Amyloid PET Quantitation and Centiloid Thresholds in the Diagnosis of Alzheimer Disease: An Individual Participant Data Meta-Analysis.

Diagnostic value of positron emission tomography using amyloid-binding radiotracers for cardiac amyloidosis: a systematic review and meta-analysis

Abstract Aims Amyloid-binding positron emission tomography (PET) tracers have emerged as a promising non-invasive tool for the diagnosis of cardiac amyloidosis (CA). This study aimed to assess the diagnostic accuracy of amyloid PET for detecting CA through a meta-analysis of diagnostic test accuracy. Methods and results PubMed, Cochrane Library, Embase, and Web of Science were searched through 16 March 2026 for studies reporting the diagnostic performance of amyloid PET for CA. The primary analysis was a bivariate random-effects (Reitsma) model yielding summary sensitivity, specificity, the summary receiver operating characteristics curve with corresponding area under the curve (AUC), and positive and negative likelihood ratios. Subgroup analyses were performed by radiotracer and by amyloid subtype. Risk of bias was assessed using QUADAS-2 and publication bias by Deeks’ funnel-plot asymmetry test. Twenty studies comprising 577 patients (407 with CA, 170 controls) met inclusion criteria, covering five radiotracers (11C-PiB, 18F-florbetaben, 18F-florbetapir, 18F-flutemetamol, and 124I-evuzamitide). In the primary bivariate model (k = 17), amyloid PET demonstrated a summary sensitivity of 0.91 (95% CI 0.83–0.96), specificity of 0.90 (95% CI 0.79–0.96), and AUC of 0.96, with low between-study heterogeneity (sensitivity I2 = 13.4%; specificity I2 = 0%). Sensitivity was high and consistent across 11C-PiB, 18F-florbetaben, 18F-florbetapir, and 124I-evuzamitide (0.96–1.00), with the exception of 18F-flutemetamol, which showed lower and heterogeneous sensitivity (0.70). Conclusion Amyloid PET demonstrates high sensitivity and specificity for CA detection, even though the evidence base remains limited in terms of the number and scope of available studies. Prospective multicentre studies in consecutive patients with suspected CA are required to establish its clinical role and standardize acquisition protocols.

Baseline Amyloid PET Centiloid Score and Risk of Amyloid-Related Imaging Abnormalities in Patients Treated With Lecanemab.

BACKGROUND AND PURPOSE Amyloid-related imaging abnormalities (ARIA) are a known complication of anti-amyloid monoclonal antibody therapy for Alzheimer's disease. Centiloid score, derived from amyloid PET/CT, provides a quantitative assessment of baseline amyloid burden; however, its relationship with ARIA risk remains uncertain. This study evaluated whether baseline Centiloid score was associated with ARIA in patients treated with lecanemab and included a secondary exploratory analysis of regional amyloid uptake. MATERIALS AND METHODS We retrospectively identified patients treated with lecanemab within a single academic health system who underwent pretreatment florbetaben amyloid PET/CT. Centiloid scores were generated using a standardized processing pipeline. Multivariable logistic regression evaluated the association between baseline Centiloid and ARIA, adjusting for age, sex, APOE ε4 carrier status, and baseline cerebral microbleed presence. ARIA-H and ARIA-E subgroups were evaluated separately using Firth penalized logistic regression. A secondary Cox proportional hazards analysis accounted for unequal follow up durations. Exploratory regional analysis compared baseline amyloid uptake in regions that subsequently developed ARIA-E with that in mirrored contralateral regions. RESULTS The primary analysis included 41 patients with ARIA and 72 controls who completed at least 14 lecanemab infusions without ARIA. Baseline Centiloid was not independently associated with ARIA (adjusted OR per 10-Centiloid increase, 1.01 [95% CI, 0.89-1.15]; P = .90), ARIA-H (OR, 1.01 [95% CI, 0.89-1.14]; P = .91), or ARIA-E (OR, 1.02 [95% CI, 0.87-1.21]; P = .78). In the Cox analysis of 41 patients with ARIA and 100 patients without ARIA, baseline Centiloid was not associated with time to ARIA (adjusted HR, 1.01 [95% CI, 0.91-1.11]; P = .91). Among 19 patients with ARIA-E included in the regional analysis, baseline uptake was modestly greater in regions that subsequently developed ARIA-E than in mirrored contralateral regions for SUVmax (3.44 ± 0.78 versus 3.25 ± 0.77; P = .02) and SUVmean (2.60 ± 0.56 versus 2.45 ± 0.64; P = .01). CONCLUSIONS Baseline global Centiloid was not independently associated with ARIA in patients treated with lecanemab. Exploratory regional analysis demonstrated modest differences in baseline amyloid uptake in regions that subsequently developed ARIA-E, warranting confirmation in larger prospective studies.

Amyloid-β PET Radioligands in Alzheimer's Disease: From Plaque Detection to Biomarker-Guided Patient Stratification and Therapeutic Monitoring.

Amyloid-PET pipeline choice influences classification of preclinical Alzheimer's disease

BACKGROUND: Quantitative amyloid-beta (A{beta})-PET is increasingly used in AD prevention trials. Although the Centiloid (CL) framework provides a common scale, variability persists across processing pipelines, including differences in template/native space, partial volume correction (PVC), and reference region. These choices may influence cut-points, and in turn positivity rates, as well as longitudinal accumulation rates. We examined cut-point estimates and inter-pipeline discordance in a community cohort where many are expected to have early A{beta} deposition. METHODS: We analysed [18F]florbetapir PET/MR data from predominantly cognitively unimpaired (~95%) individuals aged ~71 years at baseline (n=433) and at follow-up (n=328; ~2.4-year interval) in Insight 46 (1946 British birth cohort). Centiloids were derived using the standard pipeline and ten in-house pipelines employing alternative reference regions and PVC in native space. Gaussian mixture modelling estimated cut-points with bootstrapped uncertainty. We assessed A{beta}-discordance across pipelines as a function of standard CLs and examined follow-up CSF A{beta}42/A{beta}40 (n=120) and PET in individuals with discordant baseline classifications. RESULTS: Baseline cut-points were 10-23 CL across pipelines, classifying 16-25% as A{beta}-positive. Reliable accumulation cut-points were 3.5-6 CL/year, identifying 16-22% as accumulators. Uncertainty varied across pipelines. At baseline, 18% were discordant across PET measures, predominantly between 11-35 standard CLs. The discordant group showed higher A{beta}-PET accumulation and lower CSF A{beta}42/A{beta}40 than concordant negatives. CONCLUSIONS: Disagreement between A{beta}-PET methods was highest between 11-35 standard Centiloids and was frequently associated with accumulating A{beta}. These findings highlight the importance of considering cut-point uncertainty and methodological influences when interpreting early-stage amyloidosis.

Prognostic value of Amyloid PET in Real-World Amnestic MCI: Influence of reader experience and interpretation method.

PURPOSE This study assessed the prognostic value and inter-/intra-observer reliability of three amyloid PET interpretation methods-conventional visual reading, assisted visual interpretation and standardized uptake value ratio (SUVR)-based quantification-for predicting conversion to Alzheimer's disease (AD). METHODS This retrospective longitudinal study included 145 patients with amnestic mild cognitive impairment who underwent amyloid PET and were followed for up to 8 years at a single memory clinic. Two certified nuclear medicine physicians performed structured visual reads and assisted visual interpretations. Semiquantitative SUVR thresholds validated in prior studies were applied as a third method. Inter- and intra-observer agreement was assessed using Cohen's kappa (κ). Cox regression models estimated the association of conversion to AD in PET-positive versus PET-negative patients for each method, adjusting for age, sex and education. RESULTS Inter-observer agreement was excellent for structured visual reading (κ = 0.877) and assisted visual interpretation (κ = 0.904). Intra-observer reliability was also high (κ = 0.891 for Reader 1; κ = 0.859 for Reader 2). Consensus agreement for the assisted method reached κ = 0.936. Amyloid PET positivity was strongly associated with progression to AD across all methods. Hazard ratios were highest for assisted visual interpretation (HR = 3.23, 95% CI 1.94-5.38, p < 0.0001), followed by SUVR quantification (HR = 2.19, 95% CI 1.55-3.10, p < 0.0001) and structured visual reading (HR = 1.83, 95% CI 1.10-3.06, p = 0.02). CONCLUSION Amyloid PET positivity consistently predicted conversion to AD regardless of interpretation method. Assisted visual and semiquantitative approaches showed numerically higher prognostic discrimination, while expert structured visual reading remained clinically reliable.

Comparison of Expert Reads Versus Local Clinical Reads of Amyloid PET Scans in the IDEAS Study.

Amyloid-targeting therapies and growing reimbursement are expected to increase the clinical use of amyloid PET. The Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study captured more than 18,000 clinical scan interpretations from local radiologists and nuclear medicine physicians in the United States. This study aimed to evaluate the reliability of these interpretations by comparing local clinical reads of a representative sample of IDEAS scans to retrospective majority interpretations by expert readers. Methods: A representative subset of amyloid PET scans from the IDEAS study, 500 performed with each of the Food and Drug Administration-approved tracers (18F-florbetaben, 18F-florbetapir, 18F-flutemetamol) and previously interpreted by local readers, was assigned to vendor-selected panels of 3 expert readers (1 panel per tracer). The scan subset was stratified to match the overall study frequencies by participant age, level of cognitive impairment (mild cognitive impairment vs. dementia), positive or negative local interpretation, and PET facility type. Expert readers performed visual interpretations using tracer-specific criteria, blinded to clinical and demographic data. Cohen κ assessed agreement between local reads and the majority expert panel reads, and Fleiss κ measured overall agreement among expert readers. Results: Expert panels interpreted 1497 scans. Participants were a median age of 75 y (range, 65-96 y), 51.4% were female, and 60.5% had mild cognitive impairment. Local readers interpreted 60.9% of scans as positive and 39.1% as negative. Across all radiotracers, agreement between majority expert and local reads was good (κ = 0.76; 95% CI, 0.73-0.80), with 86.6% (790/912) agreement for positive scans and 91.5% (535/585) agreement for negative scans. Agreement did not vary significantly by PET tracer (κ = 0.73-0.78). Agreement between individual experts and local readers was also good (pairwise κ = 0.61-0.78), and agreement within the expert reader group was similarly high (κ = 0.79; 95% CI, 0.77-0.81). Lower concordance between local and expert reads was associated with low local reader confidence (P < 0.001). Conclusion: We found good agreement between local readers and the majority assessment of 3-member expert panels. Visual interpretation of amyloid PET can be performed in a real-world clinical setting with high reliability.