Citations

Abstract Background Cognitive resilience to Alzheimer's disease (AD) pathology has been widely studied, but distinguishing resilient individuals from those with typical tau pathologies remains challenging due to the overlap in imaging and plasma biomarker profiles. We hypothesize that our machine learning‐based (ML) tau heterogeneity score, THETA (JNUMED, July 2024), could serve as an effective marker of resilience and provide a better estimation of tau's temporal progression. Method Longitudinal imaging data from the Mayo Clinic Study of Aging (MCSA, n = 1834) and ADRC ( n = 246) were analyzed. Participants were categorized into typical AD and resilient groups using amyloid PiB‐PET (abnormal PiB‐PET≥25 Centiloid units), Flortaucipir (FTP‐PET) (meta‐ROI≥1.29 SUVr, ERC≥1.27 SUVr) and Mini‐Mental State Examination (MMSE). Typical AD was defined as abnormal PiB‐PET and abnormal FTP‐PET for both biomarkers (Figure 1). Resilience to AD pathology was determined by predicted values of MMSE >28 from a linear mixed effects model for cognitively unimpaired participants. In addition, a resistant group was broadly defined as having normal PiB‐PET. To capture the spatial heterogeneity of tau distribution in the brain, regional THETA scores were generated using ML model and visual ratings. Additionally, a progression model, Sampled Iterative Local Approximation (SILA), was fitted using AD and plasma biomarkers ( p ‐tau181 and GFAP) for validation. Result THETA identified regions of reduced tau uptake in the frontal, parietal, temporal, occipital, and limbic regions when compared to the typical AD group (Figure 2A). This was confirmed by the preserved cortical thickness in these same regions (Figure 2D). In addition, SILA showed THETA can distinguish global tau temporal progressions of typical AD, resilient, and resistant groups compared to the other biomarkers (Figure 3). Interestingly, the onset age for GFAP was younger for resilient and typical AD, indicating earlier onset of inflammation in the presence of pathology. Conclusion The significant regions identified by THETA, showing reduced tau and preserved cortical thickness, combined with the clear offset in progression models between resilient and typical AD, suggest that THETA may help uncover pathological tau mechanisms that differentiate these groups. These findings highlight the potential of THETA to provide valuable insights into resilience mechanisms and enhance our understanding of AD.

Abstract Background Individuals with mild cognitive impairment (MCI) experience challenges in maintaining independence in their instrumental activities of daily living (IADLs). The memory support system (MSS) is a paper‐based planner intervention to train individuals with MCI to complete personal goals and IADLs independently. As more individuals use electronic calendar systems, the MSS will need to adapt. This project aimed to develop and test an electronic prototype of the MSS (eMSS). Method Drawing on the MSS, an eMSS prototype intended for phone/tablet use was developed in Axure, allowing participants to interact with the planner and its sections (calendar, notes, to do list). The prototype was evaluated with MSS trainers and individuals with MCI and their partners using a computer or tablet over a virtual platform. Participants were asked to go through fictional ‘planning’ scenarios which were assessed using cognitive task analysis (CTA). The scenarios were designed to evaluate overall ease of use, and specifics such as navigation between pages/sections and developing schedules and task lists. During sessions, participants were encouraged to 'think aloud,' providing insight into their eMSS experience. Result To date, CTA has been conducted with 6 MSS trainers, and 2 patient/partner dyads that completed the MSS training program. Early results provide insight on strengths, challenges and opportunities to optimize the eMSS. Participants could identify and use key features (e.g., menus) and found the symbols and language consistent. However, participants didn’t notice some features (e.g., interactive arrows to navigate across dates) and requested more ‘cueing’ or ‘interactive prompts.’ Participants would prefer to see all information entered on individual pages (which is possible with the MSS) to support better situation awareness. Conclusion To respond to the everyday planning needs of individuals with MCI in a digital age, an eMSS was developed, drawing on a clinically trialed hardcopy version (MSS). Positive feedback from MSS trainers and patients with MCI and their partners suggests promise for the overall design. Improvements for the next iteration include designing cues to help users know actions have been completed or when to attend to important information, as well as providing more fulsome information on pages to support awareness of daily tasks.

Abstract Background The Alzheimer's Association workgroup criteria (AA‐2024) suggest four biological stages based on PET imaging. However, the application of this framework may vary depending on the tau PET tracer used, and the distribution of clinical stages by biological stage may differ. Here, we aim to compare the diagnostic performance of the biological staging of Alzheimer Disease using two different tau PET tracers. Method We analyzed 446 individuals and further stratified 167 Aβ‐positive participants from the HEAD study (Longitudinal multicenter head‐to‐head harmonization of tau PET tracers) that underwent both MK‐6240 and Flortaucipir (FTP) tau PET. Four clinical stages (normal, transitional, MCI, and dementia) were defined based on the AA‐2024 criteria. Within stage‐2 we assessed subgroups: subjective cognitive decline (SCD), subtle objective cognitive decline (SOCD), and mild behavioral impairment (MBI). Logistic and linear models corrected by age and sex tested association of groups with amyloid and tau pathology. The biological staging was performed using tracer‐specific thresholds for regional SUVR and testing two regions of interest schemes: (i) proposed by AA‐2024 and (ii) Braak stages (Figure 1). Cohen's weighted‐kappa (K) statistic measured clinical‐biological agreement. Positive predictive value (PPV) of an individual being clinically impaired (MCI or dementia) was calculated for each biological stage. Result Clinical stages showed a progressively increased prevalence of Aβ‐positivity and higher entorhinal tau PET pathology from cognitively normal (CN) to SOCD, MCI, and dementia in both tracers. MBI and SCD transitional groups showed no increased Aβ or tau pathology compared to CN (Figure 2). For this reason, only SOCD was considered part of stage 2 for following analyses. All tested biological staging strategies showed moderate agreement (0.34‐0.59) with clinical stages using either tracers. The distribution of biological across clinical stages were similar for FTP and MK, with MK‐6240 showing lower PPV values in earlier stages than FTP (Table 1). Conclusion Our results support that AA‐2024 biological and clinical stages show similar clinical‐biological concordance using either Flortaucipir or MK‐6240, although this can vary based on methods tested in the study. The MBI and SCD clinical subgroups showed no difference of pathological burden to clinical stage 1, while SOCD transitional stage showed higher burden compared to stage 1.

ABSTRACT Photogrammetry has emerged as a powerful tool in medical education, offering precise and cost‐effective 3D anatomical models that enhance spatial learning and accessibility. This systematic review synthesizes evidence from forty‐eight (48) peer‐reviewed studies (2000–2025) to evaluate photogrammetry's applications, technical workflows, and educational outcomes in anatomy and surgical training. Findings demonstrate its effectiveness across training levels, with high learner satisfaction (e.g., 96.4% preference over traditional methods) and sub‐millimeter accuracy in rendering complex structures like neuroanatomy and musculoskeletal systems. Photogrammetry's adaptability for remote learning and specimen preservation addresses critical gaps in resource‐limited settings. However, challenges persist, including the lack of tactile feedback and difficulties in visualizing deep anatomical relationships. Future directions should focus on integrating artificial intelligence (AI)‐assisted processing, hybrid digital–physical models, and immersive technologies like virtual reality (VR)/augmented reality (AR) to bridge these gaps. By balancing innovation with evidence‐based implementation, photogrammetry can further solidify its role as a transformative adjunct in modern medical curricula.

Abstract Background White matter (WM) plays a dual role in interacting with tau pathology. There is an intricate dynamic relationship with WM acting as highways for tau spreading, while the increasing tau burden ultimately compromises WM health. We aimed at studying the associations between tau accumulation and WM integrity using longitudinal data with focus on sex differences. Method We included 374 participants who had longitudinal multishell diffusion MRI and flortaucipir PET (baseline mean age = 70.9 years, 52% male, 17% MCI/AD dementia) scans from the Mayo ADRC and Mayo Clinic Study of Aging. Rate of tau accumulation was calculated from the entorhinal cortex (ERC) and inferior temporal cortex (IT) SUVRs, with IT‐WM serving as the WM highway between the two regions. IT‐WM was defined by JHU “Eve” WM atlas, and its integrity was assessed using neurite density index (NDI), which reflects the packing density of neurites. Structural equation modeling (SEM) evaluated relationships between tau and WM metrics. Result At baseline, males and females showed no significant differences in tau SUVR or IT‐WM NDI ( p >0.05), though males had higher vascular risk and averaged two years older than females (Table 1). Figure 1a showed that baseline ERC‐tau influenced baseline IT‐tau, as well as both rate of ERC‐tau and baseline IT‐tau influenced rate of IT‐tau. After incorporating IT‐WM NDI as a mediator (Figure 1b), we discovered 1) baseline ERC‐tau influencing rate of IT‐tau accumulation through baseline IT‐WM NDI, suggesting the role of WM health in the rate of tau accumulation; 2) Rate of IT‐tau accumulation negatively affected follow‐up IT‐WM NDI suggesting the deterioration of WM health as tau accumulation progresses. These relationships were stronger in males compared to females. We also observed greater impact of vascular risk on WM health in males and greater rates of IT‐tau accumulation in females. Conclusion Our work sheds light on the mechanistic role of intact WM in tau accumulation (through dense microtubules and synaptic connections) and the deterioration of WM that is associated with higher rates of tau accumulation. We found interesting sex differences that warrant further investigation.

Abstract Background Corticobasal syndrome (CBS) is a neurodegenerative disease usually associated with accumulation of tau in the cortex and basal ganglia, leading to cognitive, movement, and behavioral symptoms that progressively impair function. Few clinical trials have ever been conducted in CBS, and perceptions and preferences about clinical trials in this population are largely unknown. Method An online survey was conducted (February 2015 ‐ November 2020) among research participants recruited through a multisite observational study (ARTFL). Responses from patients with CBS were tabulated and reported below. Result N=66 respondents had CBS as a primary or secondary phenotype (determined by study clinician), with 62% of surveys patient‐reported, and 38% completed by a caregiver/family member. Within CBS, 91% requested to be contacted about clinical trials. 2/6 decliners commented that disease severity precluded participation. 97% were willing to come in annually, 88% quarterly (3 months), 66% monthly, 43% weekly, and 17% would come in more than weekly; two patients could not travel due to disease severity. Comments included “we would live here for trials” and “whatever is needed.” Full day evaluations were acceptable to 91%, whereas 9% preferred a half‐day or less, although 65% would complete multi‐day evaluations spread over a week. Numerous remote and in person modes of assessment (e.g., surveys, examinations, cognitive testing, blood/saliva sampling, MRI, PET), were broadly acceptable by respondents (80‐93%), whereas remote activity monitoring (70%), lumbar puncture (68%), and remote video conferencing memory testing (67%) were less preferred, though still broadly acceptable. For distance willing to travel, 95% would travel 30 minutes, 91% one hour, 65% three hours, 54% five hours, and 37% would travel more than five hours or take a flight if needed. Travel reimbursement was very/extremely important for 40%, and unimportant for 26% (34% neutral). Feedback about clinical progression (81%), study results (74%), and an open‐label extension (68%) were factors identified as the highest importance to patients. Conclusion Patients with CBS are eager to participate in clinical trials, even trials that are complex, far away, and have visits over multiple days. Travel reimbursement, providing feedback to patients, and access to experimental treatments were key considerations.

Abstract Background HEAD is a longitudinal, multi‐site, non‐randomized study aiming to harmonize different tau PET tracers onto a common scale for enrichment and monitoring of anti‐tau clinical trials. To achieve this, the Uniτ scale is being developed using data from participants scanned head‐to‐head with Flortaucipir and MK6240, with a subset also scanned with PI2620 and RO948. However, access to the Uniτ scale has been limited to the study community and collaborators. To address this limitation, we have developed the Uniτ Ecosystem – a set of tools for tau PET harmonization designed to support research and clinical trials ( www.unitau.app ). Method The Uniτ Ecosystem was developed for multiple operating systems (Web/macOS/Windows/Ubuntu) (Figure 1) and currently include four tools. The Uniτ harmonization is an online ROI harmonization module that allows the user to harmonize SUVRs from spreadsheets. The Uniτ packages (R, Python and MATLAB) facilitates the transformation of SUVR values to the Uniτ scale using the most used programming languages in research settings. The Uniτ calculator app allows rapid and convenient harmonization. The Uniτ desktop app is a 3D harmonization module for voxel‐wise harmonization. The Uniτ parameters were calculated using a training set of 200 participants with head‐to‐head MK6240 and Flortaucipir, and 90 individuals with additional PI2620 and RO948. Researchers can use their own datasets and convert tau PET data to the Uniτ scale. Result The online ROI harmonization module allows users to harmonize tau PET SUVRs uploaded from spreadsheets and offers interactive visualizations such as scatter plots and histograms for tau positivity thresholds (Figure 2). The calculator app enables users to harmonize single SUVR values effortlessly. The desktop application for 3D tau PET harmonization leverages the functionalities of the previous modules to harmonize entire 3D images, eliminating the need for predefined ROIs. Additionally, this module provides visualization tools for the parametric Uniτ images in 2D and 3D (Figure 3). Uniτ tools never store any data on any external servers. Conclusion The Uniτ Ecosystem represents a significant advance in tau PET harmonization, providing a user‐friendly platform to harmonize and visualize tau PET data for research and clinical trials.

Abstract Objective Intraoperative parathyroid hormone (ioPTH) monitoring is crucial during parathyroid surgery to ensure chemical cure. However, delays in processing can prolong operative times. This study evaluates the effectiveness of a checklist to expedite ioPTH assay processes. Methods A multidisciplinary checklist was developed to standardize ioPTH collection and workflow. Thirty patients treated with use of the checklist were prospectively studied, while 30 patients treated without use of the checklist were retrospectively reviewed. Time intervals for post–15‐minute ioPTH assay results were compared. Results Thirty age‐ and sex‐matched patients were included in each group (n = 60) involving 5 surgeons. The intervention and control group had a mean baseline PTH of 140.9 and 130.3 pg/mL and a post–15‐minute ioPTH of 69.6 and 52.0 pg/mL, respectively. The mean time from sample collection to the post–15‐minute ioPTH assay result was significantly reduced in the intervention as compared to the control group (22.2 vs 33.3 minutes; P < .01). The proportional operative time spent awaiting ioPTH assay results was also reduced (24.4 vs 34.1%; P < .01). In subgroup analysis, a significant difference in the total operative time was found in adenomatous disease (68.0 vs 92.2 minutes, P < .05) but not four‐gland hyperplasia (119.3 vs 142.3 minutes). Discussion The implementation of a simple intraoperative checklist effectively reduces the overall ioPTH assay processing time, creating a more efficient surgical workflow. It is low‐cost and requires minimal additional resources. Implications for Practice This quality improvement intervention holds promise for broader adoption in parathyroid surgery to reduce delays and optimize patient care.