Heterogeneity of Amyloid Binding in Cognitively Impaired Patients Consecutively Recruited from a Memory Clinic: Evaluating the Utility of Quantitative 18F-Flutemetamol PET-CT in Discrimination of Mild Cognitive Impairment from Alzheimer’s Disease and Other Dementias

Abstract

Background: With the more widespread use of 18F-radioligand-based amyloid-β (Aβ) PET-CT imaging, we evaluated Aβ binding and the utility of neocortical 18F-Flutemetamol standardized uptake value ratio (SUVR) as a biomarker. Objective: 18F-Flutemetamol SUVR was used to differentiate 1) mild cognitive impairment (MCI) from Alzheimer’s disease (AD), and 2) MCI from other non-AD dementias (OD). Methods: 109 patients consecutively recruited from a University memory clinic underwent clinical evaluation, neuropsychological test, MRI and 18F-Flutemetamol PET-CT. The diagnosis was made by consensus of a panel consisting of 1 neuroradiologist and 2 geriatricians. The final cohort included 13 subjective cognitive decline (SCD), 22 AD, 39 MCI, and 35 OD. Quantitative analysis of 16 region-of-interests made by Cortex ID software (GE Healthcare). Results: The global mean 18F-Flutemetamol SUVR in SCD, MCI, AD, and OD were 0.50 (SD-0.08), 0.53 (SD-0.16), 0.76 (SD-0.10), and 0.56 (SD-0.16), respectively, with SUVR in SCD and MCI and OD being significantly lower than AD. Aβ binding in SCD, MCI, and OD was heterogeneous, being 23%, 38.5%, and 42.9% respectively, as compared to 100% amyloid positivity in AD. Using global SUVR, ROC analysis showed AUC of 0.868 and 0.588 in differentiating MCI from AD and MCI from OD respectively. Conclusion: 18F-Flutemetamol SUVR differentiated MCI from AD with high efficacy (high negative predictive value), but much lower efficacy from OD. The major benefit of the test was to differentiate cognitively impaired patients (either SCD, MCI, or OD) without AD-related-amyloid-pathology from AD in the clinical setting, which was under-emphasized in the current guidelines proposed by Amyloid Imaging Task Force.

Computed Tomography Density and β-Amyloid Deposition of Intraorbital Optic Nerve May Assist in Diagnosing Mild Cognitive Impairment and Alzheimer’s Disease: A 18F-Flutemetamol Positron Emission Tomography/Computed Tomography Study

“…Considering that the sample size was not large enough might be the possible reason why the results were different than expected; especially, the sample size of the NC group was small due to the difficulty in recruiting normal subjects. A previous study using 18 F-flutemetamol PET showed that the differences of both the left and right occipital SUVR between subjects with MCI and AD were statistically significant with high efficacy ( bao et al, 2021 ).…”

The Use of Diffusion Kurtosis Imaging for the Differential Diagnosis of Alzheimer’s Disease Spectrum

“…Participants with other neurological conditions (such as stroke, tumors, infection, movement disorders, demyelinating diseases, seizure, and migraine) and psychiatric disorders were excluded. Detailed descriptions of inclusion and exclusion criteria for the participants have been reported previously [ 27 , 28 , 29 ]. AD and MCI were defined mainly according to the core criteria of AD and MCI from the National Institute on Aging-Alzheimer’s Association separately [ 4 , 17 ].…”

“…Filtered back-projection reconstruction was adopted with a slice thickness of 2 to 4 mm, and matrix size was 128 × 128 with a pixel size of 2 mm. Details of the acquisition scheme have been reported previously [ 27 ].…”

Relationship between Amyloid-β Deposition and the Coupling between Structural and Functional Brain Networks in Patients with Mild Cognitive Impairment and Alzheimer’s Disease

“…The diagnosis of cognitive impairment was determined by the consensus between a neuroradiologist (HKFM) and two geriatricians (YFS, PC, or JSKK) based on the findings from clinical (baseline and follow-up) and neuropsychological (HK-MoCA) evaluations, 18 F-flutemetamol PET-CT scans, structural MRI, MRA, and ASL [ 20 ]. The diagnoses of MCI were determined using the clinical criteria from [ 23 ] and those of AD from [ 24 ] together with a positive Aβ diagnosis.…”

“…The central hypothesis of this study is that SC-FC coupling is a novel biomarker for the characterization of the effect of Aβ accumulation along the AD continuum. We have previously shown that the majority of MCI patients can be distinguished from AD patients based on 18 F-flutemetamol PET-CT scans with high efficacy [ 20 ]. Those who could not be differentiated were the MCI_Aβ+ patients who had similar Aβ retention as AD patients.…”