SAN DIEGO—Despite arguments to the contrary, amyloid imaging can have clinical benefits for patients with suspected dementia, according to research presented at the 65th Annual Meeting of the American Academy of Neurology. The method can improve diagnostic certainty, affect patient management, and give patients a sense of closure.
Predicting Conversion from MCI to Alzheimer’s Disease
Between 40% and 75% of patients with mild cognitive impairment (MCI) have a positive amyloid PET scan, which predicts conversion to Alzheimer’s disease, said Gil D. Rabinovici, MD, Assistant Professor of Neurology at the University of California, San Francisco. In various studies that followed patients for two years or longer, between 40% and 80% of patients with MCI and positive amyloid PET scans developed Alzheimer’s disease, compared with 0% to 7% of patients with MCI and negative amyloid PET scans. But patients with MCI and negative PET scans could potentially develop non-Alzheimer’s dementia, noted Dr. Rabinovici.
Neurodegenerative biomarkers can provide additional information about when a patient will convert from MCI to Alzheimer’s disease. A multicenter study in Europe measured CSF amyloid-beta (a technique whose results are highly consistent with those of amyloid imaging), glucose metabolism (using FDG–PET), and hippocampal atrophy (using MRI) in patients with MCI. “If we were only to consider the amyloid-beta biomarker, we’d conclude that 62% of the amyloid-beta–positive patients in the study converted from MCI to dementia,” said Dr. Rabinovici. In comparison, three of 11 patients who were positive for amyloid-beta but negative on FDG–PET and MRI developed dementia. Seven of 11 patients who were positive for amyloid-beta and FDG–PET developed dementia, compared with 100% of patients with all three biomarkers. “It’s really the combination of amyloid-beta and a neurodegeneration biomarker that’s giving you prognostic information,” said Dr. Rabinovici.
Alzheimer’s Disease Versus Frontotemporal Dementia
Dr. Rabinovici and colleagues performed a study to compare how well amyloid imaging and FDG–PET could differentiate between patients with Alzheimer’s disease and patients with frontotemporal dementia (FTD). Researchers examined more than 100 patients with either disease, and all patients were well matched for dementia severity and age. Subjects underwent amyloid imaging and FDG–PET scans that were visually interpreted.
Visual reads of the amyloid scans had 90% sensitivity and 83% specificity for the diagnosis of Alzheimer’s disease. Inter-rater agreement on the scans’ interpretation was almost perfect, said Dr. Rabinovici. In contrast, visual reads of FDG–PET scans had significantly lower sensitivity, similar specificity, and significantly lower inter-rater agreement. “Amyloid imaging outperformed FDG–PET in differentiating Alzheimer’s disease and FTD,” said Dr. Rabinovici.
Amyloid Imaging May Reduce Patients’ Costs
Some neurologists question the value of amyloid imaging for patients with suspected Alzheimer’s disease, given the scarcity of effective therapies. Others argue that diagnostic uncertainty entails hidden costs. “Patients who have complicated clinical presentations often end up seeking second and third opinions. They have huge laboratory batteries, multiple imaging tests, [and] they might get unnecessary treatments,” said Dr. Rabinovici. The diagnosis that results from amyloid imaging also can have an intangible value for patients and families, who often are grateful to have closure. Therefore, amyloid imaging “may be cost effective in certain scenarios,” said Dr. Rabinovici.
Amyloid imaging also may play a major role in the development of new therapies for Alzheimer’s disease. Researchers performed amyloid imaging in subsets of patients enrolled in two large studies of monoclonal antibodies for amyloid that were conducted this year. “It was quite eye opening that 35% of the APOE ε4-negative patients who were diagnosed with mild to moderate Alzheimer’s disease were negative on PET scans,” said Dr. Rabinovici. “A positive amyloid scan might be an inclusion criterion in future clinical trials.” In addition, a positive amyloid PET scan is a criterion for entering a clinical trial of antiamyloid therapy for asymptomatic individuals with biomarker evidence of amyloid that is scheduled to begin this year.
During clinical trials, amyloid imaging can help investigators confirm drug engagement and monitor biologic effects. One study used amyloid imaging to examine changes in the binding of the amyloid tracer Pittsburgh compound B over time in patients who received bapineuzumab and those who received placebo.
“The need for molecular diagnostics is intimately tied to the availability of molecular treatments,” said Dr. Rabinovici. “If amyloid imaging can help accelerate and validate molecular treatments, then we are on the cusp of a paradigm shift, not only in how we diagnose the disease, but ultimately how we treat, and maybe even prevent, Alzheimer’s disease.”
Senior Associate Editor
Rabinovici GD, Rosen HJ, Alkalay A, et al. Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD. Neurology. 2011;77(23):2034-2042.