BackgroundThe relationship between a number of primary sleep disorders and Parkinson's disease (PD) is still debated. There are limited case control polysomnographic studies in PD and most of these study sample sizes are small.Methodology/FindingsWe conducted one of the largest case-control studies involving overnight polysomnographic evaluation, with prospective recruitment of unselected Parkinson's disease patients and healthy controls from an Asian population. The cases were recruited from the specialized movement disorder outpatient clinics in a tertiary referral center, and controls from the same geographical locations. All subjects underwent an overnight polysomnographic study and a multiple sleep latency test.A total of 124 subjects including 56 patients and 68 controls frequency-matched for age and sex were included. Multivariate analysis revealed that patients had significantly shorter total sleep time than controls (p = 0.01), lower sleep efficiency (p = 0.001) and increased REM latency (p = 0.007). In patients, multivariate analysis showed that reduced total sleep time was significantly associated with increased age (p = 0.001) and increased levodopa dose (p = 0.032). The mean Insomnia Severity Index was higher in PD patients (9.0±7.1) compared to controls (3.3±3.9, p<0.001). The mean Epworth Sleepiness Scale score was higher in PD patients (9.3±5.9 vs. 5.7±4.8, p<0.001). Nocturnal arousals, obstructive sleep apnea, periodic leg movements and objective abnormal sleepiness were not increased in our patients.Conclusions/SignificanceOur case-control polysomnographic study, the first-ever performed in an Asian population, revealed altered sleep architecture and reduced sleep in PD patients compared to controls. Reduced total sleep time was associated with increased age and levodopa dose. However, nocturnal arousals, primary sleep disorders and abnormal sleepiness were not increased in our PD patients suggesting that ethnic/genetic differences may be a factor in the pathophysiology of these conditions.

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Evidence of LRRK2 haplotypes associated with Parkinson's disease (PD) risk was recently found in the Chinese population from Singapore, and a common LRRK2 missense variant, Gly2385Arg, was independently detected as a putative risk factor for PD in the Chinese population from Taiwan. To test the association between the Gly2385Arg variant in a large case-control sample of Chinese ethnicity from Singapore, and to perform functional studies of the wild type and Gly2385Arg LRRK2 protein in human cell lines. In a case-control study involving 989 Chinese subjects, the frequency of the heterozygous Gly2385Arg genotype was higher in PD compared to controls (7.3 vs. 3.6%, odds ratio = 2.1, 95% CI: 1.1-3.9, P = 0.014); these values yield an estimated population attributable risk (PAR) of approximately 4%. In a multivariate logistic regression analysis with the disease group (PD vs. controls) as the dependent variable and the genotype as an independent factor with adjustments made for the effect of age and gender, the heterozygous Gly2385Arg genotype remained associated with an increased risk of PD compared to wild type genotype (odds ratio = 2.67, 95% CI: 1.43-4.99, P = 0.002). The glycine at position 2385 is a candidate site for N-myristoylation, and the Gly2385Arg variant replaces the hydrophobic glycine with the hydrophilic arginine, and increases the net positive charge of the LRRK2 WD40 domain. In transfection studies, we demonstrated that both the wild type and Gly2385Arg variant LRRK2 protein localize to the cytoplasm and form aggregates. However, under condition of oxidative stress, the Gly2385Arg variant was more toxic and associated with a higher rate of apoptosis. Our study lends support to the contention that the Gly2385Arg is a common risk factor for PD in the Chinese population. Our bioinformatics and in-vitro studies also suggest that the Gly2385Arg variant is biologically relevant and it might act through pro-apoptotic mechanisms.