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 New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>