The classical approach for testing statistical images using spatial extent inference (SEI) thresholds the statistical image based on the p-value. This approach has an unfortunate consequence on the replicability of neuroimaging findings because the targeted brain regions are affected by the sample size-larger studies have more power to detect smaller effects. Here, we use simulations based on the preprocessed Autism Brain Imaging Data Exchange (ABIDE) to show that thresholding statistical images by effect sizes has more consistent estimates of activated regions across studies than thresholding by p-values. Using a constant effect size threshold means that the p-value threshold naturally scales with the sample size to ensure that the target set is similar across repetitions of the study that use different sample sizes. As a consequence of thresholding by the effect size, the type 1 and type 2 error rates go to zero as the sample size gets larger. We use a newly proposed robust effect size index that is defined for an arbitrary statistical image so that effect size thresholding can be used regardless of the test statistic or model.
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http://dx.doi.org/10.1002/hbm.25374 | DOI Listing |
Alzheimers Dement
December 2024
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Background: Genome-wide association studies (GWAS) in Alzheimer's disease (AD) leveraging endophenotypes beyond case/control diagnosis, such as brain amyloid β pathology, have shown promise in identifying novel variants and understanding their potential functional impact. In this study, we leverage two brain amyloid β pathology measurement modalities, PET imaging and neuropathology, to address sample size limitations and to discover novel genetic drivers of disease.
Method: We conducted a meta-analysis on an amyloid PET imaging GWAS (N = 7,036, 35% amyloid positive, 53.
Alzheimers Dement
December 2024
New York University, New York, NY, USA.
Background: Alzheimer's disease (AD) exhibits considerable phenotypic heterogeneity, suggesting the potential existence of subtypes. AD is under substantial genetic influence, thus identifying systematic variation in genetic risk may provide insights into disease origins. We previously identified a genetic heterogeneity across two levels.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Columbia University Irving Medical Center, New York, NY, USA.
Biofluidic biomarkers concord with postmortem molecular studies, suggesting that the endosomal recycling pathway regulated by SORL1's interaction with the retromer protein VPS2b is commonly disrupted in late-onset, 'sporadic', Alzheimer's disease (AD). Here, a program for developing a neuroimaging-based biomarker will be reviewed. The program is anchored by findings in support of the conclusion that, because of its distinct network properties, the trans-entorhinal cortex is heavily dependent on the recycling pathway.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Qingdao Municipal hospital, Qingdao university, Qingdao, Shandong, China.
Background: Bridging integrator 1 (BIN1), one of the most strongly associated gene with Alzheimer's disease (AD). It has been reported to play a role in the pathological processes of AD; however, the exact mechanism has not yet been completely found.
Method: Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 495) was the discovery cohort, and the Chinese Alzheimer's Biomarker and LifestylE (CABLE, N = 619) study was used to replicate the results.
Alzheimers Dement
December 2024
University of Washington, Seattle, WA, USA.
Background: The structural, cellular, and biomolecular research necessary for a mechanistic understanding of Alzheimer's Disease (AD) relies on brain tissue collected according to a brain sampling protocol (BSP) and preserved in biorepositories. Such research involves discipline-specific terminology such as cytoarchitectonic domains, brain network nodes, etc. This specificity can result in iterative, time-consuming, and error-prone request processes.
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