Objective: To compare the allele frequencies of genetic variants associated with cognitive impairment between Parkinson’s Disease (PD) patients and controls and to examine their interaction with cognitive performance.
Background: PD patients not only present motor symptoms (e.g., tremor or rigidity) but also psychological and cognitive symptoms, such as decline in their cognitive1. The susceptibility for developing cognitive decline (CD) has been associated with genetic factors, e.g., variants in the SNCA, APOE and GBA1 genes2. However, there is a lack of understanding regarding whether the genetic variants associated with the European population replicate their effects in admixed populations, such as the Mexican population.
Method: We used a subset of data from the Mexican Parkinson’s Research Network consisting of a cohort of 44 PD patients (mean age ± SD; 65.2 ± 10.1) and 74 healthy controls (53.5 ±7.6). DNA samples were collected from participants using buccal swabs. Following extraction, the samples were genotyped with the Illumina NeuroBooster Array, underwent variant calling, quality control, and were imputed using the TOPMed Imputation server. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA; version 7). We analyzed 9 SNPs from APOE, SNCA, CR1, BIN1, INPP5D, ALDH1A1, SORL1, PMVK and GBA1 genes, based on the results of Adams et al., 20152. A linear regression model was used to assess the association between genetic variants and cognitive performance, considering the interaction between genetic variants and the status group. The model was adjusted for sex, age and the first five principal components to account for population stratification.
Results: Only the rs114138760 variant of PMVK gene was significantly associated with PD (p= 0.015) and showed an effect (β = 0.0179, SE = 0.0073) with cognitive performance within PD patients (Figure 1.); however, this effect did not survive the FDR correction (p=0.139).
Conclusion: This study represents an initial approach to understanding the association between the genetics of PD and CD in the Mexican population. Due to the small sample size, our ability to detect significant associations is limited; however, future analyses with larger cohorts will allow for a more in-depth investigation.
Figure 1.
References: 1. Tolosa, E., Garrido, A., Scholz W, S., & Werner, P. (2021). Challenges in the diagnosis of Parkinson’s disease. Lancet Neurology, 20(5), 385–397. https://doi.org/10.1016/S1474-4422(21)00030-2
2. Adams, H. H., de Bruijn, R. F., Hofman, A., Uitterlinden, A. G., van Duijn, C. M., Vernooij, M. W., … & Ikram, M. A. (2015). Genetic risk of neurodegenerative diseases is associated with mild cognitive impairment and conversion to dementia. Alzheimer’s & Dementia, 11(11), 1277-1285.
To cite this abstract in AMA style:
A. Lázaro Figueroa, P. Reyes-Pérez, A. Morales, E. Morelos-Figaredo, C. Guerra-Galicia, I. Estrada-Bellmann, N. Gandarilla-Martínez, K. Salinas-Barboza, D. Oropeza, J. Esquivias, I. Hernández-Ruiz, G. de Anda, E. Waldo, T. Leal, M. Inca-Martinez, I. Mata, S. Alcauter, M. Rentería, A. Medina-Rivera, A. Ruiz-Contreras. Approach into the genetics of cognitive performance in Mexican Parkinson’s Disease patients. [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/approach-into-the-genetics-of-cognitive-performance-in-mexican-parkinsons-disease-patients/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/approach-into-the-genetics-of-cognitive-performance-in-mexican-parkinsons-disease-patients/