PET Imaging May Spot First Signs of Alzheimer's

by Charles Bankhead for MedPage Today:Brain imaging with a beta amyloid-specific tracer identified patients who had a high risk of rapid progression from mild cognitive impairment to Alzheimer's disease, an Australian study showed.Three-fourths of patients with high uptake of 18F-florbetaben (¹⁸FBB) progressed to Alzheimer's disease within 24 months. In contrast, half of patients with hippocampal atrophy met diagnostic criteria for Alzheimer's disease within 2 years.The results suggest that PET imaging with¹⁸FBB could offer the earliest test yet developed for diagnosis of Alzheimer's disease, according to a study reported at the Society of Nuclear Medicine meeting in Miami Beach, Fla."Diagnosis of Alzheimer's disease can now be made when the patient first presents symptoms and still has largely preserved mental function," Christopher Rowe, MD, of Austin Health in Melbourne, said in a statement."Previously, there was an average delay of 3 years between consulting a doctor over memory concerns and the diagnosis of Alzheimer's, as the diagnosis required the presence of dementia," he added.The study was one of several linking the burden of beta-amyloid to Alzheimer's disease.Rowe and colleagues presented data from two of the studies. In the first, they longitudinally assessed beta-amyloid accumulation in 45 patients with mild cognitive impairment, performing¹⁸FBB-PET imaging and 3D MRI at 12 and 24 months.At baseline, 53% of the study participants had high neocortical FBB binding (>1.4 SUVR), and 76% had hippocampal atrophy, both of which correlated with the patients' composite memory scores.At the 24-month follow-up, investigators observed increased neocortical SUVR in patients who had high FBB binding. Three-fourths of those patients had progressed to Alzheimer's disease, which represented a 10.9-fold increased risk of progression compared with patients who had low FBB binding (P<0.0001).Rowe reported that 53% of patients with hippocampal atrophy had progressed to Alzheimer's disease (RR 4.1, P=0.03). For progression to any dementia, hippocampal atrophy had a predictive RR of (P=0.009).The authors pointed out that hippocampal atrophy lost significance in multivariate analysis.In their second study, Rowe and colleagues evaluated 194 healthy individuals, 92 patients with mild cognitive impairment, and 70 patients with Alzheimer's disease, using a PET imaging agent known as Pittsburgh Compound C (PiB).Similar to the first study, the results showed that extensive beta-amyloid accumulation over a 3-year period predicted an increased risk of progression to Alzheimer's disease and other forms of dementia.Overall, 46 of the patients with mild impairment progressed to Alzheimer's disease, including 60% of the patients who were PiB-positive (SUVR >1.5) at baseline versus 10% of those who were PiB negative (RR 8.7, P<0.0001). Moreover, 15% of PiB-positive healthy controls developed mild cognitive impairment or Alzheimer's disease compared with 3% of those who were PiB negative (RR 2.7, P=0.05).On multivariate analysis, PiB (RR 5.9) and memory score (RR 5.5) remained significant predictors in mild cognitive function, but only memory score (RR 3.6) remained a significant predictor in the controls.Investigators at the University of Wisconsin in Madison also used PET with PiB and with ¹⁸F-FDG to evaluate 100 late-middle-age adults with normal cognition. Overall, 15% of the study participants had evidence of beta-amyloid accumulation. Both tracers identified beta-amyloid, but inter-reader agreement on imaging results was higher with PiB, Guofan Xu, MD, PhD, and colleagues reported.Moreover, the results showed that PiB-positive study participants were more likely to be positive for the APO E4 polymorphism, which, in turn, was associated with beta-amyloid accumulation.A fourth study reported at the SNM meeting involved use of the tracer ¹⁸F-florbetapir with PET to examine the effect of beta-amyloid accumulation on neural connectivity associated with cognition, specifically the default-mode and salience networks.The study involved 137 healthy adults, ages 30 to 89. The results showed that increased beta-amyloid burden was associated with decreased connectivity to the default-mode network from several areas of the brain. The decreased connectivity predicted poorer performance on tests of cognitive function.Beta-amyloid accumulation had a less robust association with decreased connectivity in the salience network and with cognitive function."Increasing amyloid burden impairs default mode network functional connectivity and inappropriately enhances salient-network functional connectivity," Michael Devous, PhD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues concluded."Both changes in functional connectivity are associated with impaired cognitive performance in several critical domains of cognition," they said.Source: http://www.medpagetoday.com/MeetingCoverage/AdditionalMeetings/33238