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By 1999 Progress Report by the NIA/NIH • • December 13, 1999

One of the most exciting developments in neuroscience research during the past 10 years has been the refinement of techniques that allow scientists to visualize the activity and interactions of particular brain regions as they are used during cognitive operations such as memorizing, recalling, speaking, reading, learning, and other sorts of information processing. This window on the living brain can help scientists measure early changes in brain function or structure to identify those individuals who are at risk of Alzheimer's disease even before they develop the symptoms of the disease. These imaging techniques include positron emission tomography (PET) scans and single photon emission computed tomography (SPECT), which produce "maps" of the brain that give information about activity in particular regions as a person responds to a task or stimuli, and magnetic resonance imaging (MRI), which provides a way to look at the size and characteristics of brain structures. Three different recent studies using MRI show how it may be useful in the early diagnosis of AD and in evaluating its progression. Eventually, clinicians may be able to use imaging techniques to assess a patient's response to treatment over time.

Researchers at the Mayo Clinic have conducted several important studies in the use of MRI to measure shrinkage in the volume of the hippocampus. The initial studies were cross-sectional studies, which compared groups of individuals with various levels of mental function, from healthy to diagnosed AD. In their newest study, the team actually followed a group of men and women with MCI over time (a longitudinal study) to test the hypothesis that MRI-based measurements of hippocampal volume could predict the risk of future development of AD (Jack et al., 1999). The team followed the patients for nearly 3 years, providing annual clinical exams and tests of mental function. Twenty-seven of the 80 MCI patients developed dementia over the course of the study, and the investigators found that there was indeed a clear association between hippocampal shrinkage at the beginning of the study in these patients and later conversion to AD.

In a second study, investigators at the New York University School of Medicine hypothesized that changes in the size of the entorhinal cortex (EC), a part of the brain important in recent memory and the site where tangles first begin to appear as AD develops, could be potentially useful in the early diagnosis of the disease (Bobinski et al., 1999). Using brain tissue from deceased individuals with and without AD, the researchers first developed and validated a way to measure EC size using MRI. Then they applied the method in living study participants to compare those with mild AD with age-matched healthy individuals. Using three different types of measurements, the researchers showed that the size of the EC was smaller in mild AD patients than in the healthy individuals, suggesting that this use of MRI could also be useful in the early diagnosis of the disease.

A third study using MRI was a follow-up to an earlier study of individuals at risk of AD. All of the individuals had a family history of AD; some also carried the APOE e4 allele. In the earlier study, which used PET, a group of investigators at the University of Arizona showed that compared to those without the APOE e4 allele, those with the allele had significantly reduced glucose metabolism in particular brain regions (Reiman et al., 1996). In the new study, the team used MRI to compare hippocampal volume in the same two groups of patients (Reiman et al., 1998). They found that although the individuals with the APOE e4 allele tended to have smaller hippocampal volumes, this was not statistically significant. However, the smaller volumes were associated with lower scores on a test of long-term memory. The researchers suggest that perhaps the results seen in the PET scans indicate changes occurring before the onset of memory decline, whereas the changes in hippocampal volume seen with MRI occur at the same time as memory declines.

National Institutes of Health
National Institute on Aging

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