Impact of the apolipoprotein E? 4 allele on early Parkinson ? s disease progression

Objective: Emerging evidence shows that apolipoprotein E (APOE) ?4 exacerbates alpha-synuclein pathology. We aimed to investigate whether the APOE ?4 allele contributes to early Parkinson?s disease (PD) progression. Methods: This cohort study included 361 early PD patients who were classified as APOE ?4 carriers (n = 90) and noncarriers (n = 271). The patients underwent yearly motor and nonmotor assessments covering neuropsychiatric, sleep-related, and autonomic symptoms over 5 years of follow-up. Dopamine transporter (DAT) imaging was conducted at baseline and the 1-, 2-, and 4-year follow-up visits. Results: The APOE ?4 carriers had steeper declines in the Montreal Cognitive Assessment score (p=0.005) and the semantic fluency test score (p=0.012) than the noncarriers. No significant between-group differences in the longitudinal changes in motor, other nonmotor, and DAT imaging variables were observed. Conclusions: Our exploratory analyses show that only cognitive performance was negatively affected by the APOE ?4 allele in the progression of early PD. More specifically, this allele was associated with poorer performance in semantic verbal fluency among cognitive domains.

Automated summary

The study found that the APOE ?4 allele has a negative impact on cognitive function in early Parkinson's disease patients; over 5 years of follow-up, APOE ?4 carriers showed steeper declines in the Montreal Cognitive Assessment score and semantic fluency test score, with no significant differences observed in other motor and nonmotor functions or DAT imaging variables.