A positive PET scan of brain amyloid ß is insufficient to establish a diagnosis of Alzheimer’s disease, according to new appropriate-use criteria for PET imaging published in the January 9 online Alzheimer’s & Dementia and in the January 28 online Journal of Nuclear Medicine. In conjunction with a thorough clinical evaluation that includes cognitive testing, however, the scan can make the diagnosis more certain, according to the criteria prepared by the Alzheimer’s Association’s Amyloid Imaging Task Force and the Society of Nuclear Medicine and Molecular Imaging.
Once a patient’s amyloid status is known, a patient and physician can focus on appropriate care. The neurologist can prescribe appropriate medications, pursue other testing, and help to plan for a patient’s future, said Keith A. Johnson, MD, Associate Professor of Radiology at Harvard Medical School in Boston and the lead author of the criteria.
“The ultimate goal was to determine whether there is evidence that using amyloid PET leads to clinically meaningful improvement in outcomes or is useful in medical or personal decision making,” stated the task force.
When used appropriately, amyloid plaque PET imaging benefits patients and physicians, whether the results are positive or negative, said Richard J. Caselli, MD, Professor of Neurology at the Mayo Clinic in Scottsdale, Arizona. “This [paper] represents an important step forward” in the clinical management of Alzheimer’s, said Dr. Caselli in an interview. “Now it is a question of convincing third-party payers, including not only the [Centers for Medicare and Medicaid Services, CMS], but private insurers as well, of its necessity in appropriately selected patients.”
The task force consisted of experts in Alzheimer’s dementia and nuclear imaging. The team reviewed 80 studies that examined amyloid imaging’s diagnostic accuracy, ability to predict disease, potential implications for treatment planning, and possible effect on the psychologic, financial, and social well-being of the patient and family.
Clinical Situations in Which PET Is Appropriate
The task force detailed three situations in which a PET scan is warranted. A scan is appropriate for a patient who has persistent or progressive, unexplained mild cognitive impairment (MCI). A positive finding would increase the certainty of a diagnosis of early Alzheimer’s pathology. A negative finding could exclude Alzheimer’s pathology, so that the clinical investigation could consider other possible causes. “
Patients with unusually slowly progressive MCI are not common, but nonetheless pose significant diagnostic challenges that result in repeated testing over the years,” said Dr. Caselli, who was not a member of the task force. “A supportive amyloid scan in such patients could reduce such duplicative testing,” he added.
PET imaging also would be appropriate for a patient who satisfied the core clinical criteria for possible Alzheimer’s disease, but had an atypical presentation. Such patients include individuals with an unusual course, such as sudden onset or episodic cognitive problems, or a comorbid condition that could confuse the clinical picture, such as cerebrovascular disease. Amyloid imaging cannot differentiate between Alzheimer’s disease and Lewy body pathology, however, according to the criteria. “
Certainly, [PET imaging] may be another diagnostic asset in the evaluation of patients with unusual clinical features, but it should be recognized that Alzheimer’s disease itself has documented variants, including visual, aphasic, and dysexecutive—all of which are recognized in the new diagnostic criteria—and apraxic, which was omitted in the new diagnostic criteria,” said Dr. Caselli. “The decision to use amyloid PET in such cases will depend on the clinician’s own level of comfort, but may be less important for those with more experience in these atypical presentations. What it should not do is prevent the appropriate reassessment of patients with an established diagnosis and course whose symptoms suddenly change [because of] a potential new disease process such as subdural hematoma or stroke.”
Amyloid PET scans also can help determine pathology in patients with young-onset dementia (ie, between ages 50 and 65). For these patients, more detailed pathologic information is crucial for long-term planning and for making decisions about work, driving, and lifestyle. “
The presence or absence of [Alzheimer’s disease] pathology in this circumstance is frequently a critical component of the initial differential diagnosis,” according to the criteria, “and it is well known from postmortem studies that clinical diagnosis based on history and examination is often wrong with regard to the presence of [Alzheimer’s disease] pathology.”
Amyloid imaging could be the most clinically helpful in these patients, said Dr. Caselli. “In my opinion, amyloid PET will be most important for this indication. Younger patients are employed, have families they are supporting, and usually present early in their course when psychiatric pathology may be suspected. Imagine the 52-year-old who receives a poor job review and states he is unable to understand the new software or recall a client’s name and seeks medical attention, with the implication of disability hanging in the balance. Such a patient will not appear physically ill and is not generally suspected to have Alzheimer’s disease, but when current clinical methods indicate MCI, an amyloid PET scan could solidify the organicity of the diagnosis.”