Alzheimer's Disease: Unraveling the Mystery

The Changing Brain in Healthy Aging

In the past several decades, investigators have learned much about what happens in the brain when people have a neurodegenerative disease such as Parkinson’s disease, AD, or other dementias. Their findings also have revealed much about what happens during healthy aging. Researchers are investigating a number of changes related to healthy aging in hopes of learning more about this process so they can fill gaps in our knowledge about the early stages of AD.

As a person gets older, changes occur in all parts of the body, including the brain:

  • Certain parts of the brain shrink, especially the prefrontal cortex (an area at the front of the frontal lobe) and the hippocampus. Both areas are important to learning, memory, planning, and other complex mental activities.
  • Changes in neurons and neurotransmitters affect communication between neurons. In certain brain regions, communication between neurons can be reduced because white matter (myelin-covered axons) is degraded or lost.
  • Changes in the brain’s blood vessels occur. Blood flow can be reduced because arteries narrow and less growth of new capillaries occurs.
  • In some people, structures called plaques and tangles develop outside of and inside neurons, respectively, although in much smaller amounts than in AD (see "The Hallmarks of AD" for more information on plaques and tangles).
  • Damage by free radicals increases (free radicals are a kind of molecule that reacts easily with other molecules; see "The Aging Process" for more on these molecules).
  • Inflammation increases (inflammation is the complex process that occurs when the body responds to an injury, disease, or abnormal situation).

What effects does aging have on mental function in healthy older people? Some people may notice a modest decline in their ability to learn new things and retrieve information, such as remembering names. They may perform worse on complex tasks of attention, learning, and memory than would a younger person. However, if given enough time to perform the task, the scores of healthy people in their 70s and 80s are often similar to those of young adults. In fact, as they age, adults often improve in other cognitive areas, such as vocabulary and other forms of verbal knowledge.

It also appears that additional brain regions can be activated in older adults during cognitive tasks, such as taking a memory test. Researchers do not fully understand why this happens, but one idea is that the brain engages mechanisms to compensate for difficulties that certain regions may be having. For example, the brain may recruit alternate brain networks in order to perform a task. These findings have led many scientists to believe that major declines in mental abilities are not inevitable as people age. Growing evidence of the adaptive (what scientists call “plastic”) capabilities of the older brain provide hope that people may be able to do things to sustain good brain function as they age. A variety of interacting factors, such as lifestyle, overall health, environment, and genetics also may play a role.

Another question that scientists are asking is why some people remain cognitively healthy as they get older while others develop cognitive impairment or dementia. The concept of “cognitive reserve” may provide some insights. Cognitive reserve refers to the brain’s ability to operate effectively even when some function is disrupted. It also refers to the amount of damage that the brain can sustain before changes in cognition are evident. People vary in the cognitive reserve they have, and this variability may be because of differences in genetics, education, occupation, lifestyle, leisure activities, or other life experiences. These factors could provide a certain amount of tolerance and ability to adapt to change and damage that occurs during aging. At some point, depending on a person’s cognitive reserve and unique mix of genetics, environment, and life experiences, the balance may tip in favor of a disease process that will ultimately lead to dementia. For another person, with a different reserve and a different mix of genetics, environment, and life experiences, the balance may result in no apparent decline in cognitive function with age.

Scientists are increasingly interested in the influence of all these factors on brain health, and studies are revealing some clues about actions people can take that may help preserve healthy brain aging. Fortunately, these actions also benefit a person’s overall health. They include:

  • Controlling risk factors for chronic disease, such as heart disease and diabetes (for example, keeping blood cholesterol and blood pressure at healthy levels and maintaining a healthy weight)
  • Enjoying regular exercise and physical activity
  • Eating a healthy diet that includes plenty of vegetables and fruits
  • Engaging in intellectually stimulating activities and maintaining close social ties with family, friends, and community

"Vascular Disease" and "Lifestyle Factors" provide more information about these issues and how they may influence the risk of developing AD.

ACTIVE Study May Provide Clues to Help Older Adults Stay Mentally Sharp

Image of older man with younger man using laptopThe phrase “use it or lose it” may make you think of your muscles, but scientists who study brain health in older people have found that it may apply to cognitive skills as well. In 2006, scientists funded by NIA and the National Institute of Nursing Research completed a study of cognitive training in older adults. This study, the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study, was the first randomized controlled trial to demonstrate long-lasting, positive effects of brief cognitive training in older adults.

The ACTIVE study included 2,802 healthy adults age 65 and older who were living independently. Participants were randomly assigned to four groups. Three groups took part in up to 10 computer-based training sessions that targeted a specific cognitive ability—memory, reasoning, and speed of processing (in other words, how fast participants could respond to prompts on a computer screen). The fourth group (the control group) received no cognitive training. Sixty percent of those who completed the initial training also took part in 75-minute “booster” sessions 11 months later. These sessions were designed to maintain improvements gained from the initial training.

The investigators tested the participants at the beginning of the study, after the initial training and booster sessions, and once a year for 5 more years. They found that the improvements from the training roughly counteracted the degree of decline in cognitive performance that would be expected over a 7- to 14-year period among older people without dementia:

  • Immediately after the initial training, 87 percent of the processing-speed group, 74 percent of the reasoning group, and 26 percent of the memory group showed improvement in the skills taught.
  • After 5 years, people in each group performed better on tests in their respective areas of training than did people in the control group. The reasoning and processing-speed groups who received booster training had the greatest benefit.

The researchers also looked at the training’s effects on participants’ everyday lives. After 5 years, all three groups who received training reported less difficulty than the control group in tasks such as preparing meals, managing money, and doing housework. However, these results were statistically significant for only the group that had the reasoning training.

As they get older, many people worry about their mental skills getting “rusty.” The ACTIVE study offers hope that cognitive training may be useful because it showed that relatively brief and targeted cognitive exercises can produce lasting improvements in the skills taught. Next steps for researchers are to determine ways to generalize the training benefits beyond the specific skills taught in ACTIVE and to find out whether cognitive training programs could prevent, delay, or diminish the effects of AD.


Publication Date: September 2008
Page Last Updated: January 22, 2015

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