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University of Pittsburgh Schools of the Health Sciences

Two Pathways Found That Lead To Alzheimer’s Disease

PITTSBURGH, January 9, 2006 — Mild cognitive impairment (MCI), a transitional stage between normal cognition and Alzheimer’s disease, exists in two different forms, according to a study published today by researchers from the University of Pittsburgh School of Medicine and the University of California, Los Angeles in the Archives of Neurology.

Using a new imaging procedure that creates 3-D maps of the brain, researchers determined specific areas that had degenerated in people with MCI. Depending on the person’s symptoms, more tissue was lost in the hippocampus, a brain area critical for memory and one of the earliest to change in Alzheimer’s disease, indicating two different paths of progression to Alzheimer’s disease. The finding could lead to better diagnosis and treatment of patients with MCI, perhaps delaying or preventing the onset of dementia.

MCI is categorized into two sub-types – currently distinguished based solely on symptoms. Those with MCI, amnesic subtype (MCI-A) have memory impairments only, while those with MCI, multiple cognitive domain subtype (MCI-MCD) have other types of mild impairments, such as in judgment or language, but also have either mild or no memory loss. Both sub-types progress to Alzheimer’s disease at the same rate. Until now it was not known if the pathologies of the two types of MCI were different, or if MCI-MCD was just a more advanced form of MCI-A.

Researchers found that the hippocampus of the patients with MCI-A was 14 percent smaller than that of the healthy subjects, nearly as great as the 23 percent shrinkage seen in Alzheimer’s disease. But, the hippocampus of those with MCI-MCD most resembled that of the controls, showing only 5 percent shrinkage.

Using highly accurate Magnetic Resonance Imaging (MRI) data from six patients with MCI-A, 20 with MCI-MCD and 20 with Alzheimer’s disease who were seen at the University of Pittsburgh’s Alzheimer Disease Research Center and 20 healthy controls, researchers created 3-D mesh reconstructions of each participant’s hippocampus that allowed them to see where the hippocampus had deteriorated. This study is the first to use such modeling technology to visualize changes in the brains of people with MCI. Prior studies have only been able to measure the volume of the hippocampus and estimate atrophy through noticeable volume loss.

“These vibrant images produced by 3-D modeling have proven what we suspected – there are at least two transitional states that lead to Alzheimer’s disease,” said James T. Becker, Ph.D., a neuropsychologist and professor of psychiatry, neurology and psychology, at the University of Pittsburgh School of Medicine and lead author of the study. “Now we can investigate these pathways and develop treatments that, we hope, may slow or stop the progression of Alzheimer’s.”

Alzheimer’s disease affects as many as 10 percent of people older than 65, and delaying or preventing the onset of dementia is an important medical priority.

“We can now see the pattern of brain damage in people with MCI and we can use these new types of images to monitor how different therapies may be working,” said Paul M. Thompson, Ph.D., associate professor of neurology, at the University of California, Los Angeles. “By imaging the brain like this, we can explore the progression of diseases, and see if therapies are protecting the brain.”

This research was conducted by the Imaging Methods and Analysis in Geriatrics Research Group.

Co-authors of this study from the University of Pittsburgh were: Simon W. Davis, department of psychiatry; Carolyn Cidis Meltzer, M.D., departments of radiology and psychiatry and Oscar L. Lopez, M.D., department of neurology. Contributing from UCLA were Kiralee M. Hayashi and Arthur W. Toga, Ph.D., both of the department of neurology.

The study was funded by grants from the National Institute on Aging, National Library of Medicine, National Center for Research Resources and National Institute of General Medical Sciences.

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