The analyses demonstrated the following: (1) PD-MCI was significantly higher than PD-NC in terms of CSF NfL baseline concentration and longitudinal change rate; (2) CSF NfL predicted the longitudinal cognitive progression of de novo PD patients and successfully marked conversion to cognitive impairment beforehand; and (3) The predictive effects of CSF NfL baseline concentration and the cognitive decline change rate among de novo PD male patients aged >65 who were ill-educated and without APOE ε4 carrier status seemed to be more obvious. Here, APOE is linked to Parkinson disease.