Impact of the apolipoprotein E ε4 allele on early Parkinson's disease progression.

Objective: Emerging evidence shows that apolipoprotein E (APOE) ε4 exacerbates alpha-synuclein pathology. We aimed to investigate whether the APOE ε4 allele contributes to early Parkinson's disease (PD) progression.

Methods: This cohort study included 361 early PD patients who were classified as APOE ε4 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 ε4 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 ε4 allele in the progression of early PD. More specifically, this allele was associated with poorer performance in semantic verbal fluency among cognitive domains.