Objective: We aim to investigate the genetic mutations related to the development of dementia in Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) using a customized microarray chip, developed to detect variants associated with PDD and DLB.
Background: Lewy Body Dementia (LBD) includes PDD and DLB. Both PDD and DLB share common clinical symptoms including dementia and parkinsonism, and they have common neuropathology. The cognitive decline is heterogeneous in PDD and DLB, and genetic risk factors might explain the heterogeneity and pathophysiology of dementia. Although genome-wide association studies investigated genetic variants associated with PD susceptibility, there was a small number of genetic studies dealing with cognitive decline in PDD and DLB.
Method: We prospectively enrolled 313 PDD, 321 PD patients without dementia, 11 patients with DLB, and 635 healthy controls. For the primary analysis, genome-wide association studies were performed using a multiple logistic regression model adjusting for age and sex. In addition, we investigated rare variants and analyzed genotypes associated with the early development of dementia in PD using Cox regression analysis.
Results: We found that MUL1 SNP rs3738128 (odds ratio = 2.52, 95% confidence interval = 1.68 – 3.79, P = 8.75 × 10-6) was significantly associated with PDD compared with PD without dementia. ERP29 and ZHX2 SNPs were also associated with PDD compared with PD without dementia. ATP7B SNP rs148399850 was most significantly associated with DLB compared with healthy controls (OR = 18.73, 95% CI = 4.64 – 75.70, P = 3.92 × 10-5), the significance of which disappeared after Bonferroni correction. Rare variants in AK5 and PIK3CG were associated with PDD. In Cox regression analysis, MUL1 SNP rs3738128 was most significantly associated with the development of dementia at a young age in PD (P = 1.63 × 10-9).
Conclusion: MUL1 SNPs were associated with PDD and early development of dementia in PD, suggesting a central role of mitochondrial function in the pathogenesis of PDD. In addition, rare variants in the AK5 and PIK3CG genes, which are involved in an inflammatory process, were also associated with PDD.
To cite this abstract in AMA style:
J. Lee, S. Jo, S. Lee, MS. Kim, SJ. Chung. Investigating genetic risk factors for Lewy body dementia [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/investigating-genetic-risk-factors-for-lewy-body-dementia/. Accessed June 14, 2025.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/investigating-genetic-risk-factors-for-lewy-body-dementia/