Abstract
Background:
Cognitive impairment is common and disabling in Parkinson’s disease (PD). Cognitive testing can be time consuming in the clinical setting. One rapid test to detect cognitive impairment in non-PD populations is the Clock Drawing Test (CDT), which calls upon the brain’s executive and visuospatial abilities to draw a clock designating a certain time.
Objective:
Test the hypothesis that PD participants would perform worse on CDT compared to controls and that CDT would correlate with other measures of cognition.
Methods:
This study evaluated two independent CDT scoring systems and differences in CDT performance between PD (N = 97) and control (N = 54) participants using a two-sample t-test. Pearson’s correlations were conducted between the CDT and tests of sleepiness (Epworth Sleepiness Scale) and vigilance (Psychomotor Vigilance Test); executive function (Trails B-A); and global cognition (Montreal Cognitive Assessment). Receiver operating characteristic curves were used to determine cut points on the CDT that identify individuals who need additional cognitive testing.
Results:
PD participants had worse performance on CDT compared to controls. The CDT was correlated with executive function (Trails B-A) and global cognition (Montreal Cognitive Assessment). The CDT correlated with vigilance (Psychomotor Vigilance Task) only in healthy controls. However, the CDT was not correlated with measures of sleepiness (Epworth Sleepiness Scale) in either group. A cut point of 9 on the Rouleau scale and 18 on the Mendez scale identified PD participants with cognitive impairment.
Conclusion:
The CDT is a rapid clinical cognitive assessment that is feasible in PD and correlates with other measures of cognition.
INTRODUCTION
Parkinson’s disease (PD), although primarily identified by its motor symptoms, also increases risk for mild cognitive impairment (MCI), which can predict later development of dementia [1]. While MCI can be assessed by tests such as the Montreal Cognitive Assessment (MoCA), we propose that the clock drawing test (CDT) can be a useful and rapid tool for investigating cognitive dysfunction in patients with PD in the clinical setting. The power of the CDT lies in its simplicity. The test can be administered in less than 5 minutes, is free, and can provide quick insights into a person’s cognitive health [2]. The CDT is typically used to screen for cognitive impairment and dementia; however, it has not been widely employed as a single assessment in a PD population [2].
Several scales exist with which a drawn clock may be scored. Two such scales are the Rouleau 10-point scale [3] and the Mendez 20-point scale [4]. The Mendez scale is a validated, quantitative scoring style for the CDT and studies have found that it is one of the most accurate assessments of cognitive changes [5, 6]. Meanwhile, the Rouleau scale is a validated, semi-qualitative assessment that studies have found better analyzes executive function domains such as abstract conceptualization, planning, and cognitive flexibility [5]. Both of these scales are frequently used with Alzheimer’s disease (AD) patients [7] and have potential to provide insight as to cognitive function among PD patients.
Prior work suggests that frontal, executive, and visuospatial deficits impair clock drawing performance in patients with PD [8]. However, the specific error aspects that motor or cognitive impairment could cause in CDT performance need further investigation in PD. Many patients with PD have MCI characterized by the decay of visuospatial organization and visuoconstructive skills [9], which are two key skills involved in the CDT [10]. One study demonstrated that the inability to obtain a perfect score on the CDT was associated with MCI in PD and PD participants struggled to align numbers along the clockface [11]. While this prior work tells us of one specific error aspect that PD participants make on the CDT that distinguishes them from healthy controls, additional research is needed to identify relationships between the CDT and measures of specific cognitive domains. Other work in PD found that the Rouleau scale can differentiate PD participants with MCI (N = 39) from those with dementia (N = 16) [12] and that CDT could distinguish PD-dementia from AD dementia [13]. In the current study. we aimed to investigate if a quantitative CDT scoring scale (Mendez scale), in addition to the semi-quantitative scale (Rouleau scale), in a larger sample would demonstrate the efficacy of using the CDT in PD [14] and establish a cut point for distinguishing impaired versus unimpaired cognitive performance. Scarpina and colleagues reported that the CDT could discriminate between impaired and unimpaired performance on the Mini-Mental State Exam (MMSE) [15]. However, the MMSE is less sensitive at recognizing cognitive issues, especially in the absence of dementia [16]. Thus, in our study, in addition to using quantitative scoring scales for the CDT, global cognition was estimated using the MoCA.
Our study’s primary objective was to determine differences in CDT performance between persons with PD and healthy controls (HC) and to evaluate correlations between CDT scores and measures of executive function, visuospatial ability, behavioral alertness, daytime sleepiness, and global cognition. We hypothesized that both the Mendez and the Rouleau CDT scoring scales would be helpful in rapidly assessing cognition in patients with PD and that the CDT scores would be correlated with other measures of cognition and vigilance. Additionally, we determined cut points on the CDT that predict which individuals with PD need evaluation with more comprehensive cognitive assessment.
METHODS
Participants
This study is of cross-sectional design. The study included 97 consecutive persons with PD and 54 consecutive HCs participating in observational studies at the University of Alabama at Birmingham (UAB). PD participants were recruited from the UAB Movement Disorders Clinic and HC participants were recruited from the community. Eligibility criteria for the PD participants were: clinical diagnosis of idiopathic PD based on the presence of bradykinesia plus rest tremor and/or rigidity, stable medication for at least 4 weeks prior to entering the study, age ≥45, Hoehn and Yahr Stages 1–3, and progressive motor symptoms of PD. Exclusion criteria included features of atypical or secondary PD such as cerebellar signs, supranuclear gaze palsy, apraxia, prominent autonomic failure, other cortical signs, lack of response to dopaminergic therapy, history of multiple strokes or head injury, or step-wise progression of disease; having neuroleptic treatment at time of onset of PD; deep brain stimulation; untreated sleep apnea; known narcolepsy; acute illness; or active alcoholism or drug addiction. Eligibility criteria for the HC participants were: age ≥45; stable medications for at least 4 weeks prior to entering study. Exclusion criteria for HC included having Parkinson’s disease or other neurodegenerative disorders. Cognitive performance was not considered an exclusion for HC as we were comparing cognition between PD and HC older adults of similar age, and were thus concerned that exclusion based on cognitive performance would introduce bias, potentially leading the results to show PD performance worse relative to the HC due to exclusion criteria rather than due to PD. This study was approved by the Institutional Review Board at the University of Alabama at Birmingham. All participants were informed of the purpose of the study and provided written informed consent for participation.
Assessments
MoCA
The MoCA was administered according to standard protocols. The same form and standardized script were used for all participants. Participants completed the MoCA in the morning, with all PD participants in the “on’ medication state. MoCA scores range from 0–30 with higher scores indicating better cognitive performance. The MoCA assesses global cognition and includes a clock drawing task, which was used as the CDT for the study. Participants were allowed as much time as needed to complete the CDT.
Psychomotor vigilance test
The Psychomotor Vigilance Test (PVT) (PVT-192, Ambulatory Monitoring, Inc. Ardsley, NY) is a hand-held device used to assess behavioral alertness and vigilance over 10 minutes [17]. The PVT displays a light at a random inter-stimulus interval and has response buttons and a stimulus screen. The participants were instructed to press the response button on the device as soon as the numbers appeared in the stimulus screen. The assessment measures reaction time for each response and provides mean reaction time, which is converted to reciprocal reaction time (RRT). In addition, the number of lapses, defined as response time longer than 500 ms, were recorded. RRT and lapses have been demonstrated to be sensitive to partial and total sleep deprivation [18].
Trail making test
The Trail Making Test (TMT) consists of two parts: A and B. The TMT was used to assess executive function. In Part A of the TMT, participants draw lines to connect numbers in ascending order, and in Part B of the TMT, participants connect numbers and letters in ascending and alternating order. The outcome for executive function was Trails B-A (duration of TMT-B minus duration of TMT-A). Trails B-A is considered a more pure measure of executive function than Trails A or Trails B alone because it reduces the influence of visuospatial and motor performance on the outcome, and this is particularly important in a population with motor deficits [19]. The TMT was administered according to standard protocols and the same standard script was used for all of the participants.
Epworth sleepiness scale
The Epworth Sleepiness Scale (ESS) is a measure of daytime sleepiness in which participants rate how likely they are to doze off in 8 situations on a 0–3 scale. The ESS score (sum of the 8 item scores) ranges from 0–24. Higher scores indicate greater daytime sleepiness.
Scoring the CDT
CDT scoring was blinded to participant diagnosis (PD vs. HC) and MoCA score. The clocks used for CDT analysis were obtained from the MoCA assessment. They were then graded using a 10-point scale [3] and a 20-point scale [4]. The 10-point Rouleau scale provides 2 points for integrity of the clock face without gross distortion with reduced points depending on degree of distortion; 4 points for placement of the numbers with reduced points based on errors in spatial arrangement or for missing, additional, or distorted numbers; and 4 points for correct placement of the clock hands, with reduced points for errors in hand placement, hand size, or extra or missing hands. The 20-point Mendez scale provides points for meeting each of 20 criteria that assess clock contour, number presence and placement, and hand presence and placement. Of note, the space on which clocks are drawn on the MoCA is smaller than CDT administration for this test alone, for which a full page is provided. Therefore, a transparent size-adjusted clock stencil was used to assess variables, such as measuring if numbers are equidistant from the clock face or are spread out evenly across the clock face. Finally, practice scoring sessions were conducted with a qualified behavioral neurologist (MNL) before study CDTs were analyzed.
Statistical analysis
Group comparisons (PD versus HC) of the CDT total and individual item scores from both the Mendez scale [4] and the Rouleau scale [3] were conducted with independent-samples t-tests. Pearson correlations were performed to investigate relationships between the CDT scores and variables of global cognition (MoCA), executive function, vigilance, and daytime sleepiness. Because the Rouleau scale was correlated with age (r = –0.21, p = 0.041) and MDS-UPDRS part III (r = –0.211, p = 0.045) in PD participants, multiple linear regression was performed, and standardized residuals were used in correlational analyses. Because the CDT accounts for 3 points on the MoCA, in assessment of correlations between CDT and MoCA, the MoCA was scored out of 27 total points (CDT removed) to avoid falsely inflating correlations between CDT and MoCA. In PD participants, the MoCA with CDT removed was correlated with race and education, and in HC, the MoCA with CDT removed was associated with race. Therefore, multiple linear regression was performed to account for the influence of these demographics and the standardized residuals were used in correlational analyses. Receiver operating characteristics (ROC) curves were evaluated via logistic regression to determine the cut point scores for the Rouleau and Mendez scales that predict PD individuals with impaired performance on the MoCA (<26). We optimized sensitivity for predicting the cut-off point in order to identify participants whose scores suggest need for additional cognitive testing. All statistical tests were two-tailed and p < 0.05 was considered significant.
RESULTS
Demographics
There were no significant differences between PD and HC in terms of age, sex, or years of education (Table 1). There were significantly fewer African American participants in the PD group (n = 5; 5.2%) compared to the HC group (n = 8; 14.8%, p = 0.048).
Participant demographics
*Difference between PD and HC.
CDT performance in PD and HC
PD participants performed significantly worse than HC on both the Mendez CDT scoring scale and the Rouleau CDT scoring scale (Table 2 and Fig. 1). As exploratory analysis to determine if there are specific error aspects of the CDT that are seen more frequently in PD compared to HC, we compared individually scored items on the CDT scoring scales. Figure 2 shows the distribution of CDT scores for PD and the HC groups and the two CDT scoring scales. With the Rouleau scale, PD participants performed significantly worse in placement of the numbers and placement of the hands on the clock, but there was no significant difference in clock face contour (Fig. 2A). For the Mendez scale, PD participants performed significantly worse on items 2 (“all marks can be classified as either part of a closed figure, a hand, or a symbol for clock numbers”), 5 (“most symbols are distributed as a circle without major gaps”), and 9 (“an ‘11’ is present and is pointed out in some way for the time”), with a trend toward worse performance on item 14 (“all symbols lie about equally adjacent to a closure figure edge”) (Fig. 2B).
Clock Drawing Test scores and other assessments
*Difference between PD and HC; **MoCA score with clock drawing score removed, so MoCA scored out of 27 total points; +ESS n = 39 for HC participants.
Differences in the CDT scores between Parkinson’s disease participants and healthy control participants in the (A) Mendez scoring scale and the (B) Rouleau scoring scale.
Error aspects of CDT. 2A: Scores for the three individual items of the Rouleau CDT scoring scale. 2B: Scores for individual items on the Mendez CDT scoring scale that showed differences between PD and HC participants along with a table indicating a description of each question. *p < 0.05, **p < 0.01.
ROC curve for accuracy of CDT in detecting MoCA<26. A) Rouleau CDT scale. B) Mendez CDT scoring scale. The true positive rate (sensitivity) is plotted against the false positive rate (1-specificity). AUC, area under the curve.
Cognition and vigilance in PD and HC
PD participants performed worse in measures of vigilance (PVT RRT and lapses), executive function (Trails B-A), and global cognition (MoCA with and without CDT) (Table 2). A trend was observed for greater subjective daytime sleepiness (ESS) among PD participants compared to HC. Similarly, there was a trend of more PD participants with ESS scores greater than 10 compared to HC.
Correlations between CDT, executive function, global cognition, and vigilance
CDT performance was correlated with executive function (Trails B-A) for both the Mendez and Rouleau CDT scales in PD and HC (Table 3). This suggests that either CDT scale can serve to identify individuals who need additional evaluation for executive dysfunction. Performance on the CDT was correlated with global cognition, as measured by the MoCA (scored out of 27 total points with clock scores removed), in PD only for the Mendez scale. In contrast, CDT performance was associated with the MoCA for both the Mendez and Rouleau scales among HC (Table 3). Taken together, these data suggest the CDT can provide an approximation of global cognitive function in HC, but the Mendez scale may be a more accurate assessment in PD. The only relationship observed between CDT performance and PVT lapses (vigilance) in the PD group was with the Rouleau scoring scale; whereas, both the Mendez and Rouleau CDT scales were associated with PVT lapses in HC participants. In addition, the only relationship observed between CDT performance and PVT mean RRT (vigilance) was with the Mendez scale in the HC group, suggesting that CDT performance may not be significantly influenced by vigilance in PD. Neither CDT scoring scale was correlated with ESS in PD or HC.
Correlations between Clock Drawing Test scores and other assessments
PD, Parkinson’s disease; HC, healthy controls; *Correlations are corrected for age and MDS-UPDRS part III; **MoCA score with clock drawing score removed (i.e., MoCA scored out of 27 total points); ***MoCA corrected for race for HC, MoCA corrected for race and education for PD; +ESS n = 39 for HC participants.
Proposed CDT cut points for identifying individuals in need of additional cognitive assessment
To explore the clinical utility of the Rouleau and Mendez CDT scales as screening tools for identifying individuals with PD who need additional cognitive evaluation, cut points for each scale were determined using ROC curves to distinguish CDT scores at which individuals showed impaired performance on the MoCA (score < 26) from those with unimpaired performance (MoCA ≥26). For the Rouleau scale, the area under the curve (AUC) was 0.640 (low accuracy). For the Mendez scale, the AUC was 0.704 (moderate accuracy), again suggesting that the Mendez scoring scale may be more useful in PD. Because the goal was to identify individuals with cognitive impairment, we chose cut points that optimized sensitivity. For the Rouleau scale, a cut point of 9.0 had a sensitivity of 81.4%and a false positive rate (1-specificity) of 54.7%(Youden index J = 0.267) to identify individuals who score <26 on the MoCA. For the Mendez scale, a cut point of 18.0 had a sensitivity of 90.7%and a false positive rate (1-specificity) of 0.679 (Youden index J = 0.228).
DISCUSSION
This cross-sectional study suggests that the CDT may be a useful screening measure to identify individuals in need of additional testing of global cognition and executive function in PD and HC populations. Specifically, individuals with PD who score 9 or less on the Rouleau scale and those who score 18 or less on the Mendez scale should have further evaluation with additional cognitive testing. Advantages of the CDT include that it can be performed rapidly and inexpensively at the bedside and that it correlates with a widely used screening measure of global cognition (MoCA) and with executive function performance. Additionally, our findings show that PD participants have impaired performance on CDT compared to HC.
In comparison of the two scoring scales, the Mendez CDT scale may be more sensitive at detecting cognitive impairment in PD because it has more scorable points (20 compared to 10 for the Rouleau scale). In addition, the Mendez scale has a higher accuracy for detecting persons with PD who have impaired MoCA scores (higher AUC) compared to the Rouleau scale. Finally, as shown in Fig. 2, several aspects of the CDT reveal errors among PD participants more often than among HC participants.
From the Mendez CDT scale, we can define some basic components of the CDT that are specific error aspects made much more frequently by PD participants than by HC participants (see Fig. 4 for clock examples). First, item 2 scoring demonstrates that 30%of the PD participants’ clocks had stray marks on them compared to only 7%of HC participants. This may be explained by the rest tremor that many PD patients experience. Secondly, on item 5, 24%of the PD participants’ clocks had unequally distributed clock numbers on the clock face compared to only 2%of HC participants. This error aspect is likely due to alterations in visuospatial function. Finally, on item 14, 80%of PD participants struggled with maintaining a constant distance between the clock numbers and the clock edge whereas only 66%of HC participants struggled with this. For PD participants, this error aspect likely occurred because of visuospatial difficulties. Other errors among PD participants included that hands were pointed in the wrong directions and/or were of wrong length, which is another aspect of visuospatial awareness.
Examples of CDT responses. A) Clock drawn by a healthy control participant; B) Clock drawn by a PD participant whose MoCA total score was 26 (normal), showing some of the error aspects commonly seen in CDT of PD participants: stray marks (scratched out items), varied distances between the numbers and the clock’s outer edge, and hands with no appreciable size difference; C) Clock drawn by a PD participant with MoCA score suggesting cognitive impairment. This clock also has some of the trademark aspects of a PD clock: unequally distributed clock numbers, varied distances between the numbers and the clock’s outer edge, hands with no appreciable size difference, and hands outside the clock face.
Unique relationships were observed between the CDT scoring scales and cognitive function. Specifically, the Mendez CDT scale and global cognition (MoCA) were correlated for both PD and HC participants, while the Rouleau CDT scale was associated with global cognition only in HC. Despite this, both CDT scales showed significant relationships with executive function (Trails B-A) in PD and HC. These findings suggest CDT scoring by Mendez or Rouleau methods can be useful screening tools for cognitive dysfunction in PD and HC participants. However, the more detailed scoring of the Mendez scale (20 single score items compared to 3 multiple score items of the Rouleau scale) may be a more sensitive measure for capturing global cognitive dysfunction in PD. This was supported by evaluation of ROC curves, with the Mendez scale showing higher accuracy (AUC) than the Rouleau scale.
Performance on CDT was not correlated with subjective sleepiness (ESS). However, both CDT scoring methods were associated with our objective measures of vigilance (PVT mean RRT and PVT lapses) in HC. In contrast, only the Rouleau scale showed a relationship with PVT lapses in PD. The correlation with PVT, but not with ESS, suggests that the PVT captures attentional aspects of cognition as well as vigilance, while ESS only measures subjective sleepiness. The reason for this discrepancy in correlation between PVT and the CDT scores in HC and PD may also be due to other confounding factors such as motor impairments faced by participants with PD on the motor component of the PVT assessment. Further study will be required in other samples of PD and HC to confirm reproducibility of these results.
Our study has several strengths, including demonstration of the feasibility of the CDT in PD, the large number of participants evaluated, the use of two separate scoring scales, and the establishment of a cut point to identify individuals who need additional cognitive assessment. Further, the current work supports and reproduces prior work showing that CDT is useful for detecting cognitive impairment in PD and is impaired in PD relative to controls [12, 20]. However, the study also has some limitations. First, this is a cross-sectional study and therefore does not demonstrate the utility of the CDT for predicting cognitive decline or show if the CDT is reproducible within participant. Additionally, the CDT was administered as part of the MoCA, which has a smaller space for drawing the clock than a full page. This has potential to make it more difficult to score certain error aspects, such as evaluating if numbers are equidistant from the clock face. However, this would make it more challenging to detect differences between PD and HC, and therefore actually make our conclusions more conservative. Further, although we documented side of symptom onset for PD individuals, we did not record dominant hand and therefore could not adjust for this in the analyses. However, participants were in the on-medication state at the time of the assessments, so this may reduce the impact of motor symptoms on the outcomes. We also did not adjust results based on medications such as anticholinergics, anxiolytics, or hypnotics, which could have affected individual performance on the cognitive screening. Finally, there are some disadvantages to using scales that were designed to assess AD to evaluate participants with PD. Specifically, the Mendez CDT scale was designed to target the specific cognitive errors in AD, which has a different cognitive profile compared to PD. However, there are some overlapping cognitive deficits in PD [21]. Additionally, PD motor symptoms could influence CDT performance unrelated to cognition.
The Rouleau CDT scale has many subjective aspects to the scoring, making the scale more challenging to use. However, the Mendez CDT scale has weaknesses for use in PD as well. For example, one error aspect of the Mendez CDT scale is that it tries to assess intent (Item 20 –“attempt made to indicate time . . . ”), which is difficult to gauge when the raters do not witness the CDT attempt (in this case, to maintain blinding to diagnosis), and are only provided the completed clock.
Despite the disadvantages of using scales that were designed for AD to assess PD clocks, there is significant potential for using the CDT to assess cognitive impairment in a clinical setting. The CDT is easy to administer without the requirement for specialized skills or training. Our findings suggest that the CDT may be useful as a rapid cognitive screening tool for clinicians to quickly gauge a patient’s cognitive health in order to identify individuals in need of more comprehensive testing. The utility of the CDT to investigate longitudinal changes in cognition was not investigated in this study, but this would be useful to investigate in future studies to determine if CDT could be a measure of cognitive decline or could be used to test responsiveness to cognitive interventions or other treatments. There is also potential for creation of a CDT scoring scale tailored to PD, which takes into account specific error aspects that are more likely to be observed in PD patients.
In conclusion, the CDT is a widely available, rapid clinical assessment that is feasible for use in patients with PD and correlates with other measures of cognition. Given that specific error aspects can be identified among PD compared to HC, the Mendez CDT scale may be more sensitive in capturing discrete components of cognitive dysfunction. Finally, the relationships observed in the current study show that the CDT is a valuable tool to gauge global cognition and executive function in PD in order to identify individuals in need of more comprehensive testing.
Footnotes
ACKNOWLEDGMENTS
This project was supported by funding from the University of Alabama at Birmingham’s Department of Neurology along with the National Institute of Health K23NS080912.
CONFLICT OF INTEREST
The authors have no conflict of interest to report.