APOE and Cognitive impairment: However, the variation of these three genes appears to alter the neural substrates for major cognitive domains even soon after diagnosis of Parkinson’s disease, which we suggest is directly relevant to their modification of the risk of cognitive impairment or dementia in the context of Parkinson’s disease (APOE4, MAPT) and the potentially deleterious effects of high dose levodopa therapy on some aspects of cognition in a subset of patients (COMT).