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 One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

nachricht The gut microbiota plays a key role in treatment with classic diabetes medication
01.06.2017 | University of Gothenburg

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: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

Im Focus: Optoelectronic Inline Measurement – Accurate to the Nanometer

Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.

New Manufacturing Technologies for New Products

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

A new technique isolates neuronal activity during memory consolidation

22.06.2017 | Life Sciences

Plant inspiration could lead to flexible electronics

22.06.2017 | Materials Sciences

A rhodium-based catalyst for making organosilicon using less precious metal

22.06.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>