Why Is Amyloid-β PET Requested After Performing CSF Biomarkers?

Abstract

Background: Amyloid-β positron emission tomography (PET) and cerebrospinal fluid (CSF) Aβ42 are considered interchangeable for clinical diagnosis of Alzheimer's disease.

Objective: To explore the clinical reasoning for requesting additional amyloid-β PET after performing CSF biomarkers.

Methods: We retrospectively identified 72 memory clinic patients who underwent amyloid-β PET after CSF biomarkers analysis for clinical diagnostic evaluation between 2011 and 2019. We performed patient chart reviews to identify factors which led to additional amyloid-β PET. Additionally, we assessed accordance with appropriate-use-criteria (AUC) for amyloid-β PET.

Results: Mean patient age was 62.0 (SD = 8.1) and mean Mini-Mental State Exam score was 23.6 (SD = 3.8). CSF analysis conflicting with the clinical diagnosis was the most frequent reason for requesting an amyloid-β PET scan (n = 53, 74%), followed by incongruent MRI (n = 16, 22%), unusual clinical presentation (n = 11, 15%) and young age (n = 8, 11%). An amyloid-β PET scan was rarely (n = 5, 7%) requested in patients with a CSF Aβ+/tau+ status. Fifteen (47%) patients with a post-PET diagnosis of AD had a predominantly non-amnestic presentation. In n = 11 (15%) cases, the reason that the clinician requested amyloid-β was not covered by AUC. This happened most often (n = 7) when previous CSF analysis did not support current clinical diagnosis, which led to requesting amyloid-β PET.

Conclusion: In this single-center study, the main reason for requesting an amyloid-β PET scan after performing CSF biomarkers was the occurrence of a mismatch between the primary clinical diagnosis and CSF Aβ/tau results.

Keywords: Alzheimer’s disease; amyloid; cerebrospinal fluid; positron emission tomography; tau proteins.

Fig.1

Flowchart for patient inclusion. *Other reasons include normal pressure hydrocephalus, increased certainty received from amyloid-β PET imaging, and imaging having a greater influence on convincing patients. CSF, cerebrospinal fluid; LP, lumbar puncture; PIB PET, positron emission tomography with ¹¹C-Pittsburgh compound B.

Fig.2

CSF Aβ₄₂, and tau/p-tau values relative to their cut-offs. We present standardized CSF values, created by calculating the percentage of the CSF value relative to its concurrent cut-off. Values of <100% represent pathologically decreased CSF Aβ₄₂ and values of >100% indicate pathologically increased CSF tau (A) and p-tau (B).

Fig.3

Clinical reasons for requesting additional amyloid-β PET after CSF. Patients are grouped based on most likely diagnosis prior to an amyloid-β PET scan. For both diagnosis groups we list characteristics that were recorded as being not compatible with the current main diagnosis, therefore leading to additional amyloid-β PET imaging. Reasons for the amyloid-β PET scan are grouped as biomarkers (red), patient history and presentation (blue), and external (purple). More than one reason is possible per patient. CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; EEG, electroencephalography; PET, positron emission tomography; FDG, [¹⁸F]fluorodeoxyglucose; SPECT, single-photon emission computed tomography.

Fig.4

Etiological diagnosis in relation to CSF Aβ/tau status and amyloid-β PET. A Sankey diagram showing 1) the distribution of baseline diagnoses to groups based on CSF Aβ/tau status, 2) the percentage of amyloid-β PET positivity by CSF Aβ/tau groups, and 3) the correlation of final diagnosis to amyloid-β PET positivity. DLB, dementia with Lewy bodies; Psych, psychiatric disorder; SCD, subjective cognitive decline; FTD, frontotemporal dementia; PPA, primary progressive aphasia.

Fig.5

Four case reports illustrating the clinical reasoning for requesting an additional amyloid-β PET.