People who have early stage Alzheimer's disease could be more capable of learning than previously thought

People who have early stage Alzheimer's disease (AD) could be more capable of learning than previously thought, according to two new studies supported by the National Institute on Aging (NIA), a part of the National Institutes of Health.

The promising studies suggest that some people with early cognitive impairment can still be taught to recall important information and to better perform daily tasks.

In a July 2004 report, researchers in Miami, FL, found mildly impaired AD patients who participated in 3-to-4 months of cognitive rehabilitation had a 170 percent improvement, on average, in their ability to recall faces and names and a 71 percent improvement in their ability to provide proper change for a purchase. The participants also could respond to and process information more rapidly and were better oriented to time and place compared to a similar group of AD patients who did not receive this targeted intervention. These improvements were still evident 3 months after the cognitive training ended.

The findings, by David A. Loewenstein, Ph.D., and colleagues at the University of Miami School of Medicine and Mount Sinai Medical Center, Miami Beach, are reported in the July-August 2004 issue of the American Journal of Geriatric Psychiatry.

The Loewenstein report follows a recent study by researchers at Washington University in St. Louis who found that older people with early-stage AD retained functioning levels of implicit memory similar to young adults and older adults who did not have AD. Implicit memory is relatively unconscious and automatic: Information from the past "pops into mind" without a deliberate effort to remember. This unconscious, implicit memory is important for common skills and activities, such as speaking a language or riding a bicycle. In many cases, people implicitly remember how to perform these activities, without being able to deliberately remember when or where they learned them. The study by Cindy Lustig, Ph.D., and Randy Buckner, Ph.D., appeared in the June 10, 2004, issue of Neuron.

"Taken together, these studies introduce the exciting notion that older people who are in the early stages of AD can be taught techniques to help stay engaged in everyday life," says Neil Buckholtz, Ph.D., head of the Dementias of Aging Branch at the NIA. "These findings show it is possible to pinpoint what memory capabilities are preserved in early AD and suggest ways to target those memory functions and make the most of them."

Cognition is the ability to think, learn, and remember. Previous studies have shown that cognitive rehabilitation can effectively improve memory and other cognitive functions in people who have had strokes or suffered traumatic brain injuries. Some of these techniques also have helped improve memory in some people with AD. However, the current research reported by Loewenstein and colleagues is believed to be the first to combine several specific cognitive memory techniques into a single rehabilitation program for those who are mildly impaired with AD.

Dr. Loewenstein and colleagues randomly assigned 44 people who were diagnosed with AD into two groups. All participants in the study were taking cholinesterase inhibitor medications, such as donepezil (Aricept), which may help prevent AD symptoms from becoming worse for a limited time.

The 25 people in the "cognitive rehabilitation" (CR) group participated in two 45-minute sessions weekly for a total of 24 sessions. During these sessions, they learned face-name recognition techniques, such as associating a prominent facial feature with a name. So a smiling man named Sam might be recalled as "Smiling Sam." To enhance time and place orientation, CR participants were given memory notebooks and encouraged to record appointments, medication schedules, and contact information for relatives, friends, and doctors in them. The participants were asked to review this central information repository twice daily throughout the study.

They also were taught effective ways to make change for a purchase and asked to use a calculator to balance a checkbook after paying three bills. In addition, they learned to click a mouse button in response to yellow boxes as they randomly appeared on a computer screen. This technique was designed to improve attention span and cognitive processing speed. Finally, the CR group was asked to manipulate objects, such as a key, as though they were using them, a technique that can jumpstart memory in some people. In addition, participants and their caregivers were encouraged to practice all of these techniques at home.

The 19 participants in a "mental stimulation" (MS) group played computer games that required memory, concentration, and problem-solving skills. In addition, participants in this group were asked to discuss various topics, such as describing the neighborhood in which they grew up. They also were asked to do crossword puzzles, word scrambles, and other "homework" assignments.

At the end of the study, those in the rehabilitation group showed, on average, significantly improved ability to associate faces and names, had faster mental processing speeds, were better oriented to time and place, and were better able to make correct change for purchases than those in the MS group. However, neither group showed memory improvement for manipulating objects or balancing a checkbook.

"Our study shows that people with early AD can learn. This learning can be greatly enhanced if you teach them certain techniques that target particular areas of the brain," Dr. Loewenstein says. "More importantly, by combining specific cognitive rehabilitation strategies, we can help people with AD remain engaged in daily activities and retain a connection to their family and friends and the world as a whole for a longer period of time."

The June 2004 study by Lustig and Buckner recruited 34 young adults, 33 older adults without any Alzheimer's symptoms, and 24 older adults with symptoms of early-stage AD. The study examined a type of implicit memory that helps people act faster on items they have previously worked on than new items. In the study, participants were shown words and asked to judge if they represented something living, such as the word "DOG" or something nonliving, such as the word "DESK". Overall, the young adults made faster judgments than their older peers and those who had AD. However, all three groups were faster when shown repeated words rather than new ones. This increase was about the same for all three groups, suggesting that this benefit of implicit memory remains in old age and even early Alzheimer's disease.

The researchers also used functional magnetic resonance imaging (fMRI) to measure brain activity during the word judgments. They were especially interested in the left prefrontal cortex, a part of the brain involved in thinking about what words mean. They found that activity in this part of the brain was less for repeated words than for new ones. Along with the faster judgments, this reduction in brain activity suggests that seeing an item again had an important effect. Because the judgment for a word was made when the person saw it initially, the brain didn't have to work as hard at making a living/non-living judgment when the same word appeared again. In fact, even when people with AD couldn't remember which words they had seen, presenting the words again still helped them classify those words faster, and they also showed changes in brain activity like those of the young adults and their healthy older peers.

"One of the exciting findings from our study is the suggestion that the brain areas supporting high level, complex thinking still have some flexibility and these areas can change with some learning as we age and even in early AD," Dr. Lustig says. "We're hoping our results will be useful in designing cognitive training and rehabilitation programs." In addition to the NIA, Lustig and Buckner's study was supported by the Alzheimer's Association and the James S. McDonnell Foundation. Dr. Buckner is a Howard Hughes Medical Institute investigator.

AD is an irreversible disorder of the brain, robbing those who have it of memory, and eventually, overall mental and physical function, leading to death. It is the most common cause of dementia among people over age 65, affecting an estimated 4.5 million Americans.