PET scans show that patients who carry a gene indicating risk for Alzheimer's disease demonstrate measurable decreases in brain glucose consumption years before they become symptomatic, according to researchers at the World Alzheimer Congress held last week in Washington, DC.
The data presented suggest that researchers are homing in on early detection at a population level, with individual predictors close behind.
The study compared 11 carriers of the apolipoprotein E4 gene with 22 noncarriers in their 50s and early 60s; patients in the two groups had no apparent cognitive differences. The carrier group showed marked reductions in the uptake of F-18 FDG in PET scans. The decrease was most notable in the posterior singulate cortex, as well as the parietal, temporal, and pretemporal lobes, said Dr. Eric Reiman of Good Samaritan Regional Medical Center in Phoenix.
In the search for more study subjects, Reiman and colleagues found that patients can be either homozygous or heterozygous for apo E4, and both groups show the same level of early metabolic decline. Homozygous patients make up about 4% of the U.S. population, while 25% carry one allele.
"The trend of decreasing metabolism seems to be greater in homozygous patients, but we haven't shown statistical significance yet," he said.
A decline in FDG uptake tracked over one or two years appears to positively predict who will go on to the progressive metabolic decline in the brain associated with advancing Alzheimer's, according to Reiman.
For statistical purposes, a trial to assess the effectiveness of an early Alzheimer's prevention or treatment could be done with just 100 patients over one year, or 30 patients over two years. A sample that small could still detect a treatment that would be 50% effective with 80% certainty. Reiman cautioned, however, that the data available apply only to a population level.
"Not all apo E4 carriers develop Alzheimer's, and our methods are still nonspecific such that I wouldn't use a test to predict individual risk," he said.
Meanwhile, researchers at the University of Michigan are beginning to tease out which patients in a group suffering memory disorders will go on to develop Alzheimer's. In a study of 23 patients who showed memory loss but fell short of the criteria for dementia, nine developed Alzheimer's during a two-year study with repeated PET scans. In that population, FDG-PET is 92% accurate in predicting onset of Alzheimer's within two or three years, said Dr. Satoshi Minoshima, an associate professor of internal medicine.
— by Jane Lowers
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