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

Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Journal of Nuclear Medicine (Impact Factor: 6.16). 01/2013; 54(3). DOI: 10.2967/jnumed.113.120618
Source: PubMed


Positron emission tomography (PET) of brain amyloid β is a technology that is becoming more available, but its clinical utility in medical practice requires careful definition. To provide guidance to dementia care practitioners, patients, and caregivers, the Alzheimer's Association and the Society of Nuclear Medicine and Molecular Imaging convened the Amyloid Imaging Taskforce (AIT). The AIT considered a broad range of specific clinical scenarios in which amyloid PET could potentially be used appropriately. Peer-reviewed, published literature was searched to ascertain available evidence relevant to these scenarios, and the AIT developed a consensus of expert opinion. Although empirical evidence of impact on clinical outcomes is not yet available, a set of specific appropriate use criteria (AUC) were agreed on that define the types of patients and clinical circumstances in which amyloid PET could be used. Both appropriate and inappropriate uses were considered and formulated, and are reported and discussed here. Because both dementia care and amyloid PET technology are in active development, these AUC will require periodic reassessment. Future research directions are also outlined, including diagnostic utility and patient-centered outcomes.

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Available from: Nico Bohnen, Nov 14, 2015
    • "Recommended guidelines for appropriate use of amyloid PET imaging were published in 2013, based on consensus of experts convened by the Society for Nuclear Medicine and Molecular Imaging and the Alzheimer's Association [54]. An appropriate indication is for " persistent or progressive unexplained MCI " , in individuals for whom clinical management may be altered and who would likely benefit from greater certainty in underlying etiology. "
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    ABSTRACT: Background: Subjective cognitive decline (SCD) in otherwise normal aging may be identified via symptom inventories in a research setting ('questionnaire-discovered complaints') or via patients seeking evaluation/services in a clinical setting ('presenting complainers'). Most studies of SCD and amyloid-β (Aβ) imaging to date have used the former approach, with inconsistent results. Objective: To test whether 'presenting SCD' participants in an academic memory clinic setting show increased brain Aβ deposition on imaging. Methods: Fourteen patients (mean age 68.1, SD 4.0 years) diagnosed with subjective cognitive complaints with normal neuropsychological testing were recruited into a Pittsburgh compound B (PiB)-PET study. Detailed self-report inventories and additional cognitive tests were administered. Results were compared to a reference cohort of cognitively normal volunteers (NC) from an independent neuroimaging study (mean age 73.6, SD 5.8 years). Results: 57% (8/14) of SCD participants were PiB-positive by a sensitive, regionally-based definition, compared to 31% (26/84) of the NC cohort. SCD participants had significantly higher PiB retention (SUVR) than NC in three of six regions of interest: frontal cortex (p = 0.02), lateral temporal cortex (p = 0.02), and parietal cortex (p = 0.04). SCD participants showed measurable deviations on questionnaires reflecting high negative affect (i.e., depressive symptoms and neuroticism). Findings were suggestive that deficits on verbal associative binding may be specific to Aβ-positive versus Aβ-negative SCD. Conclusion: Older participants with SCD presenting to a memory clinic in this pilot study sample have higher brain Aβ deposition compared to normal aging study volunteers unselected on complaints. Further study of presenting SCD are warranted to determine the prognostic significance of Aβ deposition in this context.
    No preview · Article · Sep 2015 · Journal of Alzheimer's disease: JAD
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    • "To date, the advancement of molecular imaging tracers that bind to amyloid, such as Pittsburgh Compound B (PiB), offers a noninvasive in vivo method to detect and quantify brain amyloid deposition [3] [4]. However, this approach for pre-symptomatic detection is economically challenging for routine use given the current cost [5]. Similarly, the clinical use of other useful biomarkers such as A 1-42 and phosphorylated tau in cerebrospinal fluid (CSF) is also limited, since lumbar puncture carries risks and is met with resistance in elderly subjects. "
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    ABSTRACT: Background: Detecting participants who are positive for amyloid-β (Aβ) pathology is germane in designing prevention trials by enriching for those cases that are more likely to be amyloid positive. Existing brain amyloid measurement techniques, such as the Pittsburgh Compound B-positron emission tomography and cerebrospinal fluid, are not reasonable first-line approaches limited by either feasibility or cost. Objective: We aimed to identify simple and cost-effective rules that can predict brain Aβ level by integrating both neuropsychological measurements and blood-based markers. Method: Several decision tree models were built for extracting the predictive rules based on the Alzheimer's Disease Neuroimaging Initiative cohort. Results: We successfully extracted predictive rules of Aβ level. For cognitive function variables, cases above the 45th percentile in total cognitive score (TOTALMOD), above the 52nd percentile of delayed word recall, and above the 70th percentile in orientation resulted in a group that was highly enriched for amyloid negative cases. Conversely scoring below the 15th percentile of TOTALMOD resulted in a group highly enriched for amyloid positive cases. For blood protein markers, scoring below the 57th percentile for apolipoprotein E (ApoE) levels (irrespective of genotype) enriched two fold for the risk of being amyloid positive. In the high ApoE cases, scoring above the 60th percentile for transthyretin resulted in a group that was >90% amyloid negative. A third decision tree using both cognitive and blood-marker data slightly improved the classification of cases. Conclusion: Our study demonstrated that the integration of the neuropsychological measurements and blood-based markers significantly improved prediction accuracy. The prediction model has led to several simple rules, which have a great potential of being naturally translated into clinical settings such as enrichment screening for AD prevention trials of anti-amyloid treatments.
    Full-text · Article · Aug 2014 · Journal of Alzheimer's disease: JAD
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    • "While the potential of amyloid-PET is not a matter of debate in research, its misuse in clinical sets needs a careful regulation in order to give a proper role and a specific clinical context to this technique. That is why, recently, the Society of Nuclear Medicine and Molecular Imaging and the Alzheimer's Association have jointly convened the Amyloid Imaging Task Force (AIT) and published the Appropriate Use Criteria for amyloid-PET [132, 133]. They provided the appropriate use criteria for Amy-PET in which the circumstances for executing Amy-PET are listed. "
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    ABSTRACT: PET based tools can improve the early diagnosis of Alzheimer's disease (AD) and differential diagnosis of dementia. The importance of identifying individuals at risk of developing dementia among people with subjective cognitive complaints or mild cognitive impairment has clinical, social, and therapeutic implications. Within the two major classes of AD biomarkers currently identified, that is, markers of pathology and neurodegeneration, amyloid- and FDG-PET imaging represent decisive tools for their measurement. As a consequence, the PET tools have been recognized to be of crucial value in the recent guidelines for the early diagnosis of AD and other dementia conditions. The references based recommendations, however, include large PET imaging literature based on visual methods that greatly reduces sensitivity and specificity and lacks a clear cut-off between normal and pathological findings. PET imaging can be assessed using parametric or voxel-wise analyses by comparing the subject's scan with a normative data set, significantly increasing the diagnostic accuracy. This paper is a survey of the relevant literature on FDG and amyloid-PET imaging aimed at providing the value of quantification for the early and differential diagnosis of AD. This allowed a meta-analysis and GRADE analysis revealing high values for PET imaging that might be useful in considering recommendations.
    Full-text · Article · Mar 2014
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