Clinical impact of [18F]flutemetamol PET among memory clinic patients with an unclear diagnosis

Abstract

Purpose To investigate the impact of amyloid PET with [ 18 F]flutemetamol on diagnosis and treatment management in a cohort of patients attending a tertiary memory clinic in whom, despite extensive cognitive assessment including neuropsychological testing, structural imaging, CSF biomarker analysis and in some cases [ 18 F]FDG PET, the diagnosis remained unclear. Methods The study population consisted of 207 patients with a clinical diagnosis prior to [ 18 F]flutemetamol PET including mild cognitive impairment (MCI; n = 131), Alzheimer’s disease (AD; n = 41), non-AD ( n = 10), dementia not otherwise specified (dementia NOS; n = 20) and subjective cognitive decline (SCD; n = 5). Results Amyloid positivity was found in 53% of MCI, 68% of AD, 20% of non-AD, 20% of dementia NOS, and 60% of SCD patients. [ 18 F]Flutemetamol PET led, overall, to a change in diagnosis in 92 of the 207 patients (44%). A high percentage of patients with a change in diagnosis was observed in the MCI group ( n = 67, 51%) and in the dementia NOS group ( n = 11; 55%), followed by the non-AD and AD (30% and 20%, respectively). A significant increase in cholinesterase inhibitor treatment was observed after [ 18 F]flutemetamol PET (+218%, 34 patients before and 108 patients after). Conclusion The present study lends support to the clinical value of amyloid PET in patients with an uncertain diagnosis in the tertiary memory clinic setting.

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

“…Third, we observed that although amyloid-␤ PET scans were usually requested according to the AUC, our clinical practice was not wholly covered by these criteria, as it was often driven by inconclusive CSF biomarker results. Our results support previous work that CSF biomarkers that conflict with the clinical diagnosis often lead to additional amyloid-␤ PET [12,13].…”

“…In our cohort, an amyloid-␤ PET was most often requested due to inconclusive results from the CSF biomarkers. This occurred in cases when diagnostic confidence was low due to inconclusive CSF A␤/tau status, or when a clinical diagnosis of AD was contradicted by a non-pathologic CSF analysis, which is largely in agreement with previous findings [13]. In fact, there were few patients with CSF A␤+/tau+ status in our cohort, indicating that patients with a clinical suspicion of AD supported by low A␤ 42 and high tau in the CSF analysis usually do not need further confirmation with amyloid-␤ PET.…”

“…In cases with a non-AD diagnosis combined with a decreased A␤ 42 and/or an increased tau in the CSF, the added value of an amyloid-␤ PET scan is hindered by the possibility of amyloid-␤ as a secondary pathology, especially in older populations. Therefore, our results combined with previous work from other centers [12,13] suggest a group of patients (i.e., clinically diagnosed with AD without an AD-like CSF biomarker signature) might benefit from being included in updated amyloid PET AUC. However, these findings must be confirmed by larger prospective multi-center studies.…”

“…The diagnostic value of amyloid-␤ PET to a standard dementia screening has been established in many studies [9][10][11], but few studies have included subgroups of people with available CSF biomarkers. Reported reasons for performing amyloid-␤ PET in such cases included incongruent CSF biomarkers in patients with suspicion of AD or atypical clinical presentation [12,13]. We aimed to elucidate this practice by exploring the clinical reasoning for requesting amyloid-␤ PET after CSF biomarkers were disclosed, and to characterize the population that received amyloid-␤ PET after CSF examination.…”

PET Radiopharmaceuticals for Alzheimer’s Disease and Parkinson’s Disease Diagnosis, the Current and Future Landscape

“…In general, the studies have showed that the use of the Aβ-PET tracers led to a moderate to significant change in diagnosis, diagnostic confidence [140][141][142][143][144][145], and had a substantial impact on change in the treatment and management plan of AD [137,144,146]. It is likely that the new generation of Aβ-PET tracers with improved pharmacokinetics will allow for improved signal-to-noise ratio, hence will be more suitable for the quantification of disease progression and therapeutic monitoring.…”