March 29, 2000
Structural Magnetic Resonance Imaging (MRI) could become an important tool for characterizing and diagnosing Alzheimer's disease (AD) in its very early stages, well before clinical signs appear, according to a new study by researchers in Boston. The study, which measured the volume of specific regions of the brain affected early in the disease process, is a significant step toward ultimately predicting who may be at risk for AD and who might benefit from drug treatments that could prevent the disease or slow its progression.
The research, conducted by Marilyn Albert, Ph.D., and her colleagues at Massachusetts General Hospital (MGH) and Harvard Medical School, with collaborators at Brandeis and Boston Universities and Brigham & Women's Hospital, is reported in the April 2000 issue of the Annals of Neurology.
"This study is important for a couple of reasons," says Neil Buckholtz, Ph.D., chief of the Dementias of Aging Branch of the Neuroscience and Neuropsychology of Aging Program at the National Institute on Aging (NIA), which funded the study. "First, it offers evidence establishing the involvement of specific areas of the brain in the underlying early pathology of AD. It also suggests that, by zeroing in on these areas, we may be able to use already available imaging techniques to better identify people at greatest risk and those for whom early treatment could make a difference."
The study was designed to see whether people in the "preclinical" phase of AD -- people with mild memory impairments who would develop AD at the end of the study -- could be identified accurately, in advance of showing outward signs of the disease. At the outset of the study, the 119 participants were divided into two groups -- normal and those with mild memory difficulties -- and each received a baseline MRI scan. Over 3 years, the participants were followed to determine who developed AD, which was diagnosed by a standard medical evaluation. Researchers then went back to the MRIs that had been taken 3 years earlier to see if the scans could prove useful in predicting who would develop AD. The average age of study participants was the early 70s.
Previous research had indicated that measurements of hippocampal volume could identify some cases of AD before a patient met clinical criteria for dementia. But the Boston researchers were seeking to improve accuracy by honing in on select areas of the brain involved at an earlier stage in the disease process. Albert and colleagues looked at differences in volume in a number of areas, focusing on the entorhinal cortex and the banks of the superior temporal sulcus, both involved in memory, and the anterior cingulate, which affects "executive" functions such as organizing, planning, and switching back and forth among tasks and ideas. Recent studies have shown several of these areas to be affected by a significant loss of neurons early in the AD process.
The researchers found that they could identify people who would develop AD over time based on measurements of these brain regions. The MRIs were 100 percent accurate in discriminating between the participants who were normal and those from a third group looked at by Albert's team who already had mild AD. They were 93 percent accurate in discriminating between participants who were normal and those who initially had memory impairments and ultimately developed AD; the entorhinal cortex in the case of the people "converting" to AD had about 37 percent less volume than the entorhinal cortex of those who remained normal, probably reflecting a loss of brain cells. Other comparisons showed a relatively high accuracy rate as well, although it was more difficult to distinguish the people who continued to have memory problems but did not progress to AD from those who eventually converted to AD.
Albert emphasizes the importance of developing such diagnostic techniques at this time, in concert with the development and testing of dozens of new drugs it is hoped will prevent or slow the progression of AD. "Effective treatments for Alzheimer's disease are likely to be ready over the next decade or so," she notes. "In the not too distant future, we may be able to use MRI, in combination with other measures, to identify people at highest risk who can be effectively treated as these new therapies come along." Albert says that these types of measurements might be useful in monitoring response to treatments as well.
The researchers caution, however, that their MRI technique will need to be further refined and validated before it can be used in everyday practice by neurologists and MRI technicians. Albert points to the study's value in getting scientists on the "right track" about what to measure. But, she says, more research in several areas will need to be done, including follow-up of patients over a longer period of time to more precisely gauge the predictive value of the MRIs. Also, the researchers would like to look at functional MRIs and other imaging techniques to see if accuracy can be improved.
Generally, interest is intensifying in the use of imaging for study and diagnosis of AD. According to Buckholtz, serial MRIs will be used to follow participants in an NIA-sponsored trial testing the usefulness of vitamin E and donepezil to stop or slow the conversion of people with mild cognitive impairment, or MCI, to Alzheimer's disease.
The NIA is one of 25 institutes and centers at the National Institutes of Health. It leads the Federal effort to study Alzheimer's disease, supporting basic, clinical, epidemiological, and social research on aging and the special needs of older people and their families.
For specific information on Alzheimer's disease and clinical trials in progress, the public can contact the NIA's Alzheimer's Disease Education and Referral (ADEAR) Center at 1-800-438-4380 or adear@alzheimers.org. You can visit the ADEAR website at www.alzheimers.org.
