We enrolled 314 patients (age range: 42-83 years) with PD. Two neurologists independently confirmed the diagnosis of PD based on the United Kingdom PD Brain Bank’s definition . The exclusion criteria included: (1) clinically confirmed diagnosis of PD secondary to other diseases; (2) PD concurrent with severe systemic debilitating diseases, such as cardiac, renal, or liver failure; and (3) incomplete case history. This study was approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University. We obtained informed consent from each patient.
The clinical diagnosis of MSD was confirmed using scores of both the speech (oral communication) item (item 18) of the Unified Parkinson's Disease Rating Scale (UPDRS) and the Frenchay dysarthria assessment (FDA) by two separate speech therapists. In UPDRS-item 18, score 0 denotes a normal speech motor, Score 1 denotes a mild decline of oral communication and vocal frequency, score 2 denotes a moderate decline of oral communication and vocal frequency, score 3 denotes a remarkable decline of oral communication and vocal frequency, and score 4 denotes a disability of speech motor. Patients with a score 1 or higher were considered as having MSD. In FDA, there are 28 evaluation items. Grade a denotes a completely normal status. The final evaluated score was the Grade a score and patients with a score of 26a or lower were considered as having MSD. MSD diagnosis was only confirmed when the patient had both an UPDRS-item18 score of one or higher and an FDA score of 26a or lower. Based on these two scales, we assigned the PD patients to either the MSD or non-MSD group. In this study, there were 250 patients in the MSD group and 64 patients in the non-MSD group. The whole diagnostic procedure of MSD is shown in Figure 1.
Data Collection and scale evaluation
Demographic data were collected via face-to-face interviews or written questionnaires. Clinical data, including case history and magnetic resonance imaging (MRI) brain scans, were collected from the medical records of each patient. Lesions in the frontal or temporal lobe were defined as hypointense lesions on T1-weight and/or hyperintense lesions on T2-weight in the frontal or temporal lobe.
After obtaining access to each patient’s case history, we evaluated the severity of PD using the modified Hoehn & Yahr staging scale based on the corresponding clinical manifestations. Daily living ability was evaluated via the Modified Barthel Index of activities of daily living (ADL).
We comprehensively evaluated motor function, tremor, and postural instability gait difficulty (PIGD) using the UPDRS motor sum score, tremor score, and PIGD score, respectively .
The widely acknowledged NMSS was used to evaluate the degree of the NMM burden . The NMSS contains a total of thirty items that are divided into nine domains that cover different aspects of daily living functions (i.e., cardiovascular disease, sleep/fatigue, mood/apathy, perceptual problems/hallucinations, attention/memory, gastrointestinal, urinary, sexual function, and miscellaneous). Every item was evaluated quantitatively based on the severity (range: 0 to 3) and frequency (range: 0 to 4) over the previous month. The total score of each item was defined as the domain score. The total score of the NMSS, which is indicative of the overall NMM burden on each patient, was regarded as the sum of the thirty items.
All statistical analyses were carried out using SPSS software (version 18.0). Measurement data and continuous variables are presented as the mean and standard deviation or median and interquartile range, while enumeration data and categorical variables are presented as the frequency and proportion. For univariate analysis, we compared the measurement data from the MSD and non-MSD groups using t-tests or Mann-Whitney U tests. Additionally, we used the Chi-squared or Fisher’s exact tests to compare the enumeration data between the MSD and non-MSD groups in the univariate analysis.
We then carried out multivariate logistic regression analysis to determine the independent risk factors and rule out potential confounding variables. In the final logistic regression analysis model, we only included the risk factors with P values lower than 0.05 from the univariate analysis.
The demographic data of the two groups are shown in Table 1. There were 250 patients in the MSD group (168 males and 82 females) and 64 patients in the non-MSD group (40 males and 24 females). The average age was 64.3 ± 9.5 years in the MSD group and 62.3 ± 8.7 years in the non-MSD group. Student’s t-test analysis showed that there was no significant difference in the average age, age at PD onset, and duration of PD between the two groups (all P > 0.05). The proportion of patients with a family history of PD was similar in both groups (P > 0.05).
The Chi-squared test revealed that a higher percentage of patients engaged in manual labor in the MSD group (68.00%) than in the non-MSD group (53.13%; P = 0.026). More patients in the MSD group (84.00%) had a low level of education (lack of post-secondary education in university) than patients in the non-MSD group (59.37%; P < 0.001). More patients in the MSD group (70.40%) had a low income (lower than 5500 yuan) compared to those in the non-MSD group (56.25%; P = 0.031). However, there were no significant differences between these two groups in terms of gender, marital status, or leisure activities (P > 0.05 for all).
Data on the clinical characteristics of the two groups are shown in Table 2. There were no significant differences between the two groups in terms of hypertension, hyperlipidemia, ischemic heart disease, or diabetes mellitus (P > 0.05 for all).
The Chi-squared test revealed that there were more frontal lobe lesions in the MSD group (78.00%) than in the non-MSD group (59.38%; P = 0.002). Similarly, there were more temporal lobe lesions in the MSD group (51.60%) than in the non-MSD group (35.94%; P = 0.025). In addition, a higher percentage of patients had concurrent dysphagia in the MSD group (46.40%) than in the non-MSD group (31.25%; P = 0.029). However, no significant differences were found in terms of concurrence with other CNS diseases between these two groups (P > 0.05 for all).
Anti-PD drugs, such as levodopa, selegiline, and amantadine, were prescribed more often in the MSD group, while dopamine agonists were prescribed more often in the non-MSD group. However, there were no significant differences in the medication frequency or drug dose between the two groups (P > 0.05 for all).
The differences in the PD-associated evaluations between the two groups are shown in Table 3. The Mann-Whitney U test revealed that the ADL score was lower in the MSD group than in the non-MSD group (P = 0.020). However, there was no significant difference in the Hoehn & Yahr stage score and duration of PD between the MSD group and non-MSD group (P = 0.095).
Regarding the UPDRS score, the UPDRS motor sum, tremor score, and PIGD scores were numerically, but not significantly, higher in the MSD group compared to the non-MSD group after the Mann-Whitney U test (P > 0.05 for all).
In the univariate analysis of the NMSS scores, the Mann-Whitney U test revealed that both NMSS domain 4 (perceptual problem) and NMSS domain 5 (attention/memory) scores were significantly higher in the MSD group than in the non- MSD group (P = 0.033 and P < 0.001, respectively). However, there were no significant differences in the other NMSS domain scores between the two groups (P > 0.05 for all).
Multivariate logistic regression
Multivariate logistic regression analysis excluded some of the significant factors from the univariate analysis, including occupation, monthly income, temporal lobe lesions, concurrent dysphagia, ADL score, and NMSS domain 4 score (perceptual problems), from the pool of independent risk factors. On the other hand, potential risk factors, including educational level, frontal lobe lesions, and NMSS domain 5 score (attention/memory), had a significant power to predict risk for MSD in PD.
The patients with a higher educational level [OR = 0.674, 95% CI (0.590, 0.808)] had a lower likelihood of PD-associated MSD. However, patients with a higher occurrence of frontal lobe lesions [OR = 5.145, 95% CI (2.018, 7.308)], or higher NMSS domain 5 scores (attention/memory) [OR = 10.458, 95% CI (6.164, 15.209)] had a higher likelihood of PD-associated MSD.