Changes in the brain and the fluid around it may occur as much as 25 years before symptoms of early-onset Alzheimer's disease, a new study finds. The study focused on 128 people. All had a family history of early Alzheimer's caused by a gene inherited from one parent. Symptoms start in the 30s, 40s or 50s. About half of those in the study carried the gene. Researchers gave everyone several tests. They determined when symptoms would be expected to start based on the parent's age at diagnosis. About 25 years before symptoms were expected, those with the gene showed a drop in beta-amyloid in the fluid around the brain. This is a key component of Alzheimer's plaques inside the brain. About 15 years before symptoms were expected, people with the gene had smaller brains, and plaques had appeared. Fluid around the brain also had more tau protein. This is another sign of Alzheimer's. About 10 years ahead of symptoms, people's brains used less sugar for energy. Mild memory problems also started. These changes did not occur in relatives without the Alzheimer's gene. The New England Journal of Medicine published the study. HealthDay News wrote about it July 11.

By Howard LeWine, M.D.
Harvard Medical School

What Is the Doctor's Reaction?

Alzheimer's disease mostly affects the elderly. But sometimes what appears to be the same disease occurs in younger people. It's a rare inherited form of Alzheimer's disease. If either of your parents has the gene mutation that causes it, you have a 50% chance of inheriting that gene. Having the gene leads to early-onset Alzheimer's.

The age when symptoms appear for this type of Alzheimer's can be predicted based on the parent's age when diagnosed with the disease. The child carrying the gene mutation will follow a similar disease course as the parent.

Knowing this has provided a chance for researchers to identify when Alzheimer's disease starts and what changes occur in the brain before symptoms occur.

Alzheimer's disease develops over many years. The leading theory is that sticky deposits of a protein called beta-amyloid begin building up in the brain long before symptoms start. Over time, the buildup of beta-amyloid disrupts links between brain cells. Eventually, the process kills off brain cells.

Research results reported this week in the New England Journal of Medicine support this theory. The researchers had information on 128 people with parents who had early-onset Alzheimer's disease. They predicted the age when each person's symptoms would start based on the age when the parent developed symptoms. About 25 years before the expected start of symptoms, the amount of beta-amyloid in the fluid around people's brains started to decline.

Researchers used PET scans to look at people's brains. Fifteen years before the expected onset of symptoms, they found:

• A buildup of beta-amyloid in the brain
• Brain shrinkage
• An increased amount of tau protein in the fluid around the brain. High levels of tau protein are also seen in people with Alzheimer's disease.

Ten years before expected onset of symptoms, the brain's use of sugar for energy (metabolism) slowed down. Minor memory problems also were noted.

Studies of potential treatments to reduce beta-amyloid buildup have had disappointing results. But this new evidence provides support for the beta-amyloid theory on the cause of Alzheimer's. It suggests that scientists should continue to pursue this path.

What Changes Can I Make Now?

There are no specific treatments to prevent Alzheimer's disease and other types of dementia. While scientists keep looking, you can reduce your risk or at least delay when dementia occurs.

• Don't smoke or use other tobacco products.
• Use alcohol in moderation. That means no more than one drink per day for women, and no more than two per day for men.
• Maintain a healthy body weight. In particular, try not to let your waist expand. People with more fat in the middle have a higher risk of developing dementia, even if their body weight is normal.
• Exercise regularly. Make it your goal to get at least 150 minutes of moderate-intensity exercise per week.
• Keep your blood pressure in the normal range. To do this, get regular exercise, eat lots of fruits and vegetables, and cut down on salt. Your doctor can prescribe medicines if needed.
• Stay socially engaged with family and friends.

There is some evidence that a Mediterranean-style diet may be especially good for the brain.

These suggestions should look familiar. They are the same ones that will help keep your heart healthy and decrease your risk of stroke.

What Can I Expect Looking to the Future?

Today, more than 5 million Americans have Alzheimer's disease. Experts predict the number will be 13 million in 2050. Our best chance of not having this happen is diagnosing the disease much earlier than we do now and having a safe treatment for it. Scientists are working hard on both these avenues of research.