Alzheimer's researchers begin unique study of tangles

01/20/04

University Memory and Aging Center focuses on epilepsy drug

The University Memory and Aging Center (UMAC) of University Hospitals of Cleveland and Case Western Reserve University is one of 30 institutions participating in a $10 million National Institutes of Health study to determine if the medication valproate can reduce the occurrences of problem behaviors and affect the cognitive decline associated with Alzheimer's disease. Valproate has been successfully used for about 40 years to treat epilepsy, migraines and bipolar disorder, and may provide new hope for the more than four million Americans suffering with Alzheimer's disease.

This study is the first of its kind to research a medication that may have the potential to block "tangles," one of the hallmarks of Alzheimer's disease linked with memory loss and other symptoms of dementia. Tangles are abnormal brain tissue structures formed by unusual processing of a protein called "tau." Normally, tau is crucial for intracellular functioning and structure, but in Alzheimer's patients, a stringy cluster of tau and phosphate molecules form, leading to dysfunction that impairs the cell's ability to communicate with neighboring cells. This eventually leads to cell death, contributing to the confusion, disorientation and forgetfulness associated with Alzheimer's disease.

The "Valproate in Dementia" study, led by the Alzheimer's research group at the University of Rochester Medical Center, will target 300 patients with mild to moderate Alzheimer's who are living at home and have not yet shown signs of agitation. (Alzheimer's patients experience personality changes with symptoms of agitation: easy to anger, low frustration level and at its worst, physical aggression. The latter is one of the primary symptoms that prompt families to place loved ones in a skilled nursing facility.)

Scientists will study whether valproate reduces agitation in patients, and also can affect the deterioration of memory and daily functioning that occurs as the disease progresses, according to Alexander Auchus, MD, clinical director at UMAC.

"When we began to look at valproate in the laboratory, we were amazed to see that this simple drug blocked several key molecular events that we know are involved in the progression of Alzheimer's," Dr. Auchus says. "We are eager to learn whether these neuro-effects that valproate exhibited in the laboratory will also occur in Alzheimer's patients."

Previously, researchers have studied the effects of valproate in Alzheimer's patients already showing signs of agitation, and have found that the medication did provide a beneficial effect for agitation in some patients.

"Until we have a cure for Alzheimer's, we are continually searching for ways to provide patients with prolonged autonomy so they can live their life to the fullest for as long as possible," says Dr. Auchus.

UMAC's researchers hope to enroll 10 to 15 patients locally for the nationwide study that calls for a total of 300 patients. During their two-year participation in the study, patients may continue standard treatment with other medications.

In addition to examining valproate's possible effect on slowing progression of symptoms of Alzheimer's, researchers also will conduct two supplementary studies. One study involves a blood test that will investigate how Alzheimer's affects the manufacturing of critical cell products, messenger RNA and protein. The other study will use repeated MRI scans in a subset of 200 people to determine if valproate slows or alters the expected loss of whole brain volume in Alzheimer's.

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
    Published on PsychCentral.com. All rights reserved.

 

 

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