MADRID – PIB-PET imaging not only differentiated patients with mild cognitive impairment and Alzheimer's disease from normal controls, but it also identified amyloid pathology in subjects who did not yet express cognitive symptoms, according to findings from a small study.
The unexpected finding may have a huge effect on two of neurologists' dream goals: to identify patients destined to develop the disorder, and to initiate treatment that would avert or minimize its cognitive consequences, according to speakers at the 10th International Conference on Alzheimer's Disease and Related Disorders.
Dr. Steven T. DeKosky, chairman of the department of neurology at the University of Pittsburgh, used PIB-PET imaging (PET with Pittsburgh Compound-B) and a radiotracer known as [18F]FDDNP to examine plaque deposition and the progression of amyloid plaques and neurofibrillary tangles in 59 subjects, of whom 14 had mild cognitive impairment (MCI), 14 had confirmed Alzheimer's disease, and 31 were age-matched controls. Both compounds bind to amyloid A, allowing scans to track the progression of plaques and neurofibrillary tangling in the brain.
The scan successfully separated Alzheimer's patients from controls with no overlap. The patients had about twice the amyloid deposition.
The differentiations between subjects with MCI and controls–as well as between MCI subjects and Alzheimer's patients–were not as clear cut, however. “About 25% of our controls actually had some plaque binding, and 60% of our MCI subjects already had enough binding to put them in the Alzheimer's category,” Dr. DeKosky said.
Interestingly, the amyloid burden in MCI subjects didn't necessarily correlate with cognitive function, Dr. DeKosky noted. “We had one MCI subject with very high binding but a very good Mini-Mental State [Examination] score, and one MCI subject who had very low binding, nearer to control levels, who had a very poor MMSE.”
Dr. Gary Small, director of the memory and aging research center at the University of California, Los Angeles, used [18F]FDDNP not only to differentiate normal brains from those with MCI and Alzheimer's disease, but also to track the progression of the disorder.
His study involved 60 subjects (mean age 71 years): 20 controls, 20 with MCI, and 20 with Alzheimer's disease. All of the subjects received an [18F]FDDNP PET scan, and 12 had repeat scans 2 years later.
The scans clearly separated the groups with no overlap between the controls and the patients with Alzheimer's disease. But 60% of those with MCI had amyloid binding in the mediotemporal lobe that was of similar volume to that seen in Alzheimer's patients. “We also saw that some controls were beginning to show amyloid buildup in this area,” Dr. Small said.
Follow-up scans were performed 2 years later on eight controls and four MCI subjects. Amyloid binding was stable in those who remained cognitively stable. But in those who declined cognitively–that is, going either from normal to MCI status, or from MCI to Alzheimer's disease–amyloid binding increased 5%–11% compared with their baseline scan.
The main difference between the compounds–as both are highly accurate in distinguishing the populations–seems to be the length of their activity, Dr. Small said: [18F]FDDNP has a 2-hour half-life, whereas the half-life of PIB is only 20 minutes.
The current lack of a sensitive and accurate diagnostic method greatly impedes both treatment and research, said Dr. Ronald Petersen, who moderated a press conference at the meeting, which was presented by the Alzheimer's Association.
“Tests that would track the progression of the disease would help us treat people earlier and greatly speed testing of new drugs in treatment trials,” said Dr. Petersen, a spokesman for the association. “Imaging may be the solution, because it can help us look inside the brain and body to diagnose the disease, monitor progression and track the effects of therapy,” he said.
The scans clearly separated the groups, with no overlap between the controls and the Alzheimer's patients. DR. SMALL
These PIB-PET images show FDDNP binding to amyloid plaques in normal, MCI, and Alzheimer's brains. Arrows show lateral temporal and mediotemporal lobes. Courtesy Dr. Gary Small