Abstract
We aimed to investigate the role of the APOE genotype in cognitive and motor trajectories in Parkinson's disease (PD). Using PD registry data, we retrospectively investigated a total of 253 patients with PD who underwent the Mini-Mental State Exam (MMSE) two or more times at least 5 years apart, were aged over 40 years, and free of dementia at the time of enrollment. We performed group-based trajectory modeling to identify patterns of cognitive change using the MMSE. Kaplan-Meier survival analysis was used to investigate the role of the APOE genotype in cognitive and motor progression. Trajectory analysis divided patients into four groups: early fast decline, fast decline, gradual decline, and stable groups with annual MMSE scores decline of - 2.8, - 1.8, - 0.6, and - 0.1 points per year, respectively. The frequency of APOE ε4 was higher in patients in the early fast decline and fast decline groups (50.0%) than those in the stable group (20.1%) (p = 0.007). APOE ε4, in addition to older age at onset, depressive mood, and higher H&Y stage, was associated with the cognitive decline rate, but no APOE genotype was associated with motor progression. APOE genotype could be used to predict the cognitive trajectory in PD.