Positron emission tomography (PET) of the brain using an enhanced chemical marker has the ability to differentiate among normal aging, mild cognitive impairment, and Alzheimer disease (AD). Researchers writing in the New England Journal of Medicine said the technique is "potentially useful as a noninvasive method to determine regional cerebral patterns of plaques and tangles associated with Alzheimer's disease."1
Eighty-three volunteers with selfreported memory problems participated in the study. On the basis of cognitive testing, they were divided according to their degree of cognitive impairment. Twenty-five volunteers were classified as having AD and 28 as having mild cognitive impairment, while the remaining 30 were healthy controls with no impairment.
Previous studies have found that α- amyloid (in senile plaques) and tau (in neurofibrillary tangles) "accumulate abnormally in a predictable spatial pattern during aging and Alzheimer's disease," the researchers wrote. The investigators used a tracing agent known as FDDNP, a molecule they developed that binds to the amyloid senile plaques and tau neurofibrillary tangles. They compared the results to outcomes with a different tracer known as FDG and to MRI studies of the same patient group.
"Global values for FDDNP-PET binding . . . were [significantly] lower in the control group than in the group with mild cognitive impairment . . . and the values for binding in the group with mild cognitive impairment were [significantly] lower than in the group with Alzheimer's disease," they wrote. "FDDNP-PET binding differentiated among the diagnostic groups better than did metabolism on FDG-PET or volume on MRI."
In comparing the 3 diagnostic methods, the researchers wrote: "We found that the values of global FDDNP were more accurate than previously established sensitive measures for FDG-PET or volumetric MRI measures for diagnostic classification of subjects, suggesting that FDDNP may be useful in differentiating among Alzheimer's disease, mild cognitive impairment, and normal aging."
One of the 83 subjects died 14 months after the baseline studies were completed. A neuropathological examination following an autopsy "showed that regions of the brain with high values of FDDNP binding are characterized by high concentrations of plaques and tangles. These findings support the potential usefulness of FDDNP-PET in the development of surrogate markers for drug discovery aimed at blocking amyloid buildup and as a diagnostic tool, although the study does not provide definitive evidence of a basis for such uses."
The researchers concluded that, "FDDNP-PET scans differentiate persons with mild cognitive impairment from those with Alzheimer's disease and those without cognitive impairment. Equally important, in vivo distributions of FDDNP in the brain follow patterns of pathological distribution seen at autopsy. . . . These observations suggest that FDDNP-PET may be useful in the development of surrogate markers for monitoring the accumulation of these abnormal protein aggregates in the brain that are characteristic of Alzheimer's disease."