Research conducted at the University of California, Los Angeles, strongly suggests that FDG-PET imaging may soon be accepted as a noninvasive test to diagnose Alzheimer's disease and monitor the effectiveness of drug therapy for the condition.

Another study by the same group suggests that the roots of Alzheimer's disease may originate early in life, affecting subsequent intellectual development and educational achievement.

Previous attempts at using PET to diagnose early Alzheimer's disease have been hampered by a lack of cases in which patients who underwent FDG-PET scans exhibited symptoms of neurodegeneration that were later confirmed by autopsy. By retrospectively pooling cases from around the world, Dr. Daniel Silverman, head of the neuroimaging research group at UCLA, found that 93% of patients with confirmed neurodegenerative disease were accurately identified by PET. Results were based on 70 cases. The imaging procedure accurately ruled out neurodegenerative disease in 92% of the cases. Overall accuracy was 93%.

When examining specifically for Alzheimer's disease, the sensitivity rate rose to 96%. Of 49 patients whose Alzheimer's disease was confirmed by autopsy, 47 had had a previous PET scan positive for the condition. The specificity rate was lower (67%) because the criteria used to interpret the PET study were consistent with a diagnosis of Alzheimer's in seven of the 21 patients who did not have the condition (six of whom had neurodegenerative disorders). The overall accuracy rate was 87.1%. In contrast, clinical examinations accurately diagnose about 70% of comparable cases, Silverman said.

The results support use of an FDG-PET head scan when patients' symptoms suggest early Alzheimer's disease, he said.

"That is the time when those patients should get a functional brain imaging study to either verify or provide disparity between the clinical impression and what PET can show us," Silverman said.

In another study, the UCLA team confirmed the value of FDG-PET in testing the clinical effectiveness of anticholinesterase agents, such as tacrine and donepezil, to treat dementia. FDG-PET scans and two to 10 years of clinical follow-up information were obtained for 128 patients who were referred for early symptoms of dementia. FDG-PET accurately predicted patients who would cognitively deteriorate in 90% of cases. Its prognostic power did not differ significantly for patients who were prescribed therapy and those who were not, according to Silverman. Of 51 patients with negative scans, only seven were treated with ACT, suggesting that the attending physicians understood that their patients' conditions would not improve with drug therapy, he said.

A third UCLA study uncovered evidence of early cerebral metabolic decline in individuals who may be predisposed to Alzheimer's. The study was based on earlier research that found that low educational attainment translates into a high risk for Alzheimer's disease later in life. Silverman's group performed FDG-PET brain scans and examined medical and educational histories of 60 subjects, aged 51 to 86, to determine whether pre-neurodegenerative effects that inhibit intellectual growth and educational attainment in childhood and adolescence may be linked to Alzheimer's disease.

The researchers also extrapolated back to the age of 20 for this group with imaging in the posterior cingulate, the brain region where Alzheimer's disease is first expressed. With the aid of FDG-PET, they found statistically significant differences in the metabolic profiles of posterior cingulates of the youngest well-educated and poorly educated subjects. The mean difference in metabolic activity projected back to age 20 was about one-third of the average level of cortical metabolism at that age, Silverman said.

There also seems to be an interaction with the predominant genetic risk factor, apolipoprotein E4, for developing Alzheimer's disease in old age, according to Silverman. Patients with E4 have a greater difference of activity in the posterior cingulate at a younger age, he said. The mean education difference and metabolic activity projected for age 20 in the posterior cingulate was higher than for any other region.

"This suggests that regional cerebral metabolic decline begins decades before the clinical onset of Alzheimer's disease and early enough to affect educational level," Silverman said.

— by Jim Brice