BackgroundAmyloid‐PET had been widely used and validated in research settings, using highly selected samples, harmonized acquisition protocols, co‐registration with MRI, and central interpretation by highly experienced experts. In contrast, in clinical settings, more heterogeneous acquisition, reconstruction, and interpretation may compromise the accuracy of the imaging. We quantitatively analyzed real‐world amyloid‐PET scans to assess their validity.MethodIDEAS acquired 18,295 amyloid PET scans at 343 PET facilities in patients with MCI or dementia using 18F‐florbetapir, 18F‐florbetaben, or 18F‐flutemetamol. Scans were visually interpreted at each site as either negative or positive for cortical tracer retention. Scans from consenting patients were archived. As of December 1, 2021, amyloid‐PET scans from 6,263 unique participants were available for analysis. Exclusion for lack of valid images or clinical data and failure of quality checks resulted in 6,150 (98.2%) valid scans. We analyzed the scans using a recently validated PET‐only processing pipeline designed to process heterogeneous amyloid‐PET scans (Iaccarino et al, 2022) and quantified cortical uptake in Centiloid (CL) units. A previously established neuropathology‐based threshold of 24.4 CL was used to define amyloid‐PET positivity independent of visual reads.ResultMean CL was higher in dementia (mean±SD = 53±51) than in MCI (40±48) (mean difference: 13; 95%CI: 10‐15). Mean CL of visually negative scans (3±27) was very close to 0, as expected for patients without amyloid accumulation, and significantly lower than visually positive scans (72±41) (mean difference: 69; 95%CI: 67‐70) (table 1). High concordance was found between local visual reads and CL‐based positivity (86.5%, Cohen’s κ=0.72, figure 1). CL exhibited a bimodal distribution, with most scans clearly positive or negative, and a minority of visual‐quantitative discordant scans surrounding the positivity threshold (figure 2). CL negatively correlated with MMSE (r=‐0.19, p<.001, figure 3). CL further correlated with the level of confidence in the diagnosis of Alzheimer’s Disease (AD), as was indicated by clinicians before the performance of PET (r=0.13, p<.001, figure 4).ConclusionA large heterogeneous dataset of real‐world amyloid‐PET scans analyzed quantitatively, shows high concordance with visual reads, and expected relationships with clinical and neuropsychological measures of AD.

BackgroundThe majority of individuals with unambiguously positive tau biomarkers (T++) have positive amyloid biomarkers. Here we describe cases with clinical features associated with an unusual biomarker profile: very high tau PET binding and negative amyloid PET (A‐T++).MethodWe searched the Longitudinal Early‐Onset Alzheimer’s Disease (AD) Study, University of California San Francisco AD Research Center and the AD Neuroimaging Initiative cohorts on 09/01/2021 for participants with completed amyloid PET (Florbetapir, Florbetaben, Pittsburgh Compound B) and Tau PET (Flortaucipir (FTP)) scans and identified 1420 participants (mean age 69, 49.7% male). Using a pathology‐based, neocortical centiloid threshold of 24.4 (amyloid positivity) and a pre‐defined region of interest (Temporal MetaROI) standardized uptake value ratio (SUVR) > 1.27 threshold (tau positivity), we identified 64 amyloid negative, tau positive cases. An additional MetaROI FTP‐SUVR threshold > 2.0 (based on visual plot of data) was then applied to identify 7 A‐T++ cases (Figure 1).ResultAmong A‐T++ individuals mean age was 66.2 (range 53.8 ‐ 77.1), 4/7 were female, mean years of education was 15 (range 12 ‐ 20), mean MMSE was 20 (range 14‐29), 3/7 were APOE e3/e4 and clinical phenotypes included amnestic and atypical AD phenotypes (Table 1).Mean neocortical centiloid value was 11.4 (range: ‐1.39 ‐ 17.11) among A‐T++ cases and 4/7 had centiloid values between 12.2 ‐ 24.4 (may be indicative of early positivity). Mean FTP SUVR was 2.28 (range 2.03 ‐ 2.63) (Table 2). All A‐T++ cases demonstrated FTP tracer binding within the middle temporal cortex, medial temporal structures, and posterior cingulate regions (Figure 2). Neuropathological data from 1 case (UCSF3) revealed frequent CERAD Neuritic Plaques, Thal Amyloid Plaque Phase 5, and Braak Neurofibrillary Degeneration Stage 6 (autopsy performed 1 year after amyloid PET).ConclusionA‐T++ individuals were heterogeneous clinically but all displayed FTP tracer binding in AD‐signature regions. Four cases had amyloid centiloid values above 12.2 (threshold to detect moderate‐to‐frequent CERAD scores) but below 24.4 (threshold to detect intermediate‐to high Alzheimer’s disease neuropathologic change (ADNC) levels). Pathological data available for 1 case revealed a high level of ADNC. False negative amyloid PET in A‐T++ individuals is an important consideration; future studies are needed.

BackgroundEmergence of novel visual artistic skills has been described in neurodegenerative disorders, particularly in the frontotemporal dementia – amyotrophic lateral sclerosis (FTD‐ALS) spectrum, but associated clinical and genetic features and the underlying neural mechanisms have not been systematically examined. We aimed to address these gaps.MethodWe performed comprehensive chart review of all 734 participants in the University of California San Francisco FTD Program Project Grant who had a clinical syndrome within the FTD‐ALS spectrum. This review allowed us to ascertain subjects meeting current FTD‐ALS clinical research criteria who had: (1) an emergence of novel visual artistic skills or (2) a change in the style of visual art produced or (3) a significant increase in quantity of visual art produced. Clinical data, imaging studies, and genetic information were collected and analyzed.ResultAmong the 734 patients screened, 45 were excluded due to lack of available research notes. We identified a change in visual artistic creativity in 17/689 patients (prevalence 2.5%). Mean age of FTD symptom onset was 57.4 (±10.4), and the visual artistic creativity (VAC) change was reported an average of 0.7 years (±10.1) prior to FTD symptom onset. Of the 17 patients with VAC, 8 exhibited no prior interest in art, 2 were professional visual artists who experienced a change in artistic style, and 7 reported some prior interest in art but a substantial change of style or quantity. Artistic output was diverse however bright colors and non‐human subjects were prominent. VAC occurred in patients with semantic variant primary progressive aphasia (8), behavioral variant FTD (3), nonfluent variant primary progressive aphasia (2), progressive supranuclear palsy ‐ Richardson’s syndrome (2), corticobasal syndrome (1), and ALS (1). None carried a common pathogenic variant in a FTD gene.ConclusionChange in VAC is an uncommon but early positive symptom that occurs in patients across the FTD‐ALS clinical spectrum but appears most common in patients with anterior temporal lobe degeneration. We are pursuing the neural mechanisms of VAC through structural and functional neuroimaging studies.