Learning classification models of cognitive conditions from subtle behaviors in the digital Clock Drawing Test

The Clock Drawing Test—a simple pencil and paper test—has been used for more than 50 years as a screening tool to differentiate normal individuals from those with cognitive impairment, and has proven useful in helping to diagnose cognitive dysfunction associated with neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and other dementias and conditions. We have been administering the test using a digitizing ballpoint pen that reports its position with considerable spatial and temporal precision, making available far more detailed data about the subject’s performance. Using pen stroke data from these drawings categorized by our software, we designed and computed a large collection of features, then explored the tradeoffs in performance and interpretability in classifiers built using a number of different subsets of these features and a variety of different machine learning techniques. We used traditional machine learning methods to build prediction models that achieve high accuracy. We operationalized widely used manual scoring systems so that we could use them as benchmarks for our models. We worked with clinicians to define guidelines for model interpretability, and constructed sparse linear models and rule lists designed to be as easy to use as scoring systems currently used by clinicians, but more accurate. While our models will require additional testing for validation, they offer the possibility of substantial improvement in detecting cognitive impairment earlier than currently possible, a development with considerable potential impact in practice.

[1]  Thorsten Joachims,et al.  Making large scale SVM learning practical , 1998 .

[2]  Lu Tian,et al.  Adaptive index models for marker-based risk stratification. , 2011, Biostatistics.

[3]  Cynthia Rudin,et al.  Falling Rule Lists , 2014, AISTATS.

[4]  Roberto Alves Lourenço,et al.  The Clock Drawing Test: performance among elderly with low educational level. , 2008, Revista brasileira de psiquiatria.

[5]  T. Evgeniou,et al.  Disjunctions of Conjunctions, Cognitive Simplicity, and Consideration Sets , 2010 .

[6]  G Coppini,et al.  Detection of single and clustered microcalcifications in mammograms using fractals models and neural networks. , 2004, Medical engineering & physics.

[7]  R. Haaxma,et al.  The mental status examination in neurology. F. A. Davis Company (1977), 182 pp., Price Fl. 24,25 , 1978 .

[8]  J. Morris,et al.  The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[9]  P J Manos,et al.  The Ten Point Clock Test: A Quick Screen and Grading Method for Cognitive Impairment in Medical and Surgical Patients , 1994, International journal of psychiatry in medicine.

[10]  Wei-Yin Loh,et al.  Classification and regression trees , 2011, WIREs Data Mining Knowl. Discov..

[11]  D. Basic,et al.  A comparison of five clock scoring methods using ROC (receiver operating characteristic) curve analysis , 2001, International journal of geriatric psychiatry.

[12]  Leo Breiman,et al.  Random Forests , 2001, Machine Learning.

[13]  J. Cummings,et al.  The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment , 2005, Journal of the American Geriatrics Society.

[14]  Ella S. Franklin,et al.  Learning Data-Driven Patient Risk Stratification Models for Clostridium difficile , 2014, Open forum infectious diseases.

[15]  Cynthia Rudin,et al.  Supersparse Linear Integer Models for Predictive Scoring Systems , 2013, AAAI.

[16]  Cynthia Rudin,et al.  Supersparse linear integer models for optimized medical scoring systems , 2015, Machine Learning.

[17]  Bart Baesens,et al.  Comprehensible Credit Scoring Models Using Rule Extraction from Support Vector Machines , 2007, Eur. J. Oper. Res..

[18]  M. Rich,et al.  Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. , 2001, JAMA.

[19]  J. Friedman Greedy function approximation: A gradient boosting machine. , 2001 .

[20]  E. Petricoin,et al.  SELDI-TOF-based serum proteomic pattern diagnostics for early detection of cancer. , 2004, Current opinion in biotechnology.

[21]  Stephen T. C. Wong,et al.  Cancer classification and prediction using logistic regression with Bayesian gene selection , 2004, J. Biomed. Informatics.

[22]  B. L. Beattie,et al.  The Clock Test: A Sensitive Measure To Differentiate Normal Elderly from Those with Alzheimer Disease , 1992, Journal of the American Geriatrics Society.

[23]  J. Grafman,et al.  Clock Drawing in Alzheimer's Disease , 1989, Journal of the American Geriatrics Society.

[24]  Huan Liu,et al.  Advancing Feature Selection Research − ASU Feature Selection Repository , 2010 .

[25]  Joel T. Andrade Handbook of Violence Risk Assessment and Treatment: New Approaches for Mental Health Professionals , 2009 .

[26]  O. Almkvist,et al.  Neuropsychological features of mild cognitive impairment and preclinical Alzheimer's disease , 2003, Acta neurologica Scandinavica. Supplementum.

[27]  Shu Zheng,et al.  Application of serum protein fingerprinting coupled with artificial neural network model in diagnosis of hepatocellular carcinoma. , 2005, Chinese medical journal.

[28]  J. Ross Quinlan,et al.  C4.5: Programs for Machine Learning , 1992 .

[29]  Hongmao Sun,et al.  An Accurate and Interpretable Bayesian Classification Model for Prediction of hERG Liability , 2006, ChemMedChem.

[30]  Cynthia Rudin,et al.  Supersparse Linear Integer Models for Interpretable Classification , 2013, 1306.6677.

[31]  Cynthia Rudin,et al.  Bayesian Rule Sets for Interpretable Classification , 2016, 2016 IEEE 16th International Conference on Data Mining (ICDM).

[32]  Stephen P. Boyd,et al.  A Mathematical Model for Interpretable Clinical Decision Support with Applications in Gynecology , 2012, PloS one.

[33]  M. Mendez,et al.  Development of Scoring Criteria for the Clock Drawing Task in Alzheimer's Disease , 1992, Journal of the American Geriatrics Society.

[34]  Yimin Liu,et al.  Or's of And's for Interpretable Classification, with Application to Context-Aware Recommender Systems , 2015, ArXiv.

[35]  George Hripcsak,et al.  Analysis of Variance of Cross-Validation Estimators of the Generalization Error , 2005, J. Mach. Learn. Res..

[36]  Bart Baesens,et al.  Building comprehensible customer churn prediction models with advanced rule induction techniques , 2011, Expert Syst. Appl..

[37]  M. Prince,et al.  The Global Impact of Dementia 2013-2050 , 2013 .

[38]  Randall Davis,et al.  THink: Inferring Cognitive Status from Subtle Behaviors , 2014, AI Mag..

[39]  N Butters,et al.  Screening for dementia of the alzheimer type in the community: the utility of the Clock Drawing Test. , 1996, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[40]  Ellen Yi-Luen Do,et al.  Using Pen-Based Computing in Technology for Health , 2011, HCI.

[41]  Huan Liu,et al.  Advancing feature selection research , 2010 .

[42]  S. Borson,et al.  The Mini‐Cog: a cognitive ‘vital signs’ measure for dementia screening in multi‐lingual elderly , 2000, International journal of geriatric psychiatry.

[43]  Sudha Seshadri,et al.  The Framingham Heart Study Clock Drawing Performance: Normative Data from the Offspring Cohort , 2013, Experimental aging research.

[44]  L. Fratiglioni,et al.  Mild cognitive impairment: a concept in evolution , 2014, Journal of internal medicine.

[45]  Alex Alves Freitas,et al.  On the Importance of Comprehensible Classification Models for Protein Function Prediction , 2010, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[46]  Pei-Ning Wang,et al.  The Three-Item Clock-Drawing Test: A Simplified Screening Test for Alzheimer’s Disease , 2002, European Neurology.

[47]  H. Tuokko,et al.  A comparison of alternative approaches to the scoring of clock drawing. , 2000, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[48]  D. Royall,et al.  CLOX: an executive clock drawing task , 1998, Journal of neurology, neurosurgery, and psychiatry.

[49]  D. Basic,et al.  Accuracy of the Clock Drawing Test for Detecting Dementia in a Multicultural Sample of Elderly Australian Patients , 2002, International Psychogeriatrics.

[50]  Chih-Jen Lin,et al.  LIBLINEAR: A Library for Large Linear Classification , 2008, J. Mach. Learn. Res..

[51]  Michael S. Okun,et al.  Clock Drawing in the Montreal Cognitive Assessment: Recommendations for Dementia Assessment , 2011, Dementia and Geriatric Cognitive Disorders.

[52]  Kenneth M. Adams,et al.  The Boston Process Approach to Neuropsychological Assessment , 2014 .

[53]  Jean-Philippe Vert,et al.  The Influence of Feature Selection Methods on Accuracy, Stability and Interpretability of Molecular Signatures , 2011, PloS one.

[54]  Marcel Dettling,et al.  BagBoosting for tumor classification with gene expression data , 2004, Bioinform..

[55]  Randall Davis,et al.  Digital Clock Drawing: Differentiating “Thinking” versus “Doing” in Younger and Older Adults with Depression , 2014, Journal of the International Neuropsychological Society.

[56]  Annachiara Cagnin,et al.  Vascular Cognitive Disorder. A Biological and Clinical Overview , 2010, Neurochemical Research.

[57]  G. Wells,et al.  Clock Drawing: A Neuropsychological Analysis , 1995 .

[58]  Ellen Yi-Luen Do,et al.  Computational clock drawing analysis for cognitive impairment screening , 2010, TEI.

[59]  K. Shulman,et al.  Clock‐drawing and dementia in the community: A longitudinal study , 1993 .

[60]  K. Langa,et al.  Prevalence of Dementia in the United States: The Aging, Demographics, and Memory Study , 2007, Neuroepidemiology.

[61]  Isabelle Rouleau,et al.  Quantitative and qualitative analyses of clock drawings in Alzheimer's and Huntington's disease , 1992, Brain and Cognition.

[62]  G. Wolf-Klein,et al.  Screening for Alzheimer's Disease by Clock Drawing , 1989, Journal of the American Geriatrics Society.

[63]  Cynthia Rudin,et al.  Interpretable classifiers using rules and Bayesian analysis: Building a better stroke prediction model , 2015, ArXiv.

[64]  Christian Borgelt,et al.  An implementation of the FP-growth algorithm , 2005 .

[65]  Jenna Wiens,et al.  Active Learning Applied to Patient-Adaptive Heartbeat Classification , 2010, NIPS.

[66]  Cynthia Rudin,et al.  Methods and Models for Interpretable Linear Classification , 2014, ArXiv.

[67]  Edward H. Shortliffe,et al.  Production Rules as a Representation for a Knowledge-Based Consultation Program , 1977, Artif. Intell..

[68]  S. Birge,et al.  Clock Completion: An Objective Screening Test for Dementia , 1993, Journal of the American Geriatrics Society.

[69]  Bart Baesens,et al.  Comprehensible Credit Scoring Models Using Rule Extraction from Support Vector Machines , 2006 .

[70]  Nick C Fox,et al.  The Diagnosis of Mild Cognitive Impairment due to Alzheimer’s Disease: Recommendations from the National Institute on Aging-Alzheimer’s Association Workgroups on Diagnostic Guidelines for Alzheimer’s Disease , 2011 .

[71]  Fuhui Long,et al.  Feature selection based on mutual information criteria of max-dependency, max-relevance, and min-redundancy , 2003, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[72]  D. Libon,et al.  Clock drawing as an assessment tool for dementia. , 1993, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[73]  L. Lam,et al.  Clock-face drawing, reading and setting tests in the screening of dementia in Chinese elderly adults. , 1998, The journals of gerontology. Series B, Psychological sciences and social sciences.