Older adults with evidence of amyloid in the brain but no clinical symptoms of Alzheimer’s disease have structures in the brain that don’t communicate readily with each other, according to researchers at Washington University School of Medicine in St. Louis.
The findings, published in Biological Psychiatry, may be yet another indicator that Alzheimer’s damage to the brain begins to occur long before there are clinical symptoms of the disease.
Using brain-mapping techniques, first author Yvette I. Sheline, MD, and colleagues found that key brain structures don’t connect as efficiently in brains where positron emission tomography (PET) scans revealed the abnormal presence of the amyloid protein.
Sheline
Those PET scans involve a substance called Pittsburgh compound B (PIB) that binds with amyloid, causing it to “light up” in a brain scan. Amyloid is the substance that makes up the senile plaques characterizing Alzheimer’s disease.
“Using PET scans, we’ve been able to identify a large number of older people who are clinically normal but PIB-positive for amyloid,” says Sheline, a professor of psychiatry and director of Washington University’s Center for Depression, Stress and Neuroimaging. “We then used a different type of brain scan called functional magnetic resonance imaging, fMRI, to look at the brains at rest, and we found decreased connections between important brain structures in people who were PIB-positive compared to those who were PIB-negative.”
The investigators conducted fMRI scans on 35 older adults previously diagnosed with mild to very mild dementia from Alzheimer’s disease. They also scanned 68 others who had no clinical symptoms of the disorder. However, 20 of those cognitively normal people previously had been identified as PIB-positive for amyloid in the brain.
In the first phase of the study, researchers looked at how various brain structures communicate in people with and without Alzheimer’s disease. Then they examined those same brain regions in PIB-positive and PIB-negative older adults with no clinical symptoms of Alzheimer’s disease. The brains of those who were PIB-positive behaved like the brains of those with Alzheimer’s, according to Sheline.
“When we looked at key brain structures like the hippocampus, which is very important in learning and memory, we found decreased connections to the hippocampus in PIB-positive people compared to those who were PIB-negative,” she says. “Our findings suggest brain regions that normally talk to each other are not communicating as much as they should long before there’s any clinical evidence of memory loss or other signs of dementia.”
It’s too early to say for sure whether those who are PIB-positive will go on to develop dementia, memory loss and other symptoms of Alzheimer’s disease, Sheline says. But she believes this study provides further evidence that the PIB scans can identify people with early Alzheimer’s-like damage who later may develop clinical symptoms.
“What we need now is more effective treatments for Alzheimer’s,” she says. “We’re moving forward quickly to identify those who might be at risk at earlier stages in the disease process, but if we determine that PIB-positive people do, indeed, have a preclinical form of the disease, we still need new treatments that stop it from progressing.”
Sheline YI, Raichle ME, Snyder AZ, Morris JC, Head D, Wang S, Minton MA. Amyloid plaques disrupt testing state default mode network connectivity in cognitively normal elderly, Biological Psychiatry, vol. 67(6), pp. 584-587. March 15, 2010.
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.