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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.

The role of APOE in cognitive trajectories and motor decline in Parkinson’s disease