Aging alone does not affect brain system related to memory loss

June 06, 1999

Columbus, Ohio -- A new study in rats suggests that aging by itself may not affect brain systems responsible for important aspects of learning and memory. However, the research found that the combination of old age and pre-existing brain pathology led to serious problems in a brain system that is crucial for normal cognitive abilities.

The findings have important implications for researchers studying Alzheimer's disease and other forms of dementia in humans, said Martin Sarter, co-author of the study and a professor of psychology at Ohio State University.

"The aging of the brain may not be sufficient to produce seriously detrimental effects in humans," Sarter said. "It may be that only people who have a problem in important brain systems who will suffer dementia as they get older."

Sarter conducted the study with John Bruno, also a professor of psychology at Ohio State, and James Fadel, a former graduate student. Sarter presented their results June 6 in Denver, Colo. at the annual meeting of the American Psychological Society. The study was also published in the May 1999 issue of the journal Neuroscience.

In the study, the researchers trained rats to associate darkness with the appearance of food they liked. They did this because darkness would then stimulate the cholinergic system -- the brain system that involves memory functions and is associated with Alzheimer's disease and other forms of dementia. In order to further stimulate the cholinergic system, rats also received a drug to allow this system to react more readily to stimulation.

To measure the reaction of the rats' cholinergic systems to the stimulus of darkness and food, the researchers examined the release of acetylcholine (ACh), the crucial brain chemical that works within this system.

The researchers examined both young adult rats (four to seven months old) and old adults (24 to 28 months old). In addition, some rats had brain lesions that had destroyed some of the neurons in the cholinergic system. Other rats had no lesions.

The researchers found that, at baseline, both older and younger rats with lesions showed a similar decline in the release of ACh in the cereberal cortex of the brain.

However, when the rats were presented with a stimulus -- the appearance of darkness and food -- the older rats with lesions reacted very differently when compared with young animals with similar lesions.

The young rats with lesions still showed a significant increase in ACh release of 60 to 120 percent (compared to baseline) when presented with darkness and food. However, the older lesioned rats showed a very weak and insignificant response -- only a 20 to 40 percent increase in ACh release.

The rats with normal brains (no lesions) did not show such a significant difference between young and old rats. The young non-lesioned rats showed an increased ACh release of about 100 to 180 percent when presented with darkness and food, similar to that found in older non-lesioned rats.

Sarter said it was significant that young rats, even when they lost part of their cholinergic sytems due to lesions, were still able to respond robustly to the stimulus of darkness and food. It was only the older rats with lesions who did not respond to the darkness and food stimulus. If something similar happens in humans, it suggests that people with some kinds of pre-existing brain pathologies may not realize it until the aging process starts and it triggers Alzheimer's or other forms of dementia.

"This is something new for us -- to see an interaction between the aging process and a compromised brain," Sarter said. "We believe that people who develop Alzheimer's disease have something wrong with their brain long before the symptoms appear. It is the aging process that then makes the disease appear."

Sarter said it is not yet known exactly what pathologies some people may have in their brains that lead them to develop Alzheimer's disease as they age. Most likely, there is some kind of damage to the neurons in the cholinergic system, he said. Sarter said it is also not known what happens during aging that interacts with pre-existing conditions to cause dementia. "Aging research is really just beginning and we have a lot to learn," he said.

However, these findings suggest that if scientists can find how to identify people with brain pathologies that will lead to Alzheimer's, new treatments could be developed that will prevent or at least reduce the symptoms of the disease.

"Maybe if we start early enough, we can keep the neurons alive and working into old age," Sarter said.

Ohio State University

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