RESUMEN
Biomarkers for Alzheimer's disease (AD) diagnosis do not always correlate reliably with cognitive symptoms, making clinical diagnosis inconsistent. In this study, the performance of a graphical neural network (GNN) classifier based on data-driven diagnostic classes from unsupervised clustering on heterogeneous data is compared to the performance of a classifier using clinician diagnosis as an outcome. Unsupervised clustering on tau-positron emission tomography (PET) and cognitive and functional assessment data was performed. Five clusters embedded in a non-linear uniform manifold approximation and project (UMAP) space were identified. The individual clusters revealed specific feature characteristics with respect to clinical diagnosis of AD, gender, family history, age, and underlying neurological risk factors (NRFs). In particular, one cluster comprised mainly diagnosed AD cases. All cases within this cluster were re-labelled AD cases. The re-labelled cases are characterized by high cerebrospinal fluid amyloid beta (CSF Aß) levels at a younger age, even though Aß data was not used for clustering. A GNN model was trained using the re-labelled data with a multiclass area-under-the-curve (AUC) of 95.2%, higher than the AUC of a GNN trained on clinician diagnosis (91.7%; p = 0.02). Overall, our work suggests that more objective cluster-based diagnostic labels combined with GNN classification may have value in clinical risk stratification and diagnosis of AD.
RESUMEN
Dementia with Lewy Bodies (DLB) is the second most common form of dementia, but diagnostic markers for DLB can be expensive and inaccessible, and many cases of DLB are undiagnosed. This work applies machine learning techniques to determine the feasibility of distinguishing DLB from Alzheimer's Disease (AD) using heterogeneous data features. The Repeated Incremental Pruning to Produce Error Reduction (RIPPER) algorithm was first applied using a Leave-One-Out Cross-Validation protocol to a dataset comprising DLB and AD cases. Then, interpretable association rule-based diagnostic classifiers were obtained for distinguishing DLB from AD. The various diagnostic classifiers generated by this process had high accuracy over the whole dataset (mean accuracy of 94%). The mean accuracy in classifying their out-of-sample case was 80.5%. Every classifier generated consisted of very simple structure, each using 1-2 classification rules and 1-3 data features. As a group, the classifiers were heterogeneous and used several different data features. In particular, some of the classifiers used very simple and inexpensive diagnostic features, yet with high diagnostic accuracy. This work suggests that opportunities may exist for incorporating accessible diagnostic assessments while improving diagnostic rate for DLB. Clinical Relevance- Simple and interpretable high-performing machine learning algorithms identified a variety of readily available clinical assessments for differential diagnosis of dementia offering the opportunities to incorporate various simple and inexpensive screening tests for DLB and addressing the problem of DLB underdiagnosis.
Asunto(s)
Enfermedad de Alzheimer , Enfermedad por Cuerpos de Lewy , Enfermedad de Alzheimer/diagnóstico , Diagnóstico Diferencial , Estudios de Factibilidad , Humanos , Enfermedad por Cuerpos de Lewy/diagnóstico , Aprendizaje AutomáticoRESUMEN
Current machine learning techniques for dementia diagnosis often do not take into account real-world practical constraints, which may include, for example, the cost of diagnostic assessment time and financial budgets. In this work, we built on previous cost-sensitive feature selection approaches by generalising to multiple cost types, while taking into consideration that stakeholders attempting to optimise the dementia care pathway might face multiple non-fungible budget constraints. Our new optimisation algorithm involved the searching of cost-weighting hyperparameters while constrained by total budgets. We then provided a proof of concept using both assessment time cost and financial budget cost. We showed that budget constraints could control the feature selection process in an intuitive and practical manner, while adjusting the hyperparameter increased the range of solutions selected by feature selection. We further showed that our budget-constrained cost optimisation framework could be implemented in a user-friendly graphical user interface sandbox tool to encourage non-technical users and stakeholders to adopt and to further explore and audit the model - a humans-in-the-loop approach. Overall, we suggest that setting budget constraints initially and then fine tuning the cost-weighting hyperparameters can be an effective way to perform feature selection where multiple cost constraints exist, which will in turn lead to more realistic optimising and redesigning of dementia diagnostic assessments. Clinical Relevance-By optimising diagnostic accuracy against various costs (e.g. assessment administration time and financial budget) predictive yet practical dementia diagnostic assessments can be redesigned to suit clinical use.
Asunto(s)
Enfermedad de Alzheimer , Algoritmos , Enfermedad de Alzheimer/diagnóstico , Humanos , Aprendizaje AutomáticoRESUMEN
OBJECTIVE: Despite the potential of machine learning techniques to improve dementia diagnostic processes, research outcomes are often not readily translated to or adopted in clinical practice. Importantly, the time taken to administer diagnostic assessment has yet to be taken into account in feature-selection based optimisation for dementia diagnosis. We address these issues by considering the impact of assessment time as a practical constraint for feature selection of cognitive and functional assessments in Alzheimer's disease diagnosis. METHODS: We use three different feature selection algorithms to select informative subsets of dementia assessment items from a large open-source dementia dataset. We use cost-sensitive feature selection to optimise our feature selection results for assessment time as well as diagnostic accuracy. To encourage clinical adoption and further evaluation of our proposed accuracy-vs-cost optimisation algorithms, we also implement a sandbox-like toolbox with graphical user interface to evaluate user-chosen subsets of assessment items. RESULTS: We find that there are subsets of accuracy-cost optimised assessment items that can perform better in terms of diagnostic accuracy and/or total assessment time than most other standard assessments. DISCUSSION: Overall, our analysis and accompanying sandbox tool can facilitate clinical users and other stakeholders to apply their own domain knowledge to analyse and decide which dementia diagnostic assessment items are useful, and aid the redesigning of dementia diagnostic assessments. Clinical Impact (Clinical Research): By optimising diagnostic accuracy and assessment time, we redesign predictive and efficient dementia diagnostic assessments and develop a sandbox interface to facilitate evaluation and testing by clinicians and non-specialists.
Asunto(s)
Enfermedad de Alzheimer , Demencia , Enfermedad de Alzheimer/diagnóstico , Demencia/diagnóstico , Progresión de la Enfermedad , Humanos , Sensibilidad y EspecificidadRESUMEN
Accurate computational models for clinical decision support systems require clean and reliable data but, in clinical practice, data are often incomplete. Hence, missing data could arise not only from training datasets but also test datasets which could consist of a single undiagnosed case, an individual. This work addresses the problem of extreme missingness in both training and test data by evaluating multiple imputation and classification workflows based on both diagnostic classification accuracy and computational cost. Extreme missingness is defined as having â¼50% of the total data missing in more than half the data features. In particular, we focus on dementia diagnosis due to long time delays, high variability, high attrition rates and lack of practical data imputation strategies in its diagnostic pathway. We identified and replicated the extreme missingness structure of data from a real-world memory clinic on a larger open dataset, with the original complete data acting as ground truth. Overall, we found that computational cost, but not accuracy, varies widely for various imputation and classification approaches. Particularly, we found that iterative imputation on the training dataset combined with a reduced-feature classification model provides the best approach, in terms of speed and accuracy. Taken together, this work has elucidated important factors to be considered when developing a predictive model for a dementia diagnostic support system.
Asunto(s)
Demencia , Recolección de Datos , Demencia/diagnóstico , HumanosRESUMEN
Background: Systems Medicine is a novel approach to medicine, that is, an interdisciplinary field that considers the human body as a system, composed of multiple parts and of complex relationships at multiple levels, and further integrated into an environment. Exploring Systems Medicine implies understanding and combining concepts coming from diametral different fields, including medicine, biology, statistics, modeling and simulation, and data science. Such heterogeneity leads to semantic issues, which may slow down implementation and fruitful interaction between these highly diverse fields. Methods: In this review, we collect and explain more than100 terms related to Systems Medicine. These include both modeling and data science terms and basic systems medicine terms, along with some synthetic definitions, examples of applications, and lists of relevant references. Results: This glossary aims at being a first aid kit for the Systems Medicine researcher facing an unfamiliar term, where he/she can get a first understanding of them, and, more importantly, examples and references for digging into the topic.
RESUMEN
BACKGROUND: Dementia is caused by a variety of neurodegenerative diseases and is associated with a decline in memory and other cognitive abilities, while inflicting an enormous socioeconomic burden. The complexity of dementia and its associated comorbidities presents immense challenges for dementia research and care, particularly in clinical decision-making. MAIN BODY: Despite the lack of disease-modifying therapies, there is an increasing and urgent need to make timely and accurate clinical decisions in dementia diagnosis and prognosis to allow appropriate care and treatment. However, the dementia care pathway is currently suboptimal. We propose that through computational approaches, understanding of dementia aetiology could be improved, and dementia assessments could be more standardised, objective and efficient. In particular, we suggest that these will involve appropriate data infrastructure, the use of data-driven computational neurology approaches and the development of practical clinical decision support systems. We also discuss the technical, structural, economic, political and policy-making challenges that accompany such implementations. CONCLUSION: The data-driven era for dementia research has arrived with the potential to transform the healthcare system, creating a more efficient, transparent and personalised service for dementia.