The authors thank Xiaode Chen for digital technology support.

The development of the dTMT and initial application was approved by The Seventh Medical Center of PLA Army General Hospital Review Board. Subjects signed approved informed consent documents prior to testing TMT.
1. General Method Development
<ol>
	<li>Use a tablet (e.g., Microsoft Surface Pro 2) with high-quality inertial sensors embedded within the device and a compatible electronic pen (Figure 1).</li>
	<li>Use the Intelligent Device for Energy Expenditure and Activity (IDEEA) monitor, composed of five sensors (each 16 x 14 x 4 mm3, 2 g), with one attached over the sternum, two attached to the front side of each thigh, and the other two attached under each foot. Connect the sternum and thigh sensors via a solid cable to a small 32-bit microprocessor (70 x 44 x 18 mm3, 59 g), and wire the foot sensors (Figure 2).</li>
</ol>
2. Design and Testing of the dTMT
NOTE: As mentioned earlier, dTMT has two parts: dTMT-A and dTMT-B. These two tests should be performed sequentially (dTMT-A proceeding dTMT-B), without being reversed.
<ol>
	<li>dTMT-A procedure
	<ol>
		<li>Carry out the dTMT-A in a quiet and comfortable environment. 
		NOTE: Participants enrolled to complete dTMT should have the educational level of more than 2 years of preliminary school; otherwise, they might have difficulty in reading and recognizing Chinese characters in dTMT-B. Meanwhile, ensure that the participants have no obvious visual and upper limb disability.</li>
		<li>Ask the participants to sit in front of a desk, and adjust the computer position, background light, and the electronic pen.</li>
		<li>Check the near visual acuity of participants to ensure that they can easily read the numbers on the screen. 
		NOTE: Some aged subjects maybe need a pair of glass in case that the circles on the screen are too small for the subjects with presbyopia.</li>
		<li>Show the instructions of dTMT-A as follows: Please draw a line as rapidly as possible joining consecutive numbers (i.e., 1-&#62;2-&#62;3&#8230;9) in the circles randomly distributed on the screen. A pre-test trial (150 s maximum) is necessary because most participants need to familiarize how to draw on the surface of a computer.</li>
		<li>Demonstrate the major differences between dTMT-A and standard TMT-A. First, if the circle is correctly lined, its color can be changed. Second, if the circle is not correctly lined, its color remains unchanged, and the subjects need to re-line it from the last circle. 
		NOTE: Connecting all the circles fluently with straight lines is encouraged.</li>
		<li>Advise the participants to avoid errors and time wastage. Encourage the participants to draw the line fluently, but as accurately as possible; however, give no priority.</li>
		<li>Ask the participants to select PartA on the screen (Figure 1 lower panel) to complete dTMT-A without interruption. All the dTMT-A data are gathered on the computer automatically. 
		NOTE: If data are collected for investigating intermanual differences, one more test needs to be carried out with the other hand. The sequence of left-/right- hand test is at random.</li>
	</ol>
	</li>
	<li>dTMT-B procedure
	<ol>
		<li>Repeat step 2.1.</li>
		<li>Show the instructions of dTMT-B as follows: Please draw a line as rapidly as possible joining the numbers and Chinese characters (i.e., 1-&#62;<img alt="graphic 1" src="/files/ftp_upload/60456/img1.jpg" style="opacity: 0.9;" />-&#62;2-&#62;<img alt="graphic 1" src="/files/ftp_upload/60456/img2.jpg" style="opacity: 0.9;" />&#8230;<img alt="graphic 1" src="/files/ftp_upload/60456/img3.jpg" style="opacity: 0.9;" />) alternatively in the circles randomly distributed on the screen. 
		NOTE: Make sure all the Chinese characters are recognized by subjects. A pre-test trial (150 s maximum) is also necessary because some participants need to familiarize how to draw in the numbers and Chinese characters alternatively on their own.</li>
		<li>Ask the subjects to select PartB on the screen (Figure 1 lower panel) to complete dTMT-B without interruption. All the dTMT-B data are gathered in computer automatically. 
		NOTE: If data are collected for investigating intermanual differences, one more test needs to be carried out with the other hand. The sequence of left-/right- hand test is at random.</li>
	</ol>
	</li>
</ol>
3. Direct Data Collection and Definitions in dTMT
<ol>
	<li>Determine the total time to completion: the time taken (ms) to draw a line connecting all circles in the correct order.</li>
	<li>Determine the number of errors: the number of times a line is drawn to a circle in the incorrect order.</li>
	<li>Determine the time to completion for each step: the time taken in milliseconds to draw each step.</li>
	<li>Determine the time inside each circle: the time spent in milliseconds to draw inside circles.</li>
	<li>Determine the inside circle percentage (%): time inside each circle divided by total time to completion.</li>
	<li>Determine the time inside each tolerance circle: the time spent in milliseconds to draw inside tolerance circles.</li>
	<li>Determine the inside circle tolerance percentage (%): time inside each tolerance circle divided by total time to completion</li>
	<li>Determine the line canceling times in each step: the times a line is canceled in each step. The tolerance circle has a diameter five times more than that of a real circle.</li>
	<li>Determine the optimal pathway of each step: the nearest line in millimeters of each step.</li>
	<li>Determine the actual pathway of each step: the actual line in millimeters of each step.</li>
	<li>Determine the pathway deviation of each step: the actual line in millimeters minus the nearest line in millimeters of each step.</li>
	<li>Determine the variability of pathway deviation: Coefficient of the variation of the pathway deviation of each step.</li>
	<li>Determine the velocity of drawing of each step: the actual line in millimeters of each step divided by the time to completion for each step. 
	NOTE: The average value was calculated by summing up the values collected step by step. Indirect data reflecting different points between hands or parts were derived based on the direct data.</li>
</ol>
4. Design and Testing of the WTMT
NOTE: Similar to dTMT, WTMT also has two parts: WTMT-A and WTMT-B. These two tests should be performed sequentially (WTMT-A proceding WTMT-B), without being reversed.
<ol>
	<li>WTMT-A procedure
	<ol>
		<li>Carry out WTMT-A in a quiet and comfortable environment. Ensure that there is room light. Randomly distribute coins with numbers at each of 15 positions in a 16 m2 area (4 x 4 m2). Draw a 30 cm diameter around each coin (Figure 3). 
		NOTE: The participants enrolled to complete WTMT should have the educational level of more than 2 years of preliminary school; otherwise, they might have difficulty in reading and recognizing Chinese characters in WTMT-B. Meanwhile, ensure that the participants have no obvious visual and lower limb disability.</li>
		<li>Connect the Intelligent Device for Energy Expenditure and Activity (IDEEA) to the PC and enter the subject&#39;s anthropometric data.</li>
		<li>Attach five biaxial mini-accelerometers (16 x 14 x 4 mm3, 2 g) with medical tape over the sternum, to the front side of each thigh and under each foot (Figure 4). Connect all the accelerometers through thin, flexible cables to a microprocessor/storage unit (70 x 44 x 18 mm3, 59 g) attached with a clip to the clothes. 
		NOTE: The IDEEA is a multiple accelerometer-based system comprising five biaxial accelerometers located on the upper trunk, thighs and feet. The IDEEA was initially developed to estimate energy expenditure during activities of daily living22,23, but has an additional capability to quantify many of the commonly used gait cycle parameters24.</li>
		<li>After the device is equipped, ask participants to walk up and down a walkway without any targets at a comfortable walking speed to warmup.</li>
		<li>Show the instructions of WTMT-A as follows: Please walk on numbered targets in a sequential order as rapidly as possible joining consecutive numbers (i.e., 1-&#62;2-&#62;3&#8230;15) in the coins randomly distributed on the floor.</li>
		<li>Encourage the participants to walk fluently, but as accurately as possible; However, no priority is given. Perform WTMT-A only once.</li>
		<li>Ensure the safety of the participants, because dual-task walking in a challenging environment may increase the risk of falling25. For both pre- and post- tests, a 5 s step pause is needed for IDEEA to discriminate walking from standing. 
		NOTE: Either footstep on the coin is considered as on the target. If the participants walk in the wrong order, guide them until they walk in the right order. All the WTMT-A data are gathered in the IDEEA microprocessor/storage unit automatically.</li>
	</ol>
	</li>
	<li>WTMT-B procedure
	<ol>
		<li>Repeat the steps as in Section 4.1.1.</li>
		<li>Show the instructions of WTMT-A as follows: Please walk on numbered targets in a sequential order as rapidly as possible joining consecutive numbers (i.e., 1-&#62;<img alt="graphic 1" src="/files/ftp_upload/60456/img4.jpg" style="opacity: 0.9;" />-&#62;2-&#62;<img alt="graphic 1" src="/files/ftp_upload/60456/img5.jpg" style="opacity: 0.9;" />&#8230;<img alt="graphic 1" src="/files/ftp_upload/60456/img6.jpg" style="opacity: 0.9;" />&#62;8) in the coins randomly distributed on the floor. Make sure all the Chinese characters are recognized by the participants.</li>
		<li>Perform WTMT-B only once.</li>
		<li>Ensure the safety of the participants, because dual-task walking in a challenging environment may increase the risk of fallings25. For both pre- and post- tests, a 5 s step pause is needed for IDEEA to discriminate walking from standing. 
		NOTE: Either footstep on the coin is considered as on the target. If the subjects walked in the wrong order, guide them until they walk in the right order. All the WTMT-B data are gathered in the IDEEA microprocessor/storage unit automatically.</li>
	</ol>
	</li>
</ol>
5. Direct Data Collection and Meaning Explanation in WTMT
NOTE: As shown in Figure 5, the human gait cycle has been divided into different subphases. In detail, spatial and temporal parameters are defined and calculated as follows.
<ol>
	<li>Determine the steps (n): the number of steps completed during level walking, including the right and left limbs.</li>
	<li>Determine the swing duration (%): the phase percentage starting from toe-off until initial ground or stair contact for any given foot.</li>
	<li>Determine the stance duration (%): phase percentage between the heel strike of one foot and the heel strike of the contra-lateral foot.</li>
	<li>Determine the speed (m/s): the average velocity over two consecutive strides.</li>
	<li>Determine the step length (m): the difference in length between the initial heel strike of the right or left foot and the heel strike of the contralateral foot.</li>
	<li>Determine the stride length (m): the distance between the successive points of the initial contact of the same foot, right-left-right (R-L-R) or left-right- left (L-R-L).</li>
	<li>Determine the gait variability of step length: coefficient of the variation of step length. 
	NOTE: Completion time and errors are also collected and counted by the examiner, instead of IDEEA.</li>
</ol>
6. Data Collection and Statistics
<ol>
	<li>Use one-way-ANOVA and Fisher&#8217;s LSD to compare the differences between the groups. The demographic data are listed in Table 1. dTMT-A, dTMT-B, WTMT-A, and WTMT-B data are shown in Tables 2-5 respectively. A P &#60; 0.05 was considered to indicate a statistically significant difference.</li>
</ol>

<ol>
	<li>Wei, 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=Diagnostic+accuracy+of+the+Chinese+version+of+the+Trail-Making+Test+for+screening+cognitive+impairment.">Diagnostic accuracy of the Chinese version of the Trail-Making Test for screening cognitive impairment.</a> Journal of the American Geriatrics Society. 66 (1), 92-99 (2018).</li><li>Schroeter, M. L., 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=Executive+deficits+are+related+to+the+inferior+frontal+junction+in+early+dementia.">Executive deficits are related to the inferior frontal junction in early dementia.</a> Brain. 135 (1), 201-215 (2012).</li><li>Rabin, L. A., Burton, L. A., Barr, W. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Utilization+rates+of+ecologically+oriented+instruments+among+clinical+neuropsychologists.">Utilization rates of ecologically oriented instruments among clinical neuropsychologists.</a> The Clinical Neuropsychologist. 21 (5), 727-743 (2007).</li><li>Sacco, G., 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=Comparison+between+a+paper-pencil+version+and+computerized+version+for+the+realization+of+a+neuropsychological+test:+the+example+of+the+trail+making+test.">Comparison between a paper-pencil version and computerized version for the realization of a neuropsychological test: the example of the trail making test.</a> Journal of Alzhemier's Disease. 68 (4), 1657-1666 (2019).</li><li>Faria, C. A., Alves, H. V. D., Charchat-Fichman, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+most+frequently+used+tests+for+assessing+executive+functions+in+aging.">The most frequently used tests for assessing executive functions in aging.</a> Dementia &amp; Neuropsychologia. 9 (2), 149-155 (2015).</li><li>Lezak, M. D., Howieson, D. D., Loring, D. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Neuropsychological assessment. 4th ed. , 317-374 (2004).</li><li>Lu, J. C., Guo, Q. H., Hong, Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trail+making+test+used+by+Chinese+elderly+patients+with+mild+cognitive+impairment+and+mild+Alzheimer'+dementia.">Trail making test used by Chinese elderly patients with mild cognitive impairment and mild Alzheimer' dementia.</a> Chinese Journal Clinical Psychology. 14 (2), 118-120 (2006).</li><li>Lee, S., Lee, J. A., Choi, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Driving+Trail+Making+Test+part+B:+a+variant+of+the+TMT-B.">Driving Trail Making Test part B: a variant of the TMT-B.</a> Journal of Physical Therapy Science. 28 (1), 148-153 (2016).</li><li>Bastug, G., 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=Oral+trail+making+task+as+a+discriminative+tool+for+different+levels+of+cognitive+impairment+and+normal+aging.">Oral trail making task as a discriminative tool for different levels of cognitive impairment and normal aging.</a> Archives of Clinical Neuropsychology. 28 (5), 411-417 (2013).</li><li>Perrochon, A., Kemoun, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Walking+Trail-Making+Test+is+an+early+detection+tool+for+mild+cognitive+impairment.">The Walking Trail-Making Test is an early detection tool for mild cognitive impairment.</a> Clinical Interventions in Aging. 9, 111-119 (2014).</li><li>McIntyre, R. 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=The+THINC-Integrated+Tool+(THINC-it)+screening+assessment+for+cognitive+dysfunction:+validation+in+patients+with+major+depressive+disorder.">The THINC-Integrated Tool (THINC-it) screening assessment for cognitive dysfunction: validation in patients with major depressive disorder.</a> The Journal of Clinical Psychiatry. 78 (7), 873-881 (2017).</li><li>Schott, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trail+Walking+Test+zur+Erfassung+der+motorisch-kognitiven+Interferenz+bei+&#228;lteren+Erwachsenen.">Trail Walking Test zur Erfassung der motorisch-kognitiven Interferenz bei &#228;lteren Erwachsenen.</a> Zeitschrift f&#252;r Gerontologie und Geriatrie. 48 (8), 722-733 (2015).</li><li>Thompson, M. 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=Clinical+utility+of+the+Trail+Making+Test+practice+time.">Clinical utility of the Trail Making Test practice time.</a> The Clinical Neuropsychologist. 13 (4), 450-455 (1999).</li><li>Mahurin, R. K., 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=Trail+making+test+errors+and+executive+function+in+schizophrenia+and+depression.">Trail making test errors and executive function in schizophrenia and depression.</a> The Clinical Neuropsychologist. 20 (2), 271-288 (2006).</li><li>Klaming, L., Vlaskamp, B. N. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Non-dominant+hand+use+increases+completion+time+on+part+B+of+the+Trail+Making+Test+but+not+on+part+A.">Non-dominant hand use increases completion time on part B of the Trail Making Test but not on part A.</a> Behavior Research Methods. 50 (3), 1074-1087 (2017).</li><li>Christidi, F., Kararizou, E., Triantafyllou, N., Anagnostouli, M., Zalonis, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Derived+trail+making+test+indices:+demographics+and+cognitive+background+variables+across+the+adult+life+span.">Derived trail making test indices: demographics and cognitive background variables across the adult life span.</a> Aging, Neuropsychology, and Cognition. 22 (6), 667-678 (2015).</li><li>Dahmen, J., Cook, D., Fellows, R., Schmitter-Edgecombe, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+analysis+of+a+digital+variant+of+the+Trail+Making+Test+using+machine+learning+techniques.">An analysis of a digital variant of the Trail Making Test using machine learning techniques.</a> Technology and Health Care. 25 (2), 251-264 (2017).</li><li>Woods, D. L., Wyma, J. M., Herron, T. J., Yund, E. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effects+of+aging,+malingering,+and+traumatic+brain+injury+on+computerized+Trail-Making+Test+performance.">The effects of aging, malingering, and traumatic brain injury on computerized Trail-Making Test performance.</a> Plos ONE. 10 (6), 0124345 (2014).</li><li>Naomi, K., 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+new+device-aided+cognitive+function+test,+User+eXperience-Trail+Making+Test+(UX-TMT),+sensitively+detects+neuropsychological+performance+in+patients+with+dementia+and+Parkinson's+disease.">A new device-aided cognitive function test, User eXperience-Trail Making Test (UX-TMT), sensitively detects neuropsychological performance in patients with dementia and Parkinson's disease.</a> BMC Psychiatry. 18 (1), 220 (2018).</li><li>Persad, C. C., Jones, J. L., Ashton-Miller, J. A., Alexander, N. B., Giordani, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Executive+function+and+gait+in+older+adults+with+cognitive+impairment.">Executive function and gait in older adults with cognitive impairment.</a> The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 63 (12), 1350-1355 (2008).</li><li>Zhang, K., Werner, P., Sun, M., Pi-Sunyer, F. X., Boozer, C. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Measurement+of+human+daily+physical+activity.">Measurement of human daily physical activity.</a> Obesity Research. 11 (1), 33-40 (2003).</li><li>Zhang, K., Pi-Sunyer, F. X., Boozer, C. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improving+energy+expenditure+estimation+for+physical+activity.">Improving energy expenditure estimation for physical activity.</a> Medicine and Science in Sports and Exercise. 36 (5), 883-889 (2004).</li><li>Gorelick, M. L., Bizzini, M., Maffiuletti, N. A., Munzinger, J. P., Munzinger, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Test-retest+reliability+of+the+IDEEA+system+in+the+quantification+of+step+parameters+during+walking+and+stair+climbing.">Test-retest reliability of the IDEEA system in the quantification of step parameters during walking and stair climbing.</a> Clinical Physiology and Functional Imaging. 29 (4), 271-276 (2009).</li><li>Nordin, E., Moe-Nilssen, R., Ramnemark, A., Lundin-Olsson, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Changes+in+step-width+during+dual-task+walking+predicts+falls.">Changes in step-width during dual-task walking predicts falls.</a> Gait and Posture. 32 (1), 92-97 (2010).</li><li>Liebherr, M., Weiland-Breckle, H., Grewe, T., Schumacher, P. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+performance+under+motor+demands+-+On+the+influence+of+task+difficulty+and+postural+control.">Cognitive performance under motor demands - On the influence of task difficulty and postural control.</a> Brain Research. 1684, 1-8 (2018).</li><li>Herold, F., Hamacher, D., Schega, L., M&#252;ller, N. G. <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+&#8211;+Concepts+of+motor-cognitive+training+for+cognitive+performance+enhancement.">Thinking while moving or moving while thinking &#8211; Concepts of motor-cognitive training for cognitive performance enhancement.</a> Frontiers in Aging Neuroscience. 10, 228 (2018).</li><li>Kim, H., Hsiao, C. P., Do, Y. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Home-based+computerized+cognitive+assessment+tool+for+dementia+screening.">Home-based computerized cognitive assessment tool for dementia screening.</a> Journal of Ambient Intelligence &amp; Smart Environments. 4, 429-442 (2012).</li><li>Mancini, 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=Trunk+accelerometry+reveals+postural+instability+in+untreated+Parkinson's+disease.">Trunk accelerometry reveals postural instability in untreated Parkinson's disease.</a> Parkinsonism &amp; Related Disorders. 17 (7), 557-562 (2011).</li><li>Ozinga, S. 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=Three-dimensional+evaluation+of+postural+stability+in+Parkinson's+disease+with+mobile+technology.">Three-dimensional evaluation of postural stability in Parkinson's disease with mobile technology.</a> NeuroRehabilitation. 41 (1), 211-218 (2017).</li><li>Fellows, R. P., ahmen, J., Cook, D., Schmitter-Edgecombe, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multicomponent+analysis+of+a+digital+Trail+Making+Test.">Multicomponent analysis of a digital Trail Making Test.</a> Clinical Neuropsychologist. 31 (1), 154-167 (2017).</li><li>Au, R., Piers, R. J., Devine, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=How+technology+is+reshaping+cognitive+assessment:+Lessons+from+the+Framingham+Heart+Study.">How technology is reshaping cognitive assessment: Lessons from the Framingham Heart Study.</a> Neuropsychology. 31 (8), 846-861 (2017).</li></ol>

The authors have nothing to disclose.

Traditional paper-pencil TMT has been well used worldwide for more than 50 years. However, digital TMT is advantageous. First, traditional TMT is considered as an executive function tool, while both dTMT and WTMT have aspects reflecting motor ability besides cognitive function. Considering that the cognitive-motor dual task has gained great attention in recent years26, digital technologies can provide researchers with more information on this integrated task compared with the traditional TMT<sup c...

With a rapidly aging population, dementia is considered to be a major public health concern. The number of elderly patients with dementia worldwide is about 47 million according to the World Health Organization1. Executive function impairment is not only a common type of cognitive dysfunction in aged individuals, but has been reported as a predictor of progression from mild cognitive impairment (MCI) to clinical Alzheimer&#8217;s disease (AD)2,3. As the third most widely used test in neuropsychology4, the Trail Making Test (TMT) is employed as a well-accepted tool to evaluate executive functions, especially sustained attention and set-shifting5, even in elderly patients6.
The standard TMT is a paper-pencil test consisting of two parts: tMT-A and TMT-B5. The former calls for the test-taker to draw lines connecting randomly distributed numbers (1&#8211;25) on a test paper in ascending order (1-&#62;2-&#62;3&#8230;), whereas the latter requires the test-taker to set numbers and letters (1-&#62;A-&#62;2-&#62;B&#8230;) alternatively. The performance of TMT is generally scored in the time taken to complete each part correctly7. TMT has been translated into different languages. The Chinese version of TMT was developed in 20068. Since Chinese characters are quite distinct from English letters, the Chinese version of TMT was used in our procedure.
Apart from the standard version, TMT has been modified in different ways by researchers (e.g., oral TMT9, driving TMT10, walking TMT (WTMT)11) to assess specific populations or find details under different conditions, such as driving and walking. Of note, some studies conferring different numbers compared with the standard TMT are also reported to be of high validity and reliability. For example, THINC-Integrated Tool (THINC-it) developed by the McIntyre group used 9 numbers and letters for TMT-B12; WTMT reported by Schott and colleagues used 15 numbers for TMT-A13. In the same way, many evaluating systems of TMT have been built beyond the complete time scoring, which are reported to be helpful in finding more items besides executive dysfunction, or to be accessible for participants who are not suitable to complete the standard TMT. For example, some researchers investigated the errors in TMT and found that errors in TMT-B were associated with mental tracking and working memory in patients with psychiatric disorder14. Another group from Greece suggested derived TMT scores [TMT-(B&#8722;A) or TMT(B/A)] as indices to detect impairment in cognitive flexibility across the adult life span15. Generally, alternative evaluating systems of TMT can be summarized as follows: (1) completion time analysis&#8212;TMT completion time is calculated in seconds16; (2) error analysis&#8212;different types of TMT errors are classified and quantified14; (3) intermanual differences&#8212;different abilities of completing TMT between the dominant hand and the nondominant hand are compared17; and (4) derived Trail Making Test indices&#8212;different characterizations between completing TMT-A and TMT-B are analyzed15. The alternative scoring methods provide additional information. For example, the utility of TMT error analysis could reveal cognitive deficits not traditionally captured using completion time as the sole outcome variable in patients with schizophrenia and depression14. The lack of any significant intermanual difference helped to discriminate the cognitive dysfunction from the influence of the motor disorder17. Derived TMT indices could detect impairment in cognitive flexibility across the adult life span and minimize the effect of demographics and other cognitive background variables15.
With advances in modern technology, computer-based digital applications have been increasingly integrated into traditional cognitive interventions, most of which are designed as similar to the original test as possible, rather than created as new tools. Digital or computerized TMT (dTMT) has been proven to have the potential to capture additional information, with the structure of the existing test mainly unchanged in recent years18,19.
This study aimed to introduce a computer-based Chinese version of dTMT-A and dTMT-B, as well as a WTMT. Both are modified TMTs and have been confirmed to have high sensitivity and specificity to screen patients with MCI, Parkinson&#8217;s Disease, Alzheimer&#8217;s Disease, and so forth, based on the movement of upper and lower limbs20,21. Detailed scoring methods were also presented because digital technologies incorporated into dTMT and WTMT might help capture more information compared to the paper-pencil version of TMT.

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traditional trail making test modified into brand-new assessment tools: digital and walking trail making test

The Trail Making Test (TMT) is a well-accepted tool for evaluating executive function. The standard TMT was invented more than 60 years ago and has been modified into many versions. With the development of digital technologies, TMT is now modified to a digitized version. The present study demonstrated digital TMT (dTMT) performed on a computer, and Walking TMT (WTMT) on the floor. Both revealed more information compared with the traditional version of TMT.

Seven aged patients with Mild Cognitive Impairment (Elderly with MCI), seven aged subjects with Parkinson&#8217;s Disease (Elderly with PD), and seven aged healthy individuals (Healthy Elderly) were recruited, and dTMT-A, dTMT-B, WTMT-A, and WTMT-B, were performed. After the tests, data were collected and analyzed using SPSS software.
As a whole, the demographical data of participants showed that all groups were matched well in terms of age, gender, educational level, dominant hand, Clinical D...

Watch this Scientific Journal Video about Traditional Trail Making Test Modified into Brand-new Assessment Tools: Digital and Walking Trail Making Test at JoVE.com

Traditional Trail Making Test Modified into Brand-new Assessment Tools: Digital and Walking Trail Making Test

Here, we present a protocol to show how to perform two types of cognitive assessment tools derived from the paper-pencil version of the Trail Making Test.

The Trail Making Test (TMT) is a well-accepted tool for evaluating executive function. The standard TMT was invented more than 60 years ago and has been ...

traditional-trail-making-test-modified-into-brand-new-assessment

Research

JoVE Journal

Medicine

10.9K Views.  The Seventh Medical Center of PLA Army General Hospital. Here, we present a protocol to show how to perform two types of cognitive assessment tools derived from the paper-pencil version of the Trail Making Test.

Video: Traditional Trail Making Test Modified into Brand-new Assessment Tools: Digital and Walking Trail Making Test

Making Sense of Listening: The IMAP Test Battery

The ability to hear is only the first step towards making sense of the range of information contained in an auditory signal. Of equal importance are the abilities to extract and use the information encoded in the auditory signal. We refer to these as listening skills (or auditory processing AP). Deficits in these skills are associated with delayed language and literacy development, though the nature of the relevant deficits and their causal connection with these delays is hotly debated.
When a child is referred to a health professional with normal hearing and unexplained difficulties in listening, or associated delays in language or literacy development, they should ideally be assessed with a combination of psychoacoustic (AP) tests, suitable for children and for use in a clinic, together with cognitive tests to measure attention, working memory, IQ, and language skills. Such a detailed examination needs to be relatively short and within the technical capability of any suitably qualified professional. Current tests for the presence of AP deficits tend to be poorly constructed and inadequately validated within the normal population. They have little or no reference to the presenting symptoms of the child, and typically include a linguistic component. Poor performance may thus reflect problems with language rather than with AP. To assist in the assessment of children with listening difficulties, pediatric audiologists need a single, standardized child-appropriate test battery based on the use of language-free stimuli.
We present the IMAP test battery which was developed at the MRC Institute of Hearing Research to supplement tests currently used to investigate cases of suspected AP deficits. IMAP assesses a range of relevant auditory and cognitive skills and takes about one hour to complete. It has been standardized in 1500 normally-hearing children from across the UK, aged 6-11 years. Since its development, it has been successfully used in a number of large scale studies both in the UK and the USA. IMAP provides measures for separating out sensory from cognitive contributions to hearing. It further limits confounds due to procedural effects by presenting tests in a child-friendly game-format. Stimulus-generation, management of test protocols and control of test presentation is mediated by the IHR-STAR software platform. This provides a standardized methodology for a range of applications and ensures replicable procedures across testers. IHR-STAR provides a flexible, user-programmable environment that currently has additional applications for hearing screening, mapping cochlear implant electrodes, and academic research or teaching.

A test battery (IMAP) for performing an in-depth assessment of auditory and cognitive abilities contributing to listening skills is described. It is quick to administer, child-friendly and free from linguistic confounds. Stimulus generation and protocol management are controlled via a software platform (IHR-STAR) to ensure replicable procedures.

The ability to hear is only the first step towards making sense of the range of information contained in an auditory signal. Of equal importance are the ...

The &alpha;-test: Rapid Cell-free CD4 Enumeration Using Whole Saliva

There is an urgent need for affordable CD4 enumeration to monitor HIV disease. CD4 enumeration is out of reach in resource-limited regions due to the time and temperature restrictions, technical sophistication, and cost of reagents, in particular monoclonal antibodies to measure CD4 on blood cells, the only currently acceptable method. A commonly used cost-saving and time-saving laboratory strategy is to calculate, rather than measure certain blood values. For example, LDL levels are calculated using the measured levels of total cholesterol, HDL, and triglycerides1. Thus, identification of cell-free correlates that directly regulate the number of CD4+ T cells could provide an accurate method for calculating CD4 counts due to the physiological relevance of the correlates.
The number of stem cells that enter blood and are destined to become circulating CD4+ T cells is determined by the chemokine CXCL12 and its receptor CXCR4 due to their influence on locomotion2. The process of stem cell locomotion into blood is additionally regulated by cell surface human leukocyte elastase (HLECS) and the HLECS-reactive active &alpha;1proteinase inhibitor (&alpha;1PI, &alpha;1antitrypsin, SerpinA1)3. In HIV-1 disease, &alpha;1PI is inactivated due to disease processes 4. In the early asymptomatic categories of HIV-1 disease, active &alpha;1PI was found to be below normal in 100% of untreated HIV-1 patients (median=12 &mu;M, and to achieve normal levels during the symptomatic categories4, 5. This pattern has been attributed to immune inactivation, not to insufficient synthesis, proteolytic inactivation, or oxygenation. We observed that in HIV-1 subjects with &gt;220 CD4 cells/&mu;l, CD4 counts were correlated with serum levels of active &alpha;1PI (r2=0.93, p&lt;0.0001, n=26) and inactive &alpha;1PI (r2=0.91, p&lt;0.0001, n=26) 5. Administration of &alpha;1PI to HIV-1 infected and uninfected subjects resulted in dramatic increases in CD4 counts suggesting &alpha;1PI participates in regulating the number of CD4+ T cells in blood 3.
With stimulation, whole saliva contains sufficient serous exudate (plasma containing proteinaceous material that passes through blood vessel walls into saliva) to allow measurement of active &alpha;1PI and the correlation of this measurement is evidence that it is an accurate method for calculating CD4 counts. Briefly, sialogogues such as chewing gum or citric acid stimulate the exudation of serum into whole mouth saliva. After stimulating serum exudation, the activity of serum &alpha;1PI in saliva is measured by its capacity to inhibit elastase activity. Porcine pancreatic elastase (PPE) is a readily available inexpensive source of elastase. PPE binds to &alpha;1PI forming a one-to-one complex that prevents PPE from cleaving its specific substrates, one of which is the colorimetric peptide, succinyl-L-Ala-L-Ala-L-Ala-p-nitroanilide (SA3NA). Incubating saliva with a saturating concentration of PPE for 10 min at room temperature allows the binding of PPE to all the active &alpha;1PI in saliva. The resulting inhibition of PPE by active &alpha;1PI can be measured by adding the PPE substrate SA3NA. (Figure 1). Although CD4 counts are measured in terms of blood volume (CD4 cells/&mu;l), the concentration of &alpha;1PI in saliva is related to the concentration of serum in saliva, not to volume of saliva since volume can vary considerably during the day and person to person6. However, virtually all the protein in saliva is due to serum content, and the protein content of saliva is measurable7. Thus, active &alpha;1PI in saliva is calculated as a ratio to saliva protein content and is termed the &alpha;1PI Index. Results presented herein demonstrate that the &alpha;1PI Index provides an accurate and precise physiologic method for calculating CD4 counts.

The &#945;-test: Rapid Cell-free CD4 Enumeration Using Whole Saliva

A CD4 enumeration method, the &#x03B1;-test, is described which uses whole saliva to provide rapid and accurate CD4 counts. The &alpha;-test costs pennies and eliminates the need for technical training, costly reagents such as monoclonal antibodies, instrumentation, refrigeration, transport of samples, as well as collection and handling of blood.

There is an urgent need for affordable CD4 enumeration to monitor HIV disease. CD4 enumeration is out of reach in resource-limited regions due to the time ...

Cardiac Stress Test Induced by Dobutamine and Monitored by Cardiac Catheterization in Mice

Dobutamine is a &beta;-adrenergic agonist with an affinity higher for receptor expressed in the heart (&beta;1) than for receptors expressed in the arteries (&beta;2). When systemically administered, it increases cardiac demand. Thus, dobutamine unmasks abnormal rhythm or ischemic areas potentially at risk of infarction. 
Monitoring of heart function during a cardiac stress test can be performed by either ecocardiography or cardiac catheterization. The latter is an invasive but more accurate and informative technique that the former.
Cardiac stress test induced by dobutamine and monitored by cardiac catheterization accomplished as described here allows, in a single experiment, the measurement of the following hemodynamic parameters: heart rate (HR), systolic pressure, diastolic pressure, end-diastolic pressure, maximal positive pressure development (dP/dtmax) and maximal negative pressure development (dP/dtmin), at baseline conditions and under increasing doses of dobutamine.
As expected, in normal mice we observed a dobutamine dose-related increase in HR, dP/dtmax and dP/dtmin. Moreover, at the highest dose tested (12 ng/g/min) the cardiac decompensation of high fat diet-induced obese mice was unmasked.

We describe the protocol to perform a cardiac stress test induced by dobutamine and monitored by cardiac catheterization in normal mice. Also we show its application to unmask subclinical cardiac disease in high fat diet-induced obese mice.

Dobutamine is a &beta;-adrenergic agonist with an affinity higher for receptor expressed in the heart (&beta;1) than for receptors expressed in the ...

An in vivo Assay to Test Blood Vessel Permeability

This method is based on the intravenous injection of Evans Blue in mice as the test animal model. Evans blue is a dye that binds albumin. Under physiologic conditions the endothelium is impermeable to albumin, so Evans blue bound albumin remains restricted within blood vessels. In pathologic conditions that promote increased vascular permeability endothelial cells partially lose their close contacts and the endothelium becomes permeable to small proteins such as albumin. This condition allows for extravasation of Evans Blue in tissues. A healthy endothelium prevents extravasation of the dye in the neighboring vascularized tissues. Organs with increased permeability will show significantly increased blue coloration compared to organs with intact endothelium. The level of vascular permeability can be assessed by simple visualization or by quantitative measurement of the dye incorporated per milligram of tissue of control versus experimental animal/tissue. Two powerful aspects of this assay are its simplicity and quantitative characteristics. Evans Blue dye can be extracted from tissues by incubating a specific amount of tissue in formamide. Evans Blue absorbance maximum is at 620 nm and absorbance minimum is at 740 nm. By using a standard curve for Evans Blue, optical density measurements can be converted into milligram dye captured per milligram of tissue. Statistical analysis should be used to assess significant differences in vascular permeability.

An in vivo Assay to Test Blood Vessel Permeability

We are presenting an in vivo assay to test blood vessel permeability. This assay is based on intravenous injection of a dye and subsequent visualization of its diffusion into interstitial spaces.

This method is based on the intravenous injection of Evans Blue in mice as the test animal model. Evans blue is a dye that binds albumin. Under ...

Assessment of Gastric Emptying in Non-obese Diabetic Mice Using a [13C]-octanoic Acid Breath Test

Gastric emptying studies in mice have been limited by the inability to follow gastric emptying changes in the same animal since the most commonly used techniques require killing of the animals and postmortem recovery of the meal1,2. This approach prevents longitudinal studies to determine changes in gastric emptying with age and progression of disease. The commonly used [13C]-octanoic acid breath test for humans3 has been modified for use in mice4-6 and rats7 and we previously showed that this test is reliable and responsive to changes in gastric emptying in response to drugs and during diabetic disease progression8. In this video presentation the principle and practical implementation of this modified test is explained. As in the previous study, NOD LtJ mice are used, a model of type 1 diabetes9. A proportion of these mice develop the symptoms of gastroparesis, a complication of diabetes characterized by delayed gastric emptying without mechanical obstruction of the stomach10.
This paper demonstrates how to train the mice for testing, how to prepare the test meal and obtain 4 hr gastric emptying data and how to analyze the obtained data. The carbon isotope analyzer used in the present study is suitable for the automatic sampling of the air samples from up to 12 mice at the same time. This technique allows the longitudinal follow-up of gastric emptying from larger groups of mice with diabetes or other long-standing diseases.

Assessment of Gastric Emptying in Non-obese Diabetic Mice Using a [13C]-octanoic Acid Breath Test

Determination of gastric emptying with a non-invasive [13C]-octanoic acid breath test for tracking gastroparesis in female NOD LtJ mice.

Gastric emptying studies in mice have been limited by the inability to follow gastric emptying changes in the same animal since the most commonly used ...

The Multiple Sclerosis Performance Test (MSPT): An iPad-Based Disability Assessment Tool

Precise measurement of neurological and neuropsychological impairment and disability in multiple sclerosis is challenging. We report a new test, the Multiple Sclerosis Performance Test (MSPT), which represents a new approach to quantifying MS related disability. The MSPT takes advantage of advances in computer technology, information technology, biomechanics, and clinical measurement science. The resulting MSPT represents a computer-based platform for precise, valid measurement of MS severity. Based on, but extending the Multiple Sclerosis Functional Composite (MSFC), the MSPT provides precise, quantitative data on walking speed, balance, manual dexterity, visual function, and cognitive processing speed. The MSPT was tested by 51 MS patients and 49 healthy controls (HC). MSPT scores were highly reproducible, correlated strongly with technician-administered test scores, discriminated MS from HC and severe from mild MS, and correlated with patient reported outcomes. Measures of reliability, sensitivity, and clinical meaning for MSPT scores were favorable compared with technician-based testing. The MSPT is a potentially transformative approach for collecting MS disability outcome data for patient care and research. Because the testing is computer-based, test performance can be analyzed in traditional or novel ways and data can be directly entered into research or clinical databases. The MSPT could be widely disseminated to clinicians in practice settings who are not connected to clinical trial performance sites or who are practicing in rural settings, drastically improving access to clinical trials for clinicians and patients. The MSPT could be adapted to out of clinic settings, like the patient&#8217;s home, thereby providing more meaningful real world data. The MSPT represents a new paradigm for neuroperformance testing. This method could have the same transformative effect on clinical care and research in MS as standardized computer-adapted testing has had in the education field, with clear potential to accelerate progress in clinical care and research.

The Multiple Sclerosis Performance Test MSPT: An iPad-Based Disability Assessment Tool

Precise measurement of neurological and neuropsychological impairment and disability in multiple sclerosis is challenging. We report methodologic details on a new test, the Multiple Sclerosis Performance Test (MSPT). This new approach to the objective of quantification of MS related disability provides a computer-based platform for precise, valid measurement of MS severity.

Precise measurement of neurological and neuropsychological impairment and disability in multiple sclerosis is challenging. We report a new test, the ...

Determining The Electromyographic Fatigue Threshold Following a Single Visit Exercise Test

Theoretically, the electromyographic (EMG) fatigue threshold is the exercise intensity an individual can maintain indefinitely without the need to recruit more motor units which is associated with an increase in the EMG amplitude. Although different protocols have been used to estimate the EMG fatigue threshold they require multiple visits which are impractical for a clinical setting. Here, we present a protocol for estimating the EMG fatigue threshold for cycle ergometry which requires a single visit. This protocol is simple, convenient, and completed within 15-20 min, therefore, has the potential to be translated into a tool that clinicians can use in exercise prescription.

This protocol describes the electromyographic fatigue threshold which demarcates between nonfatiguing and fatiguing exercise workloads. This information could be used to develop a more individualized training program.

Theoretically, the electromyographic (EMG) fatigue threshold is the exercise intensity an individual can maintain indefinitely without the need to recruit ...

Design, Fabrication, and Administration of the Hand Active Sensation Test (HASTe)

The concept of personalizing neurologic rehabilitation, based on individual impairments, has experienced a recent surge. In parallel, the number of outcome measures of upper extremity motor performance has grown. However, clinicians and researchers lack practical, quantitative measures of the hand&#8217;s natural role as a receptor of the environment. The Hand Active Sensation Test (HASTe), developed by Williams and colleagues in 2006, is a valid and reliable measure of haptic performance. Though not available commercially, the HASTe can be fabricated from inexpensive materials, and it has been used successfully to identify impairments in haptic touch in individuals with stroke. (Williams, 2006). This paper presents the methods of design and fabrication of the HASTe testing kit, as well as a visual screen to be used during administration, and instructions for the tests administration and scoring.

Design, Fabrication, and Administration of the Hand Active Sensation Test HASTe

The Hand Active Sensation Test (HASTe) is a valid and reliable measure of haptic performance, which has been used successfully to identify impaired haptic touch in individuals with stroke. The purpose of this paper is to describe the design, fabrication and administration of the HASTe.

The concept of personalizing neurologic rehabilitation, based on individual impairments, has experienced a recent surge. In parallel, the number of ...

A Rat Carotid Balloon Injury Model to Test Anti-vascular Remodeling Therapeutics

The rat carotid balloon injury is a well-established surgical model that has been used to study arterial remodeling and vascular cell proliferation. It is also a valuable model system to test, and to evaluate therapeutics and drugs that negate maladaptive remodeling in the vessel. The injury, or barotrauma, in the vessel lumen caused by an inflated balloon via an inserted catheter induces subsequent neointimal growth, often leading to hyperplasia or thickening of the vessel wall that narrows, or obstructs the lumen. The method described here is sufficiently sensitive, and the results can be obtained in relatively short time (2 weeks after the surgery). The efficacy of the drug or therapeutic against the induced-remodeling can be evaluated either by the post-mortem pathological and histomorphological analysis, or by ultrasound sonography in live animals. In addition, this model system has also been used to determine the therapeutic window or the time course of the administered drug. These studies can leadto the development of a better administrative strategy and a better therapeutic outcome. The procedure described here provides a tool for translational studies that bring drug and therapeutic candidates from bench research to clinical applications.

The rat carotid balloon injury model described below allows researchers to evaluate drugs or therapeutics that negate injury-induced arterial hyperplasia. Detailed pre-surgical preparation, surgical procedure, and post-surgical cares of the animal are described.

The rat carotid balloon injury is a well-established surgical model that has been used to study arterial remodeling and vascular cell proliferation. It is ...

Ultrasound Assessment of Endothelial Function: A Technical Guideline of the Flow-mediated Dilation Test

Cardiovascular disease is the primary cause of mortality and a major cause of disability worldwide. The dysfunction of the vascular endothelium is a pathological condition characterized mainly by a disruption in the balance between vasodilator and vasoconstrictor substances and is proposed to play an important role in the development of atherosclerotic cardiovascular disease. Therefore, a precise evaluation of endothelial function in humans represents an important tool that could help better understand the etiology of multiple cardio-centric pathologies.
Over the past twenty-five years, many methodological approaches have been developed to provide an assessment of endothelial function in humans. Introduced in 1989, the FMD test incorporates a forearm occlusion and subsequent reactive hyperemia that promotes nitric oxide production and vasodilation of the brachial artery. The FMD test is now the most widely utilized, non-invasive, ultrasonic assessment of endothelial function in humans and has been associated with future cardiovascular events.
Although the FMD test could have clinical utility, it is a physiological assessment that has inherited several confounding factors that need to be considered. This article describes a standardized protocol for determining FMD including the recommended methodology to help minimize the physiological and technical issues and improve the precision and reproducibility of the assessment.

The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans. Although the FMD test has been related with the prediction of future cardiovascular disease and events, it is a physiological assessment with many inherent confounding factors that need to be considered.

Cardiovascular disease is the primary cause of mortality and a major cause of disability worldwide. The dysfunction of the vascular endothelium is a ...