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Back To Vidyya Imaging Study Shows How Cholinesterase Inhibitor Improves Working Memory

Good News For Alzheimer's Disease Research

Scientists from the National Institute of Mental Health (NIMH) have used functional brain imaging to show how visual working memory may be affected by a class of drugs that is used with modest effectiveness to improve cognitive functioning in some patients with Alzheimer's Disease (AD). This class of drugs, cholinesterase inhibitors, includes the only FDA-approved treatments for AD.

Research results from "Cholinergic Enhancement and Increased Selectivity of Perceptual Processing during Working Memory," appear in the December 22 issue of Science magazine.

In this study researchers compared brain images as well as visual working memory performance of seven normal, young subjects while on physostigmine to when they were off the drug. Physostigmine is a cholinesterase inhibitor that is not used to treat AD because it is cleared from the blood too fast for clinical use. The researchers' findings suggest that when subjects were on physostigmine, their working memory may have been more efficient. Brain images showed that physostigmine had a selective effect on activity in visual processing areas at the time when new memories were acquired.

Cholinesterase inhibitors like physostigmine prevent the breakdown of the neurotransmitter acetylcholine, which is known to play an important role in learning and memory, and is found to be significantly reduced in AD.

Working memory refers to short-term memory for information that is temporarily maintained for immediate use, like remembering a telephone number until it is dialed or the locations of cars that you see in the rearview mirror while driving. In working memory, a widely distributed set of brain areas acquires new information through perception (encoding), holds that information in an active representation (maintenance), and uses the information to perform a task (recall).

In their experiment, Maura L. Furey, Ph.D., of the Laboratory of Brain and Cognition, NIMH, and her colleagues used functional magnetic resonance imaging (fMRI), which can measure changes in brain activity from second to second. Brain activity during working memory was measured both during infusion of physostigmine and during infusion of a placebo. The results showed that physostigmine may have improved the efficiency of working memory. In the brain, physostigmine had a selective effect on activity in visual processing areas during the perceptual encoding of new information. Physostigmine had no effect on activity in these same areas when subjects were looking at nonsense patterns during a control task. These results indicate that the way that cholinesterase inhibitors may improve memory is by enhancing the selectivity of perceptual processing of information that is to be remembered. Enhanced perception may produce more vivid memories, thus simplifying the processing demands for memory maintenance and retrieval.

The research suggests that the memory-enhancing effect of cholinesterase inhibitors in patients with AD may be attributable to a clearer perception of newly acquired information.

"With functional brain imaging, we can dissect the brain activity underlying a complex behavior like working memory into responses to task components that are mediated by different brain structures at different times during task performance. Here we have shown how a drug may influence neural activity in a complex neural system to result in a change in a complex behavior," said principal investigator Furey.

Other researchers were James V. Haxby, Ph.D., Chief, Section on Functional Brain Imaging, Laboratory of Brain and Cognition, NIMH, and Pietro Pietrini, M.D., Ph.D., Department of Clinical Biochemistry, Medical School, University of Pisa, Italy.

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Editor: Susan K. Boyer, RN
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