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.

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.

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 ~50% 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.

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.

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. Many popular methods of handling missing data are unsuitable for handling such missing test data. This work addresses the problem by evaluating multiple imputation and classification workflows based not only on diagnostic classification accuracy but also computational cost. 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 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, compromising speed and accuracy. Taken together, this work has elucidated important factors to be considered when developing or maintaining a dementia diagnostic support system, which can be generalized to other clinical or medical domains, particularly with extreme data missingness.