SALZBURG, AUSTRIA — The investigational Pittsburgh B compound that binds to cerebral β-amyloid and is visible on positron emission tomography maintains its promise as a way to distinguish the elderly patients presenting with memory problems who will go on to develop Alzheimer's disease from those who won't progress.
A series of presentations at an international conference on Alzheimer's and Parkinson's diseases suggested that the ligand Pittsburgh B (PIB) compound, although still at the research stage, may also prove to be an invaluable biomarker to track disease modification in clinical trials.
Kerryn Pike, a research officer at Austin Health, Melbourne, presented the results of a study that examined the relationship between amyloid burden and cognitive function.
The researchers studied 108 individuals with varying degrees of cognitive impairment: 38 of the participants were healthy aging controls (mean Mini Mental State Examination [MMSE], 29.1), 34 had mild cognitive impairment (mean MMSE, 26.3), and 36 had mild Alzheimer's disease (mean MMSE, 22.1).
The average age of the participants was 72 years, and there was no significant difference in age among the three groups. All the individuals were given neuropsychological tests, including the MMSE, California verbal learning test second edition, Rey complex figure test, digit span, verbal fluency, Boston naming test, and digit symbol coding tests.
The researchers calculated a composite episodic memory score and a composite nonmemory cognition score from these neuropsychological tests for each participant. The participants also had a PET scan after being given an intravenous dose of the radiotracer 11C-PIB. A “positive” PIB test was noted in 26% of the 38 healthy aging controls, 59% of the 34 patients with mild cognitive impairment (MCI), and 97% of the 36 patients with Alzheimer's disease (AD), suggesting that they had amyloid deposited in their brains. “About a quarter of healthy elderly are known to have amyloid plaques at autopsy,” noted Ms Pike.
Two of the MCI patients have gone on to develop AD and the researchers plan to follow up the cohort over the coming years.
Individuals with MCI who had a positive PIB test did much worse in the neuropsychological memory tests than did participants with MCI who were negative for amyloid deposition (−2.95 standard deviations from control values vs. −1.1 standard deviations). “This suggests to us that amyloid deposition is a very early pathological process that affects memory specifically,” said Ms Pike.
Indeed, those people with mild cognitive impairment who were PIB positive did almost as badly in the memory tests as did the patients with Alzheimer's disease (−3.22 standard deviations from control values). The researchers found a correlation of 0.72 between amyloid load and memory score.
In addition, participants with MCI who were PIB positive were significantly older than the PIB-negative participants (73.6 years vs. 66.1 years), and the 6 nonamnestic MCI participants were significantly younger than the 28 amnestic MCI participants (mean 63.7 years vs. 71.9 years).
“All our nonamnestic MCI participants were PIB negative and this suggests to us that they have different underlying pathology such as frontotemporal dementia, which doesn't have amyloid plaques,” said Ms Pike.
In a separate presentation, Dr. David Brooks, professor of neurology at Imperial College School of Medicine, London, presented data from a case series of 13 patients with dementia with Lewy bodies (DLB) and 13 patients with Parkinson's disease dementia (PDD) who were imaged using PIB.
The patients with DLB had a mean MMSE of 21, compared with 20 in the patients with PDD. The mean Unified Parkinson's Disease Rating Scale score was 31 in the patients with DLB and 35 in the patients with PDD.
Amyloid levels were raised in 11 of the 13 patients with DLB, although those levels were not as high as those seen previously in patients with AD.
By contrast, only 2 of the 13 patients with PDD showed an increased amyloid burden, suggesting that PIB could potentially be used in the differential diagnosis of PDD and DLB.