Detection of changes in micrographia as a manifestation of symptomatic progression or therapeutic response in Parkinson's disease (PD) is challenging as such changes can be subtle. A computerized toolkit based on quantitative analysis of handwriting samples would be valuable as it could supplement and support clinical assessments, help monitor micrographia, and link it to PD. Such a toolkit would be especially useful if it could detect subtle yet relevant changes in handwriting morphology, thus enhancing resolution of the detection procedure. This would be made possible by developing a set of metrics sensitive enough to detect and discern micrographia with specificity. Several metrics that are sensitive to the characteristics of micrographia were developed, with minimal sensitivity to confounding handwriting artifacts. These metrics capture character size-reduction, ink utilization, and pixel density within a writing sample from left to right. They are used here to “score” handwritten signatures of 12 different individuals corresponding to healthy and symptomatic PD conditions, and sample control signatures that had been artificially reduced in size for comparison purposes. Moreover, metric analyses of samples from ten of the 12 individuals for which clinical diagnosis time is known show considerable informative variations when applied to static signature samples obtained before and after diagnosis. In particular, a measure called pixel density variation showed statistically significant differences (  $p   ) between two comparison groups of remote signature recordings: earlier versus recent, based on independent and paired  t -test analyses on a total of 40 signature samples. The quantitative framework developed here has the potential to be used in future controlled experiments to study micrographia and links to PD from various aspects, including monitoring and assessment of applied interventions and treatments. The inherent value in this methodology is further enhanced by its reliance solely on static signatures, not requiring dynamic sampling with specialized equipment.
['Naiqian Zhi', 'Beverly K. Jaeger', 'Andrew Gouldstone', 'Rifat Sipahi', 'Samuel Frank']
Toward Monitoring Parkinson's Through Analysis of Static Handwriting Samples: A Quantitative Analytical Framework