Amyloid PET imaging criteria for Alzheimer's outlined in report

New appropriate-use criteria for PET imaging with beta-amyloid agents stress that a positive scan cannot on its own indicate a diagnosis of Alzheimer’s disease. But in conjunction with a thorough clinical evaluation – including cognitive testing – the scan can add some degree of certainty to ruling Alzheimer’s in or out, according to the Amyloid Imaging Task Force of the Alzheimer’s Association 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. That can mean getting on the right medications, pursuing other testing, and even effectively planning a patient’s future, task force members Dr. Keith A. Johnson of Harvard Medical School, Boston, and his coauthors wrote in the paper establishing the criteria, which was published online Jan. 28 in the Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association and in the Journal of Nuclear Medicine (doi:10.1016/j.jalz.2013.01.002).

"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," the task force wrote.

When used appropriately, amyloid plaque PET imaging benefits both patients and physicians, whether the results are positive or negative, said Dr. Richard J. Caselli, a professor of neurology at the Mayo Clinic, Scottsdale, Ariz.

"This represents an important step forward," in Alzheimer’s clinical management," Dr. Caselli said in an interview. "Now it is a question of convincing third-party payers, including not only CMS [Centers for Medicare and Medicaid Services] but private insurers as well, of its necessity in appropriately selected patients."

CMS is convening its Medicare Evidence Development & Coverage Advisory Committee on Jan. 30 to vote on whether there is adequate evidence to determine if PET imaging of brain beta-amyloid changes health outcomes.

The task force consisted of experts in Alzheimer’s dementia and nuclear imaging. The team reviewed 80 studies that examined amyloid imaging, its diagnostic accuracy, ability to predict disease, potential implications on treatment planning, and even its possible impact on the psychological, financial, and social well-being of the patient and family.

The task force detailed three situations that warrant testing and – just as importantly – seven in which it is not indicated.

Clinical situations in which to test

The first indication is testing a patient who has persistent or progressive unexplained mild cognitive impairment. A positive finding would increase the certainty of an early Alzheimer’s pathology. A negative finding could exclude Alzheimer’s pathology at that point in time, 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."

The second indication would be testing a patient who satisfied the core clinical criteria for possible Alzheimer’s, but had an atypical presentation. This would include patients with an unusual course, such as sudden onset or episodic cognitive problems, or a comorbid condition that could confuse the clinical picture, like cerebrovascular disease. The indication notes that amyloid imaging can’t differentiate between Alzheimer’s disease and Lewy body pathology.

"Certainly, this 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, who serves as associate director and clinical core director of the Alzheimer’s Disease Center at the Mayo Clinic in Arizona. "The decision to utilize 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."

The third indication for an amyloid PET scan is to determine pathology in patients with young-onset dementia – usually someone in the age range of 50-65 years, or sometimes even younger. For these patients, more detailed pathologic information is critical to decision making around issues like work, driving, lifestyle, and long-term planning.

"The presence or absence of AD [Alzheimer’s disease] pathology in this circumstance is frequently a critical component of the initial differential diagnosis," the document noted, "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 AD pathology."

This is where amyloid imaging could be the most clinically helpful, Dr. Caselli said.

"In my opinion, the use of 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 mild cognitive impairment, an amyloid PET scan could solidify the organicity of the diagnosis."

Clinical situations in which not to test

The document’s seven contraindications spell out scenarios in which amyloid imaging is unhelpful. These include:

• Patients who meet both the clinical criteria for Alzheimer’s and the typical age of onset. The potential benefit of detecting amyloid pathology probably would not alter patient management.

• Determining dementia severity. There’s no indication that amyloid burden correlates with symptom severity.

• Relying on reasons based solely on family history or positive apolipoprotein E–epsilon 4 status.

• Investigating a clinically unconfirmed cognitive complaint.

• Using this imaging instead of genotyping patients who have a suspected autosomal mutation.

• Making disease predictions in cognitively normal older adults

• Testing for any nonmedical use, such as for medicolegal, disability, insurance, or employment-related issues.

Patients who undergo the imaging procedure need to understand its benefits and its limitations, the task force said. Amyloid plaques don’t always mean Alzheimer’s disease is present. For example, as age increases, so does the likelihood of amyloid deposition, even in cognitively normal people. "Another major caveat is that a positive amyloid scan can also be seen in not only AD, but also in other medical conditions," such as Lewy body dementia and amyloid angiopathy, the document noted. The scan can’t differentiate these, and it is not useful when evaluating patients with frontotemporal dementia.

But amyloid imaging does confer a number of benefits when used appropriately, according to the task force. Whether the result is positive or negative, it furthers clinical decision-making in appropriately selected patients. It can guide medication management by getting patients on the right drugs faster and keeping them off those that won’t help. The results can shape other diagnostic investigations in the same way by letting patients avoid unnecessary tests or proceed to more informative ones.

There is much benefit in "the value of knowing" amyloid PET scan status, the document noted. About 25% of dementia cases can have reversible causes, like depression or vitamin B₁₂ deficiency. And U.S. surveys have shown that most Americans would prefer to know if their symptoms could be caused by Alzheimer’s so that they can make independent decisions about the future.

But "what such polls often fail to mention are the number of people who would suffer psychological harm if they received ‘bad news’ from such testing," Dr. Caselli cautioned. "In another poll we have been conducting, more than 10% of patients stated they would ‘seriously consider suicide’ if they found there was biomarker evidence of preclinical Alzheimer’s disease. This is a powerful diagnostic modality, but one in which implications of results are not fully understood. What we offer our patients therefore must be limited to the scenarios the committee has described, at least until we have much more experience and understanding of the implications and reliability of test results."

Dr. Johnson and some of the other task force members reported multiple relationships with drug companies. Dr. Caselli has no financial disclosures.

michele.sullivan@elsevier.com

New appropriate-use criteria for PET imaging with beta-amyloid agents stress that a positive scan cannot on its own indicate a diagnosis of Alzheimer’s disease. But in conjunction with a thorough clinical evaluation – including cognitive testing – the scan can add some degree of certainty to ruling Alzheimer’s in or out, according to the Amyloid Imaging Task Force of the Alzheimer’s Association 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. That can mean getting on the right medications, pursuing other testing, and even effectively planning a patient’s future, task force members Dr. Keith A. Johnson of Harvard Medical School, Boston, and his coauthors wrote in the paper establishing the criteria, which was published online Jan. 28 in the Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association and in the Journal of Nuclear Medicine (doi:10.1016/j.jalz.2013.01.002).

"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," the task force wrote.

When used appropriately, amyloid plaque PET imaging benefits both patients and physicians, whether the results are positive or negative, said Dr. Richard J. Caselli, a professor of neurology at the Mayo Clinic, Scottsdale, Ariz.

"This represents an important step forward," in Alzheimer’s clinical management," Dr. Caselli said in an interview. "Now it is a question of convincing third-party payers, including not only CMS [Centers for Medicare and Medicaid Services] but private insurers as well, of its necessity in appropriately selected patients."

CMS is convening its Medicare Evidence Development & Coverage Advisory Committee on Jan. 30 to vote on whether there is adequate evidence to determine if PET imaging of brain beta-amyloid changes health outcomes.

The task force consisted of experts in Alzheimer’s dementia and nuclear imaging. The team reviewed 80 studies that examined amyloid imaging, its diagnostic accuracy, ability to predict disease, potential implications on treatment planning, and even its possible impact on the psychological, financial, and social well-being of the patient and family.

The task force detailed three situations that warrant testing and – just as importantly – seven in which it is not indicated.

Clinical situations in which to test

The first indication is testing a patient who has persistent or progressive unexplained mild cognitive impairment. A positive finding would increase the certainty of an early Alzheimer’s pathology. A negative finding could exclude Alzheimer’s pathology at that point in time, 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."

The second indication would be testing a patient who satisfied the core clinical criteria for possible Alzheimer’s, but had an atypical presentation. This would include patients with an unusual course, such as sudden onset or episodic cognitive problems, or a comorbid condition that could confuse the clinical picture, like cerebrovascular disease. The indication notes that amyloid imaging can’t differentiate between Alzheimer’s disease and Lewy body pathology.

"Certainly, this 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, who serves as associate director and clinical core director of the Alzheimer’s Disease Center at the Mayo Clinic in Arizona. "The decision to utilize 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."

The third indication for an amyloid PET scan is to determine pathology in patients with young-onset dementia – usually someone in the age range of 50-65 years, or sometimes even younger. For these patients, more detailed pathologic information is critical to decision making around issues like work, driving, lifestyle, and long-term planning.

"The presence or absence of AD [Alzheimer’s disease] pathology in this circumstance is frequently a critical component of the initial differential diagnosis," the document noted, "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 AD pathology."

This is where amyloid imaging could be the most clinically helpful, Dr. Caselli said.

"In my opinion, the use of 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 mild cognitive impairment, an amyloid PET scan could solidify the organicity of the diagnosis."

Clinical situations in which not to test

The document’s seven contraindications spell out scenarios in which amyloid imaging is unhelpful. These include:

• Patients who meet both the clinical criteria for Alzheimer’s and the typical age of onset. The potential benefit of detecting amyloid pathology probably would not alter patient management.

• Determining dementia severity. There’s no indication that amyloid burden correlates with symptom severity.

• Relying on reasons based solely on family history or positive apolipoprotein E–epsilon 4 status.

• Investigating a clinically unconfirmed cognitive complaint.

• Using this imaging instead of genotyping patients who have a suspected autosomal mutation.

• Making disease predictions in cognitively normal older adults

• Testing for any nonmedical use, such as for medicolegal, disability, insurance, or employment-related issues.

Patients who undergo the imaging procedure need to understand its benefits and its limitations, the task force said. Amyloid plaques don’t always mean Alzheimer’s disease is present. For example, as age increases, so does the likelihood of amyloid deposition, even in cognitively normal people. "Another major caveat is that a positive amyloid scan can also be seen in not only AD, but also in other medical conditions," such as Lewy body dementia and amyloid angiopathy, the document noted. The scan can’t differentiate these, and it is not useful when evaluating patients with frontotemporal dementia.

But amyloid imaging does confer a number of benefits when used appropriately, according to the task force. Whether the result is positive or negative, it furthers clinical decision-making in appropriately selected patients. It can guide medication management by getting patients on the right drugs faster and keeping them off those that won’t help. The results can shape other diagnostic investigations in the same way by letting patients avoid unnecessary tests or proceed to more informative ones.

There is much benefit in "the value of knowing" amyloid PET scan status, the document noted. About 25% of dementia cases can have reversible causes, like depression or vitamin B₁₂ deficiency. And U.S. surveys have shown that most Americans would prefer to know if their symptoms could be caused by Alzheimer’s so that they can make independent decisions about the future.

But "what such polls often fail to mention are the number of people who would suffer psychological harm if they received ‘bad news’ from such testing," Dr. Caselli cautioned. "In another poll we have been conducting, more than 10% of patients stated they would ‘seriously consider suicide’ if they found there was biomarker evidence of preclinical Alzheimer’s disease. This is a powerful diagnostic modality, but one in which implications of results are not fully understood. What we offer our patients therefore must be limited to the scenarios the committee has described, at least until we have much more experience and understanding of the implications and reliability of test results."

Dr. Johnson and some of the other task force members reported multiple relationships with drug companies. Dr. Caselli has no financial disclosures.

michele.sullivan@elsevier.com

New appropriate-use criteria for PET imaging with beta-amyloid agents stress that a positive scan cannot on its own indicate a diagnosis of Alzheimer’s disease. But in conjunction with a thorough clinical evaluation – including cognitive testing – the scan can add some degree of certainty to ruling Alzheimer’s in or out, according to the Amyloid Imaging Task Force of the Alzheimer’s Association 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. That can mean getting on the right medications, pursuing other testing, and even effectively planning a patient’s future, task force members Dr. Keith A. Johnson of Harvard Medical School, Boston, and his coauthors wrote in the paper establishing the criteria, which was published online Jan. 28 in the Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association and in the Journal of Nuclear Medicine (doi:10.1016/j.jalz.2013.01.002).

"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," the task force wrote.

When used appropriately, amyloid plaque PET imaging benefits both patients and physicians, whether the results are positive or negative, said Dr. Richard J. Caselli, a professor of neurology at the Mayo Clinic, Scottsdale, Ariz.

"This represents an important step forward," in Alzheimer’s clinical management," Dr. Caselli said in an interview. "Now it is a question of convincing third-party payers, including not only CMS [Centers for Medicare and Medicaid Services] but private insurers as well, of its necessity in appropriately selected patients."

CMS is convening its Medicare Evidence Development & Coverage Advisory Committee on Jan. 30 to vote on whether there is adequate evidence to determine if PET imaging of brain beta-amyloid changes health outcomes.

The task force consisted of experts in Alzheimer’s dementia and nuclear imaging. The team reviewed 80 studies that examined amyloid imaging, its diagnostic accuracy, ability to predict disease, potential implications on treatment planning, and even its possible impact on the psychological, financial, and social well-being of the patient and family.

The task force detailed three situations that warrant testing and – just as importantly – seven in which it is not indicated.

Clinical situations in which to test

The first indication is testing a patient who has persistent or progressive unexplained mild cognitive impairment. A positive finding would increase the certainty of an early Alzheimer’s pathology. A negative finding could exclude Alzheimer’s pathology at that point in time, 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."

The second indication would be testing a patient who satisfied the core clinical criteria for possible Alzheimer’s, but had an atypical presentation. This would include patients with an unusual course, such as sudden onset or episodic cognitive problems, or a comorbid condition that could confuse the clinical picture, like cerebrovascular disease. The indication notes that amyloid imaging can’t differentiate between Alzheimer’s disease and Lewy body pathology.

"Certainly, this 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, who serves as associate director and clinical core director of the Alzheimer’s Disease Center at the Mayo Clinic in Arizona. "The decision to utilize 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."

The third indication for an amyloid PET scan is to determine pathology in patients with young-onset dementia – usually someone in the age range of 50-65 years, or sometimes even younger. For these patients, more detailed pathologic information is critical to decision making around issues like work, driving, lifestyle, and long-term planning.

"The presence or absence of AD [Alzheimer’s disease] pathology in this circumstance is frequently a critical component of the initial differential diagnosis," the document noted, "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 AD pathology."

This is where amyloid imaging could be the most clinically helpful, Dr. Caselli said.

"In my opinion, the use of 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 mild cognitive impairment, an amyloid PET scan could solidify the organicity of the diagnosis."

Clinical situations in which not to test

The document’s seven contraindications spell out scenarios in which amyloid imaging is unhelpful. These include:

• Patients who meet both the clinical criteria for Alzheimer’s and the typical age of onset. The potential benefit of detecting amyloid pathology probably would not alter patient management.

• Determining dementia severity. There’s no indication that amyloid burden correlates with symptom severity.

• Relying on reasons based solely on family history or positive apolipoprotein E–epsilon 4 status.

• Investigating a clinically unconfirmed cognitive complaint.

• Using this imaging instead of genotyping patients who have a suspected autosomal mutation.

• Making disease predictions in cognitively normal older adults

• Testing for any nonmedical use, such as for medicolegal, disability, insurance, or employment-related issues.

Patients who undergo the imaging procedure need to understand its benefits and its limitations, the task force said. Amyloid plaques don’t always mean Alzheimer’s disease is present. For example, as age increases, so does the likelihood of amyloid deposition, even in cognitively normal people. "Another major caveat is that a positive amyloid scan can also be seen in not only AD, but also in other medical conditions," such as Lewy body dementia and amyloid angiopathy, the document noted. The scan can’t differentiate these, and it is not useful when evaluating patients with frontotemporal dementia.

But amyloid imaging does confer a number of benefits when used appropriately, according to the task force. Whether the result is positive or negative, it furthers clinical decision-making in appropriately selected patients. It can guide medication management by getting patients on the right drugs faster and keeping them off those that won’t help. The results can shape other diagnostic investigations in the same way by letting patients avoid unnecessary tests or proceed to more informative ones.

There is much benefit in "the value of knowing" amyloid PET scan status, the document noted. About 25% of dementia cases can have reversible causes, like depression or vitamin B₁₂ deficiency. And U.S. surveys have shown that most Americans would prefer to know if their symptoms could be caused by Alzheimer’s so that they can make independent decisions about the future.

But "what such polls often fail to mention are the number of people who would suffer psychological harm if they received ‘bad news’ from such testing," Dr. Caselli cautioned. "In another poll we have been conducting, more than 10% of patients stated they would ‘seriously consider suicide’ if they found there was biomarker evidence of preclinical Alzheimer’s disease. This is a powerful diagnostic modality, but one in which implications of results are not fully understood. What we offer our patients therefore must be limited to the scenarios the committee has described, at least until we have much more experience and understanding of the implications and reliability of test results."

Dr. Johnson and some of the other task force members reported multiple relationships with drug companies. Dr. Caselli has no financial disclosures.

michele.sullivan@elsevier.com