July 15, 2022
We are writing to express our views regarding the Centers for Medicare and Medicaid Services (CMS) National Coverage Determination (NCD) for beta-amyloid positron tomography (PET Aß) in dementia and neurodegenerative disease that currently stands at one scan per patient per lifetime.
The National Center for Health Research (NCHR) is a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.
We agree that there is evidence that PET Aß imaging is a useful tool to support a diagnosis of Alzheimer’s Disease as part of a clinical trial protocol. However, there are conflicting data regarding its usefulness to determine the effectiveness of Alzheimer’s Disease treatment strategies. There are numerous studies in the published literature that suggest that FDG-PET is a superior tool for determining the effectiveness of Alzheimer’s therapies and for tracking disease advancement. For example, Khosravi et al. reported that “giving patients an amyloid PET scan is not an effective method for measuring their cognitive function,” whereas FDG-PET [a non-amyloid PET scan] is “a better means for determining the effectiveness of Alzheimer’s therapies, as well as tracking patients’ disease advancement, in both clinical and research settings.”1,2 Several other studies appear to confirm the superiority of FDG-PET. Similarly, a 2022 study noted that “previous studies have shown that Aß protein deposition can also be seen in healthy populations” and found that FDG-PET was more closely correlated with neuropsychological function than tau PET results in patients with Alzheimer’s disease.3
PET Aß is focused on evaluating amyloid beta plaque, but since the goal of the clinical trials of monoclonal antibodies such as Aduhelm is to determine its efficacy on cognitive function, why not evaluate cognitive function instead? It seems that either FDG-PET or cognitive tests would be more useful. We suggest that CMS consider whether one PET Aß is useful in distinguishing Alzheimer’s from other types of dementia in order to enroll patients in the clinical trials. Also, we suggest CMS consider that a PET Aß scan may be less useful than other tests to determine whether a treatment increases the likelihood of meaningful clinical benefits. Moreover, since concerns about brain swelling and other adverse events can be monitored with MRI, PET Aß are probably not needed to monitor safety.
- Penn Medicine News. Measuring the Brain’s Amyloid Buildup Less Effective in Identifing Severity, Progression of Alzheimer’s Disease Compared to other Imaging Methods. https://www.pennmedicine.org/news/news-releases/2019/august/measuring-brains-amyloid-buildup-less-effective-alzehimers-disease-compared-imaging-methods
- Khosravi, M., Peter, J., Wintering, N. A., Serruya, M., Shamchi, S. P., Werner, T. J., Alavi, A., & Newberg, A. B. (2019). 18F-FDG Is a Superior Indicator of Cognitive Performance Compared to 18F-Florbetapir in Alzheimer’s Disease and Mild Cognitive Impairment Evaluation: A Global Quantitative Analysis. Journal of Alzheimer’s disease: JAD, 70(4), 1197–1207. https://doi.org/10.3233/JAD-190220
- Qiao, Z., Wang, G., Zhao, X., Wang, K., Fan, D., Chen, Q., Ai, L. (2022). Neuropsychological Performance is Correlated with Tau Protein Deposition and Glucose Metabolism in Patients with Alzheimer’s Disease. Front. Aging Neurosc., https://doi.org/10.3389/fnagi.2022.841942