Molecular imaging helps follow the progression of Alzheimer's disease

Jun 16 2008

In the past, physicians were able only to follow the progression of Alzheimer's disease (AD) through careful clinical histories, noting the often subtle changes associated with cognitive decline over a number of years.

Recent research suggests that the use of molecular imaging in the management of neurodegenerative disease, particularly for early diagnosis of AD, will enable researchers to monitor the progression of the disease, identifying those at risk and assessing the effectiveness of new therapies.

Some studies have suggested that the characteristic signs of AD are present up to a decade before dementia sets in. The difficulty was being able to look into a living person's brain to see the deposits of plaque (an abnormal accumulation of insoluble fibrous beta-amyloid protein aggregates) thought to be responsible for the onset of the disease.

Using positron emission tomography (PET) and a radiotracer known as Pittsburgh Compound-B (PiB) that is capable of binding to plaques found in the brains of AD patients, researchers at the University of Pittsburgh found that beta-amyloid imaging could provide early detection of AD and more accurate differential diagnosis of other dementias (by revealing the presence or absence of beta-amyloid plaques).

In a current longitudinal study following participants for more than four years, the Pittsburgh research team has recently sought to compare patients with AD to elderly control individuals and to subjects with mild cognitive impairment (MCI) to determine control subjects at risk of developing cognitive impairment and those MCI subjects who were most likely to progress on to a clinical diagnosis of AD. Thirty-five people (four with mild to moderate AD, 10 with MCI and 21 elderly controls) were scanned at yearly intervals over four years.

"The research literature shows that 30 to 40 percent of people with MCI do not progress to AD during five to 10 years of follow-up testing. Our hypothesis was that MCI subjects with brain plaque would develop AD and MCI subjects without plaque would not advance to AD," said Chester Mathis, Ph.D., professor of radiology at the University of Pittsburgh. "We found that about 60 percent of the MCI subjects had plaque loads comparable to AD subjects, while about 35 percent of MCI subjects had no detectable plaque. After monitoring our study MCI participants for four years, we have found that only those with plaque progressed on to the clinical diagnosis of AD. In AD subjects, there appears to be a ceiling to plaque deposition, and plaque concentration does not increase as the disease progresses from mild to advanced stages of AD," he said.

"We had also assumed that the elderly control group would have little PiB retention (indicating no amyloid deposits), but the results were otherwise," he added. "We found that about 25 percent of participants between 65 and 80 years of age had significant deposits of amyloid plaque in their brains. We hypothesize that these control subjects are in a presymptomatic, at-risk state that will eventually lead to AD."

Dementia is a general term for a progressive brain dysfunction that results in the loss of memory and other intellectual abilities serious enough to interfere with daily life. MCI patients demonstrate a decline of cognitive performance that is more pronounced than expected from age but not severe enough to meet criteria for the clinical diagnosis of dementia. The clinical course of these patients is challenging to forecast on the basis of clinical measures alone. Many diseases can result in a form of dementia, the most common one being AD, a progressive and fatal brain disease. According to the Alzheimer's Association, more than five million people in the United States have AD, and by 2050, that number could triple. Currently it is the seventh leading cause of death in the United States.