequently in women. “It is not known if that is due to the fact that women live longer or may have more amyloid,” explained Sperling. Education may also be a factor. Researchers at Rush University in Chicago found that black participants with lower levels of education had poorer cognitive and physical function, such as balance, compared to whites with similar education. Interestingly, however, at levels of education beyond high school blacks experienced greater gains in physical and cognitive health when compared with whites.

Diagnosing AD has improved considerably. Testing involves an evaluation of memory, blood and urine tests as well as MRIs and PET scans, which can detect plaques in the brain. Part of this testing is to make sure that the changes are not due to another condition, such as a nutritional deficit or brain tumor. By using this comprehensive approach, clinicians can now diagnose AD with up to 90 percent accuracy, according to the Alzheimer’s Foundation of America.

AD is one of the most feared diseases. It’s right up there with cancer. However, the incidence of cancer begins to drop after the age of 75, as noted by the National Cancer Institute, while AD is on the upswing. In addition, while death rates from cancer dropped 32 percent between 2000 and 2010, death rates from AD increased 39 percent during that time period.

By age 50, people begin to panic at the slightest slip in memory or deterioration of some capability. One slip up does not spell AD, emphasized Sperling. A person’s memory can falter for a number of reasons, including stress, anxiety or sleep deprivation. Multitasking contributes to the problem. “You’re working on 40 things at once but can’t remember the other 39,” she said.

However, if you notice that you are forgetting many things and you are having difficulty performing activities that you normally do, such as paying bills, these are probably not normal signs of aging. You might be experiencing the early signs of AD or another type of dementia.

Failure to recognize the symptoms is part of the problem and can significantly delay diagnosis. Studies have shown that minorities are often diagnosed at later stages of the disease. Instead of dementia they attribute the changes to “mind-slipping” or that the person is an “old-timer.”

Early testing

It is important to get tested early. Four medications for AD have been approved by the Food and Drug Administration, but some work best in the early stages of the disease. The medications treat the symptoms and not the underlying disease in the brain.

There is no cure for AD.

The cause of death is often pneumonia. Falls are another cause due to poor balance. In others it is “failure to thrive,” explained Sperling. People stop eating and drinking.

As devastating as this disease is, Sperling is upbeat. She correlates AD to heart disease, which can be controlled by a combination of healthy eating, exercise and medication, such as cholesterol-lowering statins. She envisions the same triad approach for AD. She is convinced that the disease is preventable and she is out to prove it. She is heading a clinical trial called the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s study — A4 for short. This is a landmark study to test whether a new investigational treatment can prevent memory loss caused by Alzheimer’s disease in people who do not yet show any symptoms.

“We’re not looking for a cure,” Sperling explained. “We are looking for an extra five years.” To an 85-year-old person, that’s a life time.