Objective: We aimed to investigate the progression patterns of cognitive impairment in patients with Parkinson’s disease (PD), and to identify the baseline predictors, including both genetic and environmental factors, for the progression of cognitive impairment in PD.

Background: Cognitive impairment is one of the common non-motor symptoms of PD. The progression patterns of cognitive impairment are heterogenous, and little is known about the cognitive trajectory in PD.

Method: We retrospectively investigated a total of 246 patients with PD from a cohort of Korean genome wide association study, aged over 40 years, free of dementia at study enrollment, and who underwent two or more timepoints of Mini-Mental State Exam (MMSE) with total time interval over 3 years. We performed trajectory analyses to classify PD patients according to the progression, measured by z score on MMSE. Baseline variable used to predict progression included carriage of the apolipoprotein E4 (APOE4) allele, weighted polygenic risk score (PRS) of PD risk single nucleotide polymorphisms, sociodemographic factors, and comorbidities.

Results: Trajectory analyses showed that patients with PD were divided into 3 groups: fast decliner (11.8%), slow decliner (21.1%), and stable group (67.1%) with mean follow-up duration of 5.6 ± 2.3 years. Mean annual change on z score were -1.23, -0.25, and -0.05 in the subgroups of fast decliner/slow decliner/stable group, respectively. Fast decliners had the higher frequency of APOE4 allele, compared to stable groups (39% vs. 18%, P = 0.03). There was no significant difference in PRS of PD risk since nucleotide polymorphisms between 3 groups. Fast decliners were older at diagnosis (mean 63.5 vs. 59.1, P < 0.001), had longer education year (12.3 vs. 9.4, P = 0.007), and had more diabetes mellitus (27.6% vs. 8.5%, P = 0.004), compared to stable groups. Consumption of caffeine, alcohol, and smoking, and the use of pesticide at study enroll were not significantly different between 3 groups. Other non-motor symptoms at study enroll, including hyposmia, pain, fatigue, autonomic dysfunction, depressive mood, and rapid eye movement behavior disorders, were not significantly different between 3 groups.

Conclusion: In this study, we elucidated heterogenous cognitive trajectories of PD, and found that APOE4 allele and diabetes mellitus at the diagnosis of PD were associated with fast cognitive progression.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-and-environmental-prognostics-of-cognitive-trajectories-in-patients-with-parkinsons-disease/