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Published: Monday, 2/2/2004

Memory-enhancing drugs may work better if taken in daytime

BY MICHAEL WOODS
BLADE SCIENCE EDITOR

Millions of Alzheimer's disease (AD) patients who take memory-boosting drugs may impair their ability to remember by taking the medicine at bedtime, rather than during the day, a study concluded Monday.

Experts said it also raised the possibility that "brain foods" and memory-boosting nutrient supplements -- popular among older people without Alzheimer's disease -- may backfire and impair memory if consumed before bed.

"It would be of great interest to assess the possibility that aged individuals or patients with Alzheimer's disease - both of which have impaired sleep and impaired memory - may be altered by high choline levels via diet prior to bedtime," Dr. Lisa Teather said in an interview.

She does research on choline and memory at Laurier University in Canada, and was not involved in the study.

The brain uses choline to make acetylcholine, a messenger molecule important in memory. Individuals with Alzheimer's disease have abnormally low levels of acetylcholine.

The mostly widely used AD drugs work by keeping levels of acetylcholine high. They are Aricept, Exelon, and Reminyl. Memantine, a new AD drug, works in a different way.

Doctors usually have patients take acetylcholine drugs at bedtime because it reduces side effects, Dr. Steven T. DeKosky, professor and chairman of neurology at the University of Pittsburgh, explained in an interview.

In the new study, Dr. Steffen Gais, of the University of Lubeck in Germany, tested memory in 29 men given bedtime doses of a drug that keeps acetylcholine levels high. The men were young, aged 18-35, and healthy. The "Proceedings of the National Academy of Sciences," a major scientific journal, published the results.

The drug seriously impaired memory. Men given the drug were less able to remember words learned the previous day than men who took none.

Dr. Ann Power, a memory expert at the University of California-Irvine, termed the results "compelling." The discovery may seem like a contradiction, she explained in an interview, but it makes sense.

Low acetylcholine levels are a hallmark of AD, Dr. Power said. In AD patients, brain cells that make acetylcholine have been damaged, resulting in lower levels of the chemical. During the day, drugs like Aricept keep acetylcholine levels high, and boost memory.

Dr. Gais' study, however, revealed that the brain needs a temporary drop in acetylcholine during sleep. It allows the brain to upload data from a temporary storage depot to another region that holds more permanent memories.

"This study teaches us that although patients may need increased acetylcholine during waking, keeping it constantly elevated may block a certain component of memory consolidation that requires a temporary drop in acetylcholine," Dr. Power said.

Both Dr. Power and Dr. Gais said physicians should consider advising AD patients to take medicine during the day, rather than at bedtime.

Although Dr. Kotsky praised the study as "very carefully done," he cited the need for more research to see if the results do apply to people with AD.

He directs Pitt's Alzheimer's Disease Research Center, one of 30 established nationwide by the Federal Government to translate research advances into improved care for AD patients.

"I think as people get used to the medicines, they are taking them more and more during the day," Dr. Kotsky said. "This study just represents one reason to consider taking them earlier."

Experts disagreed on the study's implications for healthy people who take choline dietary supplements or eat choline-rich foods in an effort to boost their memory. Eggs, milk, beef, peanut butter, and soy are among the foods naturally rich in choline.

Several said that bedtime choline would have no effect on memory in healthy individuals. Dr. Gais called for more study.

"We do not know whether choline-rich food, or choline supplements, consumed at bedtime could have an adverse effect on memory," he said in an interview. "That is a very interesting question. In my opinion, it is necessary to study the topic in more depth,. At this point we cannot exclude it."



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