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Evidence-based Interpretation of Amyloid-β PET Results: A Clinician’s Tool

Bergeron, David, MS*; Ossenkoppele, Rik, PhD; Jr Laforce, Robert, MD, PhD, FRCPC*

Alzheimer Disease & Associated Disorders: January-March 2018 - Volume 32 - Issue 1 - p 28–34
doi: 10.1097/WAD.0000000000000239
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Background: Amyloid-β positron emission tomography (PET) allows for in vivo detection of fibrillar amyloid plaques, a pathologic hallmark of Alzheimer’s disease (AD). However, amyloid-β PET interpretation is limited by the imperfect correlation between PET and autopsy, and the fact that it is positive in about 20% to 30% of cognitively normal individuals and non-AD dementias, especially when older or carrying the ε4 allele of apolipoprotein E (ApoE4). When facing a positive amyloid PET, clinicians have to evaluate the probability of a pathologic false positive as well as the probability of amyloid positivity being age-related, comorbid to a primary non-AD dementia (clinicopathologic false positive). These probabilities can be calculated to reach an evidence-based interpretation of amyloid-β. As literature review and calculations cannot be easily performed in the day-to-day clinic, we propose a clinician friendly, evidence-based Bayesian approach to the interpretation of amyloid-β PET results in the differential diagnosis of patients with cognitive impairment.

Methods: We defined AD as a clinicopathologic entity in which amyloid-β is the primary cause of cognitive impairment. We systematically reviewed the literature to estimate the sensitivity and specificity of amyloid-β PET against neuropathologic examination. We inferred rates of clinicopathologic false positivity (non-AD dementia with comorbid amyloid) based on age-dependent and ApoE-dependent prevalence of amyloid positivity in normal individuals and AD patients provided in large meta-analyses published by the Amyloid Biomarker Study Group. We calculated positive predictive value (PPV) and negative predictive value (NPV) of amyloid-β PET, which are presented in a clinician-friendly table.

Results: PPV of PET is highest in young ApoE4− patients with high pre-PET probability of AD. In older ApoE4+ patients with low pre-PET probability of AD, positive amyloid-β PET scans must be interpreted with caution. A negative amyloid-β PET makes a diagnosis of AD unlikely except in old patients with high pre-PET probability of AD.

Conclusion: This evidence-based approach might provide guidance to clinicians and nuclear medicine physicians to interpret amyloid-β PET results for early and differential diagnosis of patients with progressive cognitive impairment.

*Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques du CHU de Québec, Faculté de Médecine, Université Laval, QC, Canada

Department of Neurology and Alzheimer Center, VU University Medical Center Amsterdam, Amsterdam, The Netherlands

D.B. designed the PPV table and drafted the initial version of the manuscript. R.O. and R.L. Jr made substantial intellectual inputs in the conception of the table and critically revised the manuscript.

The authors declare no conflicts of interest.

Reprints: David Bergeron, MS, Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques, CHU de Québec, G1V0G2, QC, Canada (e-mail: david.bergeron.5@ulaval.ca).

Received June 28, 2017

Accepted November 27, 2017

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