Longitudinal changes in 18F-Flutemetamol amyloid load in cognitively intact APOE4 carriers versus noncarriers: Methodological considerations

Luckett, Emma S.; Schaeverbeke, Jolien; Meyer, Simon De; Adamczuk, Katarzyna; Laere, Koen Van; Dupont, Patrick; Vandenberghe, Rik

doi:10.1016/j.nicl.2023.103321

Cited by 2 publications

(4 citation statements)

References 53 publications

(89 reference statements)

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“…Finally, in assessing the longitudinal CL trajectories over time, two primary factors emerged as influential on the ARC: APOE‐ε4 carriership and level of education. Although we found a significant impact of APOE‐ε4 carriership on the ARC, this might not be generalizable to cohorts with higher amyloid burden or mostly cognitively impaired individuals 23,55,56 . Indeed, compared to non‐carriers, APOE‐ε4 carriers are more likely to accumulate Aβ pathology and tend to develop the disease earlier 57,58 .…”

Section: Discussioncontrasting

confidence: 61%

“…Although we found a significant impact of APOE‐ε4 carriership on the ARC, this might not be generalizable to cohorts with higher amyloid burden or mostly cognitively impaired individuals. 23 , 55 , 56 Indeed, compared to non‐carriers, APOE‐ε4 carriers are more likely to accumulate Aβ pathology and tend to develop the disease earlier. 57 , 58 In addition, the level of education is sometimes used as a proxy for conceptualizing resistance to amyloid deposition 59 , 60 ; however, further studies with more specific markers are warranted to elucidate the potential protective factors against amyloid accumulation.…”

Section: Discussionmentioning

confidence: 99%

“…The CL approach was introduced in 2015 as a means of calibrating measures of Aβ deposits to a tracer‐independent unbounded scale, where 0 (value characteristic of young healthy controls) and 100 (typical AD subjects) act as anchor points 16 . Longitudinal trajectories of Aβ accumulation have been previously described, 1,17,18 with more recent studies using the CL scale to characterize the pathophysiological rates of Aβ increase 19–25 . Although visual reading is currently the approved method for image interpretation in clinical practice (requiring a binary classification of normal/abnormal), the importance of quantifying PET measurement and its uncertainty has been highlighted in the latest Radiological Society of North America Quantitative Imaging Biomarkers Alliance (QIBA) profile 26 .…”

Section: Introductionmentioning

confidence: 99%

“… 16 Longitudinal trajectories of Aβ accumulation have been previously described, 1 , 17 , 18 with more recent studies using the CL scale to characterize the pathophysiological rates of Aβ increase. 19 , 20 , 21 , 22 , 23 , 24 , 25 Although visual reading is currently the approved method for image interpretation in clinical practice (requiring a binary classification of normal/abnormal), the importance of quantifying PET measurement and its uncertainty has been highlighted in the latest Radiological Society of North America Quantitative Imaging Biomarkers Alliance (QIBA) profile. 26 Quantitative information generated by CE‐marked software can also now be used as an adjunct to visual interpretation.…”

Section: Introductionmentioning

confidence: 99%

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Investigating reliable amyloid accumulation in Centiloids: Results from the AMYPAD Prognostic and Natural History Study

Bollack,

Collij,

García

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONTo support clinical trial designs focused on early interventions, our study determined reliable early amyloid‐β (Aβ) accumulation based on Centiloids (CL) in pre‐dementia populations.METHODSA total of 1032 participants from the Amyloid Imaging to Prevent Alzheimer's Disease–Prognostic and Natural History Study (AMYPAD‐PNHS) and Insight46 who underwent [18F]flutemetamol, [18F]florbetaben or [18F]florbetapir amyloid‐PET were included. A normative strategy was used to define reliable accumulation by estimating the 95th percentile of longitudinal measurements in sub‐populations (NPNHS = 101/750, NInsight46 = 35/382) expected to remain stable over time. The baseline CL threshold that optimally predicts future accumulation was investigated using precision‐recall analyses. Accumulation rates were examined using linear mixed‐effect models.RESULTSReliable accumulation in the PNHS was estimated to occur at >3.0 CL/year. Baseline CL of 16 [12,19] best predicted future Aβ‐accumulators. Rates of amyloid accumulation were tracer‐independent, lower for APOE ε4 non‐carriers, and for subjects with higher levels of education.DISCUSSIONOur results support a 12–20 CL window for inclusion into early secondary prevention studies. Reliable accumulation definition warrants further investigations.

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Section: Discussioncontrasting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Investigating reliable amyloid accumulation in Centiloids: Results from the AMYPAD Prognostic and Natural History Study

Bollack,

Collij,

García

et al. 2024

Alzheimer's & Dementia

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Impact of simulated reduced injected dose on the assessment of amyloid PET scans

Young,

Heeman,

Axelsson

et al. 2023

Eur J Nucl Med Mol Imaging

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Purpose To investigate the impact of reduced injected doses on the quantitative and qualitative assessment of the amyloid PET tracers [18F]flutemetamol and [18F]florbetaben. Methods Cognitively impaired and unimpaired individuals (N = 250, 36% Aβ-positive) were included and injected with [18F]flutemetamol (N = 175) or [18F]florbetaben (N = 75). PET scans were acquired in list-mode (90–110 min post-injection) and reduced-dose images were simulated to generate images of 75, 50, 25, 12.5 and 5% of the original injected dose. Images were reconstructed using vendor-provided reconstruction tools and visually assessed for Aβ-pathology. SUVRs were calculated for a global cortical and three smaller regions using a cerebellar cortex reference tissue, and Centiloid was computed. Absolute and percentage differences in SUVR and CL were calculated between dose levels, and the ability to discriminate between Aβ- and Aβ + scans was evaluated using ROC analyses. Finally, intra-reader agreement between the reduced dose and 100% images was evaluated. Results At 5% injected dose, change in SUVR was 3.72% and 3.12%, with absolute change in Centiloid 3.35CL and 4.62CL, for [18F]flutemetamol and [18F]florbetaben, respectively. At 12.5% injected dose, percentage change in SUVR and absolute change in Centiloid were < 1.5%. AUCs for discriminating Aβ- from Aβ + scans were high (AUC ≥ 0.94) across dose levels, and visual assessment showed intra-reader agreement of > 80% for both tracers. Conclusion This proof-of-concept study showed that for both [18F]flutemetamol and [18F]florbetaben, adequate quantitative and qualitative assessments can be obtained at 12.5% of the original injected dose. However, decisions to reduce the injected dose should be made considering the specific clinical or research circumstances.

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Longitudinal changes in 18F-Flutemetamol amyloid load in cognitively intact APOE4 carriers versus noncarriers: Methodological considerations

Cited by 2 publications

References 53 publications

Investigating reliable amyloid accumulation in Centiloids: Results from the AMYPAD Prognostic and Natural History Study

Investigating reliable amyloid accumulation in Centiloids: Results from the AMYPAD Prognostic and Natural History Study

Impact of simulated reduced injected dose on the assessment of amyloid PET scans

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