A semi-mechanism approach based on MRI and proteomics for prediction of conversion from mild cognitive impairment to Alzheimer's disease.
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ABSTRACT:
SUBMITTER: Liu H
PROVIDER: S-EPMC4896009 | biostudies-other | 2016 Jun
REPOSITORIES: biostudies-other
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Project description:IntroductionCurrently, there are no tools that can accurately predict which patients with mild cognitive impairment (MCI) will progress to Alzheimer's disease (AD). Texture analysis uses image processing and statistical methods to identify patterns in voxel intensities that cannot be appreciated by visual inspection. Our main objective was to determine whether MRI texture could be used to predict conversion of MCI to AD.MethodsA method of 3-dimensional, whole-brain texture analysis was used to compute texture features from T1-weighted MR images. To assess predictive value, texture changes were compared between MCI converters and nonconverters over a 3-year observation period. A predictive model using texture and clinical factors was used to predict conversion of patients with MCI to AD. This model was then tested on ten randomly selected test groups from the data set.ResultsTexture features were found to be significantly different between normal controls (n = 225), patients with MCI (n = 382), and patients with AD (n = 183). A subset of the patients with MCI were used to compare between MCI converters (n = 98) and nonconverters (n = 106). A composite model including texture features, APOE-?4 genotype, Mini-Mental Status Examination score, sex, and hippocampal occupancy resulted in an area under curve of 0.905. Application of the composite model to ten randomly selected test groups (nonconverters = 26, converters = 24) predicted MCI conversion with a mean accuracy of 76.2%.DiscussionEarly texture changes are detected in patients with MCI who eventually progress to AD dementia. Therefore, whole-brain 3D texture analysis has the potential to predict progression of patients with MCI to AD.
| S-EPMC6240791 | biostudies-literature
Project description:Optimized magnetic resonance imaging (MRI) features and abnormalities of brain network architectures may allow earlier detection and accurate prediction of the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). In this study, we proposed a classification framework to distinguish MCI converters (MCIc) from MCI non-converters (MCInc) by using a combination of FreeSurfer-derived MRI features and nodal features derived from the thickness network. At the feature selection step, we first employed sparse linear regression with stability selection, for the selection of discriminative features in the iterative combinations of MRI and network measures. Subsequently the top K features of available combinations were selected as optimal features for classification. To obtain unbiased results, support vector machine (SVM) classifiers with nested cross validation were used for classification. The combination of 10 features including those from MRI and network measures attained accuracies of 66.04, 76.39, 74.66, and 73.91% for mixed conversion time, 6, 12, and 18 months before diagnosis of probable AD, respectively. Analysis of the diagnostic power of different time periods before diagnosis of probable AD showed that short-term prediction (6 and 12 months) achieved more stable and higher AUC scores compared with long-term prediction (18 months), with K-values from 1 to 30. The present results suggest that meaningful predictors composed of MRI and network measures may offer the possibility for early detection of progression from MCI to AD.
| S-EPMC4836149 | biostudies-literature
Project description:Accurately identifying the patients that have mild cognitive impairment (MCI) who will go on to develop Alzheimer's disease (AD) will become essential as new treatments will require identification of AD patients at earlier stages in the disease process. Most previous work in this area has centred around the same automated techniques used to diagnose AD patients from healthy controls, by coupling high dimensional brain image data or other relevant biomarker data to modern machine learning techniques. Such studies can now distinguish between AD patients and controls as accurately as an experienced clinician. Models trained on patients with AD and control subjects can also distinguish between MCI patients that will convert to AD within a given timeframe (MCI-c) and those that remain stable (MCI-s), although differences between these groups are smaller and thus, the corresponding accuracy is lower. The most common type of classifier used in these studies is the support vector machine, which gives categorical class decisions. In this paper, we introduce Gaussian process (GP) classification to the problem. This fully Bayesian method produces naturally probabilistic predictions, which we show correlate well with the actual chances of converting to AD within 3 years in a population of 96 MCI-s and 47 MCI-c subjects. Furthermore, we show that GPs can integrate multimodal data (in this study volumetric MRI, FDG-PET, cerebrospinal fluid, and APOE genotype with the classification process through the use of a mixed kernel). The GP approach aids combination of different data sources by learning parameters automatically from training data via type-II maximum likelihood, which we compare to a more conventional method based on cross validation and an SVM classifier. When the resulting probabilities from the GP are dichotomised to produce a binary classification, the results for predicting MCI conversion based on the combination of all three types of data show a balanced accuracy of 74%. This is a substantially higher accuracy than could be obtained using any individual modality or using a multikernel SVM, and is competitive with the highest accuracy yet achieved for predicting conversion within three years on the widely used ADNI dataset.
| S-EPMC3777690 | biostudies-literature
Project description:ObjectiveThe aim of this study was to explore the prognostic values of biomarkers of neurodegeneration as measured by magnetic resonance imaging (MRI) and amyloid burden as measured by amyloid positron emission tomography (PET) in predicting conversion to Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI).MethodsPubMed and EMBASE databases were searched for structural MRI or amyloid PET imaging studies published between January 2000 and July 2014 that reported conversion to AD in patients with MCI. Means and standard deviations or individual numbers of biomarkers with positive or negative status at baseline and corresponding numbers of patients who had progressed to AD at follow-up were retrieved from each study. The effect size of each biomarker was expressed as Hedges's g.ResultsTwenty-four MRI studies and 8 amyloid PET imaging studies were retrieved. 674 of the 1741 participants (39%) developed AD. The effect size for predicting conversion to AD was 0.770 [95% confidence interval (CI) 0.607-0.934] for across MRI and 1.316 (95% CI 0.920-1.412) for amyloid PET imaging (p<0.001). The effect size was 1.256 (95% CI 0.902-1.609) for entorhinal cortex volume from MRI.ConclusionOur study suggests that volumetric MRI measurement may be useful for the early detection of AD.
| S-EPMC5355020 | biostudies-literature
Project description:Alzheimer's Disease (AD) conversion prediction from the mild cognitive impairment (MCI) stage has been a difficult challenge. This study focuses on providing an individualized MCI to AD conversion prediction using a balanced random forest model that leverages clinical data. In order to do this, 383 Early Mild Cognitive Impairment (EMCI) patients were gathered from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Of these patients, 49 would eventually convert to AD (EMCI_C), whereas the remaining 334 did not convert (EMCI_NC). All of these patients were split randomly into training and testing data sets with 95 patients reserved for testing. Nine clinical features were selected, comprised of a mix of demographic, brain volume, and cognitive testing variables. Oversampling was then performed in order to balance the initially imbalanced classes prior to training the model with 1000 estimators. Our results showed that a random forest model was effective (93.6% accuracy) at predicting the conversion of EMCI patients to AD based on these clinical features. Additionally, we focus on explainability by assessing the importance of each clinical feature. Our model could impact the clinical environment as a tool to predict the conversion to AD from a prodromal stage or to identify ideal candidates for clinical trials.
| S-EPMC8084194 | biostudies-literature
Project description:BackgroundProgression of mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia can be predicted by clinical features and a combination of biomarkers may increase the predictive power. In the present study, we investigated whether the combination of olfactory function and plasma neuronal-derived exosome (NDE) Aβ1-42 can best predict progression to AD dementia.Methods87 MCI patients were enrolled and received the cognitive assessment at 2-year and 3-year follow-up to reevaluate cognition. In the meanwhile, 80 healthy controls and 88 AD dementia patients were enrolled at baseline as well to evaluate the diagnose value in cross-section. Olfactory function was evaluated with the sniffin sticks (SS-16) and Aβ1-42 levels in NDEs were determined by ELISA. Logistic regression was performed to evaluate the risk factors for cognitive decline in MCI at 2-year and 3-year revisits.ResultsIn the cross cohort, lower SS-16 scores and higher Aβ1-42 levels in NDEs were found in MCI and AD dementia compared to healthy controls. For the longitudinal set, 8 MCI individuals developed AD dementia within 2 years, and 16 MCI individuals developed AD dementia within 3 years. The two parameter-combination of SS-16 scores and Aβ1-42 level in NDEs showed better prediction in the conversion of MCI to AD dementia at 2-year and 3-year revisit. Moreover, after a 3-year follow-up, SS-16 scores also significantly predicted the conversion to AD dementia, where lower scores were associated with a 10-fold increased risk of developing AD dementia (p = 0.006). Similarly, higher Aβ1-42 levels in NDEs in patients with MCI increased the risk of developing AD dementia by 8.5-fold (p = 0.002).ConclusionA combination of two biomarkers of NDEs (Aβ1-42) and SS-16 predicted the conversion of MCI to AD dementia more accurately in combination. These findings have critical implications for understanding the pathophysiology of AD dementia and for developing preventative treatments for cognitive decline.
| S-EPMC7397685 | biostudies-literature
Project description:BackgroundWhile there is no cure for Alzheimer's disease (AD), early diagnosis and accurate prognosis of AD may enable or encourage lifestyle changes, neurocognitive enrichment, and interventions to slow the rate of cognitive decline. The goal of our study was to develop and evaluate a novel deep learning algorithm to predict mild cognitive impairment (MCI) to AD conversion at three years after diagnosis using longitudinal and whole-brain 3D MRI.MethodsThis retrospective study consisted of 320 normal cognition (NC), 554 MCI, and 237 AD patients. Longitudinal data include T1-weighted 3D MRI obtained at initial presentation with diagnosis of MCI and at 12-month follow up. Whole-brain 3D MRI volumes were used without a priori segmentation of regional structural volumes or cortical thicknesses. MRIs of the AD and NC cohort were used to train a deep learning classification model to obtain weights to be applied via transfer learning for prediction of MCI patient conversion to AD at three years post-diagnosis. Two (zero-shot and fine tuning) transfer learning methods were evaluated. Three different convolutional neural network (CNN) architectures (sequential, residual bottleneck, and wide residual) were compared. Data were split into 75% and 25% for training and testing, respectively, with 4-fold cross validation. Prediction accuracy was evaluated using balanced accuracy. Heatmaps were generated.ResultsThe sequential convolutional approach yielded slightly better performance than the residual-based architecture, the zero-shot transfer learning approach yielded better performance than fine tuning, and CNN using longitudinal data performed better than CNN using a single timepoint MRI in predicting MCI conversion to AD. The best CNN model for predicting MCI conversion to AD at three years after diagnosis yielded a balanced accuracy of 0.793. Heatmaps of the prediction model showed regions most relevant to the network including the lateral ventricles, periventricular white matter and cortical gray matter.ConclusionsThis is the first convolutional neural network model using longitudinal and whole-brain 3D MRIs without extracting regional brain volumes or cortical thicknesses to predict future MCI to AD conversion at 3 years after diagnosis. This approach could lead to early prediction of patients who are likely to progress to AD and thus may lead to better management of the disease.
| S-EPMC8176545 | biostudies-literature
Project description:IntroductionAlzheimer's disease (AD) is the most common form of dementia. Finding biomarkers to prognosticate transition from mild cognitive impairment (MCI) to AD is important to clinical medicine. Promising imaging biomarkers of AD conversion identified so far include atrophy of the cerebral cortex and subcortical gray matter nuclei.MethodsThis study introduces thickness and bending angle of the corpus callosum as a putative white matter marker of MCI to AD conversion. The corpus callosum is computationally less demanding to segment automatically compared to more complicated structures and a subject can be processed in a few minutes. We aimed to demonstrate that callosal shape and thickness measures provide a simple, effective, and accurate prognostication tool in ADNI dataset. Using longitudinal datasets, we classified MCI subjects based on conversion to AD assessed via cognitive testing. We evaluated the classification accuracy of callosal shape features in comparison with the existing "gold standard" cortical thickness and subcortical gray matter volume measures.ResultsThe callosal thickness measures were less accurate in classifying conversion status by cognitive scores compared to gray matter measures for AD.ConclusionsWhile this paper presented a negative result, this method may be more suitable for a disease of the white matter.
| S-EPMC6305917 | biostudies-literature
Project description:Mild cognitive impairment (MCI) is the prodromal stage of Alzheimer's disease (AD). Identifying MCI subjects who are at high risk of converting to AD is crucial for effective treatments. In this study, a deep learning approach based on convolutional neural networks (CNN), is designed to accurately predict MCI-to-AD conversion with magnetic resonance imaging (MRI) data. First, MRI images are prepared with age-correction and other processing. Second, local patches, which are assembled into 2.5 dimensions, are extracted from these images. Then, the patches from AD and normal controls (NC) are used to train a CNN to identify deep learning features of MCI subjects. After that, structural brain image features are mined with FreeSurfer to assist CNN. Finally, both types of features are fed into an extreme learning machine classifier to predict the AD conversion. The proposed approach is validated on the standardized MRI datasets from the Alzheimer's Disease Neuroimaging Initiative (ADNI) project. This approach achieves an accuracy of 79.9% and an area under the receiver operating characteristic curve (AUC) of 86.1% in leave-one-out cross validations. Compared with other state-of-the-art methods, the proposed one outperforms others with higher accuracy and AUC, while keeping a good balance between the sensitivity and specificity. Results demonstrate great potentials of the proposed CNN-based approach for the prediction of MCI-to-AD conversion with solely MRI data. Age correction and assisted structural brain image features can boost the prediction performance of CNN.
| S-EPMC6231297 | biostudies-literature
Project description:Background: Early prediction of disease progression in patients with amnestic mild cognitive impairment (aMCI) is important for early diagnosis and intervention of Alzheimer's disease (AD). Previous brain network studies have suggested topological disruptions of the brain connectome in aMCI patients. However, whether brain connectome markers at baseline can predict longitudinal conversion from aMCI to AD remains largely unknown. Methods: In this study, 52 patients with aMCI and 26 demographically matched healthy controls from a longitudinal cohort were evaluated. During 2 years of follow-up, 26 patients with aMCI were retrospectively classified as aMCI converters and 26 patients remained stable as aMCI non-converters based on whether they were subsequently diagnosed with AD. For each participant, diffusion tensor imaging at baseline and deterministic tractography were used to map the whole-brain white matter structural connectome. Graph theoretical analysis was applied to investigate the convergent and divergent connectivity patterns of structural connectome between aMCI converters and non-converters. Results: Disrupted topological organization of the brain structural connectome were identified in both aMCI converters and non-converters. More severe disruptions of structural connectivity in aMCI converters compared with non-converters were found, especially in the default-mode network regions and connections. Finally, a support vector machine-based classification demonstrated the good discriminative ability of structural connectivity in differentiating aMCI patients from controls with an accuracy of 98%, and in discriminating converters from non-converters with an accuracy of 81%. Conclusion: Our study provides potential structural connectome/connectivity-based biomarkers for predicting disease progression in aMCI, which is important for the early diagnosis of AD.
| S-EPMC6335339 | biostudies-literature