Stereopsis impairment is associated with decreased color perception and worse motor performance in Parkinson’s disease

Between July 2011 and November 2011, 114 PD patients were recruited at the Movement Disorder Center at Xuanwu Hospital Capital Medical University in Beijing, China, to participate in the study. All patients signed the consent forms for participation. All experimental and clinical procedures were reviewed and approved by the Ethics Committee of Xuanwu Hospital, Capital Medical University.

The diagnosis of movement disorders in PD patients was made according to the UK Parkinson’s Disease Society Brain Bank clinical diagnostic criteria [14]. Patients with identified brain lesions or any other neurological disorders were excluded. Patients’ spouses and relatives were screened to participate in this study as age-matched controls. All participants underwent tests for visual acuity and strabismus. To eliminate the influence of ametropia, corrective lenses were permitted during the stereopsis and color perception tests. The exclusion criteria were presence of strabismus, nystagmus, ocular motility disturbance or poor visual acuity, even after correction in either eye (<20/40 Snellen fraction). Furthermore, the patients were asked about their history of eye diseases. Those with a history of unoperated symptomatic cataracts, untreated glaucoma, diabetic eye disease, congenital color blindness or significant cognitive impairment were also excluded from the study. After applying these criteria, 19 of the 114 patients were excluded from the study.

Standardized neurologic examinations and clinical assessments were performed. All evaluations were carried out in the morning, and patients were asked not to take any antiparkinsonian medications for at least 12 hours (18 hours for combined levodopa and carbidopa) to ensure a practically defined off state [15]. The Hoehn and Yahr (H&Y) stage and Unified Parkinson’s Disease Rating Scale (UPDRS) scores were determined. The Purdue Pegboard Test (PPT) was used to test hand dexterity and motor speed. Briefly, this test requires the person to place as many pins as possible in vertical columns of holes on a board within 30 seconds. The pins were placed in the right, left and both hands three times for each, and the average number of the pins placed under the three conditions were recorded. The total average number (TAN) of Purdue Pegboard Test scores was used as the measurement method.

Seven patients who had obvious “on and off” phenomenon were evaluated on the basis of two sets of UPDRS score, H&Y stage and PPT scores: after they had taken or not taken their usual antiparkinsonian medication. The Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess patients’ cognitive function.

Data were analyzed using SPSS version 11.5 software (SPSS, Chicago, IL, USA). As age might influence visual function [16], comparisons of visual function between PD patients and controls were performed with one-way analysis of variance, including age as a confounding covariate. To assess the characteristics of participants with normal or abnormal stereopsis, a t-test was carried out. The logistic regression model was used to determine the independent risk factors for stereopsis impairment in PD patients. The multiple linear regression model was used to study the independent factors affecting color perception and UPDRS part III score in PD patients. Visual and motor functions in PD patients while taking or not taking medication were assessed by performing a paired t-test. Differences were considered to be significant if the P-value was <0.05.

A total of 114 participants, comprising 53 PD patients and 61 non-PD patients (controls), were included in this study. From among these participants, 19 were excluded because of concomitant brain lesions (n = 3), poor visual acuity (n = 8), symptomatic cataracts (n = 6) or congenital color blindness (n = 2). As a result, 45 PD patients (26 men and 19 women, mean age of 65.40 years, range from 45 to 81 years) and 50 controls (22 men and 28 women, mean age of 65.48 years, range from 47 to 83 years) were enrolled into the study. The PD patients had the following characteristics: mean H&Y stage 2.22 ± 0.68, mean UPDRS motor score 25.18 ± 13.06, mean MMSE score 27.50 ± 3.09, mean MoCA score 23.95 ± 5.03 and mean disease duration 6.60 ± 4.52 years. The mean TAN (PPT scores) in PD patients was 34.28 ± 10.12, which is significantly lower than the mean score of 49.56 ± 6.50 in controls (P = 0.0001). TAN (PPT scores) was correlated with UPDRS total score, UPDRS motor score and H&Y stage in PD patients (P = 0.0001, P = 0.0001 and P = 0.029, respectively). However, they were not associated with MMSE score, MoCA score or disease duration (P = 0.519, P = 0.135 and P = 0.160, respectively). TAN (PPT scores) was correlated with age in controls (P = 0.0001), as younger control participants had better values than elderly ones. Overall, the demographic features of participants and the clinical rating scales used to assess PD patients are listed in Table 1. The TAN correlation factors are shown in Table 2.

We compared stereopsis and color perception between PD patients and controls after matching for age between the two groups. For color perception, the TES and PES for red, green, blue and purple were all significantly higher in PD patients than in controls (P = 0.0001, P = 0.001, P = 0.0001, P = 0.001 and P = 0.0001, respectively). The LG values on the FLY Stereo Acuity Test with LEA Symbols were significantly lower in PD patients than in controls (P = 0.0001), and the percentage of abnormal stereopsis in PD patients (42.2%) was significantly higher than that in controls (12.0%) (P = 0.001). The comparisons of color perception and stereopsis are presented in Table 3.

A multiple linear regression model was used to study the factors influencing color perception in PD patients, with TES used as the dependent variable. The probed stereopsis factors included age, H&Y stage, UPDRS total score, duration of disease, MMSE score, MoCA score, TAN (PPT scores) and LG values. Our results show that only age was independently and significantly associated with TES in PD patients (t = 2.583, P = 0.015).

To study the factors associated with stereopsis function, PD patients with normal stereopsis (PDNS) and PD patients with abnormal stereopsis (PDAS) were compared. These data are shown in Table 4. We found no significant differences with regard to age, H&Y stage, disease duration or MMSE and MoCA scores between PDNS and PDAS. However, in PDAS, UPDRS total scores and UPDRS motor scores were higher (P = 0.033 and P = 0.018, respectively), whereas TAN (PPT scores) was lower (P = 0.014). The TES and the PES for green and purple were significantly higher in PDAS than in PDNS (P = 0.019, P = 0.001 and P = 0.039, respectively). To study the independent risk factors for stereopsis impairment in PD patients, we used a logistic regression model. The factors with significant mean values in one-factor analysis were examined using this model. The results show that only the PES for green remained significant, as the adjusted P-value was 0.027 and the odds ratio (OR) of the PES for green was 1.093 (approximately 1.010 to 1.182). In addition, when we compared normal and abnormal stereopsis in the controls, we found no significant differences in TAN (PPT scores), TES or PESs in FMT(Farnsworth-Munsell 100-Hue Test).

The influence of visual function on motor symptoms in PD patients was analyzed using a multiple linear regression model. The UPDRS motor score was considered the dependent variable, and age, H&Y stage, course of disease, MMSE and MoCA scores, TES and LG values on the FLY Stereo Acuity Test with LEA Symbols were used as independent variables. Our results show that LG values on the FLY Stereo Acuity Test with LEA Symbols (P = 0.008) and H&Y stage (P = 0.018) were independently associated with UPDRS motor scores. Our results also show that PD patients with higher H&Y stages and decreased stereopsis had higher UPDRS motor scores and worse motor function. PDAS had higher scores on the UPDRS part III in rigidity, finger taps, hand movements, rapid alternating movements and leg agility, than those of PDNS (P = 0.009, P = 0.001, P = 0.036, P = 0.007 and P = 0.007, respectively) (Table 5).

The UPDRS motor scores and TAN (PPT scores) of the 16 PD patients were significantly improved while taking medications (P < 0.05 and P < 0.05, respectively) (Table 6). TES and PESs for green were lower while taking medications vs not (P < 0.05). We found no difference in stereopsis between when the patients were or were not taking medication (P > 0.05).