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Alzheimer’s Disease: Researchers Test Prevention Strategies

alzheimer's disease prevention alzheimer Alzheimer’s disease is the most common form of dementia, which is a general term used for memory loss and loss of other like kind intellectual abilities that are serious enough to interfere with a person’s daily life. Alzheimer’s accounts for 50 to 80 percent of all dementia cases. In an on-going study of Alzheimer’s disease, researchers suggest that modifying therapies in patients should be targeted toward earlier stages of the disease before symptoms that are more serious have time to develop, and therefore, they are testing prevention strategies.

Alzheimer’s disease is a progressive condition that gradually worsens dementia over a period of years. Memory loss is mild in the early stages; however, as late stage Alzheimer’s sets in, individuals lose their ability to speak using a rational conversation or respond to the environment around them.

Alzheimer’s disease is the sixth leading cause of death in the United States, and most patients live on average approximately eight years after their symptoms initially begin to show. However, the length of survival is different depending on the patient’s age and other medical conditions.

In an on-going study, published in The Journal of the American Medical Association (JAMA), researchers noted that profound brain alterations are formed as much as 10 to 20 years before mild cognitive impairment or dementia is diagnosed. They estimate that by the time memory loss begins and other problems with cognition become apparent, too much damage has been done to the brain and therefore cannot be reversed by experimental treatments.

With this in mind, researchers decided to design therapy trials that would delay or prevent the onset of Alzheimer’s disease in volunteer patients who were cognitively healthy but demonstrated at-risk factors. Because differences may exist between people who have early onset Alzheimer’s disease and those with sporadic, late onset Alzheimer’s disease, researchers said it was imperative to conduct the studies using different risk groups.

Researchers developed three preventative initiatives in 2012, the Dominantly Inherited Alzheimer Network (DIAN), the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4), and Alzheimer’s Prevention Initiative (API), all of which were formed under an umbrella group called the Collaboration for Alzheimer’s Prevention.

Researchers say they are testing several preclinical Alzheimer’s disease prevention strategies, and those trials will test investigational antiamyloid treatments in at-risk patients before the disease has time to ravage their brain. These trials will target various toxic forms of the amyloid proteins, which researchers hope will provide a better test for their amyloid hypothesis that states the buildup of amyloid is primarily responsible for Alzheimer’s disease.

These studies further aim to determine whether brain imaging and the cerebral spinal fluid biomarkers that are used during the course of the trials are related to the clinical outcome. Dr. Pierre Tarot, API co director explained that this is a quality referred to as the agnostic utility of a biomarker. “If the treatments biomarker effects prove likely to predict clinical benefit, those biomarkers could potentially be used as surrogate endpoints for future trials, which will produce faster results.”

The first prevention trial began last year and is expected to run for five years. The trial enrolled 300 cognitively healthy individuals who were at least 30 years old, from an estimated 5000 member group, which they will use to test the antimyloid monoclonal antibody crenezumab or a placebo. Injections will be given every two weeks for 260 weeks. At the same time, 100 non-carriers will also be given the placebo.

Another prevention trial, DIAN launched in December 2012 and also focuses on asymptomatic individuals who are at risk for early onset Alzheimer’s disease. This trial will last for four years. During that time researchers will test to antimyloid interventions, gantenerumab and solanezumab, which are monoclonal antibodies directed at different forms of amyloid-beta. During the first stage of the trial researchers, monitor the response of imaging and fluid biomarkers to the drugs so they can determine which ones are more promising to use in the second phase follow-up.

The third prevention trial, A4 focuses on a much more common group of older adults who are at risk for Alzheimer’s disease because their brain scans show evidence of amyloid accumulation. This is a three-year trial that began enrolling volunteers earlier this year. Researchers say they will screen a large number of individuals consisting of 5000 healthy adults between the ages of 65 and 85 for this trial.

A fourth prevention study is expected to begin in late 2015, the API-APOE4 Treatment Trial. Older people who carry certain markers, representing two to three percent of the population, who are at high risk for developing Alzheimer’s disease later in life will be included in this trial.

Alzheimer’s disease is a serious condition that carries life-altering consequences. Researchers are hopeful that testing prevention strategies will be successful and become a vital step toward making an impression on Alzheimer’s disease.

By Donna W. Martin


Alzheimer’s Association

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