Amyloid PET Is Aiding Drug Development, If Not Patient Outcomes

Even an expert clinical diagnosis of Alzheimer’s disease has only moderate sensitivity and specificity, compared with the gold standard of neuropathology.¹ Amyloid PET has the potential to improve diagnostic accuracy by directly detecting a core element of Alzheimer’s disease pathology during life. In their large study of end-of-life patients, Sabbagh and colleagues demonstrated that florbetaben PET scans during life predicted the presence or absence of amyloid pathology at autopsy with high accuracy. A weakness of the study is that an end-of-life population may not be representative of the spectrum of pathology likely to be found in patients who visit memory clinics. These patients presumably would be studied at a much earlier disease stage. Although amyloid PET can be helpful in diagnostically challenging cases, it is critical for scan results to be interpreted in the context of a comprehensive clinical evaluation because amyloid plaques also can be found in non-Alzheimer’s dementias and in 20% to 30% of cognitively normal individuals.²

With this pivotal study, florbetaben becomes the third amyloid PET tracer approved by the FDA for clinical use. However, patient access has been severely restricted because it is not reimbursed by third-party payers, who require evidence that the scans not only increase diagnostic accuracy, but also improve patient outcomes. Studies evaluating the clinical impact of amyloid PET are under way. In the meantime, amyloid PET is already playing a critical role in Alzheimer’s disease drug development by enabling screening for amyloid in patients enrolling in clinical trials for Alzheimer’s disease.³

—Gil Rabinovici, MD
Associate Professor of Neurology
Memory and Aging Center
University of California, San Francisco

References

1. Beach TG, Monsell SE, Phillips LE, Kukull W. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005-2010. J Neuropathol Exp Neurol. 2012;71(4):266-273.
2. Johnson KA, Minoshima S, Bohnen NI, et al. Appropriate use criteria for amyloid PET: A report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association. Alzheimers Dement. 2013;9(1):e-1-e16.
3. Salloway S, Sperling R, Fox NC, et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014;370(4):322-333.

Even an expert clinical diagnosis of Alzheimer’s disease has only moderate sensitivity and specificity, compared with the gold standard of neuropathology.¹ Amyloid PET has the potential to improve diagnostic accuracy by directly detecting a core element of Alzheimer’s disease pathology during life. In their large study of end-of-life patients, Sabbagh and colleagues demonstrated that florbetaben PET scans during life predicted the presence or absence of amyloid pathology at autopsy with high accuracy. A weakness of the study is that an end-of-life population may not be representative of the spectrum of pathology likely to be found in patients who visit memory clinics. These patients presumably would be studied at a much earlier disease stage. Although amyloid PET can be helpful in diagnostically challenging cases, it is critical for scan results to be interpreted in the context of a comprehensive clinical evaluation because amyloid plaques also can be found in non-Alzheimer’s dementias and in 20% to 30% of cognitively normal individuals.²

With this pivotal study, florbetaben becomes the third amyloid PET tracer approved by the FDA for clinical use. However, patient access has been severely restricted because it is not reimbursed by third-party payers, who require evidence that the scans not only increase diagnostic accuracy, but also improve patient outcomes. Studies evaluating the clinical impact of amyloid PET are under way. In the meantime, amyloid PET is already playing a critical role in Alzheimer’s disease drug development by enabling screening for amyloid in patients enrolling in clinical trials for Alzheimer’s disease.³

—Gil Rabinovici, MD
Associate Professor of Neurology
Memory and Aging Center
University of California, San Francisco

References

1. Beach TG, Monsell SE, Phillips LE, Kukull W. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005-2010. J Neuropathol Exp Neurol. 2012;71(4):266-273.
2. Johnson KA, Minoshima S, Bohnen NI, et al. Appropriate use criteria for amyloid PET: A report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association. Alzheimers Dement. 2013;9(1):e-1-e16.
3. Salloway S, Sperling R, Fox NC, et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014;370(4):322-333.

Even an expert clinical diagnosis of Alzheimer’s disease has only moderate sensitivity and specificity, compared with the gold standard of neuropathology.¹ Amyloid PET has the potential to improve diagnostic accuracy by directly detecting a core element of Alzheimer’s disease pathology during life. In their large study of end-of-life patients, Sabbagh and colleagues demonstrated that florbetaben PET scans during life predicted the presence or absence of amyloid pathology at autopsy with high accuracy. A weakness of the study is that an end-of-life population may not be representative of the spectrum of pathology likely to be found in patients who visit memory clinics. These patients presumably would be studied at a much earlier disease stage. Although amyloid PET can be helpful in diagnostically challenging cases, it is critical for scan results to be interpreted in the context of a comprehensive clinical evaluation because amyloid plaques also can be found in non-Alzheimer’s dementias and in 20% to 30% of cognitively normal individuals.²

With this pivotal study, florbetaben becomes the third amyloid PET tracer approved by the FDA for clinical use. However, patient access has been severely restricted because it is not reimbursed by third-party payers, who require evidence that the scans not only increase diagnostic accuracy, but also improve patient outcomes. Studies evaluating the clinical impact of amyloid PET are under way. In the meantime, amyloid PET is already playing a critical role in Alzheimer’s disease drug development by enabling screening for amyloid in patients enrolling in clinical trials for Alzheimer’s disease.³

—Gil Rabinovici, MD
Associate Professor of Neurology
Memory and Aging Center
University of California, San Francisco

References

1. Beach TG, Monsell SE, Phillips LE, Kukull W. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005-2010. J Neuropathol Exp Neurol. 2012;71(4):266-273.
2. Johnson KA, Minoshima S, Bohnen NI, et al. Appropriate use criteria for amyloid PET: A report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association. Alzheimers Dement. 2013;9(1):e-1-e16.
3. Salloway S, Sperling R, Fox NC, et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014;370(4):322-333.