Random forest model for feature-based Alzheimer's disease conversion prediction from early mild cognitive impairment subjects.
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ABSTRACT:
SUBMITTER: Velazquez M
PROVIDER: S-EPMC8084194 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Random Survival Forests (RSF) has recently showed better performance than statistical survival methods as Cox proportional hazard (CPH) in predicting conversion risk from mild cognitive impairment (MCI) to Alzheimer's disease (AD). However, RSF application in real-world clinical setting is still limited due to its black-box nature.For this reason, we aimed at providing a comprehensive study of RSF explainability with SHapley Additive exPlanations (SHAP) on biomarkers of stable and progressive patients (sMCI and pMCI) from Alzheimer's Disease Neuroimaging Initiative. We evaluated three global explanations-RSF feature importance, permutation importance and SHAP importance-and we quantitatively compared them with Rank-Biased Overlap (RBO). Moreover, we assessed whether multicollinearity among variables may perturb SHAP outcome. Lastly, we stratified pMCI test patients in high, medium and low risk grade, to investigate individual SHAP explanation of one pMCI patient per risk group.We confirmed that RSF had higher accuracy (0.890) than CPH (0.819), and its stability and robustness was demonstrated by high overlap (RBO > 90%) between feature rankings within first eight features. SHAP local explanations with and without correlated variables had no substantial difference, showing that multicollinearity did not alter the model. FDG, ABETA42 and HCI were the first important features in global explanations, with the highest contribution also in local explanation. FAQ, mPACCdigit, mPACCtrailsB and RAVLT immediate had the highest influence among all clinical and neuropsychological assessments in increasing progression risk, as particularly evident in pMCI patients' individual explanation. In conclusion, our findings suggest that RSF represents a useful tool to support clinicians in estimating conversion-to-AD risk and that SHAP explainer boosts its clinical utility with intelligible and interpretable individual outcomes that highlights key features associated with AD prognosis.
| S-EPMC10657350 | biostudies-literature
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: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: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: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:BACKGROUND:Predicting progression from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD) is an utmost open issue in AD-related research. Neuropsychological assessment has proven to be useful in identifying MCI patients who are likely to convert to dementia. However, the large battery of neuropsychological tests (NPTs) performed in clinical practice and the limited number of training examples are challenge to machine learning when learning prognostic models. In this context, it is paramount to pursue approaches that effectively seek for reduced sets of relevant features. Subsets of NPTs from which prognostic models can be learnt should not only be good predictors, but also stable, promoting generalizable and explainable models. METHODS:We propose a feature selection (FS) ensemble combining stability and predictability to choose the most relevant NPTs for prognostic prediction in AD. First, we combine the outcome of multiple (filter and embedded) FS methods. Then, we use a wrapper-based approach optimizing both stability and predictability to compute the number of selected features. We use two large prospective studies (ADNI and the Portuguese Cognitive Complaints Cohort, CCC) to evaluate the approach and assess the predictive value of a large number of NPTs. RESULTS:The best subsets of features include approximately 30 and 20 (from the original 79 and 40) features, for ADNI and CCC data, respectively, yielding stability above 0.89 and 0.95, and AUC above 0.87 and 0.82. Most NPTs learnt using the proposed feature selection ensemble have been identified in the literature as strong predictors of conversion from MCI to AD. CONCLUSIONS:The FS ensemble approach was able to 1) identify subsets of stable and relevant predictors from a consensus of multiple FS methods using baseline NPTs and 2) learn reliable prognostic models of conversion from MCI to AD using these subsets of features. The machine learning models learnt from these features outperformed the models trained without FS and achieved competitive results when compared to commonly used FS algorithms. Furthermore, the selected features are derived from a consensus of methods thus being more robust, while releasing users from choosing the most appropriate FS method to be used in their classification task.
| S-EPMC6299964 | 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
Project description:BACKGROUND:Centenarians with normal cognitive function have a "longevity phenotype" characterized by large low-density lipoproteins (LDL) and high-density lipoproteins (HDL) and low incidence of metabolic syndrome, hypertension, and cognitive impairment. Alzheimer's disease (AD) is associated with a number of cardiovascular risk factors, but it is not known if they have or lack the "longevity phenotype". OBJECTIVE:The study was designed to determine LDL size and body fat content and distribution in subjects with mild cognitive impairment (MCI) and AD. RESULTS:Fifty-eight persons with MCI or AD (cases) and 42 control subjects of similar age had measurement of LDL size and lipoprotein lipids after a 12 h fast and analysis of body composition by dual x-ray absorptiometry. Cases had small LDL size more often than controls (73% versus 66%) associated with significantly higher triglycerides, lower HDL cholesterol, and higher triglyceride/HDL cholesterol ratio (p ? 0.02). Cases with large LDL had a better lipoprotein profile than those with small LDL. Cases and controls had similar percent body fat, fat index, and lean mass index. Forty-seven percent of cases and 39% of controls were obese. CONCLUSION:The prevalence of small LDL phenotype in MCI and AD cases contrasts with the "longevity phenotype" reported for centenarians with preserved cognitive function. The small LDL phenotype is an atherogenic lipoprotein profile found in metabolic syndrome, type 2 diabetes, and insulin resistance. It is now also reported in persons with MCI and AD.
| S-EPMC4082186 | biostudies-literature
Project description:ObjectiveTo estimate the incidence of psychotic symptoms in Alzheimer's disease.MethodsThe study consists of 776 elderly subjects presenting to the Alzheimer Disease Research Center at the University of Pittsburgh (Pittsburgh, Pennsylvania) between May 9, 2000, and August 19, 2014. All participants were diagnosed with mild cognitive impairment (National Institute on Aging-Alzheimer's Association workgroup criteria) or possible or probable Alzheimer's disease (National Institute of Neurologic and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria) and were without psychosis at entry. Psychotic symptoms were evaluated using the Consortium to Establish a Registry for Alzheimer's Disease Behavioral Rating Scale every 6 months. One-, 3- and 5-year cumulative incidences of psychosis were calculated.ResultsThe 1-year psychosis incidence was 10% (95% CI, 8%-12%), and this annual rate remained remarkably consistent at 3 and 5 years. Psychosis incidence was related to cognitive status at all time points. However, the incidence rate reached a plateau during the disease course. Cumulative psychosis incidence at 5 years was 61% (95% CI, 52%-69%) in individuals with moderate to severe Alzheimer's disease, not statistically significantly different from the cumulative incidence at 3 years in this group, which was 48% (95% CI, 40%-55%) or from the 5-year incidence in individuals who entered the study with mild Alzheimer's disease, which was 48% (95% CI, 41%-56%).ConclusionsPsychosis in Alzheimer's disease has been associated with a number of adverse clinical outcomes. We provide estimates of the risk of psychosis onset within clinically defined subgroups of individuals, a tool clinicians can use in treatment planning. Anticipating which subjects are at high risk for psychosis and the poor outcomes associated with it can help with family education and support decisions to implement nonpharmacologic strategies that may reduce or prevent symptoms.
| S-EPMC5372698 | biostudies-literature
Project description:Alzheimer's Disease is a complex, multifactorial, and comorbid condition. The asymptomatic behavior in the early stages makes the identification of the disease onset particularly challenging. Mild cognitive impairment (MCI) is an intermediary stage between the expected decline of normal aging and the pathological decline associated with dementia. The identification of risk factors for MCI is thus sorely needed. Self-reported personal information such as age, education, income level, sleep, diet, physical exercise, etc. is called to play a key role not only in the early identification of MCI but also in the design of personalized interventions and the promotion of patients empowerment. In this study, we leverage a large longitudinal study on healthy aging in Spain, to identify the most important self-reported features for future conversion to MCI. Using machine learning (random forest) and permutation-based methods we select the set of most important self-reported variables for MCI conversion which includes among others, subjective cognitive decline, educational level, working experience, social life, and diet. Subjective cognitive decline stands as the most important feature for future conversion to MCI across different feature selection techniques.
| S-EPMC7692490 | biostudies-literature