IMPORTANCE Large-scale genome-wide association studies in the European population have identified 90 risk variants associated with Parkinson disease (PD); however, there are limited studies in the largest population worldwide (ie, Asian).OBJECTIVES To identify novel genome-wide significant loci for PD in Asian individuals and to compare genetic risk between Asian and European cohorts.DESIGN SETTING, AND PARTICIPANTS Genome-wide association data generated from PD cases and controls in an Asian population (ie, Singapore/Malaysia, Hong Kong, Taiwan, mainland China, and South Korea) were collected from January 1, 2016, to December 31, 2018, as part of an ongoing study. Results were combined with inverse variance meta-analysis, and replication of top loci in European and Japanese samples was performed. Discovery samples of 31 575 individuals passing quality control of 35 994 recruited were used, with a greater than 90% participation rate. A replication cohort of 1 926 361 European-ancestry and 3509 Japanese samples was analyzed. Parkinson disease was diagnosed using UK Parkinson's Disease Society Brain Bank Criteria. MAIN OUTCOMES AND MEASURESGenotypes of common variants, association with disease status, and polygenic risk scores. RESULTS Of 31 575 samples identified, 6724 PD cases (mean [SD] age, 64.3 [10] years; age at onset, 58.8 [10.6] years; 3472 [53.2%] men) and 24 851 controls (age, 59.4 [11.4] years; 11 030 [45.0%] men) were analyzed in the discovery study. Eleven genome-wide significant loci were identified; 2 of these loci were novel (SV2C and WBSCR17) and 9 were previously found in Europeans. Replication in European-ancestry and Japanese samples showed robust association for SV2C (rs246814; odds ratio, 1.16; 95% CI, 1.11-1.21; P = 1.17 × 10 −10 in metaanalysis of discovery and replication samples) but showed potential genetic heterogeneity at WBSCR17 (rs9638616; I 2 =67.1%; P = 3.40 × 10 −3 for hetereogeneity). Polygenic risk score models including variants at these 11 loci were associated with a significant improvement in area under the curve over the model based on 78 European loci alone (63.1% vs 60.2%; P = 6. 81 × 10 −12 ).CONCLUSIONS AND RELEVANCE This study identified 2 apparently novel gene loci and found 9 previously identified European loci to be associated with PD in this large, meta-genome-wide association study in a worldwide population of Asian individuals and reports similarities and differences in genetic risk factors between Asian and European individuals in the risk for PD. These findings may lead to improved stratification of Asian patients and controls based on polygenic risk scores. Our findings have potential academic and clinical importance for risk stratification and precision medicine in Asia.

Background/Aims: To evaluate the psychometric properties of the Hong Kong Montreal Cognitive Assessment (HK-MoCA) in patients with cerebral small vessel disease (SVD). Methods: 40 SVD patients and 40 matched controls were recruited. Concurrent and criterion validity, inter-rater and test-retest reliability, internal consistency of the HK-MoCA were examined and clinical observations were made. Results: Performance on the HK-MoCA was significantly predicted by both executive (β = 0.23, p = 0.013) and non-executive (β = 0.64, p < 0.001) composite scores. It differentiated SVD patients from controls (area under the curve = 0.81, p < 0.001) with an optimal cutoff at 21/22. Reliability, internal consistency and clinical utility were good. Conclusion: The HK-MoCA is a useful cognitive screening instrument for use in SVD patients.

Background and Purpose The NINDS-CSN vascular cognitive impairment (VCI) Harmonization working group proposed a brief cognitive protocol for screening of VCI. We investigated the validity, reliability and feasibility of the Montreal Cognitive Assessment 5-minute protocol (MoCA 5-min protocol) administered over the telephone. Methods Four items examining attention, verbal learning and memory, executive functions/language and orientation were extracted from the MoCA to form the MoCA 5-min protocol. One hundred and four patients with stroke or TIA, including 53 with normal cognition (CDR 0) and 51 with cognitive impairment (CDR 0.5 or 1), were administered the MoCA in clinic and a month later, the MoCA 5-min protocol over the telephone. Results Administration of the MoCA 5-min protocol took five minutes over the telephone. Total score of the MoCA 5-min protocol correlated negatively with age (r=-0.36, p<0.001) and positively with years of education (r=0.41, p<0.001) but not with gender (rho=0.03, p=0.773). Total scores of the MoCA and MoCA 5-min protocol were highly correlated (r=0.87, p<0.001). The MoCA 5-min protocol performed equally well as the MoCA in differentiating patients with cognitive impairment from those without (AUC for MoCA 5-min protocol=0.78; MoCA=0.74, p>0.05 for difference; Cohen's d for group difference 0.801.13). It differentiated cognitively impaired patients with executive domain impairment from those without (AUC=0.89, p<0.001; Cohen's d=1.7 for group difference). 30-day test-retest reliability was excellent (Intraclass correlation coefficient=0.89). Conclusions The MoCA 5-min protocol is a free, valid and reliable cognitive screen for stroke and TIA. It is brief and highly feasible for telephone administration.