Statistical analysisDifferences in baseline characteristics between diagnostic groups were tested using ANOVAs for continuous and chi-squared tests for categorical data.
To compare the accuracy of different tau-PET ROIs for predicting cognitive decline, we performed bootstrapped linear regression with 1000 iterations per cognitive domain and tau-PET ROI. Within each iteration, cognitive changes on MEM/LAN/EF/VS were included as dependent variables, and tau-PET ROIs as independent variables. For ADNI, all models were controlled for age, sex, education, clinical status, APOE4 status, and baseline performance of the respective cognitive composite.
Next, we aimed to determine patient-specific cognitive composites that are informed by the baseline tau-PET-based prediction of cognitive decline, using ADNI as a discovery sample and A05 as a validation sample. Within ADNI Aβ+, we ran 1000 bootstrapped regressions controlled for age, sex, clinical status, and APOE4 status to extract 1000 beta-values of the association between cognitive-domain-specific tau-PET and cognitive changes for each variable of the regression model ).
Next, we entered patient-specific baseline data of both ADNI and A05 subjects in the 1000 linear model equations to determine mean patient-specific estimates of cognitive decline. To generate a personalized cognitive composite, we computed squared ranks of predicted cognitive changes across MEM/LAN/EF/VS for each subject , in order to maximize the information weight of cognitive domains with fast predicted cognitive decline.
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Imaging of C-X-C Motif Chemokine Receptor 4 Expression in 690 Patients with Solid or Hematologic Neoplasms Using 68Ga-Pentixafor PETIn recent years, molecular imaging addressing the C-X-C motif chemokine receptor 4 (CXCR4) has increasingly been used in various clinical settings. Here, we aimed to assess radiopharmaceutical uptake and image contrast to determine the most relevant clinical applications for CXCR4-directed imaging. We also investigated the impact of specific activity on scan contrast. Methods: Patients ( n=690) with a variety of neoplasms underwent a total of 777 PET/CT scans with 68Ga-Pentixafor, serving as the CXCR4-specific radioligand. A semiquantitative target lesion analysis was conducted (providing SUVmax and target-to-blood pool ratio [TBR], defined as SUVmax [from target lesion] divided by SUVmean [from blood pool]). The applied specific activity (in MBq/μg) was compared with semiquantitative assessments. Results: Of the 777 scans, 242 did not show discernible uptake in disease sites, leaving 535 PET scans (68.9%) for further analysis. Very high tracer uptake (SUVmax | 12) was found in multiple myeloma ( n=113), followed by adrenocortical carcinoma ( n=30), mantle cell lymphoma ( n=20), adrenocortical adenoma ( n=6), and small cell lung cancer ( n=12). Providing information on image contrast, comparable results for TBR were recorded, with TBR (|8) in multiple myeloma, mantle cell lymphoma, and acute lymphoblastoid leukemia ( n=6). When comparing specific activity with semiquantitative parameters, no significant correlation was found for SUVmax or TBR ( P ≥ 0.612). Conclusion: In this large cohort, 68Ga-Pentixafor demonstrated high image contrast in a variety of neoplasms, particularly for hematologic malignancies, small cell lung cancer, and adrenocortical neoplasms. The present analysis may provide a roadmap for detecting patients who may benefit from CXCR4-targeted therapies.
Source: medical_xpress - 🏆 101. / 51 Read more »
Genetically predicted telomere length and Alzheimer’s disease endophenotypes: a Mendelian randomization study - Alzheimer's Research & TherapyTelomere length (TL) is associated with biological aging, consequently influencing the risk of age-related diseases such as Alzheimer’s disease (AD). We aimed to evaluate the potential causal role of TL in AD endophenotypes (i.e., cognitive performance, N=2233; brain age and AD-related signatures, N=1134; and cerebrospinal fluid biomarkers (CSF) of AD and neurodegeneration, N=304) through a Mendelian randomization (MR) analysis. Our analysis was conducted in the context of the ALFA (ALzheimer and FAmilies) study, a population of cognitively healthy individuals at risk of AD. A total of 20 single nucleotide polymorphisms associated with TL were used to determine the effect of TL on AD endophenotypes. Analyses were adjusted by age, sex, and years of education. Stratified analyses by APOE-ɛ4 status and polygenic risk score of AD were conducted. MR analysis revealed significant associations between genetically predicted longer TL and lower levels of CSF Aβ and higher levels of CSF NfL only in APOE-ɛ4 non-carriers. Moreover, inheriting longer TL was associated with greater cortical thickness in age and AD-related brain signatures and lower levels of CSF p-tau among individuals at a high genetic predisposition to AD. Further observational analyses are warranted to better understand these associations. Graphical Abstract
Source: BioMedCentral - 🏆 22. / 71 Read more »