The study, led by Dr. Mony J. de Leon, Director of the Center for Brain Health and Professor of Psychiatry at NYU School of Medicine, shows that metabolic changes occur in particular regions of the brain years before there are any clinical signs of memory loss. The study demonstrated these changes with PET (positron imaging tomography), a brain scan that employs radioactively labeled glucose to show the brain at work.
The brain scan, along with other tests, may one day provide physicians with the tools to identify those individuals at risk for Alzheimer's disease.
"Our work extends the use of PET scanning to identifying in normal aging subjects the earliest metabolic abnormalities that may lead to the memory losses referred to as mild cognitive impairment (MCI). The diagnosis of MCI carries a high risk for future Alzheimer's disease," says Dr. de Leon. "The results will allow us to distinguish individuals at increased risk of memory impairment, but it is still too early to apply the brain scans outside of a research setting. We need to confirm our results with a larger group of subjects and to identify the biological and physiological factors leading to the metabolism losses. If we can identify these factors, then we may be able to find a way to delay the onset of Alzheimer's or prevent it altogether."
The new study followed a group of 48 healthy men and women between the ages of 60 and 80. At the beginning of the study, everyone scored within the normal range on a battery of tests typically used to detect early loss of memory and other mental skills. However, PET scans revealed a reduction in glucose metabolism in an area of the brain called the entorhinal cortex among 12 people. Three years later, 11 of these people had experienced MCI and one developed Alzheimer's disease. The individuals with normal PET scans did not show any signs of mental decline at the three-year follow-up.
Moreover, among the group whose mental acuity declined, carriers of the apolipoprotein E4 gene, a biomarker linked to Alzheimer's, showed large reductions in brain metabolic activity over the course of the study. Such metabolic changes may account for the increased risk for Alzheimer's associated with the gene, says Dr. de Leon.
The study is published in the September 11 issue of The Proceedings of the National Academy of Sciences.
Over the years, Dr. de Leon's laboratory has used PET and MRI (magnetic resonance imaging) brain scans to study normal aging of the brain and Alzheimer's disease. His team was the first to demonstrate with MRI scans that deterioration of the hippocampus in MCI patients predicts future Alzheimer's disease.
Along with Antonio Convit, M.D., Associate Professor of Psychiatry at NYU School of Medicine, and Susan DeSanti, Ph.D., Research Assistant Professor of Psychiatry at NYU School of Medicine, Dr. de Leon has been characterizing the changes in brain architecture and metabolism that may point to future losses in memory and intellectual ability. They are also studying biomarkers, such as forms of a protein called tau, which accumulate in the cerebrospinal fluid. They hope that the brain scans and biomarkers will one day provide a sensitive test to identify people at risk for Alzheimer's.
"We want to learn how the brain becomes vulnerable to this disease," says Dr. de Leon. Alzheimer's is a progressive illness that destroys neurons in the brain. It initially causes memory loss and eventually dementia, and there is no way to predict who will develop the disease. Alzheimer's afflicts four million older adults in the United States and perhaps three times as many individuals suffer milder forms of the disease that incapacitate memory.
In addition to Drs. de Leon, Convit, and DeSanti, the authors of the study are: O. T. Wolf; Y. Tarshish; H. Rusinek; W. Tsui; E. Kandil; A. J. Scherer; A. Roche; A. Imossi; E. Thorn; M. Bobinski; C. Caraos; P. Lesbre; and B. Reisberg; from NYU School of Medicine; and D. Schlyer; J. Poirier; and J. Fowler; from Brookhaven National Laboratory.
Journal
Proceedings of the National Academy of Sciences