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Background: Exergames often used for training purpose can also be applied to create assessments based on quantitative data derived from the game. A number of studies relate to these use functionalities developing specific assessment tasks by using the game software and provided good data on psychometric properties. However, (1) assessments often include tasks other than the original game task used for training and therefore relate to similar but not to identical or integrated performances trained, (2) people with diagnosed dementia have insufficiently been addressed in validation studies, and (3) studies did commonly not present validation data such as sensitivity to change, although this is a paramount objective for validation to evaluate responsiveness in intervention studies. Objective: Specific assessment parameters have been developed using quantitative data directly derived from the data stream during the game task of a training device (Physiomat). The aim of this study was to present data on construct validity, test–retest reliability, sensitivity to change, and feasibility of this internal assessment approach, which allows the quantification of Physiomat training effects on motor-cognitive functions in 105 multimorbid patients with mild-to-moderate dementia (mean age 82.7±5.9). Methods: Physiomat assessment includes various tasks at different complexity levels demanding balance and cognitive abilities. For construct validity, motor-cognitive Physiomat assessment tasks were compared with established motor and cognitive tests using Spearman’s rank correlations (rs). For test–retest reliability, we used intra-class correlations (ICC3,1) and focused on all Physiomat tasks. Sensitivity to change of trained Physiomat tasks was tested using Wilcoxon statistic and standardized response means (SRMs). Completion rate and time were calculated for feasibility. Results: Analyses have mostly shown moderate-to-high correlations between established motor as well as cognitive tests and simple (rs=−.22 to .68, P ≤.001-.03), moderate (rs=−.33 to .71, P ≤.001-.004), and complex motor-cognitive Physiomat tasks (rs=−.22 to .83, P ≤.001-.30) indicating a good construct validity. Moderate-to-high correlations between test and retest assessments were found for simple, moderate, and complex motor-cognitive tasks (ICC=.47-.83, P ≤.001) indicating good test–retest reliability. Sensitivity to change was good to excellent for Physiomat assessment as it reproduced significant improvements (P ≤.001) with mostly moderate-to-large effect sizes (SRM=0.5-2.0) regarding all trained tasks. Completion time averaged 25.8 minutes. Completion rate was high for initial Physiomat measures. No adverse events occurred during assessment. Conclusions: Overall, Physiomat proved to have good psychometric qualities in people with mild-to-moderate dementia representing a reliable, valid, responsive, and feasible assessment strategy for multimorbid older adults with or without cognitive impairment, which relates to identical and integrated performances trained by using the game. [JMIR Serious Games 2016;4(2):e12]