Date: February 15, 2004
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RESEARCH CLARIFIES HOW ALZHEIMER’S MEDICINES MAY REDUCE INTERFERENCE WITH LEARNING AND MEMORY

Chemicals that block brain receptors for a key neurotransmitter make it harder for people to learn new information

WASHINGTON — New evidence clarifies how the only government-approved treatments for mild-to-moderate Alzheimer’s Disease may work to improve symptoms. When scientists chemically blocked receptors for an important neurotransmitter called acetylcholine, even healthy young people found it significantly harder to learn and remember – especially in the face of interference. This finding may shed light on how cholinesterase inhibitors, FDA-approved drugs that slow the breakdown of acetylcholine in Alzheimer’s patients, help alleviate dementia symptoms.

The study appears in the February issue of Behavioral Neuroscience, which is published by the American Psychological Association (APA).

The study demonstrated that acetylcholine helps keep old information from interfering with our ability to learn and remember new information. The findings may help to explain why conditions associated with lower levels of acetylcholine in the brain, such as Alzheimer’s disease, Parkinson’s disease, dementia due to multiple strokes, multiple sclerosis and schizophrenia cause problems with memory function, as well as the hallucinations and delusions that can occur in some of these conditions.

Conversely, it offers insight into the way that higher acetylcholine levels modestly improve attention, memory, activities of daily living, and behavioral symptoms. Cholinesterase inhibitors boost acetylcholine by reducing the enzyme that breaks it down. Understanding their effects on major symptoms during disease progression may help scientists develop more targeted and effective drugs, as well as to avoid medications that may be detrimental to memory function.

A total of 28 young healthy adults participated in the study. At Massachusetts General Hospital, researchers injected 12 of the study participants with scopolamine, an “anticholinergic” drug used for decades to treat motion sickness and intestinal spasms, and as a sedative and pre-anesthetic before surgery. It also blocks acetylcholine receptors in the brain and has long been known to impair certain types of learning and memory.

After scopolamine administration, Alireza Atri, MD, PhD, a neurologist at Massachusetts General Hospital and Harvard Medical School, and his colleagues measured how well participants learned new pairs of words, a common memory test. Two other groups of eight participants each served as controls that were tested on learning but were given either no drugs or the medicine glycopyrrolate to mimic the dry mouth produced when scopolamine is given. Glycopyrrolate is a synthetic anticholinergic that crosses the blood-brain barrier more slowly and incompletely compared with scopolamine.

As expected, in the experimental group, memory for word-pairs learned after scopolamine administration suffered significantly but memory for word-pairs learned immediately before injection was spared. More to the point, scopolamine made it harder to learn when stimuli overlapped, creating “proactive” interference with learning – a condition more closely resembling everyday life. The researchers also found that even glycopyrrolate produced subtle but measurable effects on memory and learning.

Professor Michael Hasselmo, a neuroscientist at Boston University’s Center for Memory and Brain and a co-author of the study, says, “Proactive interference influences common tasks such as remembering where we parked the car or where we left the keys. If one parks in the same lot every day, the memory of previous parking locations interferes when we try to encode and retrieve a new but similar parking place.”

The findings suggest, says Atri, that anticholinergics might serve as a kind of cognitive ‘stress test’ for elderly patients who have an underlying dementia in its earliest stages, unmasking symptoms that would be hard to detect otherwise. At the same time, he adds, “From a cognitive health standpoint, the chronic use of medications with anticholinergic effects by elderly individuals, especially if they’re cognitively impaired, would be highly discouraged. Use of such medications, particularly during waking hours, would be expected to interfere with acquisition and future recall of new and, especially, related memories.”

Article: “Blockade of Central Cholinergic Receptors Impairs New Learning and Increases Proactive Interference in a Word Paired-Associate Memory Task,”
Alireza Atri, MD, PhD, Boston University, Massachusetts General Hospital/Harvard Medical School, and Massachusetts Institute of Technology; Kenneth A. Norman, PhD, Princeton University; Marlene M. Nicolas, BA, Boston University; Steven C. Cramer, MD, University of California, Irvine; Michael E. Hasselmo, DPhil, Boston University; Seth Sherman, MS,CPhil, Boston University; Brenda A. Kirchhoff, PhD, Washington University in St. Louis; Michael D. Greicius, MD, Stanford University; Hans C. Breiter, MD, Massachusetts General Hospital/Harvard Medical School; and Chantal E. Stern, DPhil, Boston University and Massachusetts General Hospital/Harvard Medical School;
Behavioral Neuroscience, Vol. 118, No. 1.

Full text of the article is available from the APA Public Affairs Office and at http://www.apa.org/journals/releases/bne1181223.pdf

Reporters: Alireza Atri can be reached by Email or by phone at (617) 726-1728. Michael Hasselmo can be reached by Email or by phone at (617) 353-1397.

The American Psychological Association (APA), in Washington, DC, is the largest scientific and professional organization representing psychology in the United States and is the world’s largest association of psychologists. APA’s membership includes more than 150,000 researchers, educators, clinicians, consultants and students. Through its divisions in 53 subfields of psychology and affiliations with 60 state, territorial and Canadian provincial associations, APA works to advance psychology as a science, as a profession and as a means of promoting health, education and human welfare.

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