By Andrew Stephens, MD
The rising prevalence of Alzheimer’s disease will be felt around the world as the aging population continues to grow. It’s estimated that nearly 5 million have Alzheimer’s disease in the United States.1 This number of new cases of Alzheimer’s and other dementias is projected to more than double by 2050.2 Unfortunately, this impending crisis is only worsened by the fact that Alzheimer’s disease is a diagnosis of exclusion3 and is incorrect in 10% to 30% of cases.4 Definitive diagnosis can only be achieved through postmortem autopsy. Early diagnosis of Alzheimer’s disease would provide patients the best opportunity to benefit from a comprehensive life-management plan, which includes symptomatic therapies that may improve overall quality of life.
Over the past five years, significant progress has been made in updating the diagnostic criteria for Alzheimer’s disease.3,5-7 Both the National Institute on Aging in conjunction with the Alzheimer’s Association and the European Federation of the Neurological Societies published guidelines that included the need for biomarkers—which include imaging—in the diagnosis of Alzheimer’s disease.3,5,6 More recently, SNMMI and the Alzheimer’s Association published appropriate use criteria for PET imaging of brain beta-amyloid.7 While each of these guidelines acknowledge that amyloid PET imaging does not replace clinical examination and patient history, they do note that imaging can increase diagnostic confidence.
I believe we are approaching the tipping point of ushering in a new era of imaging that helps paint clearer pictures of the pathology of Alzheimer’s disease, which as a biomarker, may improve diagnosis and allow earlier therapy. Given the large number of people at risk for Alzheimer’s disease and the potential for improved patient outcomes, nuclear medicine professionals are poised to play a significant role in the management of this disease. Three 18F-labeled beta-amyloid ligands—florbetapir, flutemetamol, and florbetaben—are approved by the European Commission and the FDA for PET imaging of beta-amyloid, but have largely been used in the clinical trial setting.Recently, florbetaben received approval for estimating beta-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer’s disease and other causes of cognitive decline.8
Amyloid PET imaging in the evaluation of people with cognitive impairment is not without controversy. In 2013, the Centers for Medicare & Medicaid Services (CMS) made a national coverage decision (CAG-00431N) to not cover amyloid PET imaging in dementia and neurodegenerative disease in an unrestricted manner because there was not enough evidence to suggest that imaging improved health outcomes. However, CMS acknowledged that imaging was promising and approved its use under “coverage with evidence development” to study the appropriate indication for reimbursement. As a result, the Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) Study, designed by the Alzheimer’s Association and the ACR in cooperation with CMS, will seek to determine the clinical utility of PET beta-amyloid imaging, according to the Alzheimer’s Association. Specifically, it will examine the change of clinical management of Alzheimer’s disease after patients and physicians know the result of a scan and will assess changes in hospitalization and emergency room visits using Medicare claims data from a matched control cohort of patients who have never undergone amyloid PET imaging.
This study will make beta-amyloid imaging available for reimbursement for more than 18,000 patients at centers throughout the country at more than 200 sites in the United States. Progress in this area could be a catalyst to closely align nuclear medicine professionals and neurologists in a common goal of expediting a diagnosis and plan of action to improve the lives of people suspected of having Alzheimer’s disease.
Despite the absence of disease-modifying therapies, advances in beta-amyloid imaging are already providing new data in biomarker identification, an emerging area that may improve patient selection and help drive development of disease-modifying therapies.
— Andrew Stephens, MD, is the chief medical officer of Piramal Imaging.
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2. Hebert LE, Beckett LA, Scherr PA, Evans DA. Annual incidence of Alzheimer disease in the United States projected to the years 2000 through 2050. Alzheimer Dis Assoc Disord. 2001;15(4):169-173.
3. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):263-269.
4. APA work group on Alzheimer’s disease and other dementias, Rabins PV, Blacker D, et al. Practice guideline for the treatment of patients with Alzheimer’s disease and other dementias. Second edition. Am J Psychiatry. 2007;164(12 suppl):5-56.
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6. Hort J, O'Brien JT, Gainotti G, et al. EFNS guidelines for the diagnosis and management of Alzheimer's disease. Eur J Neurol. 2010;17(10):1236-1248.
7. Johnson KA, Minoshima S, Bohnen NI, et al. Update on appropriate use criteria for amyloid PET imaging: dementia experts, mild cognitive impairment, and education. J Nucl Med. 2013;54(7):1011-1013.8. Sabri O, Sabbagh MN, Seibyl J, et al. Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer disease: phase 3 study [published online March 28, 2015]. Alzheimers Dement. 2015. pii: S1552-5260(15)00060-6. doi:10.1016/j.jalz.2015.02.004.