# Dynamic Handwriting Analysis for Neurodegenerative Disease Assessment: A Literary Review
## 1 Introduction  
### Motivations and Purposes  
Neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD), affect the structure and functions of brain regions resulting in a progressive cognitive, functional, and behavioural decline. PD is caused by the degeneration of the dopaminergic nigrostriatal neurons of the basal ganglia, resulting primarily in motor deficits:kinesia, bradykinesia, rigidity, and tremor are typically observed [1]. AD, on the other hand, is characterized by short-term memory loss in its early stages, followed by a progressive decline in other cognitive and behavioral functions as the disease advances: therefore, the dominant feature of AD is mainly of cognitive nature [2]. Unfortunately, in the case of signs of brain degeneration, there is no cure and the gradual decline of the patient can only be somehow managed during disease progression. However, an early diagnosis of neurodegeneration would be crucial in the perspective of proper medical treatment to be administered and for improving the quality of life of the patient. In addition, the assessment of signs and manifestations of a specific disease is useful for its diagnostic differentiation with respect to similar disorders and for monitoring and tracking its progression as the disease advances. To this end, a special attention is devoted to mild cognitive impairment (MCI) signs, as an individual with MCI is at a high risk of developing dementia, especially of the Alzheimer's type [3]. The evaluation of the patient's clinical status and their responsiveness to medication is typically achieved via a clinical workup including a thorough medical history, a neuropsychological test battery, and rating scales. Mini Mental State Examination (MMSE) [4], for example, is used extensively to assess cognitive impairment. However, there is still no one certain test to determine if someone is affected by a neurodegenerative disorder and a precise diagnosis is possible only _postmortem_. Getting a reliable diagnosis can require months, and symptoms need to be constantly monitored. In addition, the traditional evaluations depend to some extent on the experience of the clinician performing the assessment, and this makes the determination of the exact type of disease as well as its degree of severity difficult. For these reasons, identifying accurate _biomarkers_ for early and differential diagnosis, prognosis, and response to therapy is a primary goal of the research on neurodegenerative disorders today (e.g., References [5; 6]). Changes in the brain caused by neurodegeneration--brain atrophy, neuronal loss, synaptic dysfunction, etc.--particularly result in a dysfunction of the motor system as well as in impairments of the performance of previously learned motor skills. Therefore, a key role in the context of neurodegenerative diseases assessment can be assumed by handwriting. Handwriting, in fact, is a complex activity entailing motor as well as cognitive components [7], of which the changes are promising as a _biomarker_ for disease assessment. First, handwriting exercises are already part of neuropsychological test batteries. For instance, the Clock Drawing Test (CDT), which is part of the Mini-Cog test, requires the patient to draw a clock from memory and to put the hands at a given time: the goal is to evaluate executive functions [8]. Second, it is worth noting that, in several studies, researchers examined handwriting difficulties by using writing tests: their results showed that these difficulties are well correlated to the disease severity as well as the concomitant cognitive impairment. For example, in the seminal paper by [PERSON] et al. [9], it was pointed out how micrographia, which is an abnormally small writing typically associated with PD, can be easily detected by simple pen-and-paper exercises. Other studies, e.g., References [10; 11], used analogous tasks and found that agraphia, which encompasses a progressive disorganization of the various components of handwriting, is an early symptom of AD.