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Dementia is one of the most disabling nonmotor symptoms of Parkinson's disease (PD). However, the risk factors contributing to its development remain unclear. To investigate genetic variants associated with dementia in PD, we performed microarray genotyping based on a customized platform utilizing variants identified in previous genetic studies. Microarray genotyping was performed in 313 PD patients with dementia, 321 PD patients without dementia, and 635 healthy controls. The primary analysis was performed using a multiple logistic regression model adjusted for age and sex. SNCA single nucleotide polymorphism (SNP) rs11931074 was determined to be most significantly associated with PD (odds ratio = 0.66, 95% confidence interval = 0.56-0.78, p = 7.75 × 10 -7 ). In the analysis performed for patients with PD only, MUL1 SNP rs3738128 (odds ratio = 2.52, 95% confidence interval = 1.68-3.79, p = 8.75 × 10 -6 ) was found to be most significantly associated with dementia in PD. SNPs in ZHX2 and ERP29 were also associated with dementia in PD. This microarray genomic study identified new loci of MUL1 associated with dementia in PD, suggesting an essential role of mitochondrial dysfunction in the development of dementia in patients with PD.

Background: Around 15% to 20% of patients with clinically probable Alzheimer disease have been found to have no significant Alzheimer pathology on amyloid positron emission tomography. A previous study showed that conversion to dementia from amyloid-negative mild cognitive impairment (MCI) was observed in up to 11% of patients, drawing attention to this condition.Object: We gathered the detailed neuropsychological and neuroimaging data of this population to elucidate factors for conversion to dementia from amyloid-negative amnestic MCI.Methods: This study was a single-institutional, retrospective cohort study of amyloid-negative MCI patients over age 50 with at least 36 months of follow-up. All subjects underwent detailed neuropsychological testing, 3 tesla brain magnetic resonance imaging), and fluorine-18(18F)-florbetaben amyloid positron emission tomography scans.Results: During the follow-up period, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The converter group had more severe impairment in all visual memory tasks. The volumetric analysis revealed that the converter group had significantly reduced total hippocampal volume on the right side, gray matter volume in the right lateral temporal, lingual gyri, and occipital pole.Conclusion: Our study showed that reduced gray matter volume related to visual memory processing may predict clinical progression in this amyloid-negative MCI population. [ABSTRACT FROM AUTHOR]

We aimed to investigate the role of the APOE genotype in cognitive and motor trajectories in Parkinson's disease (PD). Using PD registry data, we retrospectively investigated a total of 253 patients with PD who underwent the Mini-Mental State Exam (MMSE) two or more times at least 5 years apart, were aged over 40 years, and free of dementia at the time of enrollment. We performed group-based trajectory modeling to identify patterns of cognitive change using the MMSE. Kaplan–Meier survival analysis was used to investigate the role of the APOE genotype in cognitive and motor progression. Trajectory analysis divided patients into four groups: early fast decline, fast decline, gradual decline, and stable groups with annual MMSE scores decline of − 2.8, − 1.8, − 0.6, and − 0.1 points per year, respectively. The frequency of APOE ε4 was higher in patients in the early fast decline and fast decline groups (50.0%) than those in the stable group (20.1%) (p = 0.007). APOE ε4, in addition to older age at onset, depressive mood, and higher H&Y stage, was associated with the cognitive decline rate, but no APOE genotype was associated with motor progression. APOE genotype could be used to predict the cognitive trajectory in PD. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is very common in Parkinson's disease (PD) and constitutes the most debilitating complication of this disease. However, to date, few studies have investigated a genome-wide association in the development of cognitive impairment of PD. We aimed to identify the genetic loci associated with cognitive impairment in patients with sporadic PD by ethnicity-specific genotyping. Materials and methods: We recruited 1,070 patients with PD and performed a genome-wide association study using the Korean Chip, a microarray chip containing 827,400 single-nucleotide polymorphisms (SNPs) optimized for the Korean population. Multiple logistic regression models adjusting for age, sex, years of education, and disease duration were used to compare between patients with and without cognitive impairment, which was defined using the Mini-Mental Status Examination (MMSE) score (MMSE score ≥ 26 vs. < 26) or the Montreal Cognitive Assessment (MoCA) score (MoCA score ≥24 vs. < 24). Results: RYR2 SNP rs10495397 was most significantly associated with cognitive impairment based on the MMSE scores (OR = 3.21; 95% CI = 1.96–5.25, P = 3.36 × 10−6) and CASC17 showed the strongest association with cognitive impairment based on the MoCA scores. However, none of the SNPs were statistically significant after Bonferroni correction. Conclusion: RYR2 may play a role in cognitive impairment in PD by the pathogenic mechanism of neuroinflammation. However, more studies are needed to replicate and validate the results of our functional study. [ABSTRACT FROM AUTHOR]