Citations

Abstract Background The Overlap Index (OI) as previously published (Lee et al., 2022) is a reliable method for detecting tau accumulation using tau‐PET imaging (flortaucipir; AV1451). It identifies voxel‐wise standardized uptake value ratio (SUVr) elevations across serial scans. Although OI showed more sensitivity to tau signal elevation and longitudinal change than standard ROI measures, to our knowledge, the relationship of the tau PET overlap index to neuropathologic findings is still unclear. This study aims to investigate the potential of OI to detect NFTs of the neuropathologic Braak tangle stage, especially the early Braak tangle stage (I–IV). Method This study included 57 participants from the Mayo Clinic Study of Aging or Mayo Alzheimer's Disease Research Center, all of whom underwent autopsy and at least two serial AV1451 tau‐PET scans and 3T T1‐weighted MRI within an average of 16 months. Tau‐PET SUVr images were normalized to cerebellar crus grey matter, and MR images were co‐registered to a single‐subject MRI mean. Tau‐PET scans were resampled into MRI space, and OI was calculated by applying intensity thresholds 1.3. Clusters with fewer than 20 contiguous voxels were excluded. An OI cutoff of 0.5 was used and an SUVr cutoff of 1.29. Postmortem immunohistochemistry (IHC) using phospho‐tau antibodies (AT8, PHF‐1) was performed on the amygdala, temporal cortex (middle and superior), and anterior/posterior hippocampus. Neuropathological Braak staging was determined based on AT8‐stained sections. We conducted visual comparison of tau‐PET overlap signal in these regions with IHC‐confirmed tau pathology across Braak tangle stages. Result OI‐detected voxels corresponded to NFT distribution across Braak stages. In early Braak stages, standard SUVr‐based META‐ROI values remained negative, whereas OI showed positive signals, indicating greater sensitivity to early tau pathology (Figure 1). The spatial distribution of OI‐derived overlap regions aligned with high NFT burden, suggesting that OI captures early‐stage tau pathology more effectively than conventional SUVr methods. Conclusion OI in serial tau‐PET imaging demonstrated better detection of early‐stage tau pathology than standard ROI‐based SUVr measures. The alignment between OI‐detected voxels and neuropathological tau burden supports its potential as an in vivo biomarker for detecting early neurofibrillary tangles.

Abstract Background Dementia with Lewy Bodies (DLB) is often misdiagnosed or conflated with Alzheimer's Disease (AD) due to overlapping clinical presentations and neuropathological features. The presence of AD‐like features correlates with accelerated cognitive decline and a worse overall prognosis. Compared to AD, studies suggest that amyloid uptake in DLB may spare the occipital lobe. This project aims to investigate whether amyloid PET could be leveraged to differentiate between AD and DLB patients, with the goal of improving diagnostic accuracy and supporting patient stratification and safety in anti‐amyloid trials. Method This study involves collaboration across six centres (University of Geneva, BioFINDER, AMPLE, AMYPAD PNHS, MCSA, GEHC), each contributing amyloid PET imaging data from patients diagnosed with DLB based on clinical or neuropathological assessments. Moreover, each center provided an additional subset of AD and healthy controls, then matched to DLB samples based on age/sex/APOE genotype/education for comparison. A sub analysis will be performed on patients with evidence of both DLB and AD markers. Given the relatively small sample size, key aspect of the methodological approach is to reduce technical sources of variability. The processing workflow includes rigorous quality control, formatting, normalisation to MNI space, harmonisation (differential smoothing), and MRI‐based segmentation. Result The dataset currently includes amyloid PET scans (acquired using [ 11 C]PiB, [ 18 F]Flutemetamol or [ 18 F]Florbetapir) and MRI scans from ∼130 DLB patients, along with ∼150 AD patients and ∼150 controls. In addition, 99 patients positive for the CSF α‐Synuclein Seeding Amplification Assay were included. Patient data were anonymized, and a harmonised database was created, including demographic characteristics, clinical history, and results from neuropsychological assessments. Conclusion The creation of a standardized, multi‐centre amyloid PET dataset for DLB will enable the study of amyloid PET patterns at the global, regional and voxel level, in comparison with uptake in AD patients and controls. This dataset will serve as a valuable resource for investigating the neuropathological underpinnings of DLB, improving diagnostic accuracy, and potentially guiding patient stratification in anti‐amyloid trials. Efforts to integrate [ 18 F]Florbetaben and additional data are ongoing.

Abstract Aims Intracardiac echocardiography (ICE) is increasingly incorporated into atrial fibrillation (AF) ablation workflows, enabling real-time anatomic guidance and procedural precision. Nevertheless, ICE utilization shows substantial geographic variability, and its clinical benefit remains incompletely understood. This meta-analysis evaluated the efficacy, safety, and procedural performance of ICE-guided vs. non-ICE-guided AF ablation. Methods and results MEDLINE, the Cochrane Library, and Scopus were systematically searched through 3 August 2025. Three reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Random-effects models were used to pool data from 44 AF ablation studies comprising 482 043 patients. ICE guidance was associated with lower odds of any complication (OR 0.69; 95% CI 0.53–0.89), including significant reductions in cardiac tamponade (OR 0.58; 95% CI 0.53–0.62) and mortality (OR 0.21; 95% CI 0.16–0.27). ICE-guided ablation was also associated with shorter total procedure and fluoroscopy times, reduced radiation exposure, and lower contrast agent utilization. Atrial tachyarrhythmia (AT) recurrence did not differ between groups (OR 0.92; 95% CI 0.79–1.06). However, ICE use was associated with higher odds of first-pass pulmonary vein isolation (OR 1.62; 95% CI 1.09–2.41) and successful isolation of all pulmonary veins at the end of the procedure (OR 2.12; 95% CI 1.37–3.27), and lower odds of repeat ablation (OR 0.65; 95% CI 0.59–0.72). Conclusion ICE-guided AF ablation is associated with superior procedural safety and efficiency and a similar risk of AT recurrence compared to non-ICE-guided approaches.

Facial pain disorders, most notoriously trigeminal neuralgia, cause substantial suffering, functional impairment, disability, and impaired quality of life. However, most pain medicine practitioners have had only limited education on the evaluation, diagnosis, and treatment of facial pain. Furthermore, this limited education often contains commonly held myths about facial pain diagnosis. These myths can result in misdiagnoses that lead to ineffective medications, interventions, or surgeries and prolonged pain. Therefore, the American Society of Regional Anesthesia and Pain Medicine’s Headache and Facial Pain Special Interest Group convened a multidisciplinary group of neurologists, anesthesiologists, and dentists to identify and dispel pervasive myths in facial pain diagnosis.

Abstract Background Despite advances in Alzheimer's disease (AD) research, limited information exists regarding the absolute risk of mild cognitive impairment (MCI) in cognitively unimpaired (CU) individuals with abnormal AD biomarkers, particularly when accounting for competing risks of death. This knowledge gap is critical as the field addresses disease‐modifying treatments targeting CU individuals with preclinical AD. We focus on the predictive value of AD amyloid stages defined by amyloid PET Centiloid values. Methods We included 5,858 participants from the Mayo Clinic Study of Aging (MCSA) to evaluate AD amyloid stage as a predictor of clinical progression to MCI or dementia. The data includes long‐term follow‐up information on death and dementia beyond active study participation, which mitigates potential bias due to dropout. We predicted 10‐year and lifetime risks of MCI and dementia, accounting for the competing risks of death, given amyloid PET stages, sex, APOE4 status, and baseline age. Results are based on a hidden Markov model. Results AD amyloid staging based on amyloid PET Centiloid values was the strongest predictor of lifetime risk for MCI or for dementia (Figure 1). Higher Centiloid levels amplified age effects on the risk of MCI, whereas for dementia, amyloid stage effects surpassed age effects. For 10‐year risk, age was the dominant factor, whereas for lifetime risk, amyloid stages had a greater influence. While smaller in magnitude than the effects of amyloid stages and age, APOE4 carrier status and (on average) male sex were also associated with increased risk of MCI and dementia. For a female APOE4 carrier at age 65, lifetime risk was 41%/61%/76% for low/moderate/high amyloid PET levels. The 10‐year absolute risk for a female APOE4 carrier with high amyloid PET was 4%/29%/58% when assessed at starting ages 65, 75, and 85. Conclusions AD amyloid staging is a critical predictor of lifetime risk for cognitive impairment, underscoring its importance in guiding treatment decisions if interventions are approved for preclinical AD in the future. Effective patient evaluation should focus on biomarker‐based amyloid staging rather than simple binary biomarker classification, with careful consideration of age, sex, and APOE4 status to ensure a comprehensive benefit‐risk assessment for future therapeutic strategies.

Abstract Objective Recurrent acute rhinosinusitis (RARS) significantly decreases quality of life. Transplant recipients (TR) are particularly vulnerable to rhinologic conditions. There is a lack of guidelines for managing RARS in this population. Our study aims to determine the prevalence of and risk factors for RARS among TR and assess the need for sinus surgery within this group. Study Design Retrospective cohort. Setting Mayo Clinic between 2017 and 2022. Methods A total of 1116 patients met the inclusion criteria and were divided based on the presence or absence of a new incident RARS diagnosis during the posttransplant period and frequency of sinus surgery. Logistic regression (LR) analysis was performed to identify the odds ratio. Results In total, 111/1116 (9.95%) had RARS. Patients with RARS had an increased history of asthma, viral infection, and rheumatoid arthritis (RA) ( P = .003) in the pretransplant period. According to the LR analysis, patients with neutropenia, RA, and mantle cell lymphoma were 1.91, 2.71, and 4.02 times more likely to develop RARS (95% CI: 1.19‐3.05, P = .01), (95% CI: 0.90‐8.14, P = .07), and (95% CI: 1.16‐13.89, P = .02) during the posttransplant period, respectively. In those that developed RARS, only 5.5% failed medical therapy and required surgery. Conclusion This is the first cohort to investigate the incidence of RARS in TR and the predictive factors associated with its development posttransplant. We found that patients with pretransplant comorbidities such as RA, viral infections, hematologic deficiencies, and malignancies were at an increased risk for developing RARS, though this is not linked to an increased necessity for sinus surgery.

Objective Cervical artery dissection (CeAD) may be limited to the extracranial extradural space or extend to the intradural space. Intradural extension can potentially increase the risk of stroke and subarachnoid hemorrhage. However, the factors associated with intradural extension and its impact on clinical outcome remain unclear. Methods This was a secondary analysis of the STOP‐CAD observational, multi‐center study. Patients with CeAD and intradural extension (CeADid) were compared with those with pure CeAD extradural dissections (CeADed) using multiple regression analyses. Results Of 4,023 patients with CeAD, 534 (13.3%) had CeADid. In comparison to patients with CeADed, those with CeADid more often had clinical overt stroke or transient ischemic attack (TIA) at presentation, acute infarcts on imaging, a vertebral artery affected, and severe stenosis of the involved vessel ( p < 0.001 for all). In contrast, carotid involvement and complete occlusions were more frequent in patients with CeADed ( p < 0.001 for both). CeADid was associated with a shift in the distribution of scores on the modified Rankin Scale (mRS) toward worse functional outcome (odds ratio [OR] = 0.76, 95% confidence interval [CI] = 0.62–0.92) but the odds for favorable outcomes (mRS = 0–2) did not differ between the groups after appropriate adjustments on multivariate analysis. CeADid was independently associated with higher mortality at 180 days on multivariate analysis (adjusted OR = 2.84, 95% CI = 1.50–5.38). Interpretation CeADid is associated with more severe clinical presentation, a shift toward less favorable outcomes, and higher mortality rates. These findings suggest that CeADid may represent a high‐risk type of CeAD. ANN NEUROL 2026;99:1189–1197

Abstract Background The Joint Propagation Model (JPM)‐based CenTauR scale was recently introduced to harmonize tau‐PET quantification across different radiotracers. This study examined how CenTauR harmonization enhances the comparability of tau‐PET quantification across matched cohorts using different tracers. The evaluation focused on three key aspects: (1) comparing tau‐PET positivity rates as defined by CenTauR, (2) evaluating its diagnostic accuracy for symptomatic AD, and (3) analyzing longitudinal changes in tau‐PET rates over time. Method The JPM, developed by the CPAD‐led Tau PET Harmonization Working Group (Leuzy et al., Alzheimers Dement. 2024; Figure 1A), models relationships between anchor point subjects and head‐to‐head tau‐PET SUVR data onto the CenTauR scale, providing conversion equations for multiple tracers. JPM equations were applied to [ 18 F]flortaucipir SUVR (Meta‐temporal ROI) data from 561 cognitively impaired participants in the ADNI and OASIS‐3 studies. Using ROC analysis, we determined the CenTauR cut‐off for positivity (T+) that maximized the Youden index for discriminating between FDA‐approved positive/negative visual reads. Three separate cohorts, scanned using [ 18 F]flortaucipir (ADNI), [ 18 F]MK‐6240 (CPAS), and [ 18 F]RO‐948 (BioFINDER‐2), were matched 1:1 by age, MMSE, amyloid‐β, and clinical diagnosis. CenTauR‐based metrics were compared across these cohorts. Result A cut‐off of 18 CenTauRs was found to optimally classify [ 18 F]flortaucipir PET visual reads (Figure 1B). The matching procedure identified 1089 participants (363 per cohort). The frequency of T+ using the 18 CenTauRs cut‐off for the Meta‐Temporal ROI was highly comparable across tracers across groups, except for the Aβ‐positive cognitively unimpaired group, where variability was more pronounced due to a smaller sample size (Figure 2A). Similarly, tau‐PET discriminative accuracy for symptomatic AD vs controls remained similar across [ 18 F]flortaucipir and [ 18 F]MK‐6240 (Figure 2B). In a separate sample of 212 matched participants from ADNI ([ 18 F]flortaucipir) and AIBL ([ 18 F]MK‐6240) with baseline and 1‐year follow‐up tau‐PET scans, 1‐year change in CenTauRs was comparable (Figure 2C). An exploratory voxelwise transformation, utilizing the Meta‐Temporal conversion equation in a representative case scanned with both [ 18 F]flortaucipir and [ 18 F]MK‐6240, demonstrates the potential for voxelwise CenTauR harmonization (Figure 3). Conclusion These analyses suggest that CenTauR harmonization increases the comparability of tau‐PET data acquired with different tracers. Additional validation analyses with larger cohorts including other radiotracers ([ 18 F]PI‐2620) are underway.