We thank Professor Hans-Leo Teulings from Neuroscript LLD for the digital technology support.
This study was supported by the Wu Jieping Foundation (Grant No.: 320.6750.18456).

Our study was approved by the Academic Ethics Committee of the Biological Sciences Division of the Chinese PLA General Hospital in Beijing, China.
1. General aspects of method development
<ol>
	<li>Use a USB digitizer (e.g., Wacom Cintiq Pro 16) and a handheld stylus pen for the handwriting movements. The detailed specifications of the digitizer are as follows: external dimensions (width x depth x height) 410 x 265 x 17.5 mm, spatial resolution 3840 x 2160 dots, pixel size 0.090 x 0.090 mm, ...

<ol>
	<li>Werner, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Handwriting+process+variables+discriminating+mild+Alzheimer's+disease+and+mild+cognitive+impairment.">Handwriting process variables discriminating mild Alzheimer's disease and mild cognitive impairment.</a> Journals of Gerontology. 61 (4), 228-236 (2006).</li><li>Kawa, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spatial+and+dynamical+handwriting+analysis+in+mild+cognitive+impairment.">Spatial and dynamical handwriting analysis in mild cognitive impairment.</a> Computers in Biology and Medicine. 82, 21-28 (2017).</li><li>De Paula, J. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impairment+of+fine+motor+dexterity+in+mild+cognitive+impairment+and+Alzheimer's+disease+dementia:+association+with+activities+of+daily+living.">Impairment of fine motor dexterity in mild cognitive impairment and Alzheimer's disease dementia: association with activities of daily living.</a> Revista Brasilra De Psiquiatria. 38 (3), 235-238 (2016).</li><li>Takehiko, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Combined+effects+of+mild+cognitive+impairment+and+slow+gait+on+risk+of+dementia.">Combined effects of mild cognitive impairment and slow gait on risk of dementia.</a> Experimental Gerontology. 110, 146-150 (2018).</li><li>Impedovo, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dynamic+handwriting+analysis+for+the+assessment+of+neurodegenerative+diseases:+a+pattern+recognition+perspective.">Dynamic handwriting analysis for the assessment of neurodegenerative diseases: a pattern recognition perspective.</a> IEEE Reviews in Biomedical Engineering. 12, 209-220 (2019).</li><li>Yu, N. Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterization+of+the+fine+motor+problems+in+patients+with+cognitive+dysfunction+-+A+computerized+handwriting+analysis.">Characterization of the fine motor problems in patients with cognitive dysfunction - A computerized handwriting analysis.</a> Human Movement Science. 65 (17), 30841-30842 (2019).</li><li>Zhou, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characteristics+of+agraphia+in+Chinese+patients+with+Alzheimer's+disease+and+amnestic+Mild+Cognitive+Impairment.">Characteristics of agraphia in Chinese patients with Alzheimer's disease and amnestic Mild Cognitive Impairment.</a> Chinese Medical Journal. 129 (13), 1553-1557 (2016).</li><li>Rosenblum, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Handwriting+process+variables+among+elderly+people+with+mild+major+depressive+disorder:+a+preliminary+study.">Handwriting process variables among elderly people with mild major depressive disorder: a preliminary study.</a> Aging Clinical &amp; Experimental Research. 22 (2), 141-147 (2010).</li><li>Caligiuri, M. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Signature+dynamics+in+Alzheimer's+disease.">Signature dynamics in Alzheimer's disease.</a> Forensic Science International. 302, 109880 (2019).</li><li>Thomas, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Handwriting+analysis+in+Parkinson's+disease:+current+status+and+future+directions.">Handwriting analysis in Parkinson's disease: current status and future directions.</a> Movement Disorders Clinical Practice. 4 (6), 806-818 (2017).</li><li>Leung, S. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+comparative+approach+to+the+examination+of+Chinese+handwriting-The+Chinese+character.">A comparative approach to the examination of Chinese handwriting-The Chinese character.</a> Journal of the Forensic Science Society. 25, 255-267 (1985).</li><li>Ma, H. I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Progressive+micrographia+shown+in+horizontal,+but+not+vertical,+writing+in+Parkinson's+disease.">Progressive micrographia shown in horizontal, but not vertical, writing in Parkinson's disease.</a> Behavioural Neurology. 27 (2), 169-174 (2013).</li><li>Yan, J. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alzheimer's+disease+and+mild+cognitive+impairment+deteriorate+fine+movement+control.">Alzheimer's disease and mild cognitive impairment deteriorate fine movement control.</a> Journal of Psychiatric Research. 42, 1203-1212 (2008).</li><li>Johnson, B. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Understanding+macrographia+in+children+with+autism+spectrum+disorders.">Understanding macrographia in children with autism spectrum disorders.</a> Research in Developmental Disabilities. 34 (9), 2917-2926 (2013).</li><li>Afonso, O., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Writing+difficulties+in+Alzheimer's+disease+and+Mild+Cognitive+Impairment.">Writing difficulties in Alzheimer's disease and Mild Cognitive Impairment.</a> Reading and Writing. 32 (1), 217-233 (2019).</li><li>Drot&#225;r, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+handwriting+kinematics+and+pressure+for+differential+diagnosis+of+Parkinson's+disease.">Evaluation of handwriting kinematics and pressure for differential diagnosis of Parkinson's disease.</a> Artificial Intelligence in Medicine. 67, 39-46 (2016).</li><li>Garre-Olmo, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Kinematic+and+pressure+features+of+handwriting+and+drawing:+preliminary+results+between+patients+with+mild+cognitive+impairment,+Alzheimer+disease+and+healthy+controls.">Kinematic and pressure features of handwriting and drawing: preliminary results between patients with mild cognitive impairment, Alzheimer disease and healthy controls.</a> Current Medicinal Chemistry. 14, 960-968 (2017).</li><li>Cohen, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Digital+clock+drawing:+differentiating+"thinking"+versus+"doing"+in+younger+and+older+adults+with+depression.">Digital clock drawing: differentiating "thinking" versus "doing" in younger and older adults with depression.</a> Journal of the International Neuropsychological Society. 20 (9), 920-928 (2014).</li><li>Rosenblum, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Handwriting+as+an+objective+tool+for+Parkinson's+disease+diagnosis.">Handwriting as an objective tool for Parkinson's disease diagnosis.</a> Journal of Neurology. 260 (9), 2357-2361 (2013).</li><li>Grace, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Do+handwriting+difficulties+correlate+with+core+symptomology,+motor+proficiency+and+attentional+behaviours.">Do handwriting difficulties correlate with core symptomology, motor proficiency and attentional behaviours.</a> Journal of Autism and Developmental Disorders. 47 (4), 1-12 (2017).</li><li>Petersen, R. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mild+cognitive+impairment+as+a+diagnostic+entity.">Mild cognitive impairment as a diagnostic entity.</a> Journal of Interactive Marketing. 256 (3), 183-194 (2004).</li><li>Ishikawa, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Handwriting+features+of+multiple+drawing+tests+for+early+detection+of+Alzheimer's+Disease:+A+preliminary+result.">Handwriting features of multiple drawing tests for early detection of Alzheimer's Disease: A preliminary result.</a> Studies in Health Technology and Informatics. 264, 168-172 (2019).</li><li>Herold, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thinking+while+moving+or+moving+while+thinking-concepts+of+motor-cognitive+training+for+cognitive+performance+enhancement.">Thinking while moving or moving while thinking-concepts of motor-cognitive training for cognitive performance enhancement.</a> Frontiers in Aging Neuroscience. 10, 228 (2018).</li></ol>

The authors have nothing to disclose.

The critical steps in the protocol confirm the legibility of &#8220;<img alt="Equation 6" src="/files/ftp_upload/61841/61841equ06.jpg" />&#8221;. In detail, within an entire character, the #3 stroke needs to be shorter than the other horizonal strokes, and the #4 stroke needs to be shorter than the #2 stroke. More specifically, more attentional resources are needed during the writing of the #3 stroke and #4 stroke6,<sup class="xref"...

Mild cognitive impairment (MCI) is considered as a transitional but progressively degenerative cognitive phase that precedes the onset of Alzheimer&#8217;s disease (AD)1. It has been reported that the AD progression rate per year is 15% while nearly 75% of moderate and severe MCI cases might remain undiagnosed2. Recent studies have reported that patients with MCI have difficulty in some aspects of fine motor tasks3, and those patients who showed motor disorders, such as slow gait, had a high risk of dementia4.
Handwriting is a complex human activity that entails an intricate blend of cognitive, kinesthetic, and perceptual-motor components including visual and kinesthetic perception, motor planning, eye-hand coordination, visual-motor integration, dexterity, and manual skills1. Handwriting analysis has been utilized to detect cognitive and motor dysfunctions in many types of neurodegenerative diseases, such as AD and Parkinson&#8217;s disease (PD)5. In addition, some aspects of handwriting problems have been reported to be an indicator for MCI and related to disease progression6. As a majority of the population uses language, studies that investigate handwriting analysis in Chinese speakers (especially simplified Chinese characters) are still lacking.
There have been several articles that have investigated handwriting abnormalities or &#8220;agraphia&#8221; in individuals with MCI. For example, by utilizing the traditional pencil&#8211;paper methods, Zhou and colleagues tried to unveil the distinct writing abilities between patients with MCI and individuals without MCI. The differences between the groups were not obvious, with the exception of writing errors7. Kawa et al. found handwriting features in patients with MCI using a smart pen, which could dynamically analyze the stroke and pen speed during writing2. WACOM hardware and MovAlyzeR software can detect more real-time information compared with traditional pencil and paper methods and smartpen paper methods. Therefore, dynamic handwriting data, such as pen-down pressure, velocity, acceleration, and jerk, have been found to be a new focus of handwriting analysis relative to static data, such as letter size and space between words2.
However, another phenomenon that cannot be overlooked is the cross-cultural effect of handwriting. The writing systems of different nations are not always the same (e.g., English letters are written from left to right while Hebrew letters are written from right to left)8. In this issue, even reviews have confirmed the effectiveness of handwriting analysis9,10 in alphabetic languages, and the wide gap between Chinese characters and western letters has hindered the interchange capability of handwriting analysis in the methods and results11 of these studies.
There exist several major dissimilarities between western languages (e.g., English) and Chinese. First, there are many more horizonal movements of the pen tip during Chinese character writing compared with letter writing12. Second, unlike the alphabet language, which is associated with phonemes, Chinese is considered to be logographic7. As a result, most Chinese characters have their own unique stroke order, and the width and height of strokes need to be strictly limited. Otherwise, unlimited widths and heights might cause increased illegibility11 (&#8220;<img alt="Equation 1" src="/files/ftp_upload/61841/61841equ01.jpg" />&#8221; and &#8220;<img alt="Equation 2" src="/files/ftp_upload/61841/61841equ02.jpg" />&#8221; are completely different Chinese characters. Also, &#8220;<img alt="Equation 3" src="/files/ftp_upload/61841/61841equ03.jpg" />&#8221;, &#8220;<img alt="Equation 4" src="/files/ftp_upload/61841/61841equ04.jpg" />&#8221;, and &#8220;<img alt="Equation 5" src="/files/ftp_upload/61841/61841equ05.jpg" />&#8221; are different Chinese characters).
&#8220;<img alt="Equation 6" src="/files/ftp_upload/61841/61841equ06.jpg" />&#8221; (pronounced &#8220;Zheng&#8221;) is a typical, simple, and commonly used Chinese character that nearly every Chinese speaker with a two-year educational level can read and write. It has been selected as a writing task in previous Chinese handwriting analysis studies6,12. Researchers decided to use &#8220;<img alt="Equation 6" src="/files/ftp_upload/61841/61841equ06.jpg" />&#8221; as the writing task because it is &#8220;square-like&#8221; and composed of five strokes, all of which are horizonal (#1, #3, #5 stroke, from left to right) or vertical (#2, #4 stroke, from up to down) (Figure 1). According to many fine motor studies, fulfilling the #3 stroke (horizonal) and the #4 stroke (vertical) requires pure wrist and finger movements, respectively6,12,13. As a result, the stroke velocity of both strokes could be a proper manifestation14.
In addition, pen pressure during handwriting is a handwriting feature that has been shown to outperform other kinematic features in reflecting motor control5,15. However, there are no relevant studies in Chinese patients, though positive results have been confirmed by research groups from the Czech Republic, Spain, Israel, and other countries8,16,17.
The signature has been commonly used as a handwriting task in numerous studies5. In general, a signature requires little thinking or in-air time18. &#8220;In-air&#8221; is defined as when the pressure of the pen tip to the screen is 0 during the handwriting, and &#8220;in-air time&#8221; is the sum of the time &#8220;in-air&#8221; during the handwriting. Individuals who suffer from many neuropsychiatric disorders might have deficits in psychomotor control, and thus they exhibit increased in-air time of the signature. For example, Rosenblum et al. found that Israeli patients with depression and Parkinson&#8217;s disease showed longer in-air time compared with healthy controls during writing their own name in Hebrew8,19. As Chinese characters have their own shape, in this study, it was decided to use the in-air length tortuosity in segmentation between characters during writing the name as a potential indicative parameter. Tortuosity, defined by the ratio of the arc length to the Euclidean distance between end points, is a measure of curvature, and therefore indexes the smoothness of a specific writing output20.

<table>
	<tbody>
		<tr>
			<td></td>
			<td>Microsoft</td>
			<td>Surface Pro 2</td>
			<td>computer</td>
		</tr>
		<tr>
			<td></td>
			<td>MovAlyeR</td>
			<td>3.4</td>
			<td>software</td>
		</tr>
		<tr>
			<td></td>
			<td>WACOM</td>
			<td>Cintiq</td>
			<td>digitizer</td>
		</tr>
	</tbody>
</table>

digital handwriting analysis of characters in chinese patients with mild cognitive impairment

An increasing amount of evidence shows that cognitive deficits and movement dysfunctions are not separated. Patients with mild cognitive impairment (MCI) can manifest fine motor disorders of the upper extremities. Handwriting is a complex and unique human activity involving both motor and cognitive coordination. Researchers from western countries have discovered that patients with MCI have abnormal handwriting features. However, no relevant studies have been conducted in the Chinese population. Owing to the cross-culture phenomenon of handwriting, the aim of this study is to find new handwriting tasks to demonstrate the differences in handwriting features between elderly patients with MCI and age-matched healthy individuals.

The demographic data of the subjects demonstrated that all the groups matched well in age, gender, educational level, dominant hand, and other parameters.
As shown in Table 1, during the writing of the Chinese character &#8220;<img alt="Equation 6" src="/files/ftp_upload/61841/61841equ06.jpg" />&#8221;, elderly subjects with MCI exhibited a lower average absolute velocity of the #3 (2.46 &#177; 0.40 vs 1.82 &#177; 0.55, P = 0.001) and #4 stroke (2.61 &#17...

Watch this Scientific Journal Video about Digital Handwriting Analysis of Characters in Chinese Patients with Mild Cognitive Impairment at JoVE.com

Digital Handwriting Analysis of Characters in Chinese Patients with Mild Cognitive Impairment

This study proposed a digital handwriting analysis of characters in individuals with mild cognitive impairment to find more information than is revealed by traditional pencil&#8211;paper handwriting analysis.

An increasing amount of evidence shows that cognitive deficits and movement dysfunctions are not separated. Patients with mild cognitive impairment (MCI) ...

Handwriting analysis has been used to detect, cognitive and motor dysfunctions. Some aspect of handwriting difficulties can be an indicator for MCI, I'm delighted to(inaudible)The main advantage of this study is that it uses a digital handwriting analysis system for simplified Chinese character users. This method can also be applied to the detection of psychomotor retardation in patients with depression, Schizophrenia, or other psychiatric disorders who are simplified Chinese users.Before beginning and analysis, select a 410 by 265 by 17.5 millimeter USB digitizer with a 3, 840 by 2, 160 dot spatial resolution, a 0.9 by 0.9 millimeter pixel size, a 30 millisecond temporal resolution, and an 8, 192 pressure level, and a handheld stylist pen for the handwriting movements. connect a laptop PC to the digitizer to collect and exhibit the handwriting traces. And install an appropriate data recording, processing, and analyzing software program.Recruit mild cognitive impairment participants who present with a memory complaint, an objectively impaired memory function, intact activity of daily living, and the absence of Dementia. To perform a handwriting task, use the stylus to create sample Chinese characters in the writing area of the digitizer. Give the digitizer and stylus to the participant and instruct the participant to use the stylus to write their name in Chinese with the dominant hand, while holding the digitizer in a comfortable position.Next, instruct the participant to use the dominant hand to write the printed version of the Chinese character, Xiang"If the character is being written in the wrong stroke order, stop the trial and trace and show the subject how to write the character in the correct stroke order. If any hesitation is derived from a lack of knowledge, stop the trial and show the participant how to write the character correctly. Then instruct the participant to use the dominant hand to sign their name in Chinese three times.To analyze the handwriting task data, in the software analysis program, right click on experiment"to select properties, processing, and segmentation. In segmentation flags"click Add first segmentation at any rate"Add last segmentation at any rate"and Move segmentation point to nearest pen down if on a pen lift"In segmentation methods"click on At pen down trajectories"and reset the previously selected segmentation flags parameters. For parameter calculation in Xiang"select the participant and click Handwriting Trials"Use the tracing system to trace the handwriting process and stroke order of Xiang"step-by-step, and locate the segmentation of stroke number three of Xiang"The average absolute velocity will be automatically calculated within the extracted data.Locate the segmentation of stroke number four of Zhang"The software will automatically calculate the average absolute velocity for strong number four. The pen pressure of each segmentation and average pen pressure will also be calculated by the software. Next, select the participant in Xiang, click handwriting trials and use the tracing system to trace the handwriting process and stroke order of the participant signature step-by-step.Locate the segmentation of the stroke between the characters. The absolute size and road length will be calculated. Then use the formula to calculate the in-air length tortuosity in the segmentation between characters, As shown in the table, during the writing of the Chinese characters Xiang, elderly subjects with mild cognitive impairment exhibited a lower average absolute velocity of the number three, a number four strokes and a higher average pen pressure compared to healthy elderly subjects.Additionally, during the signing of Chinese names, the elderly subjects with mild cognitive impairment exhibited a higher in-air length tortuosity in segmentation between the characters compared to healthy elderly subjects. The most important step is confirming the character legibility, using Xiang as example. The third stroke should be shorter than other horizontal strokes.Foreign 00:05:35

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4.4K Görüntüleme.  Chinese PLA General Hospital. El yazısı analizi bilişsel ve motor disfonksiyonları tespit etmek için kullanılmıştır. El yazısı zorluklarının bazı yönleri MCI için bir gösterge olabilir, memnunum (duyulamaz)Bu çalışmanın ana avantajı, basitleştirilmiş Çinli karakter kullanıcıları için dijital bir el yazısı analiz sistemi kullanmasıdır. Bu yöntem, basitleştirilmiş Çinli kullanıcılar olan depresyon, Şizofreni veya diğer psikiyatrik bozuklukları olan hastalarda psikomotor gerilik tesp...