Background The Rey-Osterrieth Complex Figure Test (RCFT) is a neuropsychological test that is widely used to assess visual memory and visuoconstructional deficits in patients with cognitive impairment, including Alzheimer disease (AD). Patients with AD have an increased tendency for exhibiting extraordinary behaviors in the RCFT for selecting the drawing area, organizing the figure, and deciding the order of images, among other activities. However, the conventional scoring system based on pen and paper has a limited ability to reflect these detailed behaviors. Objective This study aims to establish a scoring system that addresses not only the spatial arrangement of the finished drawing but also the drawing process of patients with AD by using digital pen data. Methods A digital pen and tablet were used to copy complex figures. The stroke patterns and kinetics of normal controls (NCs) and patients with early-onset AD (EOAD) and late-onset AD (LOAD) were analyzed by comparing the pen tip trajectory, spatial arrangement, and similarity of the finished drawings. Results Patients with AD copied the figure in a more fragmented way with a longer pause than NCs (EOAD: P=.045; LOAD: P=.01). Patients with AD showed an increased tendency to draw the figures closer toward the target image in comparison with the NCs (EOAD: P=.005; LOAD: P=.01) Patients with AD showed the lower accuracy than NCs (EOAD: P=.004; LOAD: P=.002). Patients with EOAD and LOAD showed similar but slightly different drawing behaviors, especially in space use and in the initial stage of drawing. Conclusions The digitalized complex figure test evaluated copying performance quantitatively and further elucidated the patients’ ongoing process during copying. We believe that this novel approach can be used as a digital biomarker of AD. In addition, the repeatability of the test will delineate the process of executive functions and constructional organization abilities with disease progression.

BACKGROUND The Rey-Osterrieth Complex Figure Test (RCFT) is a neuropsychological test that is widely used to assess visual memory and visuoconstructional deficits in patients with cognitive impairment, including Alzheimer disease (AD). Patients with AD have an increased tendency for exhibiting extraordinary behaviors in the RCFT for selecting the drawing area, organizing the figure, and deciding the order of images, among other activities. However, the conventional scoring system based on pen and paper has a limited ability to reflect these detailed behaviors. OBJECTIVE This study aims to establish a scoring system that addresses not only the spatial arrangement of the finished drawing but also the drawing process of patients with AD by using digital pen data. METHODS A digital pen and tablet were used to copy complex figures. The stroke patterns and kinetics of normal controls (NCs) and patients with early-onset AD (EOAD) and late-onset AD (LOAD) were analyzed by comparing the pen tip trajectory, spatial arrangement, and similarity of the finished drawings. RESULTS Patients with AD copied the figure in a more fragmented way with a longer pause than NCs (EOAD: <i>P</i>=.045; LOAD: <i>P</i>=.01). Patients with AD showed an increased tendency to draw the figures closer toward the target image in comparison with the NCs (EOAD: <i>P</i>=.005; LOAD: <i>P</i>=.01) Patients with AD showed the lower accuracy than NCs (EOAD: <i>P</i>=.004; LOAD: <i>P</i>=.002). Patients with EOAD and LOAD showed similar but slightly different drawing behaviors, especially in space use and in the initial stage of drawing. CONCLUSIONS The digitalized complex figure test evaluated copying performance quantitatively and further elucidated the patients’ ongoing process during copying. We believe that this novel approach can be used as a digital biomarker of AD. In addition, the repeatability of the test will delineate the process of executive functions and constructional organization abilities with disease progression.

Visuospatial dysfunction is a common symptom in patients with Alzheimer's disease (AD). To more focus on copying processes rather than on finally completed figures, we conceptually split the copying processes into three stages: visuoperceptual function, visuoconstructional function, and working memory function. We constructed perceptual and working spaces to investigate the different stages of copying, and then, we compared the number and duration of fixations and saccades and the number of switches across the two spaces. We used eye-tracking glasses to assess eye-tracking metrics in patients with early-onset AD (EOAD), patients with late-onset AD (LOAD), and normal control (NC) participants while they copied the simplified Rey–Osterrieth complex figure test (RCFT). Regarding eye metrics on the perceptual space, the number and duration of fixations were greater in both groups of patients with AD than in the NC participants group (number: EOAD vs. NC: p &lt; 0.001, LOAD vs. NC: p = 0. 003/ duration: EOAD vs. NC: p &lt; 0.001, LOAD vs. NC: p &lt; 0.001). On the working space, the number and duration of fixations were greater in the patients with EOAD than in the patients with LOAD and NC participants (number: EOAD vs. LOAD: p = 0. 007, EOAD vs. NC: p = 0. 001/duration: EOAD vs. LOAD: p = 0. 008, EOAD vs. NC: p = 0. 002). The number of saccades and switching was higher in patients with EOAD than in NC participants (p &lt; 0.001). The eye-tracking metrics from the simplified RCFT correlated with the neuropsychological test scores. Patients with EOAD and LOAD achieved the same level of performance at the simplified and original RCFT scores. However, patients with EOAD than LOAD showed a greater number and duration of fixations on the working space and more frequent switching between the perceptual and working spaces, which may reflect more cognitive efforts to achieve the same level of performance.

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