Associations of Apolipoprotein ε4 Genotypes with Motor and Nonmotor Symptoms in Parkinson's Disease: A Cross‐Sectional Study

BACKGROUND: The apolipoprotein E (APOE) ε4 allele has been associated with cognitive decline in Parkinson's disease (PD), but little is known about its relationship with motor and other nonmotor symptoms and whether APOE ε4 retains an influence on cognition when other factors are considered. OBJECTIVE: To investigate the impact of APOE ε4 on motor/nonmotor symptoms and its relationship with other factors affecting cognition in individuals with PD. METHODS: We analyzed data from 7616 individuals, comparing motor/nonmotor symptoms in different APOE genotypes using binary logistic regression. Multivariate logistic regression examined factors associated with cognitive impairments, including APOE ε4, Geriatric Depression Scale (GDS) score, Non‐motor Symptom Questionnaire (NMS) score, Movement Disorder Society–Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part II score, and physical activity level. RESULTS: APOE ε4 heterozygosity was modestly associated with lower cognitive scores (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.87–0.99), whereas no significant association was found for any other nonmotor and motor symptoms. However, in multivariate analysis, cognitive impairment was associated with higher GDS (OR, 1.28; 95% CI, 1.23–1.34), NMS (OR, 1.22; 95% CI, 1.19–1.25), and MDS‐UPDRS Part II (OR, 1.07; 95% CI, 1.06–1.09) scores, whereas physical activity was negatively associated (OR, 0.99; 95% CI, 0.98–0.99). APOE ε4 was no longer significant after adjusting for these factors. CONCLUSIONS: There is a link between cognition and APOE ε4 in patients with PD; however, when considering multiple factors, APOE ε4 plays a subordinate role. Other factors, such as depression, physical activity, and other nonmotor symptoms, demonstrate a stronger influence on cognitive impairment.