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INTRODUCTION: Subtle cognitive alterations that precede clinical evidence of cognitive impairment may help predict the progression to Alzheimer's disease (AD). Neuropsychological (NP) testing is an attractive modality for screening early evidence of AD. METHODS: Longitudinal NP and demographic data from the Framingham Heart Study (FHS; N = 1696) and the National Alzheimer's Coordinating Center (NACC; N = 689) were analyzed using an unsupervised machine learning framework. Features, including age, logical memory-immediate and delayed recall, visual reproduction-immediate and delayed recall, the Boston naming tests, and Trails B, were identified using feature selection, and processed further to predict the risk of development of AD. RESULTS: Our model yielded 83.07 ± 3.52% accuracy in FHS and 87.57 ± 1.19% accuracy in NACC, 80.52 ± 3.93%, 86.74 ± 1.63% sensitivity in FHS and NACC respectively, and 85.63 ± 4.71%, 88.41 ± 1.38% specificity in FHS and NACC, respectively. DISCUSSION: Our results suggest that a subset of NP tests, when analyzed using unsupervised machine learning, may help distinguish between high- and low-risk individuals in the context of subsequent development of AD within 5 years. This approach could be a viable option for early AD screening in clinical practice and clinical trials.
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INTRODUCTION: The number of glomeruli and glomerulosclerosis evaluated on kidney biopsy slides constitute standard components of a renal pathology report. Prevailing methods for glomerular assessment remain manual, labor intensive, and nonstandardized. We developed a deep learning framework to accurately identify and segment glomeruli from digitized images of human kidney biopsies. METHODS: Trichrome-stained images (n = 275) from renal biopsies of 171 patients with chronic kidney disease treated at the Boston Medical Center from 2009 to 2012 were analyzed. A sliding window operation was defined to crop each original image to smaller images. Each cropped image was then evaluated by at least 3 experts into 3 categories: (i) no glomerulus, (ii) normal or partially sclerosed (NPS) glomerulus, and (iii) globally sclerosed (GS) glomerulus. This led to identification of 751 unique images representing nonglomerular regions, 611 images with NPS glomeruli, and 134 images with GS glomeruli. A convolutional neural network (CNN) was trained with cropped images as inputs and corresponding labels as output. Using this model, an image processing routine was developed to scan the test images to segment the GS glomeruli. RESULTS: The CNN model was able to accurately discriminate nonglomerular images from NPS and GS images (performance on test data: Accuracy: 92.67% ± 2.02% and Kappa: 0.8681 ± 0.0392). The segmentation model that was based on the CNN multilabel classifier accurately marked the GS glomeruli on the test data (Matthews correlation coefficient = 0.628). CONCLUSION: This work demonstrates the power of deep learning for assessing complex histologic structures from digitized human kidney biopsies.