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Clues to Early Detection, Treatment of Alzheimer's

Brain, Blood Changes Occur Decades Before Alzheimer's Symptoms

Medically Reviewed by Laura J. Martin, MD on July 22, 2011
From the WebMD Archives

July 22, 2011 (Paris) -- Brain and blood chemistry changes that indicate Alzheimer's disease can be detected 10 to 20 years before memory loss and other cognitive symptoms develop, according to doctors studying  families with inherited forms of the disease.

Studying people genetically destined to develop Alzheimer's disease at a young age will help researchers understand the changes that occur prior to the development of the "type of Alzheimer's everyone recognizes -- the [non-inherited] form of the disease that  typically strikes people in their 60s, 70s, and 80s," says  John C. Morris, MD, of Washington University in St. Louis.

Morris heads the Dominantly Inherited Alzheimer Network (DIAN), which is recruiting about 400 people whose families harbor genetic mutations that virtually guarantee a person will develop Alzheimer's at the same young age as the parent, usually before age 60.

As part of the NIH-funded program, participants will also be enrolled in clinical trials of potentially disease-modifying drugs that target the underlying processes thought to cause Alzheimer's disease.

The hope is that such drugs will work early on to delay mental decline and slow the progressive degeneration of brain tissue. Currently available drugs like Aricept, Cognex, Exelon, and Razadyne boost mental functioning in a small percentage of people for a time, but none halts the inevitable progression of the disease.

Because study participants are almost certain to develop Alzheimer's disease at a young age, fewer of them need to be followed for a shorter amount of time to show a drug works in the early stages of the disease than if high-risk people in the general population are studied, says DIAN member Randall Bateman, MD, also of Washington University in St. Louis.

The cholesterol-lowering statin drugs that have revolutionized the prevention and treatment of heart disease were first tested in people with an inherited form of high cholesterol, Bateman tells WebMD.

Brain Changes Occur 10 Years Prior to Alzheimer's Symptoms

At the Alzheimer's Association International Conference here, the DIAN researchers presented some early findings gleaned from the first 128 patients to be enrolled in the study:

  • MRI and PET brain scans show substantial buildup of beta-amyloid plaque in the brain at least 10 years before symptoms appear.
  • Beta-amyloid and tau proteins -- both of which have been identified as biomarkers for the disease -- are elevated in the blood and cerebrospinal fluid, respectively, a decade prior to the development of symptoms.

"We think these changes start even earlier, 15 or 20 years prior to symptoms, but the patients have to be followed longer to confirm that," Morris says.
About half of study participants have gene mutations that cause Alzheimer's and half don't. Nearly all have no or only mild symptoms when recruited.
Bateman would not name the drugs that will be tested, although he did acknowledge that most target beta-amyloid plaque.

"Understanding the sequence of biomarkers has value for early diagnosis and prognosis in Alzheimer's disease. It will also put us in a position to intervene with [disease-modifying] treatments earlier, so we catch the train before it leaves the station, before it gets going and develops momentum," says New York University's Ralph Nixon, MD, PhD, vice chair of the Alzheimer’s Association's medical and scientific council.

"Once the disease starts, it is that more difficult to treat," he tells WebMD.

About 35 million people worldwide and 5.4 million Americans have Alzheimer's disease, the most common form of dementia.

These findings were presented at a medical conference. They should be considered preliminary as they have not yet undergone the "peer review" process, in which outside experts scrutinize the data prior to publication in a medical journal.

Show Sources

SOURCES:

Alzheimer's Association International Conference 2011, Paris, France, July 16-21, 2011.

John C. Morris, MD, department of neurology, Washington University School of Medicine, St. Louis; director, Dominantly Inherited Alzheimer Network.

Randall Bateman, MD, assistant professor of neurology, Washington University School of Medicine, St. Louis; associate director, Dominantly Inherited Alzheimer Network.

Ralph Nixon, MD, PhD, New York University; vice chair, medical and scientific council, Alzheimer’s Association.

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