Clinical features of Parkinson’s disease with and without rapid eye movement sleep behavior disorder

One hundred fifty PD patients were enrolled from the Parkinson’s disease and Movement Disorder Center in the Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China from January 2013 to August 2014. The diagnosis of PD was made by two movement disorder specialists according to the UK Parkinson’s Disease Society (UKPDS) Brain Bank Criteria. Patients with severe dementia (CDR ≥ 2), or other central nervous system disorders were excluded from this study. The study was approved by the Institution’s Ethics Committee and all recruited patients consented to participate in the study.

Of 150 patients, 5 patients were excluded because of probable DLB, 3 patients had probable MSA, and 1 patient had vascular Parkinsonism. A total of 141 patients were enrolled in the study. Patient evaluation was performed by movement disorder specialists. Parkinsonism staging was evaluated according to the Hoehn & Yahr staging scale. Part III of the Unified PD Rating Scale (UPDRS III) was performed during the “on” state. Motor subtype was analyzed by predominance of tremor or rigidity (UPDRS sub-scores) and predominance of limb or axial features (UPDRS sub-scores) [9], Hamilton Anxiety Scale (HAMA; cut-off point ≥8), Hamilton depression Scale (HAMD; cut-off point ≥8) and Mini-Mental State Examination (MMSE) were used to evaluate the patient’s mood and cognitive state. The patients whose MMSE score was lower than 17 (illiteracy) or lower than 20 (primary school level) or 24 (higher than middle school cultural level) [11] were considered to have dementia and were evaluated using the Clinical Dementia Rating (CDR). Patients whose CDR was higher than 2 were excluded from the study. Investigators used the REM Sleep Behavior Disorder Screening Questionnaire(RBDSQ)to detect clinical probable RBD (pRBD). We set the RBDSQ cut-off point at a score of 6 according to the highest sensitivity and specificity determined by a previous study [5]. The Parkinson’s disease Sleep Scale (PDSS) was used to evaluate patient’s sleep quality. Orthostatic hypotension (OH) was screened using a simple question:“Do you feel dizziness or weakness when you stand up?” If the answer was “yes”, a blood pressure test from the supine to standing position was checked, a fall in systolic blood pressure of ≥20 mmHg, or in diastolic blood pressure of ≥10 mmHg, was diagnosed as OH. Other items including smoking, alcohol and coffee consumption, hyposmia or anosmia, constipation were also documented by question. Patients continued with their prescribed treatment regimen, they used anti-Parkinson drugs, anti-hypnotics or anti-depressants as necessary.

The data were analyzed using the Statistical Package for Social Sciences (SPSS) 19(IBM Co., USA). The data is presented as mean, counts and percentages, and the adjusted difference in means. Analysis of descriptive variables was performed using two-tailed t tests. Mann-Whitney U tests and X² tests were used where appropriate. A P-P plot was used to test normal distribution. A p value <0.05 was considered to be significant.

Among 141 patients, 74 were male (52.48%): 18 male (60%) in pRBD⁺ group, and 56 male (50.45%) in pRBD⁻ group (p = 0.655). Thirty patients (21.28%) were diagnosed with probable RBD (pRBD) based on a RBD screening questionnaire score ≥ 6. If the cut-off score was set at 7 or 5, the incidence of RBD was 17.02% and 26.24% respectively, with little difference in the clinical features (Table 3). The mean age in the pRBD⁺ group was 68.33 ± 8.76 versus 69.32 ± 9.75 years in the pRBD⁻ group (p = 0.618). Mean PD duration years is 4.13 ± 4.216 in pRBD⁺ and 4.65 ± 3.570 in pRBD⁻ group (p = 0.5). Smoking, alcohol and coffee consumption were infrequent in both groups (NS). There was no difference between the numbers of patients who took levodopa or dopamine agonists, and the levodopa equivalent dosage was similar in both groups. However, the pRBD⁺ group had greater antidepressant and anti-hypnotic use (Table 1).

pRBD⁺ PD patients had significantly higher rates of anxiety (60% vs 22.52%, <0.001) and depression (63.33% vs 24.32%,p < 0.001) (Table 2), and a higher mean PDSS score (17.50 ± 9.60 vs 11.70 ± 8.55, p < 0.001) (Table 2). The pRBD⁺ group had lower mean MMSE score (25.30 ± 3.91 vs. 26.75 ± 3.97, p = 0.017) (Table 3). When educational status was taken into account, a diagnosis of dementia was not significantly difference between two groups (16.67% vs 11.71%, p = 0.538) (Table 2). Constipation and OH were more prominent in the pRBD⁺ group (Table 2).

There was no difference in the incidence of anosmia in pRBD⁺ vs pRBD⁻ group (46.67% vs 35.16%, p = 0.247) (Table 2). From PDSS item 7, we found that there were 13 patients who had visual hallucinations, 20% (6) in pRBD⁺ group and 6.3% (7) in pRBD⁻ group (p = 0.032) (Table 2).

The UPDRS III score was similar in the pRBD⁺ and pRBD⁻ groups (26.93 ± 14.62 vs 23.68 ± 15.93, p = 0.174). Mean H-Y stage was also similar between the two groups (2.40 ± 0.90 vs 2.26 ± 0.90, p = 0.299). When limb scores in UPDRS III was compared with axial scores, the ratio showed no difference between pRBD⁺ and pRBD⁻ groups (5.67 ± 4.22 vs 6.17 ± 4.61, p = 0.734). When rigidity scores in UPDRS III were compared with resting tremor score, the ratio was also not significantly different (3.01 ± 4.06 vs 1.79 ± 2.08, p = 0.32). Overall there was no difference between pRBD⁺ group and pRBD⁻ group for motor severity and motor subtype (Table 2). Freezing was also not different between the two groups (26.7% vs 22.52%, p = 0.75).