Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Drug Improves Brain Structure in Alzheimer’s Patients

03.11.2003


Researchers at Duke University Medical Center have determined that a medication commonly prescribed for mild to moderate Alzheimer’s disease (AD) appears to cause physical improvements in the hippocampus and other brain regions of patients with the disease. These improvements could explain why the drug, donepezil (trade name Aricept), a cholinesterase inhibitor, is beneficial in treating the symptoms of some Alzheimer’s patients, the researchers said.



The findings were made by using magnetic resonance (MR) technology to track brain changes among patients taking the drug. According to the researchers, this is the first time MR has been used to observe the effects of a medication on brain structures of patients living with AD. The feasibility of using MR for such studies is likely to improve future research into treatments for AD and other brain disorders, the researchers said.

The study results appear in the Nov. 1, 2003, issue of the American Journal of Psychiatry.


"We wanted to know if the drugs available for Alzheimer’s disease alter the brain or the progression of the disease in any way," said Ranga Krishnan, M.D., lead author of the study and chief of psychiatry at Duke University Medical Center. "We discovered that, among the patients taking donepezil, levels of a brain chemical called N-acetylaspartate increased and the hippocampus deteriorated more slowly than among the patients who received a placebo. The implication is that we may be able to do something to change the progression of this disease."

The researchers believe the drug may have a protective effect on the brains of Alzheimer’s patients because it appears to slow the progression of the disease by reducing atrophy in the hippocampus, a region of the brain that is critical to memory function and is affected earliest in AD.

"When someone has Alzheimer’s disease, the brain begins to deteriorate as the gray matter shrinks and the disease progresses," Krishnan said. "We are unsure of why and how donepezil slowed the loss of hippocampal volume but we think the drug may help to improve cognition by increasing the levels of N-acetylaspartate in the brain, at least temporarily."

This is important, the researchers say, because the data raise the possibility that a medication could affect the progression of brain changes in Alzheimer’s disease.

According to the researchers, this is the first longitudinal study to use magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) to assess brain function and the impact of a medication upon brain structures of patients with AD.

The study is a follow up to the team’s 1999 report that MRS could be used to track levels of the brain chemical called N-acetylaspartate, an amino acid found in the neurons of the central nervous system in patients with AD. The team had determined that the chemical could serve as a useful "marker" of the functional and structural integrity of neurons when proton magnetic resonance spectroscopy is used to view brain structures.

Since MR had already proven to be an excellent tool for observing function and the changes in brain structures affected by AD, Krishnan and his team wondered if it would be possible to see how a drug affects those same structures.

In the patients enrolled in this study, the researchers discovered that hippocampal volume decreased by 8.2 percent in the placebo group compared with a 0.4 percent decrease in those taking donepezil. Those on placebo also showed evidence of declining concentrations of N-acetylaspartate along with some cognitive decline. Those in the donepezil group showed evidence of increasing levels of N-acetylaspartate concentrations in two brain regions, the subcortical gray matter and the periventricular matter, which peaked between weeks six and 18. Donepezil treatment was associated with significantly greater improvements in cognition, relative to placebo, at every point during the study.

Among those on placebo, the researchers found a significant relationship between the decline in N-acetylaspartate concentrations in the noncortical gray matter region of the brain and reductions in the patients’ scores on cognition tests. The drug appeared to increase concentrations of N-acetylaspartate, although the mechanisms that underlie this are uncertain. The researchers are also unsure why donepezil appears to slow the deterioration of hippocampal tissue, uncertainty they say is compounded by a general lack of understanding about the cause of neuron loss in Alzheimer’s disease.

The researchers enrolled 67 patients aged 50 and older with a diagnosis of mild to moderate AD. Prior to the study, all of the participants received a comprehensive medical examination and verification of an Alzheimer’s disease diagnosis. At baseline, the physical exam was repeated and an MRI scan of the brain was performed. Patients were administered two identical pills - either donepezil or placebo - each evening for 24 weeks. Patients in the donepezil group received 5 milligrams per day (a 5 milligram pill plus a dummy pill) for the first 28 days and 10 milligrams (two 5 milligram pills) per day thereafter. Daily doses consisted of two identical tablets so as to not reveal the dosage scheme.

The randomized, double-blind, placebo-controlled study was conducted over a 24-week period followed by a six-week period in which all participants received only placebo pills. Each participant was treated and clinically evaluated at one of three outpatient sites – Duke University Medical Center, the Medical University of South Carolina or a private psychiatrist’s office in Raleigh, N.C. All of the MR scans were performed at Duke University Medical Center and all data were processed by the Duke Image Analysis Laboratory.

Patients were required to return at 6-week intervals for routine physical examinations, laboratory assessments, a medication compliance check, adverse events monitoring and an MRI scan. Of the 67 participants who enrolled, 34 received donepezil and 33 were given placebo. Fifty-one patients (76 percent) completed the study. Ten patients (30 percent) in the placebo group discontinued the study compared with six (18 percent) from the donepezil group.

"The study was challenging in that subjects were required to be scanned every six weeks and the MRI methods needed to be standardized," said Cecil Charles, co-director of the Center for Advanced Magnetic Resonance Development at Duke. "This study will set the stage for more effective studies of medications used for Alzheimer’s disease.

"Clearly, more effective treatments are needed for Alzheimer’s disease," Charles added. "This study further suggests that MRI and MRS may be useful tools to assess brain changes in patients with Alzheimer’s disease."

The researchers stressed the limitations of their study, saying additional placebo-controlled studies with larger numbers of patients are necessary to confirm and expand their findings.

Alzheimer’s disease is the most common form of dementia among Americans over the age of 80. Donepezil is one of four drugs currently approved by the Food and Drug Administration for the treatment of mild to moderate Alzheimer’s disease.

Research funding for the study was provided by Eisai Inc., Teaneck, N.J., and Pfizer Inc., New York. Additional study investigators include Duke’s P. Murali Doraiswamy, M.D.; Jacobo Mintzer, M.D., Medical University of South Carolina; Richard Weisler, M.D., an adjunct professor at Duke in private practice in Raleigh, N.C.; Xin Yu, Ph.D., University of Washington, St. Louis; Carlos Perdomo and John R. Ieni, Ph.D., Eisai; and Sharon Rogers, Ph.D., who was employed by Eisai at the time of the study.

Tracey Koepke | Duke University Medical Center
Further information:
http://www.mc.duke.edu

More articles from Health and Medicine:

nachricht A 'half-hearted' solution to one-sided heart failure
24.11.2017 | Boston Children's Hospital

nachricht New study points the way to therapy for rare cancer that targets the young
22.11.2017 | Rockefeller University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New proton record: Researchers measure magnetic moment with greatest possible precision

High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons

The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

IceCube experiment finds Earth can block high-energy particles from nuclear reactions

24.11.2017 | Physics and Astronomy

A 'half-hearted' solution to one-sided heart failure

24.11.2017 | Health and Medicine

Heidelberg Researchers Study Unique Underwater Stalactites

24.11.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>