The research is reported in the August, 1997 issue of The American Journal of Psychiatry (Pietrini PP et al, "Low Glucose Metabolism During Brain Stimulation in Older Down's Syndrome Subjects at Risk for Alzheimer's Disease Prior to Dementia", Am J. Psychiatry, 154:8, 1997). and was conducted by a team of NIA scientists headed by Pietro Pietrini, M.D. Ph.D., and Mark B. Schapiro, M.D. . The researchers studied volunteers with Down's syndrome because most patients exhibit neuropathology similar to that of Alzheimer's disease after middle age and develop many cognitive defects similar to those in Alzheimer's disease later in life.
In order to test whether development of an Alzheimer's-like dementia could be predicted well before the onset of any outward mental or physical signs, the researchers chose 16 healthy Down's syndrome adults. They divided the patients into a younger group between the ages of 32 to 38 and an older group between the ages 43 to 61 which might be expected to be developing early Alzheimer's-like pathology. By using positron emission tomography (PET), the scientists were able to observe brain activity while the subjects were at rest (wearing earplugs and blindfolds) or while their brains were stimulated by viewing a movie. In order to assure their comfort and ease, we monitored these patients' anxiety levels during PET testing. Variations in activity in specific regions of brain in the PET scans showed researchers where there were low activity levels, which are associated with early Alzheimer's disease. According to Dr. Pietrini, "although persons with Down's do not develop dementia at the same ages as persons who develop Alzheimer's disease, they comprise an excellent group for study because of the high incidence rate for Alzheimer's-like dementia in this population. I believe we have identified evidence of dementia at a much earlier stage than previously described by other investigators. We saw no difference in resting brain activity but when we looked at stimulated brain activity, we were able to see decreases in our older group of patients in areas of the brain that we know show Alzheimer's-like tissue changes." Dr. Schapiro adds, "The subjects in the present study were all healthy and exhibited no outward signs of dementia. The inability of this group to respond normally to visual stimulation indicates that the disease process leads to changes in brain function even sooner than we expected. We also found that in this older group, during stimulation, the left side of the brain seemed to be more impaired than the right, suggesting that the left side of the brain may be preferentially affected early in the disease process. As an interesting unexpected observation, cognitive function that was not related to memory was not impaired, suggesting some plasticity, which is the ability of the brain to compensate for metabolic impairments during the stimulation activity."
According to Dr. Pietrini, "It must be pointed out, however, that this study was done on a small group of persons with Down's and must be replicated on a much larger scale and in other people at risk for Alzheimer's before actual testing of interventions using this procedure could be advised or planned. Studies that specifically identified persons in the pre-symptomatic stages of Alzheimer's would give us early clues as to the promise of actual interventions that could be put into practice in years to come."
Alzheimer's disease affects 4 million Americans and that number is expected to increase several-fold as more people live longer. Prevention or treatment of the disease is thus of great practical importance, and as has been learned in many human diseases, the earlier one can intervene in the disease process, the greater the likelihood for a positive long-term outcome.
Other investigators who took part in the study from the NIA are Alessio Dani, M.D., Maura Furey, Ph.D., Gene E. Alexander, Ph.D., Ulderico Freo, M.D., Cheryl L. Grady, Ph.D., Marc J. Mentis, M.D., David Mangot, B.S., Elliot W. Simon, Ph.D., Barry Horwitz, Ph.D., and James V. Haxby, Ph.D. .
The National Institute on Aging, one of the 18 Institutes which make up the National Institutes of Health, leads the Federal effort supporting basic, clinical, epidemiological and social research on Alzheimer's disease and the special needs of older people.
For more information on the NIA and aging in general, please visit our web site at http://www.nih.gov/nia.
For general information on Alzheimer's disease and for information on participation in NIA clinical studies, contact NIA's Alzheimer's Disease Education and Referral (ADEAR) Center, toll-free, at 1-800-438-4380.
Journal
American Journal of Psychiatry